Chapter 11 – Eukaryotic Microbes & Parasites
Mainly a tropical issue.
Humans are hosts to ~300 species of parasitic worm (helminths) and ~70 species of protozoa. Mostly rare but about 90 are considered common Parasite – Animal that lives at expense of the host. Parasite obtains nutrients in a way that is harmful to the host
Host – A living animal or plant from which a parasite obtains nutrition. ~15,000,000/yr people die of parasitic infections or their complications. Or complications of improper treatment
This is a problem in agriculture as well. Ex: wheat rust- fungal infection that when left untreated can kill as much as 20% of crop
Ecto- parasitize the outside of organisms
Endo- parasitize the inside of their hosts
Obligate must parasitize hosts ex: plasmodium which causes
Facultative may live without host but if host is present will
Permanent/temporary permanent will be there forever even if it is killed/ temporary carries the parasite ex: mosquito
Accidental parasites that typically have a certain range of hosts but they may parasitize something outside of their host range
Hyper- parasites that parasitize other parasites
Vectors- something that transports a parasite
Biological parasite is attached to an organism and undergoes
some of its life cyle in that organism (ex: rabies is a virus → needs biological medium) Don't forget about the age old question of What is the diffusion of innovation?
Mechanical transfer without growth or life cycle;
Definitive hosts in which the parasitic organisms have sex If you want to learn more check out What are the crime rates by gender?
Intermediate hosts that harbor the parasite for a while and thin it leaves or dies
Reservoir infected hosts that make parasites available to others Yellow fever in Brazil We also discuss several other topics like In accounting systems & financial statements, what are the examples of source documents?
Mechanisms & Machinations
Most parasites have one or more special adaptation:
Encystment formation of outer protective coating and make it difficult for the host immune system to attack must be able to live off host without killing them too quickly; cysts are less injurious to the host and allows to invade immune system
Antigen switching organism reorganizes surface antigens at a rate faster than the host immune system can adapt and target
Antigen false flagging organism produces antigens that illicit and immune response that doesn’t actually target those antigens
Intracellular living live inside host cells so host immune system does not attackDon't forget about the age old question of Why is political culture powerful?
Removal often does damage all its own. Ex: ticks embedded in skin Reproduction is key to success. Reproduce a lot and forgo adaptations (usually intestinal bacteria) or do adaptations and reproduce less
Protists- form basis of food web; unicellular and sometimes colonial; eukaryotes; mostly microscopic; 5 μ – 5 mm diameter
Plantlike: white cliffs of dover made of protist shells; limestone in the great pyramids; marble
Prototheca – Protothecosis, enteritis or mastitis. One genus of eukaryotic micro algae that can parasitize; no chloroplasts; asexual reproduction; cause inflammation of bowels or breast tissue; problem in cows
Oomycota – Water molds, common plant parasites. Downy mildew, blight, white rust. Some look like fungi, some look like animals; some other species that can cause diseases in fish
Cause many diseases. Heterotrophic; mostly unicellular; free living; some commensal, some parasitic, some depending on the health of the host We also discuss several other topics like Where and when did clay pots become popular?
Mastigophorans – Sleeping sickness, giardia gastroenteritis, sandfly skin lesions.
Amebozoa – “Brain-eating”
Apicomplexans – Cause malaria.
Ciliates – The largest group.
Fungi (fig 11.8)
Fungi reproduction methods are diverse and unconventional
Zygomycota – Bread molds, generally don’t cause disease.
Ascomycota – Sac fungi, cause yeast infections, athlete’s foot, and respitory infections.
Basidiomycota – Club fungi, some produce toxins.
Deuteromycota – Fungi Imperfecti, some produce antibiotics.
Mycosis – Fungal disease
Superficial top part of skin
Subcutaneous below the skin; slow progressing
Systemic will kill the victim
Parasite members fall into one of two types.
Platyhelminthes – Flatworms, some are animal parasites and may lack circulatory and digestive systems.
Planarians = Free living, non-parasites.
Trematodes = Flukes; ecto/endo.
Cestodes = Tapeworms; endo.
Nematodes – Roundworms, parasitize plants and animals.
Look into the basic lifecycles of each. Note how many hosts they need (fig 11.18) If you want to learn more check out What curve is produced by the logistic growth model of population?
Generally not parasites, a few are.
Arachnids – Ticks and mites.
Insects – Biting flies, fleas
Crustaceans – Typically not parasites themselves.
Chapter 12 – Sterilization & Disinfection
Sterilization – Killing or removal of all [micro]organisms and viruses in a material or on an object; Not always attainable or practical; Sometimes it is essential. Disinfection – Reducing the number of pathogenic organisms in a material or on an object such that there is no threat of disease.
Disinfectants – For inanimate objects.
Antiseptics – For living tissue.
“Natural” unassisted Death rate is exponential and still is when treated with such agents.
Microbes differ in their susceptibility. Endospores in particular are resistant Bacteriocide kills bacteria vs. Bacteriostasis slows or stops bacterial growth Potency
Time more time for chemical reactions to occur
Temp speeds the rate of chemical reaction
pH impact how chemical agent enters the cell or how it affects the cell directly
Concentration few exceptions include ethanol and isopropyl alcohol are less effective if they do not have a little water in them
A unit going back to 1867 when Joseph Lister introduced phenol as a disinfectant. Testing against Salmonella typhi and Staphylococcus aureus.
<1.0 = Less effective than phenol
1.0 = Equal to phenol
>1.0 = More effective than phenol
D-value- time it takes to deactivate 90% of the population at a given concentration Filter Paper Method
Simpler than the phenol coefficient.
Soak a filter paper in a disinfectant and place it on an inoculated plate. Molecules move differently in agar.
Presence of other materials (like blood) may have differential effects. Use-Dilution Test
Almost as simple as the filter paper method.
Somewhat more current.
Not as susceptible to medium bias.
Uses a stainless steel cylinder.
Still doesn’t account for different surface types or chemical interference. Can use different concentrations of bacteria or disinfectant
Mechanism of Action – The way in which a specific antimicrobial agent does its antimicrobial work.
General categories are those that affect: Proteins, Membranes, Other cell components ex: nucleic acids, Viruses
Denaturation – Permanent Change in conformation of the protein (fig. 12.2) Permanently denature the proteins (including enzymes) and you kill the organism.
Hydrolysis breaking of peptide bond by adding water to it; strong acids and alkalides;
Attachment of elements or chemical groups. Halogens and heavy metals; alkylating agents
Membranes can be impacted by the same things that denature proteins. They also contain lipids and so can be disrupted by surfactants, alcohols and soaps (in engineering they are considered wetting agents, change surface tension) and detergents. commonly used in laboratory settings to lyse cells in a controlled fashion and keep cell parts in solution
Things that reduce the surface tension of water.
∙ Quaternary Ammonium Compounds.
∙ Anionic detergents are effective at disrupting all types of
Impacting Other Cell Components
DNA/RNA can be affected by alkylating agents.
Crystal violet inhibits cell wall formation.
Lactic or propionic acid can shut down fermentation pathways.
∙ Viruses have to be inactivated.
∙ Enveloped viruses are more susceptible.
∙ Denaturing proteins is sometimes not sufficient; Requires
damaging/destroying the nucleic acid.
∙ Alkylating agents, halogens, alcohols, detergents, some dyes. Specific Chemical Agents
Soaps are hard and are a result of saponification & Detergents liquid Acids & Alkalis effective against bacteria
Heavy Metals microbes do not build resistance but they do not kill spores; mostly surface treatments
Halogens height electronegativity, effective against viruses and bacteria, strongly impaired by organic material
Alcohols denature proteins, effective against bacteria that are growing and viruses, precipitate proteins, need water to be most effective, antimicrobial properties go up as molecular weight goes up
Phenols disrupt membranes, denature proteins, inactivate enzymes, not very susceptible to inactivation by presence of other organic material, can maintain activity for days, can add halogens to increase effectiveness, specifically effective on enveloped viruses, bacteria, fungi, does not induce resistance Oxidizing agents hydrogen peroxide, potassium permanganate, oxidize disulfide bonds in proteins to change their shape, has activity against aerobic and anaerobic organisms, can kill some of own tissue, effective against fungi, bacteria, and viruses if applied properly
Alkylating agents disrupt protein actions and nucleic acids, can be carcinogenic, formaldehyde, ethylene oxide, effective against any living thing, often effective against viruses, can be used to develop vaccines
Dyes often interfere with DNA structure and replicaqtion, interfere with cell wall synthesis, effective against bacteria and fungi, and sometime effective against viruses
Others sulfite, nitrite, essential oils
Physical Antimicrobial Agents
Heat figures 12.8 and 12.10; dry heat is typically not as effective as moist heat Thermal Death Point/Time & Decimal Reduction Time whatever the temperature and time that will kill a 24 hour old broth culture within 10 minutes
Moist- better not to crowd things in an autoclave, figure 12.11 autoclave schematic
Pasteurization sanitizing, inactivates most infectious agents, temperatures and times had to be adjusted for listeria in the mid 20th century, Refrigeration doesn’t kill things but slows down growth
Freezing for several days is enough to kill most worm parasites, standard (-20 C), science (-80 C), cryopreservation with liquid nitrogen used for preservation rather than killing
Drying stops enzymes from working,
Lyophilization freeze drying, preservation, ex: astronaut ice cream Radiation UV sterilizer, Morcherinkov radiation, gamma radiation Visible light sunlight has infrared and ultraviolet light, UV light is effective against viruses, bacteria, and fungi
Ultraviolet direct line of site, not effective against endospores, effective against bacteria, fungi and viruses, need to have frequent maintenance schedule
Ionizing knock out protons, neutrons, and electrons from body cells, can create free radicals, can sterilize plastics and foods
Microwave not as useful without pressure vessel
Sound sonic/ultrasonic waves; of limited effectiveness, useful for dislodging dirt particles, can break up cell walls
Filtration- diatomaceous earth, passing liquid through a strainer, usually inexpensive, doesn’t require a lot of maintenance, but filters can get clogged, usually let through viruses and mycoplasmas, use on media that can’t be heated Osmotic pressure draws water out to slow down organism; salt inhibits microbial growth in this way
Pasteurization sanitizing, inactivates most infectious agents, temperatures and times had to be adjusted for listeria in the mid 20th century,
Refrigeration doesn’t kill things but slows down growth
Freezing for several days is enough to kill most worm parasites, standard (-20 C), science (-80 C), cryopreservation with liquid nitrogen used for preservation rather than killing
Drying stops enzymes from working,
Lyophilization freeze drying, preservation, ex: astronaut ice cream
Chapter 13 – Antimicrobial Therapy
Chemotherapy- the administration of chemical substances for the purpose of killing pathogenic organisms with out injuring the host
Chemotherapeutic agent (drug)- chemical that has some sort of efficacy for some sort of disease
Antimicrobial agent- substances which possess systemic antimicrobial action
Antibiotic- “against life”, 1942 by Selman Waksman**, a chemical substance produced by microorganisms which has the capacity to inhibit the growth or even destroy bacteria and other
microorganisms in a dilute solution
Synthetic drug- made in the laboratory without the aid of microbes Semisynthetic drug- made with the aid of microbes
1619 A.D. – First recorded malaria cure using cinchona bark extract (quinine). ~1680 A.D. – Ipecacuanha used to treat “bloody flux”. (diarrhea), basis of syrup of ipecac
1909 A.D. – Salvarsan developed and marketed by Paul Erlich. 1929 A.D. – Alexander Fleming discovers penicillin but doesn’t publish until 1940.
1932 A.D. – Prontosil, the first sulfinlimide, is discovered.
Antimicrobial Agents – General Properties
Selective toxicity – Killing of thee and not of me; All antimicrobial agents have it.
Some are too toxic to take internally. Ex: Neosporin is toxic to liver and kidneys but can be applied topically
Chemotherapeutic index- Gap between Therapeutic <----> Toxic Min dose
Max tolerable dose/ kg
Large chemotherapeutic index equals less toxic
The greater the similarity between host and parasite, the lower the index. Worms vs. Fungi vs. Bacteria
Spectrum of Activity – can be broad or narrow; what sort of organisms the compound will work against
Broad Spectrum not enough time to examine and diagnose infection Narrow Spectrum exact source of infection can be determined; ex: strep throat; less likely to induce resistance
Modes of Action – What, specifically, does it do?
Antimicrobials can kill or slow down invaders but the host’s immune system does the elimination.
5 Basic types:
Inhibition of cell wall synthesis
Disruption of membrane function ex: polymyxins
Inhibition of protein synthesis usually interfere with translation Inhibition of nucleic acid synthesis
Antimetabolic activity. Something that looks like a key metabolite and takes up the enzymes that do that job
Side Effects – Both direct and indirect.
Allergy response of proteins that your body makes reacting with the drug to make an allergen
Disruption of microflora diarrhea, thrush, yeast infections, UTIs Microbial resistance – Antimicrobial agents decrease in effectiveness over time
Can be biochemical, locational, or based on phenotypic plasticity (ex: heteroresistance).
Chromosomal usually to a single drug or extrachromosomal multiple genes for multiple types of resistance. (Cassettes- smaller plasmids) Mechanisms of resistance
Alteration of target- target of antibiotic is altered by changing conformation of ribosome
Alteration of membrane permeability- changes to the proteins embedded in the membrane
Development of enzymes- enzymes to damage antibiotic
Alteration of an enzyme- change binding affinities of current enzymes Alteration of metabolic pathway- eliminates steps affected by antibiotics Cross-resistance resistance to one antibiotic which induces resistance to closely related antibiotics
Quorum Sensing certain bacterial infections do not start producing toxins until there is a certain quorum in body; if you can block quorum sensing it allows your body to catch up to infection and fight it
Disk Diffusion (Kirby-Bauer) nutrient Agar plate and sterile swab used to inoculate plate as thoroughly as possible, introduce small amounts of different antibiotics to the medium, lower molecular weight drugs diffuse faster, diameter of clear zones used to determine whether organism is affected by antibiotic, just because therr is a big clear zone does not mean that the antibiotic will clear the infection
E Epsilometer plastic strips with a continuous concentration gradient of a given drug, must be careful to follow manufacturers instructions for incubation time, temperature, and medium; tells you minimal inhibitory concentration (MIC) the lowest concentration that will inhibit the growth of that organism Dilution usually take place in 96 well plate, can be used to determine MIC, fairly inexpensive, need a plate reader to read results of growth which gives optical density factor
Serum Killing Power result of spontaneous clotting, what is left behind is serum; take blood samples at different intervals and test the serum for antibiotic concentration or use it as a growth medium to see if antibiotic is effective Automated Methods vitek AST- cards that are preloaded with antimicrobial drugs which are inoculated, incubated, and put into reader machine, results in 3- 6 hours, very expensive
Specific Antimicrobial Agents **need to know what are the modes of action, how they are given, and any interesting contraindications and basic uses** Cell Wall
Penicillins (Gen 4) penicillin B and G come from Penicillin notatum, susceptible to more than 1000 known beta-lactamase enzymes which cleave beta-lactam ring, when dosed with clavulanic acid which is a beta lactamase inhibitor it is effective, will occupy enzymes, work by
preventing peptidoglycan cross linking making it much weaker, penicillin fungi, mainly bacteriostatic
Cephalosporins (Gen 5) come from fungi genus Cephalosporium “head/brain like spores”, natural forms have limited use, we use semisynthetic derivatives of these, some cross resistance from penicillin’s similar activities and also has a beta-lactam ring, may set off allergies in people allergic to penicillin, often given before major surgery
Polymyxins structure figure 13.15; come in forms A ,B , C, D, and E; differ in absorption; must be either injected or inhaled; internally used as a drug of last resort, haver neuro and nephron toxicity; mainly bacteriocidal; fatty tail is responsible for lethal action; some E. coli have been found to be resistant in China, Laos, and Malaysia
Aminoglycosides come from bacteria ; disruption of peptide elongation by binding to #0s ribosomal subunit ; may also interfere with codon reading ; streptomycin ; bactreriostatic at lower doses and bacteriocidal at high doses, resistance is not uncommon but work synergistcally with many other antibiotic compounds; nephrotoxic
Tetracyclines come from same genus as aminoglycocides, bind to 30s subunit and A site of ribosome, mainly bacteriostatic and will not corss blood brain barrier, widest spectrum of known anitbiotics, cause gastrointestinal problems, kidney damage, fetal skull abnormalities, and graying of teeth (when given to children), can be affected by iron and calcium, can cause light sensitivity, actively binds to 40s subunit of eukaryotes but more effective in bacteria because they actively pump it in
Chloramphenicol used to come from stroptomyces but now almost fully synthetics ; mode of action inhibits peptide chain elongation by intefering with sticking amino acids together, binds to rRNA in50s subunit, can disrupt function of bone marrow, usually a last resort drug, bacteriostatic
Macrolides – Erythromycin. Blocking addition of new amino acids to chain, may interfer with mRNA translation, usually use in a multi drug treatment, only common treatment that will treat pnemonia caused by legionares, one of the least toxic, light snsitivity
Lincosamides 50s subunit, premature disassociation of tRNAs ; mainly bacteriostatic, clindomycin, less toxic than the originals
Nucleic Acid Synthesis
Rifampin semisynthetic from Streptomyces, binds to pocket of RNA polymerase b subunit, by binding inhibits activity of RNA polymerase by stopping mRNA elongation, bacteriocidal, high number of reactions to other drugs, causes liver damage in high doses, may cause sweat pee or cry orange red
Quinolones synthetic analogs of a former antibiotic, block DNA gyrases and topoisomerases, currently in 4th generation, known also to inhibit DNA synthesis in mitochondria and chloroplasts
Sulfonamides sulfa drugs, not all antimicrobial, one antimicrobial one diabetes drug or herbicide, entirely synthetic, block synthesis of folic acid needed to make a range of critical metabolites, bacteriostatic, can cross
blood brain barrier, nausea and rashes are not uncommon, can function against some fungi
Isoiazid analog of nyocin and b6; has to be activated by the bacterium itself; block some cytochrome parts of electron transport chains in mycobacterium, works well on rapidly dividing cells, multidrug cocktail Ethambutol inhibits cell wall synthesis by inhibiting certain enymes, makes cell wall more permeable, fully synthesitc, effective against tuberculosis, resistance rising, generally part of cocktail
Nitrofurans synthetic, amage bacterial DNA, ribosomal protein, respiration components, acute or chronic UTIs, some activity against eukaryotic cells, bacteria have specific enzyme to activate it in cells, Antifungal
Imidazoles & Triazoles higher risk of host toxicity, synthetic, most available without prescription, Zoloft almost all creams or solutions applied topically, inhibit synthesis of key membrane components
Polyenes injection only, binds to plasma membrane causing it to leak Griseofulvin come from penicillium, used often on hair skin and nails, mess with mitotic spindle to slow cell division, some nail infections will stay for a year through straight treatment
Base (purine) Analogs introduce disinformation into viral genome, fake adenine thymine and guanine
Amantadine block key protein channel crucial to flu virus budding Interferons proteins that infected cells make telling cells nearby to begin making antiviral machinery; attempting to make these synthetically Immunoenhancers stimulate T cell activity
Resistance- viruses have no biochemistry of their own, can only be grown in vivo, studying them is much slower
Quinine- isolated from the bark of the cinchona tree, used to treat malaria, alkaloid compound, mechanism not entirely clear
Chloroquine & Primaquine- used to treat malaria; inhibit parasite from attacking red blood cells
Metronidazole causes spontaneous abortions, flagellated, causes profuse vomiting with alcohol consumption
Chapter 14 – Host-Microbe Relationships
Host- any organism that harbors another organism
Symbiosis living together of living things, usually quite close associations between two or more species
Mutualism both of the members in the relationship benefit
Parasitism one organism benefits and the other is harmed
Commensalism one organism benefits and the other receives neither benefit nor harm
Contamination the presence of microorganisms that you would not like to have there
Infection the multiplication of any parasite in or on its host; refers to disease caused by microbes
Infestation usually for larger organisms, often eukaryotes
Disease a disturbance in the state of the body wherein normal functions are interrupted
Pathogenicity usually in reference to an organism, its capability of causing disease
Virulence the intensity of the disease
Animal Passage- virulence can sometimes be augmented as it passes through other animals; acquire new abilities
Attenuation via Transposal- the taking of a virus that affects one animal and infecting other animals with it to make it weaker, so it can be used to make a vaccine
There are ~10x more microbial cells in/on a typical human body than human cells comprising that body. Found on skin surface, mucous membranes, digestive tract, upper respiratory tract, reproductive tract
Second genome- The vast array of genes express by those microbes that vastly outnumber you; you can detect differences in different people, ex difference in bacterial composition of babies born through natural birth and by C-section, breastmilk vs. formula, can affect what genes you express- capable of making mRNAs that will turn on certain genes in cells adjacent to them → some make the attachment of helminths easier in the stomach walls;
“Normal” live in and on us and don’t cause disease if immune system is working properly
Resident always present, different depending on what site you are looking at
Transient ones that are present under certain conditions
Opportunist residents who under certain conditions will attack their host, ex: if immune system lags or is impaired or microbes are introduced to a site they are not normally found
Koch’s Postulates (bacterially caused diseases, used to determine causation of infections)
1) Specific causative agent must be observed in every case of disease. 2) Agent must be isolated from a diseased host and must be grown into a pure culture.
3) When cultured agent is inoculated into healthy, susceptible hosts, the same disease must result.
4) Agent must be isolated again from the diseased experimental hosts and be identified as original agent.
Kinds of Disease
Infections infectious biological factors vs. Noninfectious caused by other agents or factors
Communicable transmittable from host to host vs. noncommunicable (anthrax is noncommunicable but still infectious)
Inherited genetic information errors
Congenital structural or functional disorders developed at birth Degenerative usually a function of age, usually focus on one body system
Nutritional deficiency result of inferior diet or parasitic infection Endocrine excess or deficiency of hormones
Mental syphilis, mad cow disease
Immunological allergies, immunodeficiencies, autoimmune diseases Neoplastic abnormal cell growth, tumors
Iatrogenic doctor caused diseases, surgical errors, drug reactions Idiopathic no idea what causes it
Direct bacterial action salmonella, virulence factors help microbe infection (fig. 14.5)
Toxin production exotoxins secreted into the environment, endotoxin built into the outer membrane, different depending on infection and intoxication, infection when micorbes are living and reproducing and toxins are byproduct, intoxication is when toxins are ingested and are already in what you are eating and drinking
Viral effects (fig. 14.7) cytopathy, viral infection causes a change in the morphology of the cells,
Eukaryotes heartworms, fungi, can be direct or intoxicating, protozoans, can create substances that cause allergic reactions
Stages of Disease
Read Signs, Symptoms, and Syndromes as well as Types of Infectious Disease. Incubation (fig 14.9) asymptomatic, but may be contagious (ex: flu), length of time affected by location of infection and how far it is from optimal site Prodromal Greek for forerunner; nonspecific symptoms, not all diseases have it, definitely contagious
Invasive typical symptoms, peak of symptoms (ACME)
Decline symptoms start to subside, secondary infections may occur Convalescence symptoms are gone, tissues being repaired, strength is gradually regained, still may be contagious if you have certain organisms especially those that cause surface lesions
Treatment usually just lessens severity of symptoms. May reduce convalescent time
Duration & Recovery
Why aren’t diseases eradicated? 2010 data from the book (fig. 14.11) ∙ Available options are not exercised. Not all people are vaccinated against infectious diseases
∙ Antibiotic resistance; even if you eradicate all pathogenic organisms, more would arise
∙ New or rare diseases come to the fore.
∙ People travel and carry infections with them
Chapter 16 – Innate Defenses
Innate & Adaptive Host Defenses
Innate = Nonspecific will attack foreign things of all sizes, does not have to be programmed
Adaptive = Specific (Chapter 17) Antigen -> Antibody + lymphocyte activation Innate Immunity: Barriers
∙ Skin first line of defense, hardened against abrasions, sunlight, and microbes ∙ Mucous membranes body opening, slows and physically traps microorganisms, large number of bacteriophages present
∙ Hair creates pockets of low velocity air so that microbes and dust settle out ∙ Cough/sneeze/vomit/diarrhea/ urination remove epithelial cells and attached pathogens
∙ Tears & saliva traps particles and causes them to be moved away from possible infection site
∙ Sweat & sebum acidic and salty
∙ Stomach acid highly acidic
∙ Lysozyme enzyme capable of breaking bonds in peptidoglycan cell walls, present in tears, saliva, and mucous
∙ Transferrin present in saliva and mucous & Lactoferrin present in blood; bind up free iron in body, iron is a key nutrient for pathogen proliferation ∙ Defensins small proteins with cationic charge that can assemble to create pores in cell membranes, found in mucous
∙ Come into play once organisms make it past other barriers.
∙ Mediated in Blood
60% Plasma- water and dissolved solvents and electrolytes
40% Formed elements- elements that come from pluripotent stem cells in bone marrow
Erythrocytes red blood cells
Platelets cell fragments of megakaryocytes
Leukocytes white blood cells
Leukocytes – Defensive Cells (figure 16.1)
Granulocyte cells that when you stain them have grainy cytoplasm and irregular nuclei
Basophils release histamine, which initiates inflammatory responses Mast cells also release histamine, more common in connective tissues, also in high concentration near blood vessels
Eosinophils present in larger numbers during allergic reactions, release histamine degrading enzymes
Neutrophils found in skin, blood, mucous membranes, phagocytic, congregate in areas of injury, do not divide, have programmed apoptosis within a few days, fight bacteria and some viruses
Dendritic cells (figure 16.2) hae long membrane extensions used for phagocytosis, also have a role in adaptive response
Agranulocyte (figure 16.1) usually have round nuclei
Monocytes phagocytic, released from bone marrow, can ultimately become macrophages, can attack invaders and clean up dead neutrophils, congregate in areas of injury, not as fast as neutrophils but come in much greater numbers
Lymphocytes (T & B) circulate in blood and lymph, found in lymph nodes, spleen, thymus
Phagocytosis & Extracellular Killing- Greek, phago and cyte “eating cell”; Neutrophils, monocytes/macrophages, dendritic cells.
Chemotaxis being able to travel along a gradient of some chemical signal, cells travel in response to a call put out by injured or dying cells (cytokines or chemokines); messages received by toll-like receptors
Adherence & Ingestion attach and bring in organism as a vacuole
Digestion merge vacuole with a lysosome and then dump contents outside of cell Extracellular killing t-cells, used against things too big or too dangerous to be eaten, eosinophils also function in this by attaching to parasite surfaces and dump major basic protein (MBC) to digest
∙ Closely associated with the cardiovascular system (CVS).
∙ Has its own tissues, vessels, and nodes.
∙ Collects excess lymph from intercellular spaces.
∙ Transports digested fats to CVS.
∙ Provides many innate and adaptive responses (largely phagocytic). ∙ Circulation
Organs (figure 16.6 lymph node) b cells, plasma cell and macrophages in medulla; t cells and dendritic cells in cortex; thymus- where t-cells mature; spleen is largest Additional tissues peyer’s patches in intestinal epithelium- pockest that have high concentrations of active immune cells, tonsils
Inflammation blood vessels become leaky and open spaces for macrophages to migrate to sites of infection;
The body’s response to tissue damage: Mechanical, Heat, UV, Chemicals Acute Process response to an injury to start repair process
Damage -> histamine into capillaries/venules -> dilation -> edema -> macrophages arrive & call for more
Repair & Regeneration begins almost as soon as the injury occurs; inflammation and repair are active at the same time; this process is generally better in younger people with better circulation; vitamins A, C, and K are important to this process Damage -> inflammation -> clotting -> inflammation down -> capillary intrusion -> fibroblasts form granulation (scar) tissue
Chronic Cases (figure 16.8) can cause granuloma formation, edema can become a problem
Fever -systemic increase in temperature
Normal range = 36.1 – 37.5 oC; Fever = oral > 37.8 oC or rectal 38.4 oC; Danger = 40 oC; Death ≈ 43 oC
Cause – Pyrogens interact with body temperature regulators in brain (VLPO) to raise it
Exogenous – From infectious agents. Ex: lipopolysaccharide
Endogenous – From macrophages. Ex: interleukin 1
By raising body temperature you move out of optimal temperature for microbial growth and allows your body to overwhelm them, at slightly higher temperatures microbial toxins can be deactivated, raising temperature allows defense reactions to proceed faster; triggers an increase in interferon production
Interferon small soluble proteins that cause nearby cells to raise defenses and act as cytokines to call in backup; can prevent co infection with other organisms * lymphocytes and NK cells also produce these proteins
Type I – α and β (figure 16.9) stimulate synthesis of antiviral proteins; often interfere with RNAs
Type II – γ does not need infected cells; is produced in cells turned on by A and B
Therapeutic use almost all therapeutic interferon A is recombinant, can be used to treat genital warts, hepatitis, some cancers, some viruses have resistance mechanisms for this
∙ A cascade. Stimulus leads to a vastly amplified response, system of 20 defense regulatory proteins that start working as soon as an infection is detected
∙ Enhance phagocytosis.
∙ Lyse invading cells & enveloped viruses.
∙ Generate inflammation peptides.
Three paths to the same destination(s): (fig. 16.1)
Classical antibody-antigen stimulation
Lectin begins as phagocytosis begins to be completed
Alternative can be active earlier than the classical, complement proteins interact directly with pathogen polysaccharides
Opsonization opsonins bind to and coat the surface of an invader, allow C proteins to bind which allows phagocytosis to be completed more quickly Inflammation complement enhances acute response by stimulating chemotaxis Membrane Attack Complexes (fig. 16.11) form lesions in the membranes of pathogens;
impairment is congenital and C3 is most essential to complement system Acute Phase Response; Evident in some acutely ill persons.
Non-specific defense. Stimulated by phagocytosis, stimulates interleukin-6 Acute phase proteins. Produced in liver in response to interleukin 6 Works in an opsonin-like manner.
CRP – C-reactive protein cell surface
MBP – Mannose binding protein. Recognize carbohydrate patterns on surface of pathogenic bacteria, binds to organism, serves as activator to lectin pathway, also binds to your own cells going through apoptosis
∙ Activates complement system.
∙ Facilitates phagocytosis.
Summary figure (figure 16.12)
Which of the following chemical antimicrobial agents (activities) likely would be ineffective against enveloped viruses?
A.) Halogens (denature proteins)
B.) Phenols (dissolve membranes and denature proteins)
C.) Alkylating agents like formaldehyde (disrupts nucleic acids and proteins) D.)Crystal violet (disrupts cell wall synthesis)
E.) All of these
An object to be sterilized should be cleaned prior to treatment. This statement is in direct support of which of the principles of controlling microbial growth? A.) Sterility is not always practically achievable
B.) The fewer organisms present, the shorter the time needed to achieve sterilization
C.) Microorganisms differ in the susceptibility to antimicrobial agents D.) Two of these
E.) None of these
You have discovered a new pathogen that has a low capacity to cause disease, but once it does, the disease is very intense. This pathogen would best be described in the following way:
A.) High pathogenicity, high virulence
B.) High pathogenicity, low virulence
C.) Low pathogenicity, high virulence
D.) Low pathogenicity, low virulence
E.) None of these
Which of the following is true about fungi?
A.) Most are saprophytic
B.) Most are composed of a mycelium that consists of threadlike hyphae C.) Fungi are most important as decomposers in the ecosystem D.)All of these
E.) Two of these
A.) Oxidize disulfide bonds
B.) Dissolve lipids and denature proteins
C.) Alter nucleic acids
D.)Alter the pH
E.) None of these
This pro inflammatory cytokine causes vasodilation:
E.) None of these
Which of the following antibiotics is an inhibitor of DNA gyrase? A.) Ethambutol
E.) None of these
Sequential steps taken by a phagocytic cell destroying an invading microorganism include:
A.) Chemotaxis -> adherence -> ingestion -> digestion
B.) Finding -> filtering -> secreting ->enzymes -> streptolysin C.) Chemotaxis -> granuloma ->adherence -> histamine D.) Finding -> invading -> clotting -> regulating -> temperature E.) None of these