EXAM #4 Notes Lectures 26-34
EXAM #4 Notes Lectures 26-34 MICRB 201
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Microbiology 201 Exam 4 Lecture 26 Approximately 35 billion year history microbial evolution When did life originate Evidence suggests that life first arose around 35 billion years ago This evidence takes the form of Microfossils Ancient rock structures in South Africa and Australia called stromatolites Produced by microbes that form thin microbial films that trap mud Layers of these microbe mud mats can build up into a layered rock structure Continue to be produced today 0 Ancient and modern forms are remarkably similar Where did life originate Early Earth was anoxic and much hotter than present day At the surface there were dramatic temperature uctuations and mixing from meteor impacts dust clouds and storms Not ideal conditions for the emergence of life This has lead to the subsurface origin hypothesis that life originated at hydrothermal springs on ocean oor Conditions would have been more stable Using the DNA sequences of modern organisms biologists have tentatively traced the most recent common ancestor of all life to an aquatic microorganism that lived in extremely high temperatures a likely candidate for a deepsea hydrothermal vent inhabitant Steady and abundant supply of energy eg H2 and H25 may have been available at these sites Proof Experiments suggest how organic molecules like nucleotides could have first arisen on the primitive Earth The above figures depict the Miller Urey experiment This experiment demonstrated that very simple inorganic compounds could react to yield organic molecules RNA and DNA molecules the genetic material for all life are just long chains of nucleotides The precursors to current life may have been selfreplicating RNA molecules that did many jobs storing genetic information copying themselves and performing basic metabolic functions 0 RNA can store genetic information Recall RNA viruses 0 RNA can copy itself Recall viroids RNA can act as an enzyme 0 Recall the ribosome Selfreplicating RNA molecules would have been subject to natural selection Once a selfreplicating molecule formed some variants of these early replicators would have done a better job of copying themselves than others producing more quotoffspringquot This would have led to more complex RNA molecules capable of catalyzing more complex reactions giving rise to more complex biomolecules Spontaneous formation of a vesicle Some of the more complex biomolecules could have been lipids that can spontaneously form vesicles that can act as primitive membranes The evolution of a membrane surrounding the genetic material would provide two major advantages 0 The products of the genetic material could be kept close by The internal environment could be different than the external environment The advantages of membranes would mean that the quotencasedquot replicators would quickly outcompete the naked replicators This breakthrough would have given rise to an organism much like a modern bacterium The RNA could have evolved to code for proteins with ever more elaborate functions 0 mRNA 0 RNA could have given rise to DNA 0 Reverse transcriptase Some cell or group of cells could have evolved to use different types of molecules for different functions DNA which is more stable than RNA became the genetic material 0 Proteins which are often more efficient enzymes of chemical reactions than RNA became responsible for basic metabolic reactions in the cell 0 RNA was demoted to the role of messenger carrying information from the DNA to proteinbuilding centers in the cell Computing the phylogenetic tree of life from nucleotide sequences Mutations Changes in the nucleotide sequence of an organism s genome Occur because of errors in replication UV radiation and other factors Adaptive mutations improve fitness of an organism increasing its survival 0 Other genetic changes include gene duplication horizontal gene transfer and gene loss Phylogeny Evolutionary history of a group of organisms Inferred indirectly from nucleotide sequence data bacteria plants fungi fish mammals animals birds dragonflies beetles To infer phylogeny the most widely used nucleotide sequences are for small subunit ribosomal RNA SSU rRNA genes Found in all domains of life 16S rRNA in prokaryotes and 18S rRNA in eukaryotes Functionally constant Sufficiently conserved change slowly Sufficient length Carl Woese Pioneered the use of SSU rRNA for phylogenetic studies in the 1970s Established the presence of three domains of life Bacteria archaea and eukarya Provided a unified phylogenetic framework for bacteria Lecture 27 Importance of Microbes in Ecology Ecology is the branch of biology that deals with the relations of organisms to one another and to their physical surroundings An ecosystem is a community of living organisms plants animals and microbes in conjunction with the nonliving components of their environment things like air water and mineral soil interacting as a system Microbes form the backbone of every ecological system by controlling global biogeochemical cycling of elements essential for life Microbes support food chains Organisms at the bottom of the food chain do not feed or depend on other organisms Such life forms may have been the first to emerge on Earth 0 They derive their energy from light and or by oxidizing ubiquitous inorganic compounds Phototrophs Chemolithotrophs 0 They often derive their carbon from C02 Autotrophs They sometimes derive their nitrogen from N2 Nitrogen fixation Phototrophs Photosynthesis is the conversion of light energy to chemical energy Phototrophs carry out photosynthesis Most phototrophs are also autotrophs Photosynthesis requires lightsensitive pigments called chlorophylls and bacteriochlorophylls Photoautotrophy requires ATP production and C02 reduction 0 More than half of all photosynthetic activity on Earth is carried out by prokaryotic and eukaryotic microbes and not plants Chlorophylls and bacteriochlorophylls Chlorophylls are green photosynthetic pigments that are found in cyanobacteria and the chloroplasts of algae and plants They absorb light most strongly in the blue portion of the electromagnetic spectrum followed by the red portion They are poor absorbers of green and neargreen portions of the spectrum hence the green color of chlorophyllcontaining tissues There are different types a b c1 c2 d and f Cells that use chlorophyll for photosynthesis produce oxygen Bacteriochlorophylls are photosynthetic pigments that occur in various bacteria They absorb wavelengths of light not absorbed by cyanobacteria algae or plants There are different types a b c Cs d e f and g Bacteria that use bacteriochlorophyll for photosynthesis do not produce oxygen 0 Why green and not black Black plants such as the black pearl pepper above can absorb more radiation and yet most plants are green It still is unclear exactly why plants have mostly evolved to be green The biologist Iohn Berman has offered the opinion that evolution is not an engineering process and so it is often subject to various limitations that an engineer or other designer is not Even if black leaves were better evolution39s limitations can prevent species from climbing to the absolute highest peak on the fitness landscape The biologist Shil DasSarma has pointed out that species of archaea do use another lightabsorbing molecule retinal to extract power from the green spectrum He described the view of some scientists that such greenlight absorbing archaea once dominated the earth environment This could have left open a quotnichequot for green organisms that would absorb the other wavelengths of sunlight Location of photosynthesis 0 In prokaryotes chlorophylls and bacteriochlorophylls are integrated into the cytoplasmic membranes In eukaryotes chlorophylls are found in structures called thylakoids in chloroplasts Anoxygenic photosynthesis in some prokaryotes In bacterial photosynthesis a single photosystem is involved An electron is energy by absorption of light it is ejected from the photosystem reaction center The electron passes down through an electron transport system back to the reaction center The electron then passes down through an electron transport system and finally back to the reaction center The energy released during the electron transport is used to produce ATP since the excited electron returns to the reaction center this mechanism for making ATP is called cyclic photophosphorylation Oxygenic photosynthesis in plants and Cyanobacteria In plants photosynthesis occurs in specialized organelles called chloroplasts Chloroplasts are organized into sacs called thylakoids Surrounding the thylakoid membrane system is a semiliquid substance called stroma Photosynthetic pigments are clustered together to form photosystems When a photon of light strikes the reaction center of photosystem II it excited an electron Two water molecules bind to an enzyme at the reaction center When a photon of light strikes the reaction center of photosystem II it excited an electron Two water molecules bind to an enzyme at the reaction center When a photon of light strikes the reaction center of photosystem II it excited an electron Two water molecules bind to an enzyme at the reaction center This enzyme splits the water and uses the electrons from the water to replace the electrons removed from the reaction center Oxygen is produced in this process The primary electron acceptor for the lightenergized electrons leaVing photosystem II is a plastoquinone The reduced plastoquinone passes the excited electrons to a proton pup embedded in the membrane Arrival of the energetic electrons causes the complex to pump protons from the stroma into the thylakoid space thereby generating a proton gradient across the membrane Because the thylakoid membrane is impermeable to protons the protons in the stroma must pass through the channels provided by ATP synthase As protons pass through ADP is phosphorylated to ATP and released into the stroma This process for making ATP is referred to as photophosphorylation When photosystem I absorbs a photon of light its reaction center passes highenergy electrons to ferredoxin The enzyme NADP reductase then transfers the electrons to NADP and NADPH Electrons lost from photosystem I are replaced by electrons generated from photosystem II A small protein called plastocyanin then carries the electrons from the complex to photosystem I Photosynthesis in the cyanobacteria is very similar except that the systems are embedded n the cytoplasmic membrane Chemolithotrophs Hydrogen oxidation Many organisms are capable of using H2 as a source of energy The initial electron donor is H2 The final electron acceptor can vary depending on whether or not aerobic or anaerobic respiration is employed Many organisms employ both membranebound and cytoplasmic hydrogenases Hydrogenases H2 on gt 2H Ared 2H Dred gt H2 Dox H2 is oxidized by the membranebound hydrogenase causing proton pumping via electron transfer to various quinones and cytochromes The second cytoplasmic hydrogenase is used to generate reducing power in the form of NADH which is subsequently used to fix C02 via the Calvin cycle Reduced sulfur oxidation Some organisms are capable of using reduced sulfur as a source of energy The initial electron donor is often H25 So or 2032 The final electron acceptor is often 02 but can also be NO3 In reverse electron ow chemolithotrophs use an electron donor with a higher redox potential than NADNADH to reduce NAD Energy is supplied by consuming proton motive force to drive electrons in a reverse direction through an electron transport chain and is thus the reverse process of forward electron transport This process supplies reducing power for inorganic carbon fixation Iron Oxidation Some organisms are capable of oxidizing Fe2 Fe2 is a soluble form of iron that is stable at extremely low pHs or under anaerobic conditions Under aerobic moderate pH conditions Fe2 is oxidized spontaneously to Fe3 and then hydrolyzed abiotically to insoluble FeOH3 Organisms that use Fe2 as an energy source include acidophiles that live at very low pHs at which Fe2 exists Often associated with acidic pollution from coal mining activities The oxidation of Fe2 clear to give Fe3 red can be easily discernable Note that Fe3Fe2 pH 2 is low on the redox tower Oxidation of Fe2 is a very energetically poor process that requires large amounts of iron Lecture 28 Autotrophs The Calvin Cycle Input 30 Entering one CO at a time 2 Phase 1 Carbon xatlon s oooooo Shortlived intermediate gt 3 OOOOO 6000 Ribulose bisphosphate 3Phosphoglycerate RuBP 5 gt SADP CALVIN CYCLE 6 P O O 0 lt3 13Bisphosphoglycerate 139 V 7 6 I 7 gt 6 NADP 7 739 6 Bi 6 0 0 049 GcheraldehydeaphOSphate Phase 2 GSP Reduction Glucose and other organic Output compounds 030119 Nitrogen Fixation Nitrogen fixation is a process by which nitrogen N2 in the atmosphere is converted into ammonium NH4 0 Atmospheric nitrogen or molecular nitrogen N2 is relatively inert it does not easily react with other chemicals to form new compounds 0 The fixation process frees up the nitrogen atoms from their diatomic form N2 to be used in other ways Nitrogen fixation natural and synthetic is essential for all forms of life because nitrogen is required to biosynthesize basic building blocks of plants animals and other life forms eg nucleotides for DNA and RNA and amino acids for proteins 0 The only organisms that are known to fix nitrogen are prokaryotes Most notable are the cyanobacteria Nitrogenases are enzymes used by some organisms to fix N2 0 There is only one known family of enzymes that accomplishes this process Highly regulated process because it is such an energy demanding process Microbial Symbioses Interaction Species A Species B Commensalism Receives bene t 2 equote Mutualism Receives bene t Receives bene t Parasitism Receives bene t Harmed Lichens Leafy or encrusting microbial symbioses Often found growing on bare rocks tree trunks house roofs and the surfaces of bare soils A mutualistic relationship between a fungus and an alga or cyanobacterium Alga is photosynthetic and produces organic matter The fungus provides a structure within which the phototrophic partner can grow protected from erosion Chlorochromatium aggregatum In freshwater there are microbial mutualisms called consortia Consist of green sulfur bacteria called epibionts and a agellated rod shaped bacterium Consortium given a quotgenus speciesquot name Green sulfur bacteria are obligate anaerobic phototrophs Flagellated rod allows for movement The epibiont of quotChlorochromatium aggregatumquot has been isolated and grown in pure culture Electron micrographs of consortium reveal intimate contact between epibiont and central bacterium Plants as microbial habitats Nodules that fix nitrogen The mutualistic relationship between leguminous plants and nitrogen fixing bacteria is one of the most important symbioses known Examples of legumes include soybeans clover alfalfa beans and peas Rhizobia are the bestknown nitrogenfixing bacteria engaging in these symbioses Infection of legume roots by nitrogenfixing bacteria leads to the formation of root nodules that fix nitrogen Leads to significant increases in combined nitrogen in soil Nodulated legumes grow well in areas where other plants would not Nitrogen Fixation Root nodule formation on leguminous plants is a complex process that results in the nitrogenfixing symbiosis The plant root releases nutrients that attract rhizobia and other bacteria The first step in developing the symbiosis is attachment of the rhizobia to the surface of the plant root hair A specific adhesions protein called rhicadehesin is present on the surface of a specific Rhizobium species Carbohydratecontaining lectins are important plant cell surface receptors Following binding the root hair curls as the result of Nod factors which migrate to the plant cell nucleus and in uence transcription of genes needed for the symbiotic relation Following curling the bacteria enter the root hair and induce the plant to form a cellulosic tube called the infection thread which spreads down the root hair and into adjoining cells Plant cells become infected by movement of bacteria through the infection thread and start to divide in response to Nod factors from the rhizobia The rhizobia multiply rapidly in the plant cells and are transformed into misshapen structures called bacteroids Bacteroids become surrounded by plant cell membrane to form structures called symbiosomes Only at this stage does nitrogen fixation begin 0 characterized by nutrient exchange and several metabolic reactions The plant supplies the bacterium with various citric acid cycle intermediates including the organic acids succinate malate and fumarate The bacterium funnels the organic acids into its own citric acid cycle to produce electrons that are sent to an electron transport chain whose final electron acceptor is 02 0 The aerobic respiration produces ATP for the highly energy consuming process of nitrogen fixation The organic acids are also converted to pyruvate which provides electrons for the N2 reduction Nitrogenfixing bacteria need 02 to generate energy for N2 fixation but nitrogenases are inactivated by 02 In the nodule 02 levels are controlled by the plant s Ozbinding protein leghemoglobin A crossinoculation group is a group of related legumes that can be infected by a particular species of rhizobia Nonlegume nitrogenfixing symbiosis also occurs The water fern Azolla contains a species of heterocystous nitrogen fixing cyanobacteria known as Anabaena Agrobacterium and Crown Gall Disease Agrobacterium tumefaciens forms a parasitic symbiosis with plants causing crown gall disease Crown galls are plant tumors induced by A tumefaciens cells harboring a large plasmid the Ti tumor induction plasmid To initiate tumor formation A tumefaciens cells must attach to the wound site on the plant 0 Attached cells synthesize cellulose microfibrils and transfer a portion of the Ti plasmid to plant cells DNA transfer is mediated by Virencoded proteins The Ti plasmid has been used in the genetic engineering of plants Mycorrhizae Mycorrhizae are mutualistic associations of fungi and plant roots 0 This mutualistic association provides the fungus with relatively constant and direct access to carbohydrates such as glucose and sucrose In return the plant gains the benefits of the fungus higher absorptive capacity for water and mineral nutrients due to the comparatively large surface area of the fungus thus improving the plant39s mineral absorption capabilities Two classes Ectomycorrhizae 0 Endomycorrhizae E ctomycorrh izae Fungal cells form an extensive sheath around the outside of the root with only a little penetration into the root tissue Found primarily in forest trees particularly boreal and temperate forests 0 E ndomycorrhizae The fungal mycelium becomes deeply embedded within the root tissue 0 Are more common than ectomycorrhizae Found in gt80 of terrestrial plant species Lecture 29 The Human Microbiome quotmicrobiomequot refers to the ecological community of microorganisms that share a space Microbiome Projects 0 Frequently the microbiome is analyzed by sequencing the SSU rRNA genes 0 In a given space there can be thousands of different microbial species Launched in 2008 the 115 million Human Microbiome Project HMP was a United States National Institutes of Health initiative with the goal of identifying and characterizing the microorganisms that are found in association with both healthy and diseased humans The goal of the HMP was to test how changes in the human microbiome are associated with human health and disease In addition to the HMP there have been many other human animal and environmental microbiome projects Billions of dollars have been spent on microbiome projects uBiome is a biotechnology company based in San Francisco that gives individuals and organizations access to sequencing technology to sequence their microbiomes with a sampling kit and website Me myself and us Each of us humans can be regarded as an ecosystem A healthy adult human harbors 10 trillion human cells but 30 trillion bacterial cells in his gut alone Therefore bacterial cells outnumber human cells gt31 All the microbes bacteria archaea and eukarya that inhabit a human are collectively referred to as his microbiome A human genome consists of 23000 unique genes whereas a human microbiome consists of gt3000000 unique genes Disorders Clostridium difficile Infection Clostridium difficile also known as C di is an endosporeforming obligate anaerobe Typically C d is only a minor part of the normal colonic microbiome Antibiotic treatment can kill many of the microbes in the gut However C di r can survive due to acquired antibiotic resistance and physiological factors of the bacterium itself such as endospore formation Without competition from other bacteria C di r can proliferate This can lead to an in ammation of the colon called pseudomembranous colitis This in turn can lead to an extremely painful and lifethreatening condition called toxic megacolon One very effective treatment of C di r infections is the restoration of the colonic microbiome with a fecal microbiota transplantation The procedure involves single to multiple infusions of bacterial fecal ora originating from a healthy donor The procedure can be carried out via enema through the colonoscope or through a nasogastric or nasoduodenal tube The treatment is effective in gt90 of the cases Obesity Some of us are more prone to obesity than others Some of us find it harder to lose weight or keep weight off While many factors contribute to obesity including diet exercise and genetics there is growing evidence that our gut microbiomes play a role Lean and obese individuals tend to have different gut microbiomes An obese individual tends to have gut microbes that can better break down food allowing the individual to extract more energy per unit mass of food consumed In one study gut microbes from lean and obese humans were transferred to germ free mice The mice were feed identical diets For the mice that received the gut microbes from the lean humans there was no substantial weight gain For the mice that received the gut microbes from the obese humans there was substantial weight gain Autism Studies have found that many individuals with ASD have Gut microbiota that differ in comparison to healthy controls Gut permeability It has been hypothesized that the metabolites produced by gut microbiota may leave the gastrointestinal tract and cause alterations in brain function and behavioral disturbances such as those seen in ASD and other disorders A study by Hsiao et al in 2013 in mice has provided the most convincing data to date that the gut microbiome plays a role in autism Have much lower levels of the bacterium Bacteroides 3 fragilis in the gut Believed to be important for preventing leaky gut Addition of B fragilis to the gut eliminates autismlike symptoms Have much higher levels of 4ethylphenylsulphate 4EPS in the blood Believed to be produced by gut bacteria Believed to be neurotoxic Injection of 4EPS into the blood of the normal mice caused autismlike symptoms Lecture 30 Mood Mice who are fed Lactobacillus rhamnosus show fewer signs of anxiety and depression and are more adventurous Mice who are fed Bifidobacterium infantis produce fewer stress hormones People who regularly consume beneficial bacteria known as probiotics through yogurt show altered brain function both while in a resting state and in response to an emotionrecognition task Allergies The hygiene hypothesis states that a lack of early childhood exposure to infectious agents symbiotic microorganisms and parasites increases susceptibility to allergic diseases by suppressing the natural development of the immune system In 1989 David Strachan was the first to propose the hypothesis to explain the observation that hay fever and eczema both allergic diseases were less common in children from larger families which were presumably exposed to more infectious agents through their siblings than in children from families with only one child Several microbiome studies support the hygiene hypothesis In 2011 one study found that infants with a less diverse gut microbiome have an increased risk of developing allergic sensitization and rhinitis as they grow up Again not clear if this is causation or just correlation 16S rRNA sequencing was done to identify the fecal bacteria present in 253 infants 0 Samples were taken when the children were 1 month and 12 months old and the children were then monitored every 6 months until they were 6 years old When the children reached 6 years old the presence or absence of allergic rhinitis asthma and atopic dermatitis was identified Heart Disease In atherosclerosis an artery wall thickens as a result of the accumulation of calcium and fatty materials such as cholesterol and triglyceride Atherosclerosis can lead to a heart attack 0 Parts of the microbiome can promote atherosclerosis Choline a molecule found in eggs and meat is digested by some gut bacteria to produce trimethylamine and trimethylamine is then processed in the liver to create trimethylamine Noxide and trimethylamine Noxide encourages atherosclerosis Heritable disorders Mother to child transmission via Oral mammary breastfeeding cutaneous contact with skin vaginal child birth Microbial infections exert enormous selective pressure Measuring Virulence Virulence can be estimated from experimental studies of the leo infectious dose 50 The amount of an agent that infects 50 of the animals in a test group I Highly virulent pathogens show little difference in the number of cells required to kill 100 of the population as compared to 50 of the population Stages of Virulence Pathogens use various strategies to establish virulence Virulence is the relative ability of a pathogen to cause disease Attenuation The decrease or loss of virulence 0 T oxicigg Organism causes disease by means of a toxin that inhibits host cell function or kills host cells Toxins can travel to sites within host not inhabited by pathogen Invasiveness Ability of a pathogen to grow in host tissue at densities that inhibit host function 0 Can cause damage without producing a toxin 0 Many pathogens use a combination of toxins invasiveness and other virulence factors to enhance pathogenicity Exposure Further exposure at local sites TOXICITY COLOL IJ EATION toxin effects are TISSUE EXPOSURE ADHERENCE INVASIION GROWTH 39 a39 r systemquot 39 DAMAGE to pathogens to skin or mucosa through eP39thellum Production of DISEASE gt 9 v virulence factors INVASIVENESS 4 Q 30 o 90 o N further growth at Iquot 39590 L original and distant sites 9 J39F r r e xpos ur j J Adhesion Specific adherence A pathogen must usually gain access to host tissues and multiply before damage can be done Bacteria and viruses that initiate infection often adhere specifically to epithelial cells through macromolecular interactions on the surfaces of the pathogen and the host cell Bacterial adherence can be facilitated by Extracellular macromolecules that are not covalently attached to the bacterial cell surface Examples slime layer capsule Fimbriae and pili Invasion The availability of nutrients is most important in affecting pathogen growth Pathogens may grow locally at the site of invasion or may spread throughout the body Pathogens produce enzymes that Enhance virulence by breaking down or altering host tissue to provide access to nutrients Example hyaluronidase Protect the pathogen by interfering with normal host defense mechanisms Example coagulase Toxicity Exotoxins includes enterotoxins Cytolytic toxins AB toxins Superantigen toxins Endotoxins Exotoxins Proteins released from the pathogen cell as it grows Three subtypes cytolytic toxins AB toxins Superantigen toxins Cytolytic toxins Work by degrading cytoplasmic membrane integrity causing cell lysis and death Hemolysins Cytolytic toxins that lyse red blood cells are called hemolysins Staphylococcal atoxin Is a poreforming hemolysin that is produced by growing Staphylococcus cells Released as a monomer seven identical protein subunits oligomerize in the cytoplasmic membrane of target cells The oligmer forms a pore releasing the contents of the cell and allowing the in ux of extracellular material and the ef ux of intracellular material Red blood cells swell and lyse AB toxins Consist of two subunits A and B Work by binding to host cell receptor B subunit and transferring damaging agent A subunit across the cell membrane 0 Examples diphtheria toxin tetanus toxin botulinum toxin Clostridium botulinum AB toxin Clostridium botulinum produce potent AB toxins that affect nervous tissue Botulinum toxin consists of several related AB toxins that are the most potent biological toxins known Superantigens cause acute system wide in ammation that damages tissues and organs Enterotoxins Exotoxins cytolytic AB and superantigen whose activity affects the small intestine Generally cause massive secretion of uid into the intestinal lumen resulting in vomiting and diarrhea Example cholera toxin Endotoxins The lipopolysaccharide LPS portion of the cell envelope of certain gramnegative Bacteria which is a toxin when solubilized Elicits a variety of in ammatory responses in an animal Generally less toxic than exotoxins Lecture 3 1 Host factors in infection Compromised host One or more resistance mechanisms are inactive The probability of infection is increased Age is an important factor 0 Very young and very old individuals are more susceptible Stress can predispose a healthy individual to disease Diet plays a role in host susceptibility to infection Certain genetic conditions can compromise a host Physical and chemical barriers Components of the immune system Bone marrow is a source of immunity Bone marrow is the exible tissue in the interior of bones It produces red and white blood cells It produces 500 billion blood cells per day The blood cells enter the circulation system via the bone marrow vasculature White blood cells are the cells of a immune system White blood cells also called leukocytes are the cells of the immune system that are involved in defending the body against both infectious disease and foreign materials Leukocytes are produced and derived from a multipotent cell in the bone marrow known as a hematopoietic stem cell Leukocytes include I Monocytes and granulocytes purple I Lymphocytes orange White blood cells are found in the blood system The circulatory system is composed of i the cardiovascular system which distributes blood and ii the lymphatic system which circulates lymph The cardiovascular system The cardiovascular system is an organ system that permits blood circulation to transport nutrients oxygen carbon dioxide hormones blood cells etc to and from cells in the body to nourish it and help to fight diseases stabilize temperature and pH and maintain homeostasis Whole blood is composed of plasma and cells Plasma contains proteins and other solutes Red blood cells also called erythrocytes are 999 of the cells in the blood The cells are the vertebrate organism39s principal means of delivering oxygen 02 to the body tissues via the blood ow through the circulatory system The cells take up oxygen in the lungs or gills and release it into tissues while squeezing through the body39s capillaries The cells cytoplasm is rich in hemoglobin an ironcontaining biomolecule that can bind oxygen and is responsible for the red color of the cells They lack a cell nucleus and most organelles in order to accommodate maximum space for hemoglobin White blood cells are only 01 of the cells in the blood The lymphatic system The lymphatic system is the body39s drainage system It is composed of a network of vessels and small structures called lymph nodes It collects uid leaked from the cardiovascular system and returns it back into the blood circulation Of the 20 L of blood processed by the cardiovascular system each day 3 L is leaked and eventually collected by the lymphatic system Innate immunity nonspecific immunity The noninducible ability to recognize and destroy an individual pathogen or its products Does not require previous exposure to a pathogen or its products The innate immune system is an evolutionarily older defense strategy and is the dominant immune system found in plants insects and primitive multicellular organisms Mediated by phagocytes like macrophages and neutrophils Phagocytes interact with pathogens by recognizing pathogenassociated molecular patterns PAMPs with preformed pattern recognition receptors PRRs PAMPs include bacterial lipopolysaccharide LPS agellin lipoteichoic acid and peptidoglycan as well as viral nucleic acid variants such as dsRNA Lecture 32 Adaptive Immunity The adaptive immune system is a subsystem of the overall immune system that is composed of highly specialized systemic cells and processes that eliminate or prevent pathogen growth Acquired immunity creates immunological memory after an initial response to a specific pathogen leading to an enhanced response to subsequent encounters with that same pathogen This process of acquired immunity is the basis of vaccination The major components of the adaptive immune system are the dendritic cells and lymphocytes Dendritic cells are found throughout the body This includes the entire circulatory system both the cardiovascular and lymphatic systems Also found in tissues The lymphatic system and tissues contain 98 of circulating lymphocytes The peripheral blood contains only 2 of circulating lymphocytes A lymph node is an ovalshaped organ of the lymphatic system distributed widely throughout the body including the armpit and stomach and linked by lymphatic vessels They are packed tightly with lymphocytes and macrophages How it works Activation of the adaptive immune response typically begins when a pathogen enters the body Dendritic cells that encounter the pathogen ingest process and display the antigen gradments on their cell surfaces Dendritic cells with antigen fragments displayed on their surfaces are called antigen presenting cells APCS The APCS migragrate to the lymph nodes where there are Thelper cells The body produces Thelper cells with billions of different cell surface receptors Some of the Thelper cells will have receptors that can bind the antigen fragments on the APCs During the interaction the APC releases a chemical alarm called inerleukin1 which stimulates the Thelper cell to secrete interleukin2 Interleukin2 causes the proliferation of the Thelper cell Like Thelper cells the body produces B cells with billions of different cell surface receptors Some of these B cells will have cell surface receptors that can bind to the receptors on the proliferating Thelper cells This binding activates the B cells The activated B cells proliferate and differentiate Some of the activated B cells will differentiate into plasma cells that are antibodyproducing factories ooding the bloodstream with antibodies that can bind to the antigen involved in the infection Antibodies bind to antigens on the surfaces of the pathogens marking them for destruction by macrophages Some of the B cells do not turn into antibody factories but instead become memory B cells that may survive for several decades Because of these memory B cells the quotsecondary immune responsequot to a future infection by the same pathogen is swifter and stronger This powerful secondary immune response is what gives quotimmunity to some disease after you have had them once or after you have been vaccinated The body produces Thelper cells with billions of different cell surface receptors Some of the Thelper cells will have receptors that can bind the antigen fragments on the APCs Like Thelper cells the body produces B cells with billions of different cell surface receptors Some of these B cells will have cell surface receptors that can bind to the receptors on the proliferating Thelper cells This binding activates the B cells Virtually all microbes can trigger an antibody response 0 Successful recognition and eradication of many different types of microbes requires diversity among antibodies their amino acid composition varies allowing them to interact with many different antigens It has been estimated that humans generate about 10 billion different antibodies each capable of binding a distinct epitope of an antigen Although a huge repertoire of different antibodies is generated in a single individual the number of genes available to make these proteins is limited by the size of the human genome Several complex genetic mechanisms have evolved that allow vertebrate B cells to generate a diverse pool of antibodies from a relatively small number of antibody genes Lecture 33 In ammation In ammation is part of the complex biological response of vascular tissues to harmful stimuli such as pathogens damaged cells or irritants The classical signs of acute in ammation are pain heat redness swelling and loss of function In ammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process The major components of in ammation are neutrophils mast cells and macrophages In ammatory Response The in ammatory response is an important nonspecific defense against tissue damage It begins when injured tissue cells release chemical signals that activate the endothelial cells of nearby capillaries Within the capillaries adhesion molecules called selections are displayed on the activated endolethial cells These adhesion molecules attract neutrophils slow them down and cause the neutrophils to roll along the endothelium As the neutrophils roll along the endothelium they encounter chemicals that activate integrins which are adhesion receptors on their surfaces These inegrins then tightly attach to adhesion receptor molecules on the endothelial cells This causes the neutrophils to stick to the endothelium and stop rolling This accumulation of neutrophils along the walls of the capillary is referred to as margination This in ammatory mediators released by the injured tissue bring about changes in the environments that cause mast cells to degranulate and release histamine Histamine causes vasodilation and an opening of the junctions between the endothelial cells allowing uid and leukocytes to leave the capillary and enter the infected tissue The neutrophils now undergo dramatic changes in shape and squeeze through the endothelial wall into the interstitial tissue uid This process is called extravasation The neutrophils followed by other types of phagocytes are attracted to the damaged site by chemotactic substances released by bacteria and tissue breakdown products They ingest and destroy invading bacteria Usual outcome of in ammation is a rapid localization and destruction of the pathogen In some cases in ammation fails to localize pathogen and the reaction becomes widespread Can lead to systematic in ammation called septic shock a life threatening condition Systemic in ammatory reactions may have serious consequences Uncontrollable fever Death in up to 30 of individuals Septic shock can be more dangerous than the initial infection Prevention of disease An antibody is a protein produced by plasma cells that is used by the immune system to identify and neutralize pathogens such as bacteria and viruses The antibody recognizes a unique molecule of the harmful agent called an antigen Adaptive immunity Naturally Artificially acquired 39 acquired l l Active Active Antigens Antigens are enter the introduced body in vaccines naturally body body induces produces antibodies antibodies and and specialized specialized Immune diseases Antibody Isotypes An antibody Ab also known as an immunoglobulin lg is a large Y shape protein produced by plasma cells that is used by the immune system to identify and neutralize foreign objects such as bacteria and viruses The antibody recognizes a unique part of the foreign target called an antigen Each tip of the quotYquot of an antibody contains a paratope that is specific for one particular epitope on an antigen allowing these two structures to bind together with precision Using this binding mechanism an antibody can tag a microbe or an infected cell for attack by other parts of the immune system Alternatively an antibody can neutralize its target directly 0 Eg by blocking a part of a microbe that is essential for its invasion and survival Antibodies are typically made of basic structural units each with two large heavy chains and two small light chains Antibodies are grouped into different isotypes based on which heavy chain they possess Different isotypes perform different roles and so help direct the appropriate immune response for each different type of foreign object they encounter Five different antibody isotypes are known in mammals 0 IgA IgD IgE IgG IgM Though the structures of antibodies are all very similar a small region at the tip of the protein is extremely variable allowing billions of antibodies with slightly different tip structures or antigenbinding sites to exist This region is known as the hypervariable region Each of these variants can bind to a different antigen This enormous diversity of antibodies allows the immune system to recognize an equally wide variety of antigens The large and diverse population of antibodies is generated by random combinations of a set of gene segments that encode different antigen binding sites or paratopes followed by random mutations in this area of the antibody gene which create further diversity Allergy hypersensitivity and autoimmunity Hypersensitivity Inappropriate immune response that results in host damage Hypersensitivity diseases are categorized according to antigens and effector mechanisms that produce disease Type I Hypersensitivity Some people develop an allergic reaction or hypersensitivity when exposed to substances such as dust pollens animal dander or penicillin Sensitization occurs when the antigen makes contact with some part of the body The antigen is taken up processed by antigen presenting cells and presented to Tcell helper cells Tissues under the mucous membranes are rich in B cells committed to IgE production and IgE producing cells are more abundant in persons susceptible to allergies The Thelper cells produced cytokines which stimulate B cells in the area to proliferate and differentiate into IgEproducing plasma cells As IgE is produced in specific areas of the body the IgE molecules attach to nearby mast cells The individual is now quotsensitizedquot to the antigen When exposed to the antigen for a second time the antigen immediately binds to the IgE antibodies which are already attached to the mast cell Within seconds of this binding the mast cell releases histamine and other chemicals that cause an in ammatory response These chemicals trigger a variety of symptoms such as capillary dilation airway constriction mucus secretion pain and itching Exotoxins superantigens Superantigens Proteins capable of eliciting a strong response because they activate more T cells than a normal immune response Produced by many Viruses and bacteria that interact with the receptors on Thelper cells Superantigenactivated T cells may produce systemic diseases characterized by systemic in ammatory reactions
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