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92 Cards in this Set
- Front
- Back
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What are the mechanisms of defense?
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Non-specific
Specific |
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What are our physical defensive barriers ?
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Skin
Mucosal surfaces |
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Why do we need defense mechanisms?
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The skin can't portect us from everything
-GI/Urogenital tracts and lungs are great environments for bacterial growth |
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Why are the GI tract, urogenital tract and lungs good env't for bacterial growth?
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Warm (37C)
Humid (bathed in fluid) -pH 7-7.4 |
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What is the non-specific host response?
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INNATE
(natural/constitutive) |
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What do bacteria have to do to successfully cause an infection?
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Evade the innate response
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What are some ways that bacteria can evade in innate response?
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Attach and penetrate body surfaces
Can be introduced by a biting insect Can take advantage of preliminary damage (wound, respiratory tract damage) |
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What are some sites of microbial infection?
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Mouth
skin (pores, hair follicles, sweat glands) Digestive tract Urogenital tract Conjunctiva of the eye Lungs |
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How can you prevent exposure?
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"Clean" drinking water
Avoid spoiled food Insect repellent Hand washing (even just wearing gloves may not prevent transmission of bacteria) |
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What kind of cells are barriers?
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Epithelial cells
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What are the 2 types of epithelial cells?
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Simple epithelial cells
Stratified epithelial cells |
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Where are simple epithelial cells found?
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In the intestinal tract
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What is one of the characteristics of simple epithelial cells?
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They are MORE VULNERABLE to bacterial invasion than stratified epithelial cells
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Where are stratified epithelial cells found?
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Skin
Mouth |
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What are the characteristics of stratified epithelial cells?
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They have many layers
More resistant to bacterial invasion |
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What are the defenses of the skin?
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Dry, acidic (pH 5)
Dead, keratinized Sloughing of surface cells Toxic lipids, lysozyme Normal microbiota Langerhans and other immune cells |
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What is the fct of dry, acidic skin?
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Prevent bacterial growth
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What is the fct of dead, keratinized skin?
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Prevent colonization
Keratin is hard to degrade |
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What is the fct of sloughing of surface cells?
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Remove adherent bacteria
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What is the fct of toxic lipids, lysozymes?
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Protect hair follicles, sweat and sebaceous glands
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What is the fct of normal microbiota?
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Compete with pathogenic bacteria
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What is the fct of Langerhans and other immune cells?
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Combat bacteria at the dermis level
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When do pathogenic bacteria infect skin?
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If it is breached
-> i.e cut with glass -> Catheters are a conduit for bacteria to get into the body |
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Where are normal microbiota found?
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Usually skin, intestines etc
--> They can occupy sites that might be colonized by pathogenic bacteria |
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What kind of bacteria usually make up the normal microbiota?
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innocuous gram-negative bacteria (CHECK ANS)
--> i.e: Staphylococcus epidermidis (G+) |
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What are the barriers at mucosal sites?
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Epithelial cells in the lungs, intestinal, uro-genital tracts
Cillia Microvilli (epithelial cells, anchored in basement mb, matrix of glycoptn) |
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What are some specialized barriers of the body? Why?
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Eyes: blinking, tears (lysozyme, IgA, lactoferrin)
Nasopharynx: resident microflora (mainly G+ cocci), secretions (saliva), nose -hairs Lungs: curved path makes turbulence, coughing, sneezing, ciliated cells, macrophages |
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What are the intestinal tract barriers?
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Mouth: sloughing cells, saliva, lysozyme, IgA, microflora, lactoferrin
Stomach: low pH, proteolytic enz Small intestine: fast flow, mucus, sloughing cells Large intestine: slow flow, mucus, sloughing cells, abundant resident microflora |
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Where are M cells located?
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btw enterocytes and in close contact with subepithelial lymphocytes and dendritic cells
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Where do M cells take up Ag?
How? |
From the gut lumen
By endocytosis |
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What happens once M cells release the Ag?
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The Ag are taken up by APCs (dendritic cells)
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What kind of protection does the urogenital tract have against bacterial infection?
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Bladder: flushing action of urine, low pH, physical barrier of urethra
Vagina/cervix: low pH, resident microflora (G+/- bact, lactobacillus) Mucus plug at cervical opening protects uterus and fallopian tubes |
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Are urinary tract infections more common in men or women?
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20X more common in women
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Which cells produce mucous?
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Goblet cells
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What is mucous?
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Viscous, slimy, lubricant
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What does mucous do?
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Traps bacteria
Prevents attachment of epithelial cells |
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How is mucous made?
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In constant production
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How is excess mucous eliminated?
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Flow of urine (urine, GI)
Cilia |
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What is the nonspecific mucosal defense?
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Mucous
Saliva Tears ->these have a glycoptn matrix |
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What does the glycoptn matrix contain?
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Lysozyme
Lactoferrin |
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What does lysozyme digest?
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Digests p/g which is important vs G+ bacteria
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What does lactoferrin do?
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Sequesters iron (essential nutrient for bacteria)
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Where is lactoferrin in high concentration?
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Breast milk
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What happens when the N-terminal part of lactoferrin is cleaved?
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Get lactoferricins, which can bind bacterial LPS (endotoxin) and further protect the host
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What are defensins?
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Anti-bacterial peptides
Secreted by host cells, in the mouth, tongue, crypts of the intestine |
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What do defensins do?
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Punch holes in bacteria and collapse the PMF
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What role does trypsin play in defensins?
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Trypsin clips pro-defensin to produce the active defensin in the crypt
(Active defensin attaches to the invading bacteria) |
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What kind of molecular design do defensins have?
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Amphipathic design
Hydrophobic (larger) and hydrophilic (smaller) region |
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What kind of interactions do the antimicrobial peptides have?
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Hydrophobic (weak)
Electrostatic and hydrophobic (Strong) -> can bind bacterial cytoplasmic mb |
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What is the path of bacterial infection once inside the body?
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Binding to outside of plasma mb
Integration into plasma mb Pore formation Transport of lipids into the inner leaflet Diffusion onto intracellular targets/ Collapse of mb |
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What kind of bacteria normally reside in the GIT, mouth and lungs?
What do they do? |
G- bacteria
Help cover sites of attachment for pathogenic bacteria (the resident bacteria vary in different parts of the world) |
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Why are the uterus, urinary tract and female upper genital tract more susceptible to ALL bacteria (including "normal" bacteria)?
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No bacteria in these areas, .: they are more vulnerable
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What are the Specific and Non-specific lymphoid mucosal defenses?
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MALT (Mucosal Ass't Lymphoid Tissue)
SALT (Skin...) GALT (Gut....) Ab (IgM, polymeric IgA) specific for bacterial prroducts Phagocytic cells Cytotoxic cells Mast cells |
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Which are the cells in the first line of defense?
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Lymphoid cells
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What kind of lymphoid cells are in the BM?
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Progenitors
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Where do lymphoid cells mature and circulate?
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Blood
Lymphoid cells are resting in the blood |
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Where do lymphoid cells leak into?
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Lymphatics
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Where do lymphoid cells transmigrate to?
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Tissues (dermis)
Activated in the tissues |
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What happens to the lymphatics during bacterial infection?
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Pressure builds up in blood vessels (swelling/redness)
Get LEAKINESS at the lvl of endothelial cells (no tight jcts) .: the bacteria can get out of the blood vessels |
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Where are these leaks collected?
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Lymphatics (networks of tubes adjacent to the blood capillaries)
From lymphatics, go to lymph nodes and then thoracic duct -> bld stream |
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What happens to the bacteria that make it to the lymph nodes?
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They are killed
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Can bacteria survive killing at the nodes?
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Yes, highly pathogenic bacteria can
ex: Yersinia pestis (Bubonic plague) |
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What do swollen lymph nodes mean?
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Sign of infection
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Look at slides for figure of body and lymph nodes
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look at figures on slides
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What are the molecules involved in circulation/transmigration?
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Chemoattractants: complement components, chemokines
Cell surface addressins (selectins) Adhesion molecules on lymphoid cells and receptor/ligands on endothelial cells Regulated in some cases by cytokines |
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What are the types of phagocytic cells?
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PMNs/neutrophils
Professional APCs |
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Describe PMNs/neutrophils
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Abundant
Short lived ->elevated numbers indicate infection |
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What are the types of APCs?
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Dendritic cells/langerhan cells (skin)
Monocytes (blood) --> macrophages (motile or stationary) which can be tissue specific (ie alveola-lung) |
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Describe APCs
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Longer lived
Lower amount of them |
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Describe phagocytosis
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Bacteria engulfed by a phagosome
Phagosome merges with a lysosome Becomes a phagolysosome In the phagosome, use NADPH oxidase to get O2- -> H2O2, release proteases |
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What are NETS?
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Neutrophil Extracellular Traps
-Extracellular fiber matrix form of granule ptns and chromatin |
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What do NETS do?
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Degrade virulence factors
Kill bacteria |
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What are the key features of the phagosome?
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Production of O2-
Proteolytic activity |
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What happens to patients with defective NADPH oxidase?
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The fail to kill many strains of bacteria, yeast and fungi
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What happens to mice lacking proteases elatase and cathepsin G?
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Compromised in fighting bacterial infections
Requires a pH=8 which is a result of H2O2 for solubility of proteases |
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Which phagocytic cells produce Nitric oxide (NO)?
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Macrophages and monocytes
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What is the chemical equation for producing NO?
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L-arginine -----NO synthetase---> L-citrulline + NO + Superoxide ----> Peroxynitrate
NO synthetase can be constitutive or inucible NO attacks DNA, ptns, etc Peroxynitrate kills bacteria |
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In which cells is the inducible NOS (iNOS) expressed?
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Macrophages
Microglia Neutrophils Eosinophils Fibroblasts Endothelial cells Epithelial cells Astroglia for antimicrobial activity |
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How does iNOS work?
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As a homodimer
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What is required for iNOS dimerization?
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The presence of calmodulin and the incorporation of heme
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What regulates iNOS?
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Cytokines
↑ IL-1, TNF, IFN-y ↓ IL-10, TGF-b, IL-4 |
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What's the difference between cNOS (constitutive) and iNOS?
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cNOS is switched on by increases in Ca2+, not cytokines
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What is the role of iNOS?
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Dispensable for control: Borrelia burgdorferi, Chlamydia trachomatis, Myco leprae, Helicobacter pylori, Strep pneumoniae
Essential for control: Mycobacterium tuberculosis, Salmonella typhimurium Contributory for control: Chlamydia pneumoniae, Lysteria monocytogenes, Mycoplasma pulmonis, S. aureus Detrimental to host: M. avium, S. pneumoniae (these bacteria favor NO production) |
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Why can iNOS be detrimental to the host?
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The bacteria will favor NO production .: the host will be hurt in the process
->M. avium and S. pneumoniae can reach the blood and cause major problems |
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What is the collateral damage ass't with iNOS?
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Host tissues can be damaged as a byproduct of infection control
Lysosomal enz can be released into the tissue → cell death (PMNs etc) *the process of phagocytosis is tightly controlled by various signals: complement, cytokines, chemokines |
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What is the role of cytotoxic cells?
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Release toxins stored in granules and kill infected cells (don't ingest the bacteria)
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What type of toxins are released from cytotoxic cells?
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Perforins
Granzymes |
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What do perforins do?
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Form channels
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What do granzymes do?
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Can induce apoptosis of the target
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What are the type of cytotoxic cells? (2)
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Natural Killer Cells: important role in defense vs intracellular pathogens
Cytotoxic T cells |
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How do granzymes enter the target cell from the cytotoxic cells?
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Through perforin pores
Endocytosis Granzyme receptors |
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summary
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Multiple levels of host defense (barriers to cells to chemical warfare
Bacteria have evolved mechanisms to counteract some of these defenses Normal bacteria flora co-exist with the host Pathogenic bacteria cause damage directly or indirectly due to the methods needed by the host to control infection |
