MCDB 1 - UCSB Slides only
MCDB 1 - UCSB Slides only
Popular in Course
verified elite notetaker
Popular in Department
verified elite notetaker
This 518 page Reader was uploaded by Stephanie Miller on Tuesday February 4, 2014. The Reader belongs to a course at University of California Santa Barbara taught by a professor in Fall. Since its upload, it has received 131 views.
Reviews for MCDB 1 - UCSB Slides only
Report this Material
What is Karma?
Karma is the currency of StudySoup.
You can buy or earn more Karma at anytime and redeem it for class notes, study guides, flashcards, and more!
Date Created: 02/04/14
MCDB 1B ANIMAL AND PLANT PHYSIOLOGY f ED SClECC 1 0 MCDB 1B Course Information Winter 2010 MCDB 1B MCDB 1B is an introduction to Animal Physiology by Dr Seng vIjIMtiiIow LSB Rm 2111 shlowlifesciucsbedu Plant and Animal Physiology by Dr Ruth Finkelstein Bio II Rm2127 finkelstlifesciucsbedu MCDB 1B lectures are in Campbell Hall from 121250 PM The academic coordinator for this course is Dr Douglas Bush 4326 LSB bushlifesciucsbedu Dr Bush is responsible for handling all problems connected with laboratory enrollment petitions missed exams incomplete work and all administrative matters pertaining to MCDB 1B IBL and IBZ The best time to find Dr Bush is immediately after class in Campbell Hall Exam Schedule Midterm Exam Wed Feb 10 Dr Low39s lectures 100 pts Final Exam Wed Mar 17 Dr Finlltelstein s lectures only 100 pts 123 PM Total 200 pts The Final Exam will only cover material presented by Dr I inkelstein which includes some animal physiology as well as plant physiology No early exams No early exams No early exams Sign up for CLAS MCDB 1B Text Book and study resources The text is Life The Science of Biology by Sadava Heller Orians Purves and Hillis 8th Edition available at the bookstores The Text is also available as an ebook to view on your computer for details see the website wwwthelifewirecom ebook and is on reserve in Davidson Library The course website can be accessed at httpsgauchospaceucsbedu The website will contain PowerPoint presentations of the slides presented in lecture In addition it will have links to materials given out in class old exams extra credit quizzes for the second half of the class and other information that will help you study the material presented in lectures Use your UCSB NetID to access the website just as you do for your umail Come to lectures Study consistently Study Study Study Animal Hormones Anabolic SteroidTestosterone Abuse Testosterone Abuse Performance enhancing steroid drugs Testosterone Binds receptors Alters gene expression Male secondary sex characteristics Deep voice Facial and body hair Increased muscle mass Greatly increased risk of cancer and heart liver and kidney disease 41 What are Hormones Hormones are chemical messages that allow slow communication between distant cells in the body Hormones act on a time scale of several seconds to days can control longerterm physiological processes not useful for controlling rapid actions 41 Endocrine cells Hormonesecreting cells are called endocrine cells they secrete hormones into the interstitial space andor blood stream In contrast exocrine cells secrete substances into ducts that are connected to the outside world exampes UH Epnthet al eetts the ewtstde wertd 60 of the recognized major human cell types are classified as epithelial cells I EXTERNAL Foods Saks and water 39 H Skin separates the internal N p rill and external environments T Respiratory systems supply oxygen and remove carbon dioxide all cells of the organism Digestive systems provide Extracellular fluid bathes J nutrients Cells of organs 337 ff1f quot3 Ciquot U39at rY 7 3 2 3 exchange materials s r 5Y3t9m i y El 0 A I with each other via the i w 3 17 Cm awry SyStern internal environment I Blood 515 i moves matenas Wm q cels Pw V A quot l the b dV39 plasma 0 INTERNAL r97 I ENVIRONMENT 1 extracellular fluid Urinary system maintains salt and water balance of internal environment and eliminates waste products from the blood waste products Umbsorbed salts and water matter E 86 D 40 1 LIFE THE SCIENCE OF BIOLOGY Eighth Edition 2007 Sinauer Associates Inc and W H Freeman amp Co A Circulating hormones Endocrine glands secrete circulating hormones Secreting r cell Circulating hormones are transported by the blood and bind to receptors on Kdistant cells B Local hormones from site of release and bind to receptors on nearby cells R tor 0 g V E Paracrine hormones diffuse J Endocrine cell 1quot Paracrine Hormones affect cells in their 39 Targetcell immediate Z fAutocrine homiones bind Cells without receptors to receptors on the cells do not respond to a kthat secrete them kparticular hormone 41 AutoIParacrine Hormones Some hormones act locally Autocrine hormones act on the secreting cell itself Paracrine hormones act on cells near the site of release Autoparacrine hormones are released in tiny amounts or are inactivated rapidly by enzymes or are taken up efficiently by local cells They never get into the circulatory system 41 Circulating Hormones Circulating hormones diffuse into the blood which distributes them throughout the body When the hormone message encounters a cell with the proper receptor it binds and triggers a response The same hormone can cause different responses in different types of cells An example is epinephrine adrenaline The nervous system reacts to an emergency very quickly and stimulates adrenal cells to secrete epinephrine The result is the fightorflight response LIFE 8e Figure 414 Senses detect danger The brain sends signals to the leg muscles and to the adrenal glands which release epinephrine into the circulating blood triggering a number of effects The liver breaks down glycogen to supply glucose fuel to the blood The heart beats faster and stronger Blood pressure rises Adrenal gland Blood vessels to the gut and skin constrict while more blood flows to the escape muscles Fat cells release fatty acids fuel to the blood LIFE THE SCIENCE OF BIOLOGY Eighth Edition 2007 Sinauer Associates Inc and W H Freeman amp Co 41 Hormones and Their Actions Epinephrine acts on different cells in the body In the heart it stimulates faster and stronger hea beat Blood vessels in some areas constrict to send more blood to muscles In the liver glycogen is broken down to glucose to provide quick energy In fat tissue fats are mobilized as another energy source show movie effects of epinephrine Imin Epinephrine Norepinephrine Outside of cell Receptor Epinephrine Adenylyl Receptor Norepinephrine cyclase Phospholipase C 3 Q 8 ifs w 2 lt quotI E 39 F I m 1IEI arm 3955 3 Tc 5 quot quot1 7amp9 39s 39 I i r J o is e 0 ft i t t e P to I r iii i 0 W 0 44 Mi 0 M 414 r quot A at J G protein 3 N I n ylt Precursor Second G Pmtein 1 rOt iI1 2 molecules messengers Inside of cell G protein coupled receptors LIFE THE SCIENCE OF BIOLOGY Seventh Edition Figure 4214 Some Hormones Can Activate a Variety of Signal Transduction Pathways L2004 Sunauer Associates Inc and W H Freeman 8 Co 41 Groups of Hormones Hormones can be classified into three main groups 1 Peptides or proteins CI Are water soluble and transported by vesicles out of the cell that made them CI Peptide hormone receptors are localized in the surface of target cells CI Examples Growth hormone insulin 41 Groups of Hormones Hormones can be classified into three main groups 2 Steroid hormones CI Are lipidsoluble and membranepermeable CI Can diffuse out of the cell that made them CI Can diffuse into the target cells CI In the blood they must be bound to carrier proteins CI The receptors for lipidsoluble hormones are inside cells either in the cytoplasm or in the nucleus CI Example Estrogen a Aldosterone a mineralocorticoid cH2oH OH CO Testosterone 039 OH b Cortisol a glucocorticoid HO tri1Q C Sex steroids LIFE THE SCIENCE OF BIOLOGY Seventh Edition Figure 4211 The Corticosteroid Hormones are Built from Cholesterol 9 2004 Sinauer Assocaates Inc and W H Freeman amp Co 41 Groups of Hormones Hormones can be classified into three main groups 3 Amine hormones CI Are derivatives of the amino acid tyrosine CI Some are watersoluble and some are lipidsoluble CI Example epinephrineadrenaline OH HO HN Outside NOnpOar Transmembrane Polar of cell hOrITOne p receptor hOrITOne B Plasma O membrane 1 I U 4 1 1 I 7 m 3 1 quot 39 39 It V v V 4 f 9 IN J ax x H L Cyosi Receptor Vg Inside of cell LIFE THE SCIENCE OF BIOLOGY Seventh Edition Figure 154 Two Locations for Receptors 2004 Sinauer Associates Inc and W H Freeman 8 Co 41 Receptors for polypeptide hormones The receptors for watersoluble proteins are large glycoproteins on the cell surface with three domains A binding domain projecting outside the plasma membrane A transmembrane domain that anchors the receptor in the membrane A cytoplasmic domain that extends into the cytoplasm of the cell The cytoplasmic domain initiates the target cell s response by activating enzymes such as protein kinases or protein phosphatases 41 The insulin receptor Inside of cell receptor Insu1in response substrate IRS Cellular responses 41 Receptors for membranepermeable Hormones The receptors for lipidsoluble hormones are inside cells either in the cytoplasm or in the nucleus The action of lipidsoluble hormones is mediated by intracellular hormone receptors that usually alter gene expression 41 The estrogen receptor Nuclme TF2E 41 Endocrine glands Some endocrine cells are single cells within a tissue Digestive hormones for example are secreted by isolated endocrine cells in the wall of the stomach and small intestine examples Gastrin Secretin Cholecystokinin Gastric inhibitory peptide Some endocrine cells aggregate into secretory organs called endocrine glands In vertebrates nine major endocrine glands make up the endocrine system Pineal Hypothalamus 3 Thyroid Parathyroids Thymus Adrenals Pancreas Ovaries Testes LIFE THE SCIENCE OF BIOLOGY Seventh Edition Figure 422 The Endocrine System of Humans P 2004 Sinauer Assocuales Inc and W H Freeman 8 Co 41 The pituitary gland Hypotha la in us V The human pituitary gland is the size of a blueberry yet it secretes Kmany hormones J The pituitary gland of mammals is a link between the nervous system and many endocrine glands and plays a crucial role in the endocrine system The pituitary gland sits in a depression at the bottom of the skull and is attached to the hypothalamus The pituitary is made of two parts anterior and posterior U Inflowing blood 1 2 39 a Capillaries Posterior pituitary Axons of hypothalamic neurons The posterior pituitary releases two hormones antidiuretic hormone and oxytocin They are made by neurons in the hypothalamus are called neurohormones and are packaged in vesicles The anterior pituitary is controlled by neurohormones from the hypothalamus In owingll blood Portal blood z I l Both antenor amp postenor pituitary hormones leave the land Via blood 43939f Anterlor g V pituitary Vessels 0 O 0 Q 9 g C 0 LIFE THE SCIENCE OF BIOLOGY Seventh Edition Figure 427 Hormones from the I 2004 41 The hormones of the anterior pituitary The anterior pituitary releases four tropic hormones which control activities of other endocrine glands thyrotropin adrenocorticotropin luteinizing hormone and folliclestimulating hormone They are peptide and protein hormones each is produced by a different type of pituitary cell The anterior pituitary also releases other polypeptide hormones that are not tropic hormones growth hormone prolactin melanocytestimulating hormone endorphins and enkephalins 41 Growth hormone Growth hormone GH 191 amino acids acts on many tissues to promote growth Growth hormone signaling Ex39raceIIuIar O Cytoplasm Growth hormone signaling Figure 426 Effects of Excess Growth Hormone Gigantism is the result of overproduction of GH in children S5 39y 39393939quot h gtv 39 3 P D r I P D I I V 1 15 K 7 GH deficiency in children causes pituitary dwarfism When treated with GH a deficient child will begin to grow faster within months From the late 1950s pituitary dwarfism was treated with GH extracted from pituitaries from human cadavers years supply required 50 pituitaries Today recombinant human GH rhGH is synthesized in bacteria Cost of treatment with rhGH US 10000 to 30000 a year Pineal Hypothalamus Pituitary 3 Thyroid Parathyroids Thymus Adrenals Ovaries Testes LIFE THE SCIENCE OF BIOLOGY Seventh Edition Figure 422 The Endocrine System of Humans 2004 Sinauer Assocuales Inc and W H Freeman 8 Co Pancreatic duct Common bile duct 4quot quot I v Duodenum 41 Pancreas functions as an exocrine gland and an endocrine gland The exocrine parts accounts for 99 of the pancreas Exocrine products are delivered to the intestine via the pancreatic duct bicarbonate digestive enzymes trypsin chymotrypsin amylase lipase The Islets of Langerhans are the endocrine part of the pancreas lr 394 4 Hematoxylin and Eosin HampE Stain 41 Paul Langerhans German Pathologist 18471888 Q Exocrine pancreas 239 Islets of Langerhans 1 Fluorescence microscopy Immunostaining for insulin green I Q iv 41 Islets of Langerhans The Islets of Langerhans constitute approximately 12 of the mass of the pancreas There are about one million islets in a human pancreas Each islet contains approximately 1000 cells Beta cells produce Insulin 6580 of the islet cells Alpha cells produce Glucagon 1520 Islets of Langerhans are destroyed in type I diabetes Islet of Langerhans Immunostaining Greeninsu1in Redg1ucagon 41 Insulin consists of two polypeptide chains sgnai s qu391CI 2 Chan 3 Nter preprolnsulln proinsulin CNN C I N t chain 8 er E insulin 5 5 chain A I I Cter 41 Blood glucose Under normal physiological conditions blood glucose concentrations are maintained within a narrow range despite wide fluctuations in supply and demand eg food intake eg muscle activity The brain depends almost entirely on blood glucose as an energy source Increase in I Uptake of glucose 5 circulating insulin by cells Stimulates pancreas to secrete insulin Decreases blood glucose Decrease in blood glucose Increase in blood glucose 1 p 89 Fi9ll396 50 1 9 use me SCIENCE or amour Eighth Eamon o 2oo7 Sinauer Associates Inc and w H Freeman a C0 41 Control of blood glucose After a meal blood glucose levels rise and stimulate the 3 cells to release insulin Insulin stimulates cells to use glucose and to convert it to glycogen muscle tissue and fat adipose tissue When blood glucose levels fall the pancreas stops releasing insulin and cells switch to using glycogen and fat for energy If blood glucose falls too low the oc cells release glucagon which stimulates the liver to convert glycogen back to glucose T Watch Animation 50O2 Effects of Insulin and Glucagon 41 Insulin response Glucose taken Time hours Glucose Insulin 41 Insulin response Glucnse talzen Time hours Glucuse Insulin 39 insulin glucose 00 glucose transporter4 insulin 4 4 f receptor 1 glycogen t g Q Q 6 Q I Q 5 N V K fatty acids pyruvate Cellular effects of insulin Stimulates glucose uptake by GLUT4 Stimulates glycogen synthesis Stimulates fatty acid synthesis 41 How can insulin cause increased uptake of glucose ShOW movie httpresearchimbuqeduau1rathboneg1ut4 ashg1ut4swf How can insulin cause increased uptake of glucose Insulin triggers the exocytosis of intracellular vesicles containing the glucose transporter GLUT4 This results in an increased number of GLUT4 molecules in the plasma membrane 41 Diabetes Mellitus Diabetes Greek 5104817117 quotpassing throughquot or quotsiphonquot excessive urine production K it P K Z coined by Aretaeus of Cappadocia physician in ancient Greece Mellitus Latin sweet taste glucose in urine and blood hyperglycemia Added by Thomas Willis English physician 16211675 41 Diabetes Mellitus Epidemiology Worldwide at least 171 million people suffer from diabetes United States I 208 million people have been diagnosed with diabetes 2005 I about 62 million people undiagnosed estimate American Diabetes Association I estimated costs 132 billionyear I 5 o 10 o of diabetes cases in North America are type 1 with the rest being type 2 41 Diabetes Mellitus Before 1920s diabetes mellitus was a fatal disease Weakness lethargy dramatic loss of body mass Cells not taking up glucose use fat and protein for fuel resulting in the body s wasting away and tissue and organ damage 41 Acute complication of DM Diabetic Ketoacidosis Lack ofinsuin V No uptake of blood glucose by cells Cells use fat protein for energy High blood glucose levels Liver switches to starvation Glucose and ketone metaboism makes ketone bodies cause high blood bodies osmolarityz forces water out of cells Acidic ketone bodies lower blood I pH Ketoacidosis l Glucose excretion in urine along with water dehydration Diabetic Ketoacidosis 100 mortality rate if untreated 41 Acute complication of DM Diabetic Hypoglycemia Diabetic Hypoglycemia Can occur if insulintreatment overshoots Lack of blood glucose can lead to coma and death 41 Chronic complications of DM Diabetic Retinopathy can lead to severe vision loss or blindness most common cause of blindness among nonelderly adults in the US Diabetic Nephropathy damage to the kidney which can lead to chronic renal failure eventually requiring dialysis Diabetes mellitus is the most common cause of adult kidney failure worldwide Diabetic Foot Combination of neuropathy and arterial damage may cause skin ulcers infection necrosis and gangrene most common cause of adult amputation usually of toes or feet in the US 41 Diagnosis of DM The glucose tolerance test Table I I999 World Health Organization diagnostic criteria for diabetes mellitus World Health Organiza tion I999 Plasma glucose concentration Fasting plasma glucose concentration mmolI 2 h following a 75 g oral glucose test mmol I lt 6 2 6 69 2 70 lt 78 Normal Impaired fasting glycaemia Diabetes 2 78 0 Impaired glucose tolerance Impaired glucose tolerance Diabetes 2 I ll Diabetes Diabetes Diabetes Determine how quickly glucose is cleared from the blood 41 Types of DM Type1 diabetes juvenile diabetes 10 of all cases Due to autoimmune destruction of the insulinproducing cells pancreatic beta cells Type 2 diabetes adultonset diabetes 90 of all cases Due to insulin resistance caused by lack of sufficient functional insulin receptors on target cells Likely related to obesity 90 of type 2 diabetics are obese I00 39 932 90 70quot 60 S4 403 40 Adiustcd i C 3lV risk 90 30 276 20 J l 9 9 0 Q9 58 I T I as i 1 0lt39 390quot 399 0 quotx 393quot 3 3 5 quot0 L 3939V Q 99 9 99 40 397quotQ Q 9 4 Z ynass T Z 2czTqht 111 Body mass index kgm2 Fig 2 Risk of developing diabetes according to body mass index BMI in II4 28l women participants in the US Nurses Health Study Data from Colditz et al I995 Discovery of Insulin and the first treatment of diabetes mellitus In 1921 Frederick Banting and Charles Best University of Toronto discovered that an extract from pancreas could cure diabetic dogs They purified the active ingredient and discovered insulin In January 1922 a 14yearold boy dying of diabetes was the first patient being treated with insulin Banting and Best published the first paper on their discovery a month later in February 1922 In 1923 the Nobel Prize was awarded to Banting and Macleod Banting s boss for the discovery and each shared their portion of the prize money with the other researchers on the project Frederick Banting 1891 1941 Charles Best 1899 1978 Photograph of Banting and Best with a dog on the roof of the Medical Building Toronto August 1921 421 Principal Hormones of Humans Part 7 SECRETING TISSUE CHEMICAL OR GLAND HORMONE NATURE TARGETS IMPORTANT PROPERTIES OR ACTIONS Hypothalamus Releasing and release Peptides Anterior Control secretion of hormones of inhibiting hormones pituitary anterior pituitary see Table 422 Oxytocin antidiuretic Peptides See Posterior Stored and released by posterior hormone pituitary pituitary Anterior pituitary Thyrotropin Glycoprotein Thyroid gland Stimulates synthesis and secretion Tropic hormones of thyroxine Adrenocorticotropin Polypeptide Adrenal cortex Stimulates release of hormones ACTH from adrenal cortex Luteinizing hormone Glycoprotein Gonads Stimulates secretion of sex hormones LH from ovaries and testes Folliclestimulating Glycoprotein Gonads Stimulates growth and maturation hormone FSH of eggs in females stimulates sperm production in males Anterior pituitary Growth hormone GH Protein Bones liver Stimulates protein synthesis Other hormones muscles and growth Prolactin Protein Mammary Stimulates milk production glands Melanocytestimulating Peptide Melanocytes Controls skin pigmentation hormone Endorphins and Peptides Spinal cord Decreases painful sensations enlltephalins neurons LIFE THE SCIENCE OF BIOLOGY Seventh Edition Table 421 Part 1 cc 9004 Qinmnor Asqnmntm Inc and W H Freeman R 0 42 1 Principal Honnones of Humans Part 2 SECRETING TISSUE CHEMICAL OR GLAND HORMONE NATURE TARGETS IMPORTANT PROPERTIES OR ACTIONS Posterior pituitary Oxytocin Peptide Uterus breasts Induces birth by stimulating labor contractions causes milk ow Antidiuretic Peptide Kidneys Stimulates water reabsorption and hormone ADH raises blood pressure vasopressin Thyroid Thyroxine Iodinated Many tissues Stimulates and maintains metabolism amino acid necessary for normal development derivative and growth Calcitonin Peptide Bones Stimulates bone formation lowers blood calcium Parathyroids Parathyroid Protein Bones Resorbs bone raises blood calcium hormone Thymus Thymosins Peptides White blood Activate immune responses of T cells cells in the lymphatic system Pancreas Insulin Protein Muscles liver Stimulates uptake and metabolism fat other of glucose increases conversion tissues of glucose to glycogen and fat Glucagon Protein Liver Stimulates breakdown of glycogen and raises blood sugar Somatostatin Peptide Digestive tract Inhibits insulin and glucagon release other cells of the pancreas decreases secretion motility and absorption in the digestive tract LIFE THE SCIENCE OF BIOLOGY Seventh Edition Table 421 Part 2 3 2004 Sinauer ASSOCIEHGS Inc and W H Freeman 8 Co 42 1 Principal Hormones of Humans Part 3 SECRETING TISSUE CHEMICAL OR GLAND HORMONE NATURE TARGETS IMPORTANT PROPERTIES OR ACTIONS Adrenal medulla Epinephrine Modified Heart blood Stimulate fightorflight reactions norepinephrine amino acids vessels liver increase heart rate redistribute blood fat cells to muscles raise blood sugar Adrenal cortex Glucocorticoids Steroids Muscles Mediate response to stress reduce cortisol immune metabolism of glucose increase system other metabolism of proteins and fats reduce tissues in ammation and immune responses Mineralocorticoids Steroids Kidneys Stimulate excretion of potassium ions aldosterone and reabsorption of sodium ions Stomach lining Gastrin Peptide Stomach Promotes digestion of food by stimulating release of digestive juices stimulates stomach movements that mix food and digestive juices Lining of small Secretin Peptide Pancreas Stimulate secretion of bicarbonate intestine solution by ducts of pancreas Cholecystokinin Peptide Pancreas liver Stimulates secretion of digestive enzymes gallbladder by pancreas and other digestive juices from liver stimulates contractions of gallbladder and ducts Enterogastrone Polypeptide Stomach Inhibits digestive activities in the stomach LIFE THE SCIENCE OF BIOLOGY Seventh Edition Table 421 Part 3 19 2004 Sinauer ASSOCIEHGS Inc and W H Freeman 8 Co 421 Principal Honnones of Humans Part4 SECRETING TISSUE CHEMICAL OR GLAND HORMONE NATURE TARGETS IMPORTANT PROPERTIES OR ACTIONS Pineal Melatonin Modified amino Hypothalamus Involved in biological rhythms acid Ovaries Estrogens Steroids Breasts uterus Stimulate development and maintenance other tissues of female characteristics and sexual behavior Progesterone Steroid Uterus Sustains pregnancy helps maintain secondary female sexual characteristics Testes Androgens Steroids Various tissues Stimulate development and maintenance of male sexual behavior and secondary male sexual characteristics stimulate sperm production Many cell types Prostaglandins Modified fatty Various tissues IIave many diverse actions Heart Skin Atrial natriuretic hormone Vitamin D cholecalciferol acids Peptide Sterol Kidneys Digestive tract kidneys bone Increases sodium ion excretion Increases blood calcium levels LIFE THE SCIENCE OF BIOLOGY Seventh Edition Table 421 Part 4 9 2004 Sinauer Associates Inc and W H Freeman 8 Co Neurons and Nervous Systems The problem how to communicate over long distances fast Local hormones Slow diffusion 3 d Short distance Circulating hormones Long distance Relatively slow Q3 39 Specificity limited by O Ph receptors on target cells The probl em how to communicate over long distances fas P The problem how to communicate over long distances fast Em giraffe Legs The solution stretch the endocrine cell Neurons are excitable can generate and propagate electrical signals nerve impulsesaction potentials I I Nervous Systems Cells and Functions Neurons are specialized cells of the nervous system that receive encode and transmit information Neurons with their support cells glial cells make up nervous systems Information is received by sensory cells and converted or transduced into electrical signals that are transmitted and processed by neurons To cause behavioral or physiological responses a nervous system communicates these signals to effectors such as muscles and glands I I Nervous Systems Cells and Functions The simplest neural network consists of three cells a sensory neuron connected to a motor neuron via interneurons connected to a muscle cell Most neuronal networks are more complex The human brain has an estimated 10 neurons and 1014 synapses World population 65 x 109 Human brain has 150x more neurons The neurons and synapses in the human brain are divided into thousands of distinct but interacting networks that function in parallel I I Nervous Systems Cells and Functions Simple animals process information with a simple network of neurons nerve net that does little more than provide direct lines of communication from sensory cells to effectors The next level of nervous system complexity includes clusters of neurons called ganglia Frequently one pair of ganglia is larger and more central and is given the designation brain Nervous Systems Vary in Size and Complexity 1 Brain Segmental nerve g V in Ventral 2 2 nerve cord 3 I 39zg 3939i 5 a asa 39wII39 A pB pB L n w Sea anemone Earthworm Increasingly complex animals more complex sensory and behavioral abilities information processing is increasingly centralized in ganglia LIFE THE SCIENCE OF BIOLOGY Seventh Edition Figure 441 Nervous Systems Vary in Size and Complexity Part 1 lt 2004 Sinauer Associates Inc and W H Freeman amp Co I I CNS PNS In vertebrates most of the cells of the nervous system are found in the brain and the spinal cord which together are called the central nervous system CNS Information is transmitted from sensory cells to the CNS and from the CNS to effectors via neurons which extend or reside outside of the brain and spinal cord Neurons and supporting cells found outside the CNS are called the peripheral nervous system PNS Figure 441 Nervous Systems Vary in Size and Complexity C d I7 M t o Brain spinal cord CNS Brain V1sua1 Wh ganglion A Nerves A communicates to gut 1 V with the rest of Ganglion the body via PNS Nerves to muscles Squid Human LIFE THE SCIENCE OF BIOLOGY Seventh Edition Figure 441 Nervous Systems Vary in Size and Complexity Part 2 A Generalized neuronal anatomy Dendrites receive information from other neurons The cell body contains the nucleus and most J a Generalized neuron anatomy cell organelles The axon hillock integrates information collected by dendrites and initiates action potentials The axon conducts t2 action potentials away from the cell body Target cell Axon terminals synapse LIFE THE SCIENCE OF BIOLOGY Seventh Editir with a target Ce 2004 Sinauer Assoc I I Neurons Most neurons have four regions a cell body dendrites an axon and axon terminals The cell body contains the nucleus and most of the cell s organelles Many projections sprout from the cell body most of them are dendrites which bring information from other neurons or sensory cells to the cell body I I Nervous Systems Cells and Functions The axon usually carries information away from the cell body CI Axons conduct information to target cells which can be other neurons muscle cells or gland cells At its end the axon divides into many fine nerve endings At the tip of each nerve ending is a swelling called the axon terminal CI The axon terminal is positioned very close to the target cell CI At the axon terminal nerve impulses cause the release of neurotransmitters chemical messengers into the synapse I I Neurons are structurally diverse Z7 Specialized neurons Cerebellum I I Neurons are structurally diverse it E V I 5 Cell body Cerebral cortex Rat hippocampal neurons at 16 DIV Red Syntaxin 3 Green GFP courtesy of Dr Carol Vandenberg Red Syntaxin 4 Green GFP courtesy of Dr Carol Vandenberg The solution stretch the cell The new problem how to get the signal across the cell Transmit signals fast across long distances action potentials Transmit signals across the synapse Microelectrodes can measure the membrane potential voltage across the plasma membrane i and connected with 2 0 p a wire to an ampli er A F 7 V 77 39 t c r Ic I V 39 a AV 3 gt quot 139 I V r 39 An electrode made from a glass pipette 9 U pulted to asharptip is t 4 t l1e dw39rth aneIectricia y 3939 K coniducting soution Inside Plasma axon h membrane f Microelectrodes can measure the membrane potential voltage across the plasma membrane METHOD Two electrodes one inside The small difference and one outside the axon is ampl39r ed detect a difference in voltage V in an unstimulated neuron r a and displayed on an oscilloscope screen ll il ilII39T394 l I OUtSide axon f gt The constant difference of 60 mV between outside and L inside is the resting potential I I Resting potential The difference in voltage across the plasma membrane of a neuron is called its membrane potential In an unstimulated neuron the voltage difference is called a resting potential Membrane potentials can be measured with electrodes The membrane potential of a resting axon is about 60 millivolts mV The inside of the cell is more negative than the outside 44 Resting potential How is the resting potential generated Electrical charges move across metals copper wire as electrons However electrical charges move across cell membranes as charged ions The major ions that carry electric charges across the plasma membranes of neurons are sodium Na chloride Cl potassium K and calcium Ca2 The NatKtATPase generates a constant concentration gradient of Na and Kt across the plasma membrane a N a I pump b N a and I channels Outside of cell O ql 0 N a g N a Na 0 Shannel channel Plnside of cell g Q 0 g Intracellular Nat is always low Intracellular Kt is always high I I Ion pumps and channels Ion pumps use energy to move ions or other molecules against their concentration gradients The major ion pump in neuronal membranes is the sodium potassium pump NaIK ATPase which expels Nat ions from the cell exchanging them for K ions from outside the cell This keeps the concentration of K greater inside the cell than outside Ion channels are pores formed by proteins in the lipid bilayer that selectively allow ions to pass through Resting potential Only K channel open Outside of cell 0 C NaK 0 0 0 0 Q 0 O O K Chartnel Voltagegated Chemically gated Na channel K channel Open Closed Closed 0 Q C C Inside of cell K Open Potassium Channels Create the Resting Potential Outside of cell Na Inside of cell Negatively charged protein Oscilloscope screen Resting potential I I I 1 2 3 Milliseconds 44 Potassium equilibrium potential The sodium potassium pump keeps Kf concentration high inside the cell but Kf can diffuse out the open channels The membrane potential at which the tendency of K ions to diffuse into the cell is equal to their tendency to diffuse out is called the potassium equilibrium potential Resting potential INTRO REWIND STOP PLAY i Play animation in safari Animation 44 O1swf I I Gated ion channels Many ion channels in the plasma membranes of neurons are gated they open under some conditions but close under other conditions Voltagegated channels open or close in response to a change in the voltage across a plasma membrane Chemically gated channels open or close depending on the presence or absence of a specific chemical that binds to the channel protein 6 Membrane potential mV Membranes Can Be Degolarized or Hygergolarized a Nachannel b Cl channel 0 O V O 39 Q K channel Nachannel Voltage K channel C1 channel Voltage open Voltage gate gate open voltage gate 0 gate 9 Gated Na I Gated C1quot channel open channel open 39 K channel 1 E K channel 39 I Resting Open 0 en potential P V V Time Time 44 Membranes Can Be Depolarized or Hyperpolarized When the inside of a neuron becomes less negative in comparison to its resting condition its plasma membrane is said to be depolarized Conversely when the inside of a neuron becomes more negative in comparison to its resting condition its plasma membrane is said to be hyperpolarized Opening and closing of ion channels which result in changes in the polarity of the plasma membrane are the basic mechanisms by which neurons respond to stimuli I I Action potentials Nerve impulses are action potentials that travel along axons An action potential is a sudden and major change in membrane potential that lasts for about 12 milliseconds Action potentials are conducted along axons at speeds of up to 100 meters per second 220 mph During an action potential the voltage changes from the resting potential of 60 mV to 50 mV then rapidly returns to the resting potential Action potential Outside axon IllIllllllIlllllllllllllllllllquot Allllllllllllllllllllllllll Inside axon II Outside axon LIFE 8e Figure 4410 Part 1 Oscilloscope screen H k 4 LIFE THE SCIENCE OF BIOLOGY Eighth Edition FOE P nauer lsoc1m m ans 3939I 4 Fn o en 39lquot 3 O3 I I Action potentials Voltagegated sodium channels are primarily responsible for action potentials At resting potential most of the sodium channels are closed A specific membrane potential called the threshold potential opens voltagegated ion channels During the transmission of an action potential the sodium channels stay open for less than a millisecond in that time sodium rushes into the cell The opening of sodium channels causes the rising phase spike of the action potential The Course of an Action Potential 50 DJ G Membrane potential mV 2quot o N 39gt39 1 39quotn 27 3 A 39 4 0 I Channel Gated N a Votage gated K channel 44 Action potentials Voltagegated potassium channels open more slowly than the voltagegated sodium channels and stay open longer this allows potassium ions to carry excess positive charges out of the axon this causes the plasma membrane to return to its resting potential 44 Action potentials Another feature of voltagegated sodium channels is that once they open and close they can be triggered again only after a short delay of 12 milliseconds This delay is the refractory period the time when a plasma membrane cannot propagate an action potential 50 L I I 39 30 0 O L 1 4 5 an an 1 i T 1 O 0 0 0 I 3940 Kchannes Na channels 50 TbI esh939d Z 60 70 INTRO REWIND STOP PLAY lbw iliniinn in Siaii Anin iiI M C2suf Action Potentials Travel along Axons Electric stimulus 0 Oscilloscope screen 39 i 0 E E Point A Point B Amplifier Electrode 1 Outside axon Outs1de axon T side agtltFo4n T sic391e axor1 Ampli er Electrode2 i K J Outside axon Outside axon Time gt Electrode pair 1 Electrode pair 2 Magnitude of the action potential does not change no signal loss Action Potentials Travel along Axons 8 Time 1 Voltagegated Na channels open in A depolarizing response to the electrical stimulus current spreads generating an action potential down the axon 39 p r 39 1 n V E quot 9 i P mm mm ll nun u f an inn x r t l v in V A 1 l gt ii i if 39 quot39 39 39 139 39339 quot it III 1 15 UIlI IIIH X 2 p IIIII I3 I31 XI III 1 3 r pn i t V r iv 139 O gun on ll133 J L A X oi 0 o 0 Point A Point B AP electric current flow to adjacent areas depolarization C Time 2 Action Potentials Travel along Axons Upstream Na channels Voltagegated K As it travels down the axon the action inactivate making the channels open potential stimulates more Na channels to membrane refractory hyperpolarizing the open in a selfextending forward stream axon then ctose 0 V 0 0 0 o 0 0 0 0 0 0 A o 0 0 0 av rs s I 7quot 5B l r run until aim jun nun X AP travel down the axon in one direction I I Action Potentials Travel along Axons Action potentials travel long distances with no loss of signal Action potentials are allornothing due to the interaction between the voltagegated sodium channels and the membrane potential The action potential is selfregenerating because it spreads by current flow to adjacent regions of the membrane The action potential propagates in one direction and cannot be reversed because the part of the membrane it came from is in its refractory period Action potentials travel faster in largediameter axons than in smalldiameter axons I I Hodgkin and Huxley Squid have neurons with giant axons up to 1 mm diameter that control the water jet propulsion system In the 1940s the neurophysiologists A L Hodgkin and A F Huxley used giant axons from squid to study the electrical properties of axonal membranes and discovered the basic principle of the action potential At the time they could only hypothesize about the existence of ion channels The Nobel Prize in Physiology or Medicine 1963 Alan Lloyd Hodgkin O 13 of the prize United Kingdom University of Cambridge Cambridge United Kingdom b 1914 d 1998 I Andrew Fielding Huxley O 13 of the prize United Kingdom London University London United Kingdom b 1917 739 P it 4 Fiberquot was F 39n the at H HSIML79 flJTTL J 1 M e V and 0N 2 r1nhee 1ifi1T397 Y P aVel e39 if A e mechanisri ii e tion 5 p ew1zew f aric rectoquot u 9 tag Y Z A 1 e1a ee m J e eesting n he expe g 2 W 1 P f o PE ee Research Method Patch Clamping RESEARCH nun Ion channels and is placed in oontact with a rwr 39smembrae their properties can be studied directly Vquotquot39 Slight suction Retracting the pipette clamps a patch of removes the membrane the membrane to patch often with one or the pipette tip more ion channels in it fT ne opening and closing of ion channels kcan be recorded through the pipette J 1 Closed If g Open Oscilloscope tracing of ionic current LIFE 89 Figure 448 LIFE ms SCIENCE or erowov Eighth Edition 2 zoor Srnaaer Assocnates Inc and w H Freeman 5 Co 44 Patch clamping Patch clamping developed by Bert Sakmann and Erwin Neher is a research method developed in the 1980s that allows single ion channels to be studied A recording pipette is used to clamp a patch of neuron plasma membrane and measure the voltage differences when ion channels in that patch of membrane open and close The Nobel Prize in Physiology or Medicine 1991 Erwin Neher 0 12 of the p ze Federal Republic of Germany MaxPlanck Institut fur Biophysikalische Chemie Goettingen Federal Republic of Germany b 1944 Bert Sakmann 0 12 of the p ze Federal Republic of Germany MaxPlanck Institut fur medizinische Forschung Heidelberg Federal Republic of Germany b 1942 44 How to conduct action potentials faster Action potentials travel faster in largediameter axons than in smalldiameter axons In vertebrates it is impractical to increase propagation velocity by increasing axon size because of the very large numbers of axons present Another mechanism has evolved that increases propagation velocity What is this mechanism A LIFE 8e Figure 444 Site and direction of myelin growth i Myeiinproducing Schwann cells Nodes of Ranvier Nucleus of Schwann cell 3 Mitochondria Multiple layers of myelin insulate the axon LIFE THE SCIENCE OF BIOLOGY Eighth Edition 0 2007 Smauer Associates no and W H Fwzeman 8 Co Theodor Schwann 18101882 German physiologist histologist and cytologist oigodendrocytes inated by Axons in the CNS are myel Nodes of Ranvier I nk Schwann cells A 1 Na channels open generating Spreading current from the upstream node brings an action potential the membrane at the next node to threshold f 39539 393 T N U U Q Q Ei 39 Zgt 55 5 39 22 A quot ff XU I i lt lt gt39 i O 4 2 39 quot IXIXIIIIIUU o UHIIIIIIIIIHIIHII II III IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIHHIIIIIIIIII III III gt I hr HHIIIIIIIIIIIIIIIII III II IIICIIXIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII 39 u r I v p 7 I L J I 39 I 39x jo 39 1lt x39 M h 39 M Ofj e 39 39 39 39 1 T L 1 Iv Upstream Na channels inactivate making The action potential jumps the membrane refractory Voltagegated Kquot quickly to the new node and channels open repolarizing the axon l l quot 39 quot 1 3 IIHIUIIIIIIIIINIIIIIIIIIIIIIIIIIIHHI II IIIIIIIQIIIIIIIII V V x quot i39 39 p Time1 v quot I u s 42 IIIHII II ln l ll V I V 1 he continues from node to node Time2 v u o l l1 Ill 3939lu ll l 39l39l Ranvier The myelin sheath and the nodes were discovered by French pathologist and anatomist Louis Antoine Ranvier 18351922 I I Saltatory conduction Myelin electrically insulates the axon charged ions cannot cross the regions of the axon that are wrapped in myelin When an action potential fires at one node of Ranvier it jumps to the next via saltatory conduc on Saltatory conduction is much faster than continuous signal propagation down unmyelinated axons because electric current travels quickly through the cytoplasm compared to the time required for ion channels to open and close Ion channels are clustered at the nodes of Ranvier Watch the Schwann cell and AP movie httpwwwyoutubecomwatchvDJe33XsBOg I I Glial cells Some glial cells physically support and orient neurons Others provide insulation for axons Schwann cells are a type of glial cell that wraps around the axons of neurons in the peripheral nervous system providing electrical insulation Oligodendrocytes have a similar function for axons in the CNS Myelin is the covering produced by Schwann cells and oligodendrocytes 44 Multiple Sclerosis MS What happens when myelin is destroyed MS primarily affects adults with an age of onset typically between 20 and 40 years Affects 400000 Americans and 25 million individuals worldwide I I Pathogenesis of MS Gradual destruction of myelin demyelination MS is thought to be an autoimmune disease that affects the central nervous system CNS The exact cause remains unknown Remyelination especially in early phases of the disease can cause symptoms to decrease or disappear temporarily However scar tissue plaques lesions accumulates causing progressive irreversible nerve damage RelapsingRemitting MS 85 of cases There is no known definitive cure for multiple sclerosis Normal myelinated fibers A are demyelinated by inflammatory process B which causes conduction block Nat channel redistribution C and remyelination D restore conduction and contribute to clinical remission MRI scans of MS patient GE l39uECIC40L SYSTEMS K350 and HF GE raeoucxu SYSTEMS A 108 GEr 6J86IGNA LgtEMIw1 GE E6J88lCr 0 lgttMICMI1 Ex 3402 Ex 3002 quot 39 C so 3 Sat 5 T Im 14 Im 16 Sea F1253 39 An 8266 UFO 230cm DRZN 220cm H 1 1 QSEIH 1Ft10I0I0r2 1E1350E ECU 11 31 Hz 1122250110 lEAD FO i392bc22 50c1cJ10zsp 240K320 2 X l 1CDl X WW 118Wl39 Q 8tI B Magnetic resonance images showing bright spots where multiple sclerosis has damaged myelin in the brain I I Symptoms of MS variety of symptoms including changes in sensation in the arms legs or face complete or partial vision loss optic neuritis double vision unsteadiness when walking balance problems flickering eye movements nystagmus speech difficulties tremor clumsiness of the hands abnormal muscle spasms bladder and bowel difficulties Cognitive impairments difficulty performing multiple tasks at once difficulty following detailed instructions loss of short term memory emotional instability and fatigue The life expectancy of people with MS is now nearly the same as that of unaffected people I I Forms of MS W Progressiverelapsing MS M j Secondary Progressive MS J Primary Progressive MS RelapsingRemitting MS most common 85 Time gt e Increasing Disability I I Causes of MS The exact cause of MS remains unknown infectious agent genes environmental zinc mercury MS is approximately two to three times more common in women than in men suggesting that hormones may also play a significant role in determining susceptibility to MS Outbreaks or quotclustersquot of MS have been identified but the cause and significance of these outbreaks are not known I I Environmental trigger The risk for MS increases with greater distance from the equator Immigrants and their descendents tend to take on the risk level either higher or lower of the area to which they move Those who move before the age of 15 tend to take on the new risk themselves For those who move after the age of 15 the change in risk level may not appear until the next generation This supports the opinion that MS is caused by early exposure to some environmental trigger in geneticallysusceptible individuals Watch Multiple Sclerosis Movie httpwwwyoutubeComwatchvqgySDmRRZXY D an A neuromuscularjunction is the chemical synapse between a motor neuron and a muscle cell Presynaptic AXOquot 07 terminal motor Ul CtlOn Synap c vesicles Neuromuscular Muscle ber Mitochondrion Postsynaptic Capillary membrane Motor neuron Muscle fiber 0 H Q C H N 3 Presynaptic cell V motor neuron H 3 C O CH acetylchollne 3 V 7 Acetylcholine is broken down and the components are taken back up by the presynaptic cell Acetylcholine and vesicies are recycled Action potential I I me spreading 23 39 za m Cam Usage depolarization res an vottagegated ca2 3 quotc a39 quot t39x ane channelstoopen sWquotquot 39 39quot 39 Synaptic deft 5 2 L 3 03 enters me 06 and 5 Activated receptors open M99 quotSbquot 39 chemicalty gated cation agetytchohe Na K Caz dwannels 39 m m 39 squotquot quot and depolarize the memb39me39 postsynaptic membrane Acetyicholine molecules P 3 3Yquot3Pt39 09quot di use across the synaptic quot39US 399 09quot den and bhd to receptors on the postsynaptic membrane 44 Neurons Synapses and Communication A synapse is an axon terminal that contains many vesicles filled with chemical messenger molecules known as neurotransmitters Acetylcholine is the neurotransmitter used by all vertebrate motor neurons Acetylcholine is released when the vesicles fuse with the presynaptic membrane and moves into the narrow space called the synaptic cleft I I The Acetylcholine Receptor is a Chemically Gated Channel KThe acetylcholine N When ACh binds at specific Acetylcholinesterase receptormediated sites on the receptor the breaks down ACh channel is normally channel opens allowing Naquot causing the channel closed to enter the postsynaptic cell to close once again x J x J Outside Of CG 0 Na 0 0 Acetylchoinesterase AgtCh 0 39 I ACh receptor Inside of cell LlEE8e Fiaure 4414 I I Neuromuscularjunction The postsynaptic membrane of a neuromuscular junction motor end plate contains acetylcholinegated channels that allows Nat to pass through them this causes depolarization of the motor end plate and triggers an action potential on the muscle cell resulting in contraction About 100 acetylcholine vesicles each containing about 10000 acetylcholine molecules must release their cargo into the synaptic cleft to cause the muscle cell to fire an action potential Motor neuron Neuromuscular junction 1 39139 II II r 39I In INTRO mswmo STOP PLAY 0 play Animation44033 I I Excitatory and inhibitory synapses Synapses between neurons are categorized as excitatory or inhibitory depending on their response to neurotransmitters If a postsynaptic neuron responds to chemical stimulation by depolarizing the synapse is excitatory If the postsynaptic neuron hyperpolarizes the synapse is inhibitory I I Neurons Synapses and Communication Gamma amino butyric acid GABA and glycine are the most common inhibitory neurotransmitters in vertebrates GABA and glycine receptors are gated chloride channels When the channels are activated they can hyperpolarize the postsynaptic membrane and make the postsynaptic cell less likely to fire an action potential 11 H H 0 0 ll I I 9 I HZN ll N Q OH HllH quot I cine yannno butyrnc acid 9 y I I Neurons Synapses and Communication acetylcholinereceptor gt Na gtdepoarization gtexcitatory GABAreceptorgtC39 gt hyperpolarization gt inhibitory The Postsynaptio Neuron Sums Information 1 2 Exc1tatory DendriteS Z Synapses Cause local depolarization quot Axon hillock Axon X CCCC CCC Neuron Isrwggggys Cause local hyperpolarization I I Neurons Synapses and Communication For most neurons the critical area for the decision to fire an action potential is the axon hillock a region of the cell body at the base of the axon The plasma membrane of the axon hillock is not myelinated and has many voltagegated ion channels Inputs from the synapses are conducted through the cell body If the resulting combined potential depolarizes the axon hillock to threshold the axon fires an action potential Synapses closer to the cell body have greater influence on the axon hillock because action potentials decrease as they spread from the synapse Excitatory 1 2 Dendrites 2 Synapses Axon hillock Axon Neuron a Action 17 potential 60 Spatial summation Temporal summation 139 several synapses fire at same synapse fires rapidly same time EPSPS Threshold Membrane potential mV 3 1 I 50 60 1 1 1 1 1 1 1 1 1 1 1 1 111 1 2 3 4 1 2 1 2 3 1 1 1 1 1 1 1 1 1 Synapse number Resting Milliseconds gt potential 44 Neurons Synapses and Communication Excitatory and inhibitory postsynaptic potentials are summed spatially and temporally Spacial summation adds up the simultaneous influences of synapses at different sites on the postsynaptic cell Temporal summation adds up postsynaptic potentials generated at the same site in a rapid sequence Nutrition Digestion and Absorption 50 Nutrient Requirements Animals are heterotrophs They must obtain their Heterotrophs depend on the nutrition by eating other organisms Most plants some bacteria and some protists are autotrophs They trap solar energy through photosynthesis and use that energy to synthesize all of their components organic synthesis carried out by autotrophs A 1F ID CIHIAIIN Leastweasel predator lt g g Whitelooted mouse 3 omnivore 3 P Is Vnrgumaopossum 7 I 39 39 39 scavenger 1 I lquot gt5 bacteria amp fungi decomposers grasshopper herbivore plants producers 50 Measuring energy A calorie is the amount of heat needed to raise the temperature of 1 g of water by 1 C 1 kilocalorie kcal 1000 calories Nutritionists refer to the kilocalorie as the Calorie Cal which is capitalized to distinguish it from the single calorie Scientists are abandoning the calorie in favor of the International System of Units measure of energy called the joule 1 joule 0239 calories 5 0 Nutrient Requirements An anima s metabolic rate is the measure of the overall energy needs that must be met by the animal s food Fats carbohydrates and proteins are the components of food that provide that energy Basal metabolic rate is the metabolic rate resulting from all of the essential physiological functions that take place in a resting state Physical activity adds to the basal energy requirement the time it takes to burn off these foods Time hours 2 3 4 5 6 7 8 9 10 I I I I I I I I 6 oz lowfat Resting strawberry yogurt Walking 130 kcal Jogging Turkey sandwich 215 kcal 14 pound fastfood cheeseburger 530 kcal 10quot deepdish pizza 1300 kcal S3JnLII Time it takes a person with a bmr of 1800 kcalday to utilize energy LIFE THE SCIENCE OF BIOLOGY Seventh Edition Figure 502 Food Energy and How We Use It u 2004 Sinauer Associates Inc and W H Freeman 8 Co 50 Energy Stores Most animals store fuel molecules that can be released as needed between meals Carbohydrates are stored in liver and muscle cells as glycogen The total glycogen store is about one day s energy requirements The most important form of stored energy in animals is fat Fat has more energy per gram than glycogen and it is stored with little associated water making it more compact Protein is not used to store energy but it can be metabolized as a last resort 5 0 Nutrient Requirements Animals that do not take in enough food to meet their energy requirements are undernourished They must metabolize molecules of their own body to provide the energy they need The first storage compounds to be metabolized in this state are glycogen and fat so that protein loss is minimized for as long as possible Eventually a starving animal must use its own proteins for fuel This impairs body functions and eventually leads to death also remember diabetes mellitus Our major energy reserve is fat a person of average body weight can survive 4 or 5 weeks without food PM I 12 9 L CD CD 0 lgt Stored body energy reserves k U 2 3 4 5 Weeks of starvation 0 o1 rwhen body fat has been exhausted protein is lost at an accelerating rate with serious consequences Carbohydrate reserves are depleted by only a single day without food intake W A 1 5 0 Nutrient Requirements Animals that take in more food than is necessary to meet their energy demands are overnourished Excess nutrients are stored as increased body mass Glycogen reserves are built up and then additional carbohydrates proteins and fats are converted to body fat Some species use seasonal overnourishment to survive periods when food is unavailable In humans however overnourishment can be a serious health hazard increasing the risk of high blood pressure heart attack diabetes and other disorders 5 O Overweight 50 Digestion Humans digest their food outside of their body Food is taken into a body cavity the lumen of the gastrointestinal tract or gut that is continuous with the outside environment where it is acted on by enzymes secreted by exocrine glands These enzymes break the food down into nutrient molecules that are absorbed by the cells lining the cav y IL The gastLreLmteetLmaH tract Epttt ette ee e teee the sq we d 60 of the recognized major human cell types are classified as epithelial cells I 5 0 Protein digestion For example proteins are digested in the gut into amino acids before being used by the body Macromolecules are not readily absorbed by the cells of the gut but the smaller monomers are A protein that functions well in one species might not function well in another Foreign proteins entering the body directly from the gut would be attacked by the immune system 50 Animals must obtain their essential aa from food Eight essential amino acids for humans Tryptophan Methionine Valine Threonine Grains Phenylalanine corn in tortilla chips Lemme Legumes beans in bean dip lsoleucine Lysine 50 Digestion Most animals have a tubular gut with a mouth that takes in food and an anus for waste excretion The tubular gut has different regions that are specialized for different functions All regions within the tubular gut are outside of the body of the animal only by crossing the plasma membranes of the epithelial cells lining the gut do nutrients enter the body Earthworm Mouth Crop Intestine Anus Pharynx Esophag1s Gizzard Cockroach Esophagus Crop Gizzard Rectum Mandibles Salivary Intestine glands LIFE THE SCIENCE OF BIOLOGY Seventh Edition Figure 508 Compartments for Digestion and Absorption Part 1 lt91 2004 Sinauer Associates Inc and W H Freeman 8 Co Rabbit Salivary Pancreas Small intestine Liver Stomach Large intestine Esophagus LIFE THE SCIENCE OF BIOLOGY Seventh Edition Figure 508 Com rtments for Digestion and Absorption Part 2 L 2 Sinauer ASSOCIEHGS Inc and W H Freeman 8 Co Surface area is increased by villi and microvilli Villus Villi 5 N Q Intestinal folds Capillaries Epithelial cells Microvilli Epithelial cells LIFE THE SCIENCE OF BIOLOGY Seventh Edition Figure 509 Greater Intestinal Surface Area Means More Nutrient Absorption Part 3 2004 Sinauer Associates Inc and W H Freeman 8 Co SO Digestion The parts of the gut that absorb nutrients have evolved large surface areas to maximize nutrient absorption Vertebrates have a gut wall that is richly folded with individual folds bearing fingerlike projections called villi which in turn have projections called microvilli Together villi and microvilli present an enormous surface area for the absorption of nutrients Parotid salivary gland V K Mouth J 0 Teeth If Sublingual and Esophagus l submandibular a salivary glands Diaphragm Liver Stomach I 7 iv l Pancreas Gallbladder l g Large K l i Lquot 2 intestine I 1 Duodenunq h I Jejunum Appendix P J Heum Rectum LIFE THE SCIENCE OF BIOLOGY Seventh Edition Figure 5010The Human Digestive System pa 2004 Sunauer Associates Inc and W H Freeman amp Co The submucosa contains a neural network Lumen Mucosa Submucosa Contains blood and lymph vessels Circular muscle layer Nerve net between muscle layers Longitudinal muscle layer Peritoneum The peritoneal membrane is continuous with the lining of the abdominal cavity 50 Structure and Function of the Vertebrate Gut The vertebrate gut has four major layers of tissue throughout its length The cavity of the gut is called the lumen Starting from the lumen the first layer of tissue is the mucosa The mucosa consists of epithelial cells that have secretory and absorptive functions Just outside the mucosa is the second layer of cells the submucosa which contains blood and lymph vessels that carry absorbed nutrients to the rest of the body 50 Structure and Function of the Vertebrate Gut A fibrous coat called the serosa surrounds the gut All abdominal organs are covered and supported by a There are two layers of smooth muscle cells external to the submucosa The innermost layer is the circular muscle layer and has cells that are oriented around the gut The longitudinal muscle layer is the outermost layer and has cells that are oriented along the length of the gut tissue called the peritoneum Epithelial cells have to be polarized to be functional Apical lTJl g li NI iu lx IiJ ATP ADP Basolateral Membrane traf c establishes and maintains cell polarity Apical Direct Pathway Transcytotic Basoulateral Pathway Polarized Cells Neuron Photoreceptor Cell Structure of a villus Villi villus lacteal blood caplllarles goblet cell intestinal gland arteriole venule lymphatic vessel nlumnar cpllhcllul cells quotlt hcruill thmxh burden Connccmc llssuc core Section at lnlestlnal Wall Lymphatic luclczll 39aIO quot spillnr network quot0 0 0Ig I I 3 I0 O39Ilquot39quot39I39gquot39 M L m m d h H D e r a n m M O C V b d e m S t D V r C W B C S U m r a U C W C m U n W P n a m U H 3 4 O 5 O t O h D small intestine duodenum jejunum and ileum Folds in HampE Sta Photo 5044 Human ileum mucosa composed of villi crypts lined by simple columnar epithelium I D P 4 u 0 Q 0 I o o 39 I I 39 O I I 5 9 I s 4 K 0 I 5 4 o l I 39 g Q 5 39 39 t 39 39 39 quot390 39 I quot V 0 391 Q g I I n 0 39 0 0 39 39 39 5 39 J 9 39 0 r 39 u I 39 39 I I 39 o p 39 0 I 39 o c I a 5 U o O 39 O y 39 0 39 39 39 0 I 39 g o lo g I 0 I 39 390 C U A 39 u I 1 rt 39 39 39 39 39 39 I quot 39 0 I u 39 I 0 9 I o r a Q 39 39 39 quot 39 on o 39 39 39 4 C V 39 n n y 0 39 0 5 o 0 39 o 0 u 39 I 39r O 7 O o I I 1 Q 3 I 0 1 V In I 39 39 a 39 quot0 a quot 39 39 39 39 I so 39 39 quot I n 0 39 4 39 39 5 939 39 39 39 O C 39 1 0 39 039 g D 0 I O I O I y 39 quot u o I 39039 o 1 39 39g 39 39 o quotc U 0 x or I I I 39 39 OI o 39 l C I Q v V 39 n Q 39 I I a F g ow I 0 I 1 0 l n 39 39 f 4 0 1 39 39 1 39 u 3 39 I l I 39 n 39 o 39 o I o 4 Y 39 d o 5 I I o I 0 0 a o g O 39 39 o 39 39 39 I I I C I quot 0 390 39 I 39 g 0 39 i 39 3 I 39 0 4 I I 39 0 quot co 39 0 39 39 u I l39 I 39 39 9 g J 1 In 0w I u 4 n I 39 392 o I quot n O 39 1 s 39 o I 0 f O 39 39 I g o 9 4 39 39 39 O l u 4 d I 390 139 I 4 I v I I 39 39 1 l 39 0 g o I 0 0 o 39 39 c I o I 39 I u I 39 4 g r v C I C r 39 o I 0 39 5 39 O In 390 o 0 9 quot 1 Q u 39 I 0 o 39 I 9 o o c o I Jejunum dog central part of small intestine HampE Stain Jejunum central part of small intestine p J 39 39 Q J I 0 5 on A quot J39 i f 39 t 7 v 39 quot 7 Q 39 uamp3939 o quot I P 39 O 4 39 w A v G if r V 4 Q 0 c x h I E 5 V 3 1 Q A an I on 1 I quot quot quotl 4 E 39 B quotquot39amp P eaquotv7 A P 4 39 4 as Q o39 39 J A W a 1quotu quot o39F7 kquot c39 9 1 4 iv quot quot39 397quot 3939 quotquotquot 39 quot39 2 393 av539o1I9iquotj 1g II V 2 Ir 3949 v C 9 39 1 quot39 quot V in 3 n gt 39 7 3 W 5 C p p2 f J I uf I C C 5 19 4A 3 J I W I k V l l t 3 a J 2 Q 1 d39 A P V J 39 b 3 2 V 39rg0quot W F m 39 f39 39 V 3 39 g 33 to quotet lafquot39 939 g W c 1 g Jejunum central grt of small intesti e ti 7 quot 39 Pj quotc3 39mgwev 9 p p quot1g39t 0 I05 392 x3939 amp B t 4 Jejunum central part of small intestinej Jejunum central part of small intestine Mouse small intestine transmission EM BB brush border TJ tightjunction Mo se Small Intestine 7508 March 50 2000 vIEO 5 O Hydrolytic enzymes Hydrolytic enzymes break down protein carbohydrate and fat macromolecules into their simplest monomeric units Digestive enzymes are classified according to the substances they hydrolyze Carbohydrases hydrolyze carbohydrates Proteases hydrolyze proteins Lipases hydrolyze fats Nucleases hydrolyze nucleic acids The salivary glands Parotid Tongue salivary glancl K Y Mouth J Teeth Sublingual and Esophagus submandibular R salivary glands 5 O Hydrolytic enzymes The salivary glands secrete mucus and amylase Mucus mucins a family of large heavily glycosylated proteins and inorganic salts suspended in water Amylase is a carbohydrase that hydrolyses starch into maltose 0 0 l 0 0 ot H oa H o H o H Y H quotltf 53 H quotf I H 391 quotI H ljltl o Q o t 0 f I HO OH HO OH HO OH H0 OH Starch a glucose polymer Maltose a glucose dimer 50 Functions of saliva Lubrication and binding binds food into a slippery bolus that usually slides easily through the esophagus without inflicting damage to the mucosa Coats the oral cavity and esophagus and food basically never directly touches the epithelial cells of those tissues Solubilizes dry food eg pretzels Oral hygiene The oral cavity is almost constantly flushed with saliva which washes away food debris and keeps the mouth relatively clean Saliva also contains Iysozyme an enzyme that lyses many bacteria and prevents overgrowth of oral microbial populations Initiates starch digestion alphaamylase digests starch into maltose Amylase is not present or present only in very small quantities in the saliva of carnivores saVary Mucous cells Striated 9 I and quot I p Sero us 0 V 0 I A I cells O 53gt 0 5 p re 1 399 u L secrete mucus ntercalated A 7 7 Duct secrete amylase P A k P r ultD4uc0us quot liAli in 1 1 391 1 5 1 A Striated Duct 3 1 I vquot 3 7T l 39 V V P 39 rm 39 x3 J W 3 2 239 f 1 L qI 391 5quot quot3911 um xL Mucous cells 0 Swallowing A Swallowing Soft palate Food g Epiglottis Glottis Tongue Upper esophageal sphincter Pharynx Larynx Traohea windpipe Esophagus Food is chewed and the tongue The soft palate is pulled The larynx is pulled up and pushes the bolus of food to the up as the vocal cords forward and is covered by back of the mouth Sensory nerves are pulled together to the epiglottis The esophageal initiate the swallowing reflex close the larynx sphincter relaxes The bolus of food enters the esophagus I7 Peristalsis M Food bolus Esophagus Circular muscles contract Previous bolus Circular muscles relax 0 Longitudinal muscles contract 0 Pyloric 2 0 sphincter 5 O Gastric acid Hydrochloric acid HCI maintains a pH of 1 3 in the stomach fluid Stomach39s interior can secrete 2 to 3 liters of gastric fluid perday Functions to kill microorganisms that are taken in with food to hydrolyze acidlabile substances eg bone to activate pepsin Hydrochloric Acid Amen25 PI 39 V l iI39 vIf f739iu ll X 39n I39 quot39 39 ug 39 quotI 391 quot uvn 39 ml39 39139 quot4 39 39 Auquot39 I 39 U o ll kquotquotr4 I 391 quotamplgt lI39 UIIIl39ILInI3911quot 1 quot339 quotquot139I lI39 3939 53 quot 39 l39s h5c quot399cIn u at P D W 0quotquot The endopeptidase pepsin is the major enzyme produced by the stomach Pepsin is secreted by cells in the gastric glands as a zymogen called pepsinogen Newly formed pepsin activates other pepsinogen molecules in a process called autocatalysis Inactive zymogen Active enzyme pepsin pepsinogen Masking sequence Gastric pits I 3 amp 5Q 3 o o 0 o o 3 Si Lao uBo qua 0 yo 3 ao w h u W nmmmmmD Eounuoq8uo oouo m ms8 LwuN4ao b3ampraMa1 I r uux ltvOwClg a pd q v aunSuD CW abwomr0umO m Ouunvu 0359 Jngt AW I u 1lgtvm oau5a ampm 7caarocooo 2 OEmb Let c Vi nw 5oL2o 5 15 caE C 3 ltn CuA u a o u nan 1 uQhDA4v 1 W 4 Rahn 03 mucosa secreting cells Q er wk C mmm Wmm Les r P mC rn mm mnk PS 89 50 1 3 Part 1 LIFE ms SCIENCE or BIOLOGY Eighth Edition 0 2oo7 Sinauer Assocmes Inc and w H Fneeman as Co Surface 1lIuc0us Cell Mucous Neck Cell Parietal Cell Zymogenic Cell 3 I OJ 2 l 2 2 fr Au 9 0 In IIl I I 1 s M sH N 0 gm la1 ga4 G I Ga x 1 a 9 PM mHw 0x4 O H l A VA VA V Plt Neck Base Gland OLowpHoonverts pepshogen to pepsin Ina process called auhocat fvsis newly Eforrned Z7 pepsin ai39tiIatesp1her epsin o g en Parietal cell Acid Q secreting cellgi I X If L I 39 l w r quot v 5 I I A 3 W c I 39 ix 1 39 n 39A N K ri39 5 4 5 M A Zymogenic cell f Enzyme A e r 0 N secreting cell M Gastric gland LIFE THE SCIENCE OF BIOLOGY Seventh Edition Figure 5013 The Stomach Part 2 2004 Sinauer Associates Inc and W H Freeman amp Co Parietal cells secrete HCI C Bicarbonate is activety 3 H is actively transported transported out of the into the lumen of the blood side of the cell in gastric pit in exchange exchange for Ci for K tI Lumen of gastric pit K and Ci leak out of the cell Carbonic anhydrase catalyzes formation of carbonic acid which dissociates into H and HCO3 A Q f uAnAl T Zymogenic cell transmission EM 73 In J H 3 Av uf 39 0z lo I f D OQ A 5 4 vi l39OC Parietal cell transmission EM w V quot4 Ps 39 39V v 9 50 Mucus and stomach ulcers Mucus secreted by the stomach s mucous cells coats the walls of the stomach and protects them from being eroded and digested by HCI and pepsin When walls of the stomach are exposed directly to HCI and pepsin an ulcer can result peptic ulcer 5 O Helicobacter pylori Until recently peptic ulcers were thought to be caused by stress until it was discovered that the bacterium Helicobacter pylori can infect the stomach and cause the disease In Western countries the prevalence of Helicobacter pylori infections roughly matches age ie 20 at age 20 30 at age 30 80 at age 80 etc Prevalence is higher in third world countries In 1994 the National Institutes of Health endorsed antibiotics as the standard treatment for peptic ulcers The Nobel Prize in Physiology or Medicine 2005 quotfor their discovery of the bacterium Helicobacter pylori and its role in gastritis and peptic ulcer diseasequot p x Barry J Marshall J Robin Warren Australia Australia b 1951 b 1937 watch documentary 8 minutes Helicobacter pylori Helicobacter pylori urease converts urea to bicarbonate and ammonium ions 50 Structure and Function of the Vertebrate Gut The muscles in the walls of the stomach contract to churn its contents and mix them with the stomach secretions This mixture of gastric juice and partly digested food is called chyme Peristaltic contractions of the stomach push the chyme toward the bottom end of the stomach and into the beginning of the intestine through the pyloric sphincter The small intestine Adult human more than 6 m long 2 to 3 cm in diameter I inner surface area of about 550 m2 tennis court I The small intestine is much longer than the large intestine typically 45 times longer but has a smaller diameter Three structural parts CI duodenum 025 m site of most digestion latin duodenum digitorum 12 fingers breadths a jejunum 25 m site of 90 of the D ileum 35 m absorption of nutrients I s Liver Stomach Pancreas Gallbladder g f X 39 quot 39f39i mtestme K 4 9 Ki i 0 I Duodenum tiquot L 39vquot A 5 jejunum APl3endix g A Hf I Ileum U 9 Rectum H 1 o A H Q s 9 J1 U Hh kN k u Duodenum M 1 8H A Human ileum mucosa composed of villi crypts lined by simple columnar epithelium 0 J II c ssmL 2 hf xv 3 u 14 o 095p 90 V I0 0 O I e e p 0 1 u Io is Q oos It L at g 8 Goblet cell secretes mucus gtJ S gt 39 Common bile duct Pancreatic duct Duodenum LIFE THE SCIENCE OF BIOLOGY Seventh Edition Figure 5015 The Ducts of the Gallbladder and Pancreas 2004 Sinauer Associates Inc and W H Freeman amp Co 50 Structure and Function of the Vertebrate Gut The liver and the pancreas provide many of the The liver produces bile which aids in fat digestion When fat enters the duodenum bile is squeezed into the specialized enzymes required for digestion Bile is secreted from the liver and flows through a branch of the hepatic duct to the gallbladder where it stored until it is needed common bile duct where it flows into the duodenum a Digestion of fats Large lipid droplet A 39 Bile salts x 0 ii Micelles 4 l Monoglyceride Fatty add LIFE THE SCIENCE OF BIOLOGY Seventh Edition Figure 5016 The Digestion and Absorption of Fats Part 1 722 2004 SinauerAssocia1es Inc and W H Freeman 8 Co 50 Bile acids bile salts Bile acids are emulsifiers surfactants they have Iipophilic end and a Iipophobic end they disperse fat droplets into micelles this greatly increases the surface area of the fats that are exposed to lipases 5 fl e F KOO quot W 5 339 50 Structure and Function of the Vertebrate Gut Bile acids are synthesized from cholesterol 90 of excreted bile acids are reabsorbed by active transport in the ileum and recycled via the liver enterohepatic circulation 10 o of bile acids are lost in the feces This is the major pathway for elimination of cholesterol F 50 High cholesterol and heart disease Why Is Cholesterol Important High blood cholesterol major risk factor for heart disease The higher your blood cholesterol level the greater your risk for developing heart disease or having a heart attack Heart disease is the number one killer of women and men in the United States Too much cholesterol in your blood it builds up in the walls of your arteries Over time this buildup causes quothardening of the arteriesquot so that arteries become narrowed and blood flow to the heart is slowed down or blocked The blood carries oxygen to all the tissues of the body Not enough blood and oxygen to your heart heart attack brain stroke 5 O Bile Acid Sequestrants Bile acid sequestrants are polymeric compounds which serve as ion exchange resins that bind to the negatively charged bile acids Example cholestyramine Bile acid sequestrants are not absorbed in the Gl tract and are excreted together with the bound bile acids This results in disruption of the enterohepatic circulation and loss of bile acids this lowers the cholesterol levels Cl 1 c1 13 c1 1 c1 13 L he I Cllquotquot ClljNiCll Cl Cholestyramine quot 1 5 0 Fat absorption Lipases break fats down into diglycerides monoglycerides and fatty acids which are able to pass through the plasma membrane of microvilli Once in the cells they are resynthesized into water soluble lipoproteins called chylomicrons These pass to the lymph vessels in the submucosa They enter the blood through the thoracic ducts I9 Absorption of fats FA amp m Oglycaid s Endoplasmic reticulum TG cholesterol PL Chylomicron a Iipoprotein O Intestinal epithelial cell L01 l Lymphatic vessel LIFE THE SCIENCE OF BIOLOGY Seventh Edition Figure 5016 The Digestion and Absorption of Fats Part 2 lt9 2004 Sinauer Associates Inc and W H Freeman 8 Co INTRO REWIND STOP PLAY 0 Animation Fat Digestion open Animation50O1swf in Safari 50 Lipoproteins Lipoproteins transport fats in the aqueous circulatory system They consist of a core of fat and cholesterol covered by apolipoproteins that make them watersoluble The largest lipoproteins are the chylomicrons H Unesterified cholesterol Phospholnpud Lipoproteins are classified I Cholcstcryt ester according to their density the I Apoprotem 8100 more fat the lower its denSity Z t Egtltf 7Flt lt U7Jg Appr3r3gt h J Z hm Y p Y rm mtettter SO Lipoproteins Chylomicrons carry triaoylglyoerol fat from the intestines to the liver and to adipose tissue Very low density lipoproteins VLDL carry newly synthesized triaoylglyoerol from the liver to adipose ssue Low density lipoproteins LDL carry cholesterol from the liver to cells of the body Sometimes referred to as the quotbad ohoesterolquot lipoprotein High density lipoproteins HDL oolleots cholesterol from the body39s tissues and brings it back to the liver Sometimes referred to as the quotgood ohoesterolquot lipoprotein LDL to HDL is a risk factor for atherosolerotio heart disease 50 Watch Smoking and Atherosclerosis Ad httpWWWyoutubecomWatohV1EcRsV9pMcampfeaturere1ated Q Norma artoty 6 Narrowi ofarto NOITOWOC Plaque artery J 50 The exocrine pancreas The pancreas is a large gland that lies just beneath the stomach and functions as both an endocrine and exocrine gland The exocrine tissues of the pancreas g produce a number of digestive enzymes 1 a a C duct Duodenum released as zymogens Trypsinogen is activated in the duodenum by enterokinase which is produced in the cells lining the duodenum Active trypsin can activate other trypsinogen molecules by autocatalysis 50 The exocrine pancreas The pancreas also produces a secretion rich in bicarbonate ions which neutralize the pH of the chyme from the stomach This process is essential because intestinal enzymes function best at a neutral or slightly alkaline pH SO Absorption of nutrients Only the smallest products of digestion can be absorbed through the mucosa epithelial lining of the small intestine The final digestion that produces these absorbable products takes place at the microvilli apical plasma membrane Membranebound peptidases on microvilli that cleave peptides into tri and dipeptides and individual amino acids Intestinal epithelial cells also produce maltase lactase and sucrase which cleave common disaccharides into monosaccharides 503 Sources and Functions of the Major Digestive Enzymes of Humans ENZYME SOURCE ACTION Salivary amylase Salivary glands Starch a Maltose Pepsin Stomach Proteins gt Peptides autocatalysis Pancreatic amylase Pancreas Starch gt Maltose Lipase Pancreas Fats gt Fatty acids and glycerol Nuclease Pancreas Nucleic acids gt Nucleotides Trypsin Pancreas Proteins gt Peptides activation of zymogens Chymotrypsin Pancreas Proteins gt Peptides Carboxypeptidase Pancreas Peptides gt Peptides and amino acids Aminopeptidase Small intestine Peptides gt Peptides and amino acids Dipeptidase Small intestine Dipeptides gt Amino acids Enterokinase Small intestine Trypsinogen gt Trypsin Nuclease Small intestine Nucleic acids gt Nucleotides Maltase Small intestine Maltose gt Glucose Lactase Small intestine Lactose gt Galactose and glucose Sucrase Small intestine Sucrose gt Fructose and glucose 50 Finally The large intestine Peristalsis pushes the contents of the small intestine into the large intestine or colon The colon absorbs water and ions producing semisolid feces from indigestible material Too much water absorption results in constipation and too little water absorption results in diarrhea Large populations of bacteria live in the colon including Escherichia coli which synthesizes vitamin K and biotin that are absorbed across the wall of the colon Prolonged intake of antibiotics can lead to vitamin deficiency because the antibiotics kill the normal intestinal bacteria Sensory Systems Neuronal network pFV o lfa cto ry re ce pto rs Sensory Cell receptor oell modified neuron 45 Sensory Cells and Transduction of Stimuli Sensory cells also called receptor cells transduce physical or chemical stimuli into signals that are transmittable and interpretable Most sensory cells are modified neurons specialized for detecting different kinds of stimuli such as pressure heat or light 45 Sensory Cells and Transduction of Stimuli Most sensory cells have membrane receptor proteins that detect a stimulus and respond by altering the flow of ions across the plasma membrane Intensity of the stimulus is encoded in the frequency of the AP 45 Sensory Cells and Transduction of Stimuli Sensory cells transduce the energy from a stimulus into action potentials The first step is activation of a receptor protein in the plasma membrane of a sensory cell by a stimulus The activated protein opens or closes ion channels Outside of cell Pressure Taste smell Plasma molecule membrane J quot Zvquot 4 quot 439 1 Jquot 3939 a I1 ll 1 5 J 3 1 sJ quotl39J 39 39 M I quot 3 K 39 39Iquot l V L I v 3 7 9 5 39 39quot39 j an f 2 139 1 390 9 07 Pressure sensitiVe Na channel Na or K CGMPgated Inside of Cell channel Na channel Mechanoreceptor Chemoreceptor Light receptor 45 Sensory Cells and Transduction of Stimuli The resulting change in membrane potential causes the sensory cell to fire action potentials or to change its secretion of a neurotransmitter onto an associated neuron that fires action potentials The intensity of the stimulus is encoded in the frequency of the action potentials produced 45 Sensory Cells and Transduction of Stimuli Sensory cells and other types of cells form sensory organs such as eyes ears and noses Sensory systems include the sensory cells the associated structures and the neuronal networks that process the information 45 Sensory Cells and Transduction of Stimuli Although they are simply depolarization events sensory data are interpreted in different ways according to the different places in the CNS where messages from different kinds of sensory cells arrive A small patch of skin for example contains various sensory cells capable of detecting heat pressure movement and tissue damage pain Whether a stimulus is interpreted as one or another sensation depends on which cells of the central nervous system receive the signal 45 Sensory Cells and Transduction of Stimuli Some information is sensed without our being conscious of it For example the brain receives continuous information about levels of CO2 blood sugar and 02 Such information is important for the maintenance of homeostasis 45 Sensory Cells and Transduction of Stimuli In ionotropic sensory detection the receptor protein itself is part of the ion channel and by changing its conformation opens or closes the channel pore In metabotropic sensory detection the receptor protein is linked to a G protein that activates a cascade of intracellular events that eventually open or close ion channels Outside of cell Pressure Taste smell Plasma molecule membrane A I 393 3 C L73939 w V gm v a Aquot 39 vs 0 quot393 11 4quot b w quot L 7 fl vs339p 3 quot 39l I w 7 fl 3 3 lt quot A v 39 V I I l 39 Vs I x ll 39 39 1 1g e39el394ag Ki 4 quot gt 12 r 3939z Pressuresensitive Na channel Na or K CGMPgated Inside of Ce channel Na channel Ionotropic receptor Metabotropic receptors 45 Sensory Cells and Transduction of Stimuli Primary sensory cells generate action potentials directly An example is the crayfish stretch receptor Secondary sensory cells generate action potentials indirectly by inducing the release of neurotransmitter the stimulus Stretching a muscle is J Muscle p Q M it it that activates the opening of ion channels in stretch a quot1 a I Og De dquotte3 receptor dendrites Stretch g vonage receptor neuron The resulting depolar ization spreads to the cell body creating a receptor potential Cell bodyX Axon hillock which spreads to the axon hillock stimulating action potentials The action potentials travel d x al Axon J down the axon Sensory neurons are analogtodigital converters Oinuouuunouo cop nonco O Iltcoo D UQQAQA 39 3939p39uu g n quot so3 39 39 h39 7 no oobbho39b Lnu 4439 flquot 50056 o m3939 39rsquotnsag Z n F p Lee F 39 I Lquot quotquot 39 39 quotfrt x1 En 45 Sensory cell adaptation Some sensory cells respond less when stimulation is repeated a phenomenon called adaptation The ability of animals to ignore continuous stimuli while remaining sensitive to changing stimuli is sometimes due to sensory cell adaptation 45 Chemoreceptors Olfaction the sense of smell MCDB 1B Midterm Midterm I 0 5 0 5 3 2 2 1 mucaugum O on2 45 10 45 Olfaction Olfaction the sense of smell depends on chemoreceptors In vertebrates olfactory sensors are neurons embedded in a layer of epithelial cells at the top of the nasalcav y The axons of these sensors project to the olfactory bulb of the brain The dendrites end in olfactory hairs at the surface of the nasal epithelium Molecules from the environment diffuse through nasal mucus to reach the surface of the olfactory hairs Odorant molecules LIFE THE SCIENCE OF BIOLOGY Seventh Edition Figure 454 Olfactory Receptors Communicate Directly with the Brain Part 1 lt9 2004 Sinauer ASSOCIEHGS Inc and W H Freeman 8 Co Figure 454 Ofactory Receptors Communicate Directly with the Brain Part 2 Glomeruli Olfactory bulb Neurons in a gomerulus receive input only from receptor cells expressing the same receptor gene 0P A Action potentials 39 generated by odorant binding are transmitted 3 gr 7 Bone to glomeruli in the 139 5 0 f 7 o g 0 j 01 olfactory bulb quot Ir u 39t39 8 p U Connectlvetlssue V A Es 0 is l W p4 6 fl Basal cell L 39 r ya 3 r ll Olfactory receptor cell A Supporting cell 0 ii A l i fDendrite 1 Mucus film 39 Olfactory cilia have NaSfa39 39 receptors that bind specific Cawty 39 39 odorant molecules Odorant molecules 45 Olfactory receptors Odorants are chemicals that bind to olfactory receptor proteins Each olfactory receptor protein binds particular odorant molecules which activates a G protein The G protein then activates an enzyme that increases the level of the second messenger cAMP cAMP opens a Ca2 channels39 i Ca2 leads to opening of a N Clquot channel which depolarizes the membrane and an action potential is fired quoto39C W orirr 1quot oilaclo v 39ecogt39or ra ron LNeuron Volume 48 2005 Pages 417430 A 45 Olfactory receptors Humans have about 40 million olfactory receptor neurons Each olfactory receptor neuron in the nose expresses only type of olfactory receptor Humans have about a thousand genes for olfactory receptors Of these genes only produce functional olfactory receptors the other genes have mutations and are pseudogenes Olfactory receptor genes Species Genes Pseudogenes Human 388 414 Chimp 450 450 Rat 1430 640 Dog 1070 230 Chicken 78 476 Frog 410 478 Pufferfish 44 54 Nematode worm 1100 45 Olfaction The number of odorant molecules greatly exceeds the number of different receptor proteins Each odorant may bind to one or more specific receptor proteins A specific odorant is distinguished according to the different and unique combination of cells it activates A higher concentration of odorant molecules produces a higher frequency of action potentials and is perceived as a stronger smell 45 Combinatorial coding in olfaction Each individual olfactory receptor recognizes a number of similar structures that are part of odorants Most odorants activate more than one type of olfactory receptor This aspect provides for the identification of an almost limitless number of different molecules Like the immune system this system allows molecules that have never been encountered before to be characterized STIMULUS MO Lcl at 314 LECULES CE L S 7 Neuron Volume 48 2005 Pages 41743 The Nobel Prize in Physiology or Medicine 2004 quotfor their discoveries of odorant receptors and the organization of the olfactory systemquot Richard Axel Linda 8 Buck 0 12 of the prize 0 12 of the prize USA USA Columbia University Fred Hutchinson Cancer New York NY USA Research Center Seattle WA USA b 1946 b 1947 Gustation the sense of taste 39 I i 39 1 390 quot c 39 I I quot P tL vquot t gnss Aw nmgt mt SMFMW 45 Gustation Gustation the sense of taste depends on clusters of sensory cells called taste buds Humans have 10000 taste buds embedded in the epithelium of the tongue Many are in raised papillae the small bumps on human tongues The outer surface of each bud has a pore that exposes the tips of sensory cells Microvilli increase the surface area of the cells The sensory cells form synapses with dendrites of sensory neurons Taste buds Large taste buds iTastant molecules bind to receptors on the Taste P01 miorovilli of sensory oells V Taste pore Miorovilli Taste bud sensory cell Supporting cell Sensory neuron Axon to central nervous system Sensory cells release neurotransmitters that depolarize the dendrites of sensory neurons 45 Gustation Receptor proteins in the microvilli bind specific molecules This causes the release of neurotransmitters to the dendrites of associated sensory neurons Taste buds are replaced every few days but the associated neurons live on Taste buds can distinguish five basic tastes Sweet Bitter and Umami now sometimes called Savoury detected by Gprotein coupled receptors CI Umami is a savory meaty taste that is triggered by amino acids and by MSG monosodium glutamate Salty and Sour work through ion channels 45 Mechanoreceptors I 5 Mechanoreceptors Detecting Stimuli that Distort Membranes Mechanoreceptors are cells that are sensitive to mechanical forces They are involved in many sensory systems including skin sensations and sensing blood pressure Physical distortion of a mechanoreceptor s plasma membrane causes ion channels to open which leads to the generation of action potentials The frequency of the action potentials is related to the strength of the stimulus 45 Mechanoreceptors in the skin Skin is packed with diverse mechanoreceptors that cause various sensations Merkel s discs provide continuous information about things touching the skin Meissner s corpuscles are very sensitive mechanoreceptors found mostly in nonhairy skin They adapt rapidly and provide information about changes in things touching the skin Ruffini endings provide information about vibrating stimuli of low frequencies Pacinian corpuscles provide information about vibrating stimuli of higher frequencies Meissner s corpuscle Sensitive touch Ruffini s corpuscles Touch p pressure gt 5 Pacinian corpuscle Pressure I A A V 39 39Cquot 39 P5 l Q x 13 QC ff quot39t 2 245 2 3quot Nerves K H n p x K 39 I l 63911 5 v 7 w 39 Merkel s disks Touch gt Epidermis gt Dermis Free nerve endings Pain itch temperature LIFE THE SCIENCE OF BIOLOGY Seventh Edition Figure 456 The Skin Feels Many Sensations 2004 Sinauer Associates Inc and W H Freeman amp Co 45 Mechanoreceptors in the skin The density of tactile mechanoreceptors influences how finely stimulation can be resolved On the back two stimuli must be fairly far apart before they can be resolved On fingertips finer spatial discrimination is possible because mechanoreceptors are much more dense Auditory systems 1 Sound waves travel through the The ossicles transmit vibrations of Vibrations at oval window create a auditory canal and vibrate the the tympanic membrane to the pressure waves in uid lled tympanic membrane oval window of the cochlea cochlear canals semicircular canal A stapes Ossicles Incus i 39 Malleus P M v f I 77gt I p 39 t Tympanjc quot1quot quot 39 membrane 39 9 C C 39e3 eardrum Oval wandow under stapes Outer Middle Inner ear ear ear 1 u 2 Eustachian U59 Round window 45 Mechanoreceptors Hair cells Hair cells are also mechanoreceptors Each hair cell has a set of stereocilia microvii like When the stereocilia are bent in one direction receptor potential becomes more negative when they are bent in the other direction it becomes more positive When the membrane potential becomes more positive the hair cell releases a neurotransmitter to the sensory neuron associated with it and the sensory neuron sends action potentials to the CNS 450rgans to detect position and movement in the inner ear Vertebrate organs of equilibrium use hair cells to detect the position of the body with respect to gravity Semicircular canals and the vestibular apparatus in the mammalian inner ear use hair cells to detect position and orientation of the head as well as acceleration produced by movement Figure 4511 Organs in the Inner Ear of Mammals Provide the Sense of Equilibrium Part 1 In a semicircular canal Semicircular canals Flow of uid through semicircular canal Utricle Saccule In the semicircular canals the gelatinous cupulae are pushed one way or the other when changes in the position of the head causes the fluid in the canals to shift Cupula Stereocilia Hakcdl Support cell Axon Direction of body movement Hair cells have mechanosensors on their stereocilia Filaments linking K 4 stereocilia r N and close 4 when they are r N Ion channels f lt open when The stereocilia project stereocilia are bent in the into the middle canal b9 t if We 0PP ite which Contains a fluid kdrreotion J kdireotion high in K and low in Na Thus Whe K Stereooilia channels open K enters and depolarizes Hair Ce the cell J Vesicles Membrane depolarization opens voltagegated Ca2 channels causing neurotransmitter release Sensory neurons Figure 459 Organs in the Inner Ear of Mammals Provide the Sense of Equilibrium Part 2 I the vestibule Otoliths ear stones are granules of calcium Stemcllla l l l carbonate on top of a gelatinous layer Force of gravity it easier o o I o Ha1r cell Dendr1tes of Support cell sensory neurons Force of gravity Direction of body movement D Due to inertial mass of otholiths when head changes position V 4 lt 439 accelerates or decelerates the 139r5fell39 g 39 j fllifljl 5quotgt I gti gelatinous otholithic membrane 39 4 b 2 N I bends hair cells yr Q v K g P s p LIFE THE SCIENCE OF BIOLOGY Seventh Edition Figure 459 Organs in the Inner Ear of Mammals Provide the Sense of Equilibrium Part 2 2004 SinauerAssoca1es Inc and W H Freeman 8 Co p i A We 0 t 39 if K i 91 3 39 G 39 f 4L1 45 Photoreceptors 45 Photoreceptors and Visual Systems Responding to Light Photosensitivity is the sensitivity to light It ranges from the ability to orient to the sun to the ability to see Evolution has conserved molecules used for photosensitivity across the entire range of animal species These are a family of pigments called rhodopsins 45 Rhodopsin The light receptor molecule is rhodopsin Rhodopsin molecules can absorb photons of light and undergo conformational changes Rhodopsin molecules consist of a protein called opsin and a lightabsorbing group 11cisretinal 11cisretinal is covalently bound in the center of the opsin molecule When 11cisretinal absorbs a photon it changes to all transretinal which changes the conformation of the opsin This change signals detection of light LIFE 8e Figure 4513 Plasma membrane 1 1cisretinal covalently bound to protein when alltransretinal retums to 11cis conformation it is photoresponsive again Light 1 11cisretinal is sensitive to light Activated transducin Alltransretinal and when it absorbs a photon it becomes alltransretinal After Transdum passing through unstable intermediates G protei alltransretinal activates a G protein cascade that results in a change in membrane potential LIFE THE SCIENCE OF BIOLOGY Eighth Edition ID 2007 Sl adef Associates Inc and W H Freeman 8 Co 45 Retinal is derived from vitamin A H3C CH3 H3C H3C CH3 L alltransretinal OH Retinolz a form of vitamin A 45 Vitamin A deficiency Vitamin A deficiency is common in developing countries but rarely seen in developed countries Approximately 250000 to 500000 malnourished children in the developing world go blind each year from a deficiency of vitamin A Night blindness is one of the first signs of vitamin A deficiency KEY 0 Clinical 0 Severe subclinical 0 Moderate subclinical C Mild subclinical C VAD under control C No data available he 45 Vitamin A deficiency Night blindness the inability to see well in dim light is associated with a deficiency of vitamin A Without adequate amounts of retinal regeneration of rhodopsin is incomplete and night blindness occurs Since carrots are a good source of beta carotene there is truth in the old belief that carrots help you see better in the dark 45 Photoreceptor cells A photoreceptor rod cell is a modified neuron It releases H r neurotransmitters that influence other neurons AA Outer lt segment L V pp Rod cells have an outer segment F an inner segment and a synaptic K Electmde terminal The inner segment has the nucleus I and many mitochondria Seggjggg lt Nucleus The outer segment has a stack of discs of plasma membrane densely S ynapt1c packed with rhodopsin The discs terminal function to capture photons 45 Photoreceptor cells In the dark a rod cell has a depolarized resting potential because Nat channels are continually open Upon light exposure the outer segment becomes more negative or hyperpolarized Photoreceptor cells do not fire action potentials 7 Light flash I I 3 U1 I Receptor potential mV on L U1 U1 I I Tim e DiSC n W CD Rod cell Outside Of CGMPmediated rod cell Na Na channel ROd Ce Outer 0 o 0 in open position membrane d Cytoplasm of rod cell Cytoplasm of disc When light is absorbed by rhodopsin the conformational change due to retinal isomerization leads to activation of a G protein called transducin F CGMP is required to keep The activated transducin sodium channels open activates a phosphodiesterase which jne399r3ehS3arltrSeS converts CGMP to GMP close Na Hyperpolarization O O Disc membrane l 4 p g z 9 A Iquot 1 JD i L oquotquot 5 g 3939 39s 39 1 3 N I quot 391 I 395 2quot D x j amp A a quot run rhoquotclop v In 2 45 Photoreceptor cells The advantage of this system is that it amplifies the signal Each single photon can cause activation of several hundred transducin molecules which in turn activates many phosphodiesterase molecules A single photon can close a huge number of sodium channels 45 Eyes Vertebrate eyes are fluidfilled spheres bound by tough connective tissue called sclera A transparent cornea in the front allows light passage Inside the cornea is the pigmented iris which controls the amount of light that can enter The pupil is the region where light enters The lens makes fine adjustments in the focus of images on the photosensitive retina at the back of the eye Vitreous gel Ciliary muscle Eye of human Suspensory ligaments Optic nerve Blind spot Fovea Retina C0rnea Iris Sclera For distant vision ciliary muscles are relaxed I For near vision ciliary muscles contract causing the lens to round up 7 Ciliary muscles T Suspensory ligaments Fovea 45 The retina The retina includes layers of neurons that process visual information from the photoreceptors and produce an output signal that is transmitted via the optic nerve Light must pass through all the layers of cells before photons are captured by rhodopsin There are two types of vertebrate photoreceptors Tods and conesT Light travels through layers CZ and is absorbed by the rods and of transparent neurons cones the photoreceptive layer at ganglion amacrine bipolar K the back of the retina and horizontal cells Retina V f A To optic nerve 4 A Photggeceptors Cornea Lens Retina r Amacrine Bipolarx Cone Rod Pigmented cell cell epithelium mT I 39 I M V J V 39 39 39 g 39 7quot sc 4 S T aaaa P E quotquot 3939 C V 1 394 JFJ H K fr lt J g 1 J Vquot R ll lll l K T quot39 quotquotk I quot39 3 39 39 f 7 k I IA quot39vv 4 if I PuE 1quot f P 39 quot39 i A It 1 E l yr fl J I I l sZquot Z 9 quot Ganglion cells Horizontal cell Sclera x J H l l Axons of ganglion cells wsual information is processed through several layers of neurons and nally converges on ganglion cells which send their axons to the brain 45 The retina The human retina is organized into five layers of cells Cells at the front of the retina are ganglion cells They fire action potentials and their axons form the optic nerves The photoreceptor cells are at the back of the retina Ganglion cells and photoreceptors are connected by bipolar cells Release of neurotransmitter from the photoreceptor cells in turn causes the rate of neurotransmitter release from the bipolar cells to change Release of neurotransmitter from bipolar cells causes ganglion cells to fire action potentials In Responding to Light Horizontal cells connect neighboring pairs of photoreceptors and bipolar cells This provides a means for the lateral flow of information Amacrine cells connect neighboring pairs of bipolar cells and ganglion cells These help make eyes more sensitive to small but rapid changes PRINCIPAL NEURONS OF THE RETINA am fw A 39i pr u39 I 3 OPTIC NERVE FIBERS PHOTORECEPTORS JWI4wtrrnr quot u39aw 6 5 lt lt39 1 39 quot un39 v L f v I 39 quotquot 7 3939 pg Pl 39 0 5 A0 LquotLmquot 339339 1 quot W p V pD i 2s iy A 1 b9 jquotQ quot quotr39 1 quot lquot 77 C l39 x 393 Pb I sfV395u an 3 3fv amp fgquot 1 i 9a A Color vision Cosmic rays Gamma rays i Wavelength nm 1 wwwwwwwvwx Xrays 1 z Q Ultraviolet UV 102 Q I 39 7 7 L vrv ig 397Vf I quot quot E 39y39 39 39r 39139 I Pquot I A 39 3 tv na puo in Yellow 400 Violet Blue Green 39 Orange Red e i 700 Infrared IR I 105 Microwaves Radio waves LIFE THE SCIENCE OF BIOLOGY Seventh Edition Figure 85 The Electromagnetic Spectrum 2004 Sinauer Associates Inc and W H Freeman amp Co 45 Color vision Photoreceptor cells There are two types of vertebrate photoreceptors Tods and conesT Rod cells are more sensitive to light they provide backandwhite vision at low light levels the human retina has 125 million rods Cone cells are less lightsensitive but they respond to different wavelengths of light for color vision cones also provide the sharpest vision the human retina has 6 million cones the fovea has only cone cells I 5 Color vision cones Humans have three kinds of cone cells Ltype cones absorb longwavelength light yellow green Mtype cones absorb mediumwavelength light bluegreen Stype cones absorb shortwavelength light blue violet The L M and Stype cones differ in their expression of slightly different opsins which absorb light of different wavelengths Figure 4519 Absorption Spectra of Cone Cells 496 531 559nm 1 l 1 Relative absorbance 400 456 500 550 600 650 Wavelength nm Sensor arrays of digital cameras work essentially in the same way 45 The macula The macula is an oval yellow spot near the center of the retina of the human eye It has a diameter of about 15 mm and is specialized for high acuity vision Vitreous gel F PELOPZD DEPPOTEC II LITODPCY fDPIfCIO PIIOLCPYI 3ooagt1 counts to N 20200 20100 2070 2050 2040 2030 2025 2020 45 The retina The fovea is at the center of the macula Responsible for sharp central vision which is necessary in humans for reading watching television or movies driving and any activity where visual detail is of primary importance The human fovea has about 160000 cone cells per square millimeter a hawk has 1000000 There are no photoreceptors V e US9e39 TT HT where blood vessels and S 4T bundles of axons going to the brain pass through the back of the eye This creates a blind spot on the retina Agerelated macular degeneration AMD medical condition in which the photoreceptors in the macula malfunction and over time degenerate leading cause of central vision loss blindness in the United States today for those over the age of fifty years exact cause unknown but there are many risk factors Natural Defenses against Disease Washington contracted Smallpox in 1 751 Macrophages engulfed smallpox virus Displayed fragments of viruses on their surfaces T cells recognized the fragments and became activated Activated cells attacked virusinfected cells Prevented lethal spread of the disease 18 Animal Defense Systems Humans are nutritious and taste good to pathogens Possible pathogens vwuses bacteria singlecell eukaryotic parasites yeast parasitic worms maggots lions usually not considered pathogens The immune system is a set of mechanisms that protect an organism from infection by identifying and killing pathogens What happens in the absence of an immune system Decaying mole 40 hours compressed to 30 sec htt www outubecomwatchvcb7wB IR2 0 18 Animal Defense Systems 18 Animal Defense Systems The immune system must recognize and defeat pathogens CI viruses CI bacteria CI singlecell eukaryotic parasites fungi yeast CI parasitic worms CI maggots The immune system must be absolutely specific and not attack normal cells and tissues Pathogens are constantly evolving new ways to avoid detection by the immune system the immune system must be adaptive 18 Animal Defense Systems There are two general types of defense mechanisms Nonspecific defenses or innate defenses are inherited mechanisms that protect the body from many different pathogens MThe Innate Immune System Specific defenses are adaptive mechanisms that protect against specific targets MThe Adaptive Immune System Innate immune system Adaptive immune system Response is nonspecific Pathogen and antigen specific response Exposure leads to immediate maximal response Lag time between exposure and maximal response Cellmediated and humoral components Cellmediated and humoral components No immunological memory Exposure leads to immunological memory Found in nearly all forms of life Found only in jawed vertebrates 18 Who are the players 18 The players Components of the defense system are distributed throughout the body Lymphoid tissues thymus bone marrow spleen lymph nodes are essential parts of the defense system Blood closed circulatory system suspends red and white blood cells and platelets CI Red blood cells are found in the closed circulatory system CI White blood cells and platelets are found in the closed circulatory system and in the lymphatic system 18 The players lymphatic system Lymph consists of fluids that accumulate outside of the closed circulatory system in the lymphatic system The lymphatic system is a branching system of tiny capillaries connecting larger vessels These lymph ducts eventually lead to a large lymph duct that connects to a major vein near the hean At sites along lymph vessels are small roundish lymph nodes Lymph nodes contain a variety of white blood cells 18 The players the human lymphatic system Thoracic duct In the lymph nodes lymph is ltered and white blood cells inspect it for pathogens Lymph ducts conduct lymph In I39 l f B cells mature in f the bone marrow LIFE 8e Figure 181 LIFE THE SCIENCE OF BIOLOGY Eighth Edtion O 2007 Sinauer Associates Inc and W H Freeman 8 C0 18 The players Blood cells White blood cells leukocytes are important in defense All blood cells originate from stem cells in the bone marrow White blood cells are clear and have a nucleus and organelles Red blood cells are smaller and lose their nuclei before they become functional White blood cells can leave the circulatory system White blood cells can proliferate in response to invading pathogens 18 The players White blood cells There are two main groups of white blood cells phagocytes and lymphocytes Phagocytes engulf and digest foreign materials Lymphocytes are most abundant There are two types B and T cells T cells migrate from the circulation to the thymus where they mature B cells circulate and also collect in lymph vessels and make antibodies TYPE OF CELL FUNCTION Red blood cells Transport oxygen 2Qgglgior erythrocytes and carbon dioxide cell lt Platelets Imt1ate blood clottmg cell fragments without nuclei White blood cells leukocytes Pluripotent hematopoietic some cell next slide ITIBITOW LIFE THE SCIENCE OF BIOLOGY Seventh Edition Figure 182 Blood Cells Part 1 2004 Sinauer Associates Inc and W H Freeman 8 Co Myeloid progenitor cell V Pluripotent hematopoietic cell next slide lt gtxlt Neutrophils gtlt Monocytes Macrophages Mast cells K gtlt Dendritic cells TYPE OF CELL FUNCTION PHAGOCYTES K Basophils Release histamine may promote the develop ment of T cells Eosinophils Kill antibodycoated parasites Phagocytose antibody coated pathogens Release histamine when damaged Develop into macro phages Engulf and digest microorganisms activate T cells Present antigens to T cells LIFE THE SCIENCE OF BIOLOGY Seventh Edition Figure 182 Blood Cells Part 2 lt9 2004 Sinauer Associates Inc and W H Freeman 8 Co Pluripotent hematopoietic cell Bone I TYPE OF CELL FUNCTION marrow LYMPHOCYTES B cells Differentiate to form antibodyproducing cells and memory cells Lymphoid K progenitor cell K Plasma Secrete antibodies 4 cells T cells Kill virusinfected cells regulate activities of other white blood cells Natural Attack and lyse virusinfected killer cells or cancerous body cells LIFE THE SCIENCE OF BIOLOGY Seventh Edition Figure 182 Blood Cells Part 3 2004 Sinauer Associates Inc and W H Freeman 8 Co K eAVr m m7 4 Scanning electron microscope image from normal circulating human blood l White blood cells Platelets Nonspecific general protection mechanisms that attempt to stop pathogens from invading the body Works against all pathogens not specific M The Innate nonspecific Immune System C The Adaptive specific Immune System I It EputhetUe eetts the ewts de wertd 60 of the recognized major human cell types are classified as epithelial cells I 18 Nonspecific Innate Defenses The innate immune system is a hodgepodge of different mechanisms I The E acts as a physical barrier to pathogens I Bacteria and fungi on the surface of the body normal flora compete for space and nutrients against pathogens I Tears nasal mucus and saliva contain the enzyme lysozyme that attacks the cell walls of many bacteria I Mucus and in the respiratory system trap pathogens and remove them I lngested pathogens can be destroyed by the hydrochloric acid and proteases in the stomach I In the small intestine bile salts kill some pathogens 18 1 Human Nonspecific Defenses Part 7 DEFENSIVE AGENT FUNCTION Surface barriers Skin Acid secretions Mucous membranes ep1thel1al cells Mucous secretions Nasal hairs Cilia Gastric juice Acid in vagina Tears saliva Prevents entry of pathogens and foreign substances Inhibit bacterial growth on skin Prevent entry of pathogens Trap bacteria and other pathogens in digestive and respiratory tracts Filter bacteria in nasal passages Move mucus and trapped materials away from respiratory passages Concentrated HCl and proteases destroy pathogens in stomach Limits growth of fungi and bacteria in female reproductive tract Lubricate and cleanse contain lysozyme which destroys bacteria gtb next slide I 8 Human Nonspecific Defenses Part2 DEFENSIVE AGENT FUNCTION Nonspecific cellular chemical and coordinated defenses Normal ora Fever Coughing sneezing In ammatory response involves leakage of blood plasma and phagocytes from capillaries Compete with pathogens may produce substances toxic to pathogens Bodywide response inhibits microbial multiplication and speeds body repair processes Expels pathogens from upper respiratory passages Limits spread of pathogens to neighboring tissues concentrates defenses digests pathogens and dead tissue cells released chemical mediators attract phagocytes and specific defense lymphocytes to site gt next slide 1 81 Human Nonspecific Defenses Part3 DEFENSIVE AGENT FUNCTION Nonspecific cellular chemical and coordinated defenses Phagocytes Engulf and destroy pathogens macrophages and neutrophils that enter body Natural killer cells Attack and lyse virusinfected or cancerous body cells Antimicrobial proteins Interferons Released by virusinfected cells to protect healthy tissue from viral infection mobilize specific defenses Complement proteins Lyse microorganisms enhance phagocytosis and assist in inflammatory response LIFE THE SCIENCE OF BIOLOGY Seventh Edition Table 181 Part 3 2004 Sinauer Assocnates Inc and W H Freeman 8 Cor 1 8 Phagocytes Phagocytes ingest pathogens in a process called phagocytosis There are several types of phagocytes Neutrophils are the most abundant type of white blood cells 70 CI They attack pathogens in infected tissue CI They react fast within an hour of an insult CI The average half life of a nonactivated neutrophil in the circulation is about 410 hours Monocytes mature into macrophages They live longer and consume larger numbers of pathogens than do neutrophils Some roam and others are stationary in lymph nodes and lymphoid tissue Eosinophils kill parasites such as worms that have been coated with antibodies Dendritic cells have highly folded plasma membranes that can capture invading pathogens Phagocytosis and Bacterial Pathogens by Thomas Terry University of Connecticut Copyright 2001 Phagocytes are white blood cells that can degrade infectious organisms by the process of phagocytosis including macrophages and granulocytes This interactive tutorial explores phagocytosis in macrophages It also examines mechanisms used by two bacterial pathogens to avoid phagocytosis causing diseases such as plague and tuberculosis D Whenever you see this quotinformation buttonquot a popup box will appear when your mouse rolls over or clicks the button Try it If no box appears you need to u date the Shockwave plugin Click on this icon ljIl to access the Macromedia download web page then follow instructions dick 0 Normal phagocytosis by a macrophage arrow 0 Yersinia pestis infects a macrophage buttons to O Mycobacterium tuberculosis infects a macrophage aVi9393te 0 References play flash animation phagocytosisswf 18 Respiratory burst Neutrophils can only execute one phagocytic event expending all of their glucose reserves in an extremely vigorous quotrespiratory burstquot oxidative burst Activation of NADPH oxidase produces superoxide hydrogen peroxide and hypochlorous acid known as chlorine bleach kills all pathogens NADPH 02 NADPH Oxidase Superoxide 02quot Superoxide Dismutase Hydrogen Peroxide Fe H202 Etaase Hydroxvl 02 H20 Radkal L 0H Myeloperoxidase Hypochlorite HOCI i t Movie Human neutrophil phagocytosing bacterium Movie Human macrophage phagocytosing yeast cell 1 8 Inflammation The inflammation response is used in dealing with infection or tissue damage Mast cells and white blood cells called basophils release histamine which triggers inflammation Histamine causes capillaries to become leaky allowing plasma and phagocytes to escape into the tissue Complement proteins and other chemical signals attract phagocytes Neutrophils arrive first then monocytes which become macrophages 1 1 8 Inflammation The macrophages engulf invaders and debris and are responsible for most of the healing mopping up They produce several cytokines which may signal the brain to produce a fever Pus composed of dead cells and leaked fluid may accumulate Inflammation is triggered by release of histamine u 1 r Bacteria M introduced it by splinter next slide Histamine causes the capillaries to dilate and become leaky Bacteria 39 Complement Dead phagocytes LIFE THE SCIENCE OF BIOLOGY Seventh Edition Figure 184 Interactions of Cells and Chemical Signals in In ammation Part 2 lt 2004 Sinauer Associates Inc and W H Freeman 8 Co Movie inflammation triggered by a stab wound in ammationmov Movie Leukocyte rolling 18 Tolllike receptors How is an invading pathogen recognized Tolllike receptors TLRs are key molecules that alert the immune system to the presence of microbial infections TLRs recognize pathogenassociated molecular patterns that are highly conserved among classes of pathogens and do not occur in the host organism TLRs are present in vertebrates and invertebrates eg Drosophila Related proteins function in the immune defense in plants The TLRs are one of the most ancient conserved components of the immune system Humans have 13 TLR proteins 18 Tolllike receptors Humans have 13 TLR proteins Tolllike receptor ligand derived from TLR3 doube stranded viruses RNA TLR 4 lipopolysaccharide bacterial cell walls TLR 5 flagellin bacterial flagella TLR9 unmethylated CpG bacterial DNA DNA CD14 Outside of cell A Inside of cell W 0 N FKB 7 DNA 2 Promo ter Transcriptionl mRN A T Translationl CMV M I 39 Gas 95 xuzus Viral material from Iysed infected cell J 39 1 RSV 39 39 MMTV HSPs 39 J quot 39 Coxsackievirus B4 TLR2 D HSPs TLR4 Vcrus replication ac TLR3 Viral dsRNA Vural dsRNA Viral dsRN x TLR78 was Endosome E 7 J L 7 39 7 i 7 39 HM HPl g uh H 1 1 W 9L M W Nucleus J M01 Med 2005 83 180192 18 lnterferons are a warning signal to other cells lnterferons are secreted by cells that are infected by a virus lnterferons are glycoproteins consisting of about 160 amino acids They increase resistance of neighboring cells to infections by the same or other viruses by increasing the expression of protein kinase R PKR PKR is activated by viral dsRNA PKR activation leads to inhibition of all protein synthesis this also inhibits viral replication this kills both the virus and the host cell if this response is active for sufficient time C The Innate nonspecific Immune System M The Adaptive specific Immune System I Mediated by B and T cells with the help of APCS 18 Four characteristics of the Adaptive immune system Four characteristics of the immune system Specificity reaction to specific antigens CI Antigens are peptides or molecules that are specifically recognized by T cell receptors and antibodies CI The sites on antigens that the immune system recognizes are the antigenic determinants or epitopes CI Each antigen typically has several different antigenic determinants CI The host creates T cells andor antibodies that are specific to the antigenic determinants Antibodies react with antigenic determinants quot39 proteins Antigenic determinants epitopes small portions of antigens LIFE THE SCIENCE OF BIOLOGY Seventh Edition Figure 186 Each Antibody Matches an Antigenic erminant lt9 2004 Sinauer Assocsates Inc and W H reeman amp Co 18 Four characteristics of the Adaptive immune system 2 Diversity CI It is estimated that the human immune system can distinguish and respond to 10 million different antigenic determinants 3 Distinguishing self from nonself CI Each normal cell in the body bears a tremendous number of antigenic determinants It is crucial that the immune system leaves these alone 4 Immunological memory CI Once exposed to a pathogen the immune system remembers it and mounts future responses much more rapidly 1 8 The Adaptive Immune System The adaptive immune system has two responses against invaders The humoral immune response The cellular immune response The two responses operate in concert and share mechanisms 18 Humoral immune response The humoral immune response is based on B cells B cells produce specific antibodies that recognize antigenic determinants by shape and composition Antibodies recognize pathogens in extracellular spaces blood lymph exocrine secretions humor Latin for fluid 18 Cellular immune response The cellular immune response is able to detect antigens that reside within body cells It destroys virusinfected or mutated cells Its main component consists of T cells T cells have T cell receptors that can recognize and bind specific antigenic determinants 1 8 Specific lAdaptive Immunity Specific Immunily Divided info Cell Medialed and Humoral Immunify Cyfofoxic T cells B cells Helper T cells J Anfibodies 13 18 Fundamental questions There are millions of B and Tcells that each make different antibodies and Tcell receptors respectively How does the enormous diversity of B cells and T cells anse How are B and T cells selected to mount an immune response Why don t antibodies and T cells attack and destroy our own bodies How can the memory of postexposure be explained The answer clonal selection Clonal Selection of B Cells 0 Antigenic determinant j X 18 Effector cells and memory cells An activated lymphocyte B cell or T cell produces two types of daughter cells effector and memory cells Effector B cells called plasma cells produce antibodies Effector T cells release cytokines Memory cells live longer and retain the ability to divide quickly to produce more effector and more memory cells 18 Midterm Exam Midterm I Monday Aug 24 12302pm Includes all lectures until Aug 19th Bring ID and Blue scantrcn Students with last names A to D Please proceed to BUCHN 1910 18 Primary and secondary immune responses When the body encounters an antigen for the first time a primary immune response is activated When the antigen appears again a secondary immune response occurs This response is much more rapid because of immunological memory gt 00 Immunological Memory Primary immune response Secondary immune response O A Little or pW no lag Amount of antibody or T cells arbitrary units Q First exposure Interval Second exposure to first antigen red7 to antigen perhaps first exposure to second antigen b1ue years 18 Vaccination immunization Artificial immunity is acquired by the introduction of antigenic determinants into the body Vaccination and Immunization Shots inoculation with whole pathogens or with antigenic proteins this initiates a primary immune response that generates memory cells without making the person ill 1 8 Smallpox inoculation Since at least the 10th century AD inoculation was practiced in China Powdered wound crusts from smallpox victims were scratched into the skin Smallpox is normally contracted by inhalation of viral particles in droplets mortality rate is 2025 Inoculation through the skin leads only to localized infection but the immune system gets activated and immunological memory is established The inoculated person will be immune to future smallpox inhalation 1 8 Smallpox inoculation 7 cu Uquot quotuquotij u iiuLi1 quot 71 f3l yFTI39o 39 e At a I 0 N 39 I u u 1 X 4 quot q N 4 i P 39 39 quot5 v x 39quot 39 r 1 2 quot V V 39 I 1 I quot1 39 39 4 V A7 1 v y 39 1 f 39 t I 39 39 39 n a 7 quot u 39 p 5 z ff39 A t 5 quot39 7 o K 39 39 tv i M 39x quot I L J ltI 39 39 39V H quotVquot quot039 39 vi quot J 4 39 u u f u r 39 V 39 0quot I I During the 17th century the practice of smallpox inoculation spread to the Ottoman Empire Lady Mary Wortley Montagu 16891762 the wife of the British ambassador to the Ottoman Empire brought inoculation to the west In 1718 she had her five year od son inoculated in Constantinople After returning to England six prisoners due to be hanged were inoculated at Newgate prison in exchange for their freedom r The practice of inoculation slowly spread amongst the royal families of Europe followed by more general adoption amongst the people 4 39 I I 5 00 g 3 K 3 u g 4 39 3 139 L s i 9 I r I J u 1 1 l 9 t 5 395 J V g I J O 39 u 4 l 5 v 4 l I D is 1 I L quotwe l quotX l r 39gt I x v 39 w I I 39 n z g x v quot if 39 y J 3quot 390 quot39L39 39 39 0 1 3quot A 1 0 39 3937 gt tin H I A y 39 I I J 0 5V Fquot r 1 l V 939 1 393 I I 1 39 3 i I r 1 3 I 1 8 Smallpox inoculation During 1776 George Washington s revolutionary army lost 1000 men in battle and 10000 men to smallpox On January 6th 1777 George Washington ordered his troops to be inoculated The death rate due to smallpox plummeted afterwards In 1783 the American Revolutionary War was won by America Today smallpox is considered eradicated 18 Immunization and vaccination today Antigens used for immunization or vaccination must be processed so that they will provoke an immune response but not cause disease There are three principle ways to do this Attenuation involves reducing the toxicity of the antigenic molecule or organism eg adaptation of a virus for growth in nonhuman cells Biotechnology can produce recombinant antigenic fragments of pathogens that activate lymphocytes but are harmless by themselves DNA vaccines are being developed that will introduce a gene encoding an antigen into the body 18 Polio vaccine Poliomyelitis often called polio or infantile paralysis Acute viral infectious disease poliovirus Spread from persontoperson via the fecaloral route The majority of polio infections are asymptomatic In 1 of cases the virus enters the central nervous system There the poliovirus infects and destroys motor neurons This leads to muscle weakness or paralysis Polio predominantly affects children 1 8 Polio vaccine In the earlier 20th century the USA was plagued by polio epidemics From 1916 onward a polio epidemic appeared each summer The 1952 polio epidemic was the worst outbreak 58000 cases I 3145 died I 21269 were left with mild to disabling paralysis 2 Polio vaccine 18 18 Polio vaccine John Franklin Enders O 13 of the prize USA Harvard Medical School Research Division of Infectious Diseases ChiIdren39s Medical Center Boston MA USA b 1897 d 1985 Thomas Huckle Weller CD 13 of the prize USA Research Division of Infectious Diseases Children39s Medical Center Boston MA USA b 1915 The Nobel Prize in Physiology or Medicine 1954 quotfor their discovery of the ability of poliomyelitis viruses to grow in cultures of various types of tissuequot Frederick Chapman Robbins O 13 of the prize USA Western Reserve University Cleveland OH USA b 1916 d 2003 1 8 Polio vaccine The first effective polio vaccine was developed in 1952 by Jonas Salk at the University of Pittsburgh The ak vaccine or inactivated poliovirus vaccine IPV is based on poliovirus grown in a monkey kidney cell line Vero cell line which are then killed with formalin The Salk vaccine is injected in the skin The Salk vaccine was tested in the largest medical experiment in history starting in 1954 I 18 million children in 44 states 440000 received the vaccine 210000 children received a placebo culture media 12 million children received no vaccination The vaccine was highly effective I 39 n 41 L L Mas polio vacoinationini Columbus Georgia during theearly days of the National Polio Immunization Program 1 8 Polio vaccine Eight years after Sak39s success Albert Sabin developed the oral polio vaccine OPV The OPV is a liveattenuated vaccine 5 T The virus is attenuated because of a random mutation located in the virus internal ribosome entry site The attenuated poliovirus replicates efficiently in the gut the primary site of infection and replication but is unable to replicate efficiently within nervous system tissue The OPV proved to be superior in Dr basin sdmi1ir39ro H 9 0393 administration and also provided longer lasting immunity than the Salk vaccine quoti 39 39 g Albert Sabin 1906 1993 Cincinnati Children39s Hospital Ohio 1 8 Polio vaccine After the first vaccine became available polio cases in the US dropped by 8590 in only two years The last cases of paralytic polio caused by endemic transmission of wild virus in the United States were in 1979 when an outbreak occurred among the Amish in several Midwest states The disease was entirely eradicated in the Americas by 1994 Eav x oie on b 11 t A 11 J L 2 cg ti E 18 Self Tolerance The body is tolerant of its own molecules Failure to do so results in autoimmune disease This self tolerance is based in part on clonal deletion 18 Clonal Deletion Clonal deletion eliminates B or T cells from the immune system during their differentiation In the bone marrow about 90 of all B cells made are removed because they react against self an gens The same is true for T cells but the selection occurs in the thymus Elimination is accomplished by means of apoptosis 18 B Cells The Humoral Immune Response B cells are the basic component of the humoral immune system For a B cell to differentiate into a plasma cell it must bind an antigenic determinant A helper T cell TH must also bind the same determinant as it is presented by an antigen presenting cell Cellular division and differentiation of the B cell is stimulated by a signal from the activated TH cell Activated B cells become plasma cells and memory cells a Anti gen Antigenic binding site determinants Light Antigen Variable region of heavy chain Chain C E Variable W region of r light Chain I Constant Heavy Chain r i39ez f hOf t 1g c a1n Constant region of heavy chain Disu1fidebonds E r C E LIFE THE SCIENCE OF BIOLOGY Seventh Edition Figure 1810 Structure of lmmunoglobulins Part 1 IL 2004 Sinauer Associates Inc and W H Freeman 8 Co 17 Light chains Antigen binding site Heavy chains LIFE THE SCIENCE OF BIOLOGY Seventh Edition Figure 1810 Structure of lmmunoglobulins Part 2 12 2004 Sinauer Associates Inc and W H Freeman 8 Co 1 8 Antibodies Antibody molecules are proteins called immunoglobulins Two identical light chains and two identical heavy chains make up the tetrameric units Disulfide bonds hold the chains together Both the light and heavy chains on each peptide have variable and constant regions The constant regions are similar among the immunoglobulins and determine the class of the an body 18 B Cells The Humoral Immune Response The variable regions differ in their amino acid sequences and are responsible for the diversity of antibody specificity The heavy and light chain variable regions align and form the binding sites Each tetramer has two identical antigenbinding sites making the antibody bivalent 183 Antibody Classes Part 2 Monomer piN Secreted by plasma cells in skin and tissues lining gastrointestinal and respiratory tracts GENERAL CLASS STRUCTURE LOCATION FUNCTION IgA Dimer Monomer found in Protects mucosal surfaces plasma polymers in prevents attachment of saliva tears milk pathogens to epithelial and other body cells secretions IgE Found on mast cells and basophils when bound to antigens triggers release of histamine from mast cell or basophil that contributes to in ammation and some allergic responses LIFE THE SCIENCE OF BIOLOGY Seventh Edition Table 183 Part 2 1192 2004 Sinauer Associates Inc and W H Freeman 8 Co Macrophage Macrophages have Fc receptors which help phagocytosis Antibody K 0 Antigenic determinant V Bacterium covered with IgG antibody LIFE THE SCIENCE OF BIOLOGY Seventh Edition Figure 1811 gG Antibodies Promote Phagocytosis 2004 Sinauer Associates Inc and W H Freeman 8 Co 18 T Cell Receptors T cells like B cells possess specific surface receptors T cell receptors The genes that code for T cell receptors are similar to those for immunoglobulins T cell receptors also have constant and variable regions A major difference between antibodies and T cell receptors is that T cell receptors bind only to an antigenic determinant that is displayed on the surface of an antigenpresenting cell OL Chain gt Variable regions gt Constant Outside regions of T cell W 4 b R J 39 mmtw mww s h o 4 39 Inside of T cell LIFE THE SCIENCE OF BIOLOGY Seventh Edition Figure 1813 A T Cell Receptor lt9 2004 Sinauer Assocuates Inc and W H Freeman 8 Co 18 T Cells The Cellular Immune Response Activated T cells give rise to two types of effector cells Cytotoxic cells or TC killer T cells recognize virusinfected cells and kill them by causing them to lyse Helper T cells or TH cells assist both the cellular and humoral immune systems Activated helper T cells proliferate and stimulate both B and TC cells to divide 1 8 Specific lAdaptive Immunity Specific Immunily Divided info Cell Medialed and Humoral Immunify Cyfofoxic T cells B cells Helper T cells J Anfibodies 13 18 T Cell receptors bind only to antigens that are presented by MHC molecules What are MHC molecules LIFE Be Figure 1813 A tigequot Class II MHC protein A macrophage takes up an antigen by phagocytosis The macrophage breaks down the antigen into fragments A class II MHC protein binds an antigen fragment The MHC presents the 1 antigen to a TH cell T T cell39 receptor LIFE THE SCIENCE OF BIOLOGY Eighth Edition 0 2007 Summer Associates Inc and W H Freeman 8 Co 18 The major histocompatibility complex MHC The major histocompatibility complex MHC gene products are plasma membrane glycoproteins MHC proteins display antigens There are three classes of MHC proteins but we ll only talk about two MHC I and MHC II 18 MHC I proteins Class I MHC proteins are present on the surface of every nucleated cell in animals When cellular proteins are degraded in the proteasome an MHC I protein may bind a fragment and travel to the plasma membrane to present it outside on the cell s plasma membrane surface MHC I is a kill me protein CD8 surface protein Antigenic fragment T cell MHC I receptor protein LIFE 89 Figure 1 8 1 4 Part 2 LIFE ms science or amoav Eighth Eamon o 2oo7 Sinauer Associates Inc and w H Freeman 3 Co 1 8 Cytotoxic T Cells Foreign protein fragments from intracellular degradation are bound by class I MHC molecules and carried to the plasma membrane where TC cells can check them If a cell has been infected by a virus or has mutated it may present protein fragments that are not normally found in the body If a TC cell binds to the MHC antigen complex the TC cell is activated to proliferate and differentiate activation phase 1 8 Cytotoxic T Cells In the effector phase TC cells once again bind to the cells bearing MHC antigen complex and secrete molecules that lyse the cell TC cells can also bind to a specific target cell receptor called Fas This binding initiates apoptosis in the target for example virusinfected cell This system helps rid the body of virusinfected cells It also helps to destroy some cancer tumors Figure 1817 b Phases of the Humoral and Cellular Immune Responses Part 1 CELLULAR IMMUNE RESPONSE ACTIVATION PHASE Class I MHC A viral protein made in an A T cell receptor rocognrzes Weciled G8quot 3 degraded an antigenic rragment bound into fragments and picked to a clam I M C protch on HP DY 3 C3933 3 39 MHC D39O1 1 an infected cell 4 The Tg cell proltferates and forms 3 Clone Figure 1817 b Phases of the Humoral and Cellular Immune Responses Part 2 EFFECT OR PHASE Infected cell one of many The T cell releases De onn A T cell receptor agann recognizer an antigenic fragment lxcuncl to a 2133 I MHC proten whirh tyses the interned cell before the viruses Can rlhlliply The Cellular Immune Response Activation Phase INTRO mswmo STOP PLAY 3 Wlx lllw seMH HM 1 MHH HME 1 Figure 1814 Cytotoxic T Cells in Action L To Cells F apoptosing cells Movie Cytotoxic T cells killing melanoma cell 18 MHCll proteins on professional antigenpresenting cells Class II MHC proteins are found mostly on the surface of B cells macrophages and other professional antigenpresenting cells When an antigen is ingested by a professional antigenpresenting cell it is broken down and fragments are presented at the cell surface by class II MHC proteins Anti gen T cell 3 Class II MHC protein Macrophage receptor TH cell LIFE THE SCIENCE OF BIOLOGY Seventh Edition Figure 1815 Macrophages Are AntigenPresenting Cells 0 G 2004 Sinauer Associates Inc and W H Freeman 8 Co 18 MHC proteins SUMMARY AntigenPresenting and T Cell Types PRESENTING ANTIGEN T CELL SURFACE CELL TYPE PRESENTED MHC CLASS T CELL TYPE PROTEIN Any cell Intracellular Class I Cytotoxic T cell CD8 protein fragment TC Macrophages Fragments from Class II Helper T and B cells extracellular TH CD4 proteins 18 Activation of the autodestruct sequence Antibody production humoral response requires that a TH cell and a B cell concur Activation phase effector phase COMPUTER AUTODESTRUCT IN 5 MINUTES 5 MINUTES A TE 18 The activation phase A TH cell containing a specific Tcell receptor can bind to an antigen presented by an antigen presenting macrophage This activates the TH cell it will proliferate to produce a clonal population of identical TH cells HUMURAL 391MUNE RESPONSE ACTIVATION PHASE Class II MHC L 39 proteln J Interleulcn1 a cytokine Antigen T d A W W 3 1 meantlgenistaken U0 9 D 990CV106 3 and degraded A T oel receptor recognizes an antigenic fragment 599390 W W9 n 3 Iysosome TH cell stimulate it to proliierate bound to a clam II MHC protein on the macrophage 1 8 The effector stage An antigen of the same sort must also be recognized by a specific lgM receptor on the surface of a B cell The B cell ingests and degrades the antigen and presents a piece of processed antigen in a class II MHC protein on its cell surface One of the TH cells created in the activation stage recognizes the processed antigen on the surface of the B cell The TH cell releases cytokines which activate B cell proliferation and differentiation into plasma cells and memory cells The plasma cells secrete antibodies EFFECTOR PHASE Cytokhes activate 39 W B cell proliferation V The bhdhg of antigen to a speci c Igtvt receptor triggers endocytosis degradation and disptay ot the processed antigen A T cell receptor recognizes an antigenic tragment bound to a classll MIC protenonaBoetL and differentiate B cetls proliterate J The Humoral Response Activation phase class II MHC protein an gen as lysosome with enzymes INTRO nswmo I STOP PLAY 0 18 The Genetic Basis of Antibody Diversitl Wait a second Proteins are encoded by genes There are millions of different antibodies but the human genome has only 30000 genes It does not compute 18 The Genetic Basis of Antibody Diversitl Here is the trick There are only a few antibody genes in the genome But B cells can shuffle recombine them which can generate millions of new combinations 18 The Genetic Basis of Antibody Diversity Each gene encoding an immunoglobin is in reality a supergene assembled from several clusters of smaller genes located along part of a chromosome During B cell development these variable regions rearrange and join Pieces of DNA are deleted and DNA segments formerly distant from one another are joined together lmmunoglobulin genes are assembled from randomly selected pieces of DNA 18 Heavy chain genes Genes encoding variable region V A f Iv1v2v10O D1D2D30 J12J6l variable diversity joining I 98068 98088 genes I I I DNA 3912341oo 1 230 1639 0 It The variable region for the heavy chain of a speci c antibody is encoded by one V gene one D gene and one J gene Each of these genes is taken from a pool of like genes LIFE 8e Figure 1816 Genes encoding constant region C A J 115 K3 71 It The constant region is selected from another pool of genes 72b 72a 2 on fThe number of possible combinations to make an immunoglobulin heavy chain from this set of genes is 100 V30 D6 J8 C 144000 LIFE THE SCIENCE OF BIOLOGY Eighth Edition 0 2007 Sinauer Associates Inc ard W H F reeman 8 Co A DNA rearrangement Variable region Constant region A A f V D J segments C segments Embryon DNA 8 Transcription and 8 Cequot DNA RNA splicing if D i I4 After V D J and C DNA segments p have been joined the resulting quot39U39quotL rip quot4 functional supergene is transcribed Primary RNA transcript 0 0 I P m j I1 Splicing of the primary RNA s pnca are transcript removes the transcripts of 39 any introns and of any extra J genes mRNA quot39 V D J H Translation Q Light chain Heavy chain LIFE 89 Figure 1 8 1 7 uns rm39 SCIENCE or BIOLOGY Eighth Eamon o 2oo7 Sinauer Associates Inc and w H Freeman as Co 18 The Genetic Basis of Antibody Diversity There are multiple genes coding for each of the four kinds of segments in the polypeptide chain for the heavy chain in mice 100 V 30 D 6 J and 8 C regions Each B cell randomly selects one gene for each of the V D J and C regions A similar process occurs for the light chain Theoretically there are 144000 x 144000 possible combinations of light and heavy chains ie 21 billion possibilities B Cell Precursor cell development B Cell rearrange light chain gene rearrange heavy chain gene Immunoglobulin light chain disulfide bond heavy chain 7quot 7 7 T 7 977 7 T VJLV9 7 7 97 i f 779C i 7 977 7 T VJLV9 7 7 V 7 V 7 7 M M H Al UH c H U HM H p H Fix UH M U H c 18 The Genetic Basis of Antibody Diversity Additional diversity is possible because the recombinations do not occur at precise segments lmprecise recombinations can create new codons at thejunc ons After DNA fragments are cut out and before they are joined an enzyme terminal transferase adds some nucleotides to the free end This adds even more variability by causing frame shifts and new codons Finally the relatively high mutation rate in immunoglobulin genes leads to even more diversity 18 Autoimmune diseases If clonal deletion fails forbidden clones of B and T cells directed against selfantigens are sometimes made Examples of autoimmune diseases include Systemic lupus erythematosis Rheumatoid arthritis Multiple sclerosis Insulindependent Type 1 diabetes mellitus The problem how to communicate over long distances fast Em giraffe Legs The musculoskeletal system Muscles and skeletons the musculoskeletal system Muscles and skeletons are the effectors that produce movement Muscles Three types of vertebrate muscle Skeletal voluntary movement breathing Cardiac beating of heart Smooth involuntary movement of internal organs There are Three Kinds of Muscle A Skeletal muscle 39439 as a oquotv s s H V 391VsqfI39a IVQ o 39 39 393 1 1 a39 39 1 N quot 39 5 su quot 7i 3 2quot39 7quotV3939139quot39 o Q quotquot39 39quotf quot39 quot HuiIr5 039 A15391 144 A39 1AA AALAJ llII111 1 FAX J 39139lgt11lJi39jVAl 4 14 75um B Cardiac muscle C Smooth muscle amp39 quotltquot Q n quot quotquot kg 0 go 3 quot V gr 394 g39tn 39 9 0 quot39 J quot7 p 9 I f39f 395 Qv quotquot 39 39 39 1 on 3 quotquotquotquot an 3 5 9 rf e I 392 3 V m n W 1quot 9 LAX J V 4 50 Hm 30 um LIFE 89 Figu re 47 7 LIFE THE SCIENCE or39 BIOLOGY Eighth Edition 2007 Sinauer Associates Inc and w H Freeman 3 Co 471 How Do Muscles Contract Skeletal muscle striated Cells are called muscle fibers They are extremely large multinucleated cells Form by fusion of embryonic myoblasts One muscle consists of many muscle fibers bundled together by connective tissue The Structure of Skeletal Muscle Part 1 A skeletal muscle is made up of bundles of muscle fibers Tehdohs Bundle of muscle fibers Connective r tissue Muscle 4 V Plasma membrane sarcolemma Single muscle fiber cell Mitochondria Each muscle fiber is a multinucleate cell containing numerous myofibrils which are highly ordered assemblages of thick myosin and thin actin filaments LIFE 89 Figure 47 1 Part 1 LIFE THE SCIENCE or BIOLOGY Eighth Edition 2007 Sinauer Associates Inc and w H Freeman 8 co human skeletal muscle low power The Structure of Skeletal Muscle Part 1 Bundle of muscle fibers Tendons R Connective M uscle 0 i tIS7Ue Plasma membrane Nucleus o I v u 9 39 Single muscle fiber Mitochondria 5 89 Figure 47 1 Part 1 LIFE THE SCIENCE or39 BIOLOGY Eighth Edition 2007 Sinauer Associates Inc and w H Freeman 3 Co The Structure of Skeletal Muscle Part 2 Z line M band gtSinge I myofibril zone A band I I Single sarcomere Z line I I Actin filament IO VIO vI IIIII lo V o r39I stsosrstst IOm vIo rII III st I0 VIO M band Titin Myosin filament 89 Figure 47 1 Part LIFE THE SCIENCE OF BIOLOGY Eighth Edition 2007 Sinauer Associates Inc and w H Freeman amp Co INTRO REWIND STOP PLAY 3 show animation Animation47O1swf How Do Muscles Contract Each muscle fiber has several myofibrils bundles of actin and mycsin filaments Contractile proteins Actin thin filaments Myosin thick filaments How Do Muscles Contract Each myofibril consists of repeating units sarcomeres Sarcomere overlapping actin and myosin filaments Bundles of myosin filaments are held in place by the protein titin the largest protein in the body Figure 471 The Structure of Skeletal Muscle Part 2 Z line M band I band l a gt Single myofibril I 39 D 0 O 0 39 i 3939o 9 0 o I 39 C U C quotC a I I o 39 39 39 39 u 0 C C Q0 U 0 zone A band I I Single sarcomere 2 line I VIO I I Actln filament quotquot IIIlIIII IIIIIIIII vto to VII IO VIO Titin M band E 89 b 47 1 b LIFE THE SCIENCE OF BIOLOGY Eighth Editfon 2007 Sinauer Associates Inc and W H Freeman amp Co issionEM Transm in together appear darkest bands of actin and myos Myofibrils K NF band I I 4 Single sarcomere Z line Actin filament quotquot quotquot39 IIllI Vto I I MyOS39n fllament rtI IIItI to Vl0 rII IIIII IO VIO Titin M band pBK quotL L A me quot394 of frampug vx How Do Muscles Contract The sliding filament mechanism of muscle contraction Myosin heads can bind specific sites on actin molecules to form cross bridges Myosin changes conformation causes actin filament to slide 510 nm Sliding Filaments Muscle relaxed Z ine Actin M baQd Myosin Titin IIlIIIIII IIIIIIIlI IIIIIIIII IIIIIIIII K J E 89 2 LIFE THE SCIENCE OF BIOLOGY Eighth Edition 2007 Sinauer Associates Inc and W H Freeman amp CO Actin and Myosin Filaments Overlap to Form Myofibrils Troponin has a 3 subunits 1 binds actin 1 binds tropomyosin and 1 binds Ca2 Actin monomer Tropomyosin Troponin Single sarcomere Myosin Actin A filament filament o 0 0Q0 Globular head Myosin molecule Linear polypeptide chain 86 Figu re 47 3 LIFE THE SCIENCE or BIOLOGY Eighth Edition 2007 Smauer Associates inc and w H Freeman 8 Co 471 How Do Muscles Contract Muscle cells are excitable the plasma membrane can conduct action potentials Acetylcholine is released by the motor neuron at the neuromuscularjunction and opens ion channels in the motor end plate A neuromuscularjunction is the chemical synapse between a motor neuron and a muscle cell Presynaptic AXOquot 07 terminal motor Ul CtlOn Synap c vesicles Neuromuscular Muscle ber Mitochondrion Postsynaptic Capillary membrane P resynaptic ceA11 NerVe 39 Axon impulse A 1 Synaptic Acetylcholine receptors Mye1in 45 A efil IoA Axon h91iI e cleft Plasma membranes J Postsynaptic cell quot e mAcety1ch0lin esterase 39 Na channels The Neuromuscular Junction Axon terminals from a single motor neuron innervate multiple skeletal muscle fibers Skeletal muscle fibers l 7 I 7 1quot J lt 9 39 39 Q Axon A O terminals D I J LIFE 8e Figure 474 LIFE THE SCIENCE OF BIOLOGY Eighth Edition 2007 Sinauer Associates Inc and W H Freeman amp Co 471 How Do Muscles Contract Action potentials also travel deep within muscle fibers via T tubules T tubules transverse tubules descend into the sarcoplasm muscle fiber cytoplasm T tubules run close to the sarcoplasmic reticulum ER a closed compartment that surrounds every myofibril Motor neuron Muscle ber An action potential black arrows arrives at the motor neuron terminal and vesicles of Ach are released The neuromuscular synapse generates an action potential that spreads down T tubules Action potential Neuromuscular junction T tubule which causes the release of Ca stored in the sarcoplasmic reticulum Myo bril V 39 Released Ca2 diffuses in 53 sarcoplasm stimulating quot 39 muscle contraction Sarcoplasmic Plasma reticulum membrane sarcolemma Ca2 is taken up by the sarcoplasmic reticulum terminating muscle contraction 471 How Do Muscles Contract Sarcoplasmic reticulum Fancy name for the endoplasmic reticulum of muscle cells Has Ca2 pumps At rest there is high concentration of Ca2 in the lumen of the sarcoplasmic reticulum An action potential will open the Ca2 channels Ca2 flows out of sarcoplasmic reticulum and triggers interaction of actin and myosin 471 How Do Muscles Contract Actin filaments also include tropomyosin and troponin Troponin has three subunits one binds actin one binds tropomyosin and one binds Ca2 At rest tropomyosin blocks the binding sites on actin 471 How Do Muscles Contract When Ca2 is released it binds to troponin which changes conformation Troponin is bound to tropomyosin twisting of tropomyosin exposes binding sites on actin When Ca2 pumps remove Ca2 from sarcoplasm contraction stops Caz is released from the saroopiasmic reticulum Trotzornyosw clin 39Iament TlOJC39lll ATP is hydrolyzed If Ca2 is returned to the 2 The myosin head sarcoplasmic reticulum C 39 the a39 p am returns to its the muscle relaxes binds troponrn and exposes c0nf mauon actrn laments Myosin lament 9 A eff ca remains available the cycle repeats and muscle koontraction continues Myosin heads bind to actin release of P initiates power stroke ADP is released ATP binds to rnyosin causing it to release actin Rigor mortis In the power stroke the myosin head changes conformation laments slide past one another 89 6 LIFE THE SCIENCE OF BIOLOGY Eighth Edition 0 2007 Srnauer Associates n and W H Fwzeman 8 Co myosin moviemov 2 K siding actinmov 7 rsY1R m w C R C S U m m 6 H g xv Ru Figure 477 There are Three Kinds of Muscle A Skeletal muscle 39439 as a oquotv s pO s H V 391VsqfI39a IVQ o 39 39 1 393 1 1 a39 39 1 quot 39 5 su quot 7i 3 2quot39 7quotV3939139quot39 o quotquot39 39quotf quot39 quot HuiIr5 039 A15391 144 A39 1AA AALAJ llII111 1 FAX J 39139lgt11lJi39jVAl 4 14 75um B Cardiac muscle C Smooth muscle amp39 quotltquot Q n quot quotquot kg 0 go 3 quot V gr 394 g39tn 39 9 Z Z quot39 J quot7 9 I f39f 395 Qv quotquot 39 39 39 1 on 3 quotquotquotquot an 3 5 9 rf c I 392 3 u u n W 1quot 9 LAX J V 4 50 Hm 30 um LIFE 89 Figu re 47 7 LIFE THE SCIENCE or39 BIOLOGY Eighth Edition 2007 Sinauer Associates Inc and w H Freeman 3 Co am wa I I x r w 5 4 1 awmmampns 3 m x 1 1 z r L J W1 7 fgt mitochondria Heart muscle cell Cardiac muscle Cardiac muscle Is also striated Cells are smaller than skeletal muscle cells Cells have one nucleus Cardiac muscle cells also branch and interdigitate can withstand high pressures Cardiac Muscle Pacemaker and conducting cells initiate and coordinate heart contractions The heartbeat is myogenic generated by the heart muscle itself The autonomic nervous system modifies the rate of pacemaker cells but is not necessary for their func on this makes heart transplantations possible Gap Junctions Cardiac and smooth muscle cells are arranged in sheets Cells in the sheet are in electrical contact via gapjunc ons An action potential in one cell can spread to all others in the sheet Synchronize contractions Figure 57 Junctions Link Animal Cells Together C Plasma membranes quotquot Intercellular space Hydrophilic lj3 channel u it I m Immm mum nm quot quot mm a 1 3 39 Molecules g mm mu m 5 l pass between 2 cells 1 1 I I 1 1 I X 1 I J l UH D 1 I I 39 I 2 I u quotw 2 3 f 39 gt 1 v39 39 u i 2t gs J Connexons qesmosomes A Gap junctions junctions A Gap junctions allow communication GAP junctions Connect the cytoplasm of two neighboring cells Allows direct electrical communication between cells Allows direct chemical communication between cells small second messengers such as lP3 and Ca2 Allows passage of molecules smaller than 1000 Daltons Allow cardiac and smooth muscle cells to contract simultaneously 0 Va cacium wavesmov Smooth Muscle Smooth muscle Are the simplest muscle cells structurally Single nucleuscell Smooth because actinmyosin are not as regularly arranged Present in most internal organs eg GItract bladder blood vessels Under autonomic nervous system control Figure 477 There are Three Kinds of Muscle A Skeletal muscle 39 vv N 1 H 39T f39 W m n 23 39 V iYVK 39VTi39fw 39 3 Wvxsc s u o V l X P F L to 13935 39l v gtgXK39n ox 39quotiwwu quot 1w39r39quot 39 4 39 quot quotquot quot39quot 1 44 391 4A L44115114 1114 A4 A 11quot139lgt1JJ PA 14 VlquotAquotjA 4 Smooth Long amp spindleshaped 75um B Cardiac muscle C Smooth muscle km 1 f 39 1 j quot 3 4quot T I5 I O as 9 r 39 33 39 3 3 mmaa39 s 3 2 39 1 S Q Vquot X H V I 00 r quot quot5 v 50 pm 30 um LIFE 89 Figu re 47 7 LIFE THE SCIENCE or BIOLOGY Eighth Edition 2007 Sinauer Associates Inc and w H Freeman 3 Co Nerve Blood vessel Blood vessels Lymph node Nerves Submucosal Pancreatic nerve net duct Circular muscle layer Submucosal gland Lumen Nerve net between muscle layers LIFE THE SCIENCE OF BIOLOGY Seventh Edition Figure 5011 Tissue Layers of the Vertebrate Gut vil 2004 Sinauer Assocaates Inc and W H Freeman 8 Co 471 How Do Muscles Contract What is a twitch Skeletal muscle minimum unit of contraction a twitch Atwitch is measured in terms of tension or force it generates A single action potential generates a single twitch 471 How Do Muscles Contract Single twitch if action potentials are close together in time the twitches are summed tension increases Twitches sum because Ca2 pumps can not clear Ca2 from sarcoplasm before the next action potential arrives Tetanus when action potentials are so frequent there is always Ca2 in the sarcoplasm Twitches and Tetanus Stimulus AP from a motor neuron A A stimulus elicits a twitch the minimum Two twitches in quick succession unit of contraction of a muscle ber have a summed effect Force Stimums 1 1 t t Musoles relax when stimulation stops 3 B 39 Force Eight summed twitches bring the Tetanus is sustained by a muscle ber to maximum contraction high rate of stimulation known as tetanus 1 l l l l I I I H l I u 1 lliiiiililiiiiiiliii Time 471 How Do Muscles Contract How long muscle fiber can sustain tetanic contraction depends on ATP supply ATP is needed to break the myosinactin bonds and recock the myosin heads To maintain contraction actin myosin bonds have to keep cycling Muscle ATP supply limits performance Muscles have three systems for obtaining ATP Immediate system uses preformed ATP and creatinephosphate Glycolytic system metabolizes carbohydrates to lactic acid and pyruvate Oxidative system metabolizes carbohydrates and fatty acids to H20 and CO2 Muscle fuel supply limits performance Muscle cells have three sources of ATP Glycogen glucose or fatty acids CreatineP Glycolygis Oxidative anaem 39C phosphorylation aerobic muscle contraction Supplying Fuel for High Performance A 100 quotOx 23 39 75 gtltJ 5 50 CC D 8 E D 25 6 E e 713E E I I I 10sec 1 30sec 2 3 Time minutes 4 3 system Oxidative Sources of ATP Immediate System Muscles contain creatine phosphate CP which stores energy in a phosphate bond that can transfer to ADP Immediate system ATP CP This system is exhausted within seconds Creatine phosphate as an immediate buffer for ATP 9 K VH1 Aquot C co0H Creatine phosphate ADP Creatine kinase Creatine ATP Sources of ATP The glycolytic system Enzymes are in the cytoplasm sarcoplasm ATP generated is directly available to myosin fast Anaerobic Not very efficient low ATP yield Lactic acid accumulates Immediate and glycolytic systems provide energy for less than one minute Sources of ATP Oxidative phosphorylationz Produces large amounts of ATP Aerobic Occurs in mitochondria ATP must diffuse from mitochondria to the myosin in the cytoplasm slower than other two systems What Determines Muscle Strength and Endurance There are two main types of skeletal muscle fibers Slowtwitch muscle fibers Fasttwitch muscle fibers Myosin variants have different rates of ATPase activities What Determines Muscle Strength and Endurance Slowtwitch muscle fibers Oxidative or red muscle Contain myoglobin oxygen binding protein Contain many mitochondria Are wellsupplied with blood vessels Maximum tension develops slowly but is highly resistant to fatigue What Determines Muscle Strength and Endurance Slowtwitch fibers have reserves of glycogen and fat can produce ATP as long as oxygen is available Muscles with high proportion of slowtwitch fibers are good for aerobic work eg long distance running cycling swimming etc What Determines Muscle Strength and Endurance Fasttwitch fibers Glycolytic or white muscle Fewer mitochondria fewer blood vessels little or no myoglobin Develop greater maximum tension faster but fatigue more quickly Can t replenish ATP for prolonged contraction Asafa Powell Jamaica a 100 m world P X record 974 seconds Type I slow dark fibers and Type II fast light fibers human skeletal muscle LM Slowand FastTwitch Muscle Fibers Part 1 Distance cyclist Sprinter ge2xi39A r FSIOWtwitchxw 0T vi p Fasttwitch fr it R 39 k I I 1 Endurance athletes LIFE 8e Figure 4710 Part 1 What Determines Muscle Strength and Endurance The proportion of fast and slowtwitch fibers in skeletal muscles is determined mostly by genetic heritage Training can alter muscle properties to a certain extent What Determines Muscle Strength and Endurance Exercise Anaerobic activities increase muscle strength new actin and myosin filaments form muscle gets larger Aerobic activities increase endurance oxidative capacity is enhanced by increasing number of mitochondria blood vessels myoglobin and enzymes
Are you sure you want to buy this material for
You're already Subscribed!
Looks like you've already subscribed to StudySoup, you won't need to purchase another subscription to get this material. To access this material simply click 'View Full Document'