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83 Cards in this Set
- Front
- Back
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Commensal bacteria
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They provide SYMBIOTIC BENEFIT to the HOST
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Mice in bacteria-free environment
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Require 30% more calories than colonized mice to maintain weight.
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What do bacteria provide to mice
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Metabolic pathways that expand capacity to extract calories and micronutrients from sugar plant diet.
Some bacteria provide vitamins to humans |
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Symbiotic benefit of nonpathogenic bacteria
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out compete pathogenic bacteria for colonizing niche and colonize host
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What do bacteria produce that provide symbiotic benefit
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ANTIMICROBIAL PROTEINS
E coli and colicins |
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What are two ways pathogenic bacteria direct kill
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1) exotoxins
2) endotoxins |
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Exotoxin (how bacteria direct kills)
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Bacterial secreted molecules- usually act via a cell-surface receptor
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Endotoxins
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induce the phagocytes to secrete inappropriate cytokines, causing local or system symptoms
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EXOTOXIN Vibrio Cholerae
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Cholera
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Salmonella Typhi
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Tyhoid (endotoxin release)
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What are the innate mechanisms of protection
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Complement
Defensins (kill pathogens) Coagulation system that immobilizes bacteria by prevent COLONIZING Phagocytosis (Pathogen Recognitition receptors: Cr1, Cr3, lectins, scavenger receptors, TLR) (PAMPS aand PRRs) = Macrophages, neutrophils, monocytes Inflammatory cytokines |
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How do inflammatory cytokines of innate system work?
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Raise body temperature and induce acute phase proteins
iL1- temperature iL 6- acute phase proteins |
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How does the bacteria evade?
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Pseudomonus- produces a protein that inactivate C3a and C5a- (complement system) so blocks recruitment of other immune cells
Streptococcus pneumonaiae- produce a capsule that prevents phagocytosis |
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Streptococcus pneumoniae
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capsule prevents phagocytosis
prevents large amount of C' binding on surface BigMAC can't penetrate Need antibody to CONTROL pneumoniae |
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What are the 4 steps of bacterial infection?
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1) Attachment to host cells via adhesion molecules
2) proliferation 3) Invasion of host tissue 4) toxins induce damage to host cells |
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Body fights host cell attachement
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host defense
Blocked by igA: prevents them from attaching to surface, lining and therefore bacteria can't colonize and proliferate |
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How does body prevent proliferation
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phagocytosis/ complement lysis (innate or igG molecules)
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How does the body prevent bacteria invasion of tissue
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Antibody agglutination
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Prevent toxin damage to host cells
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Antibody neutralizes them
"sponges them all up" |
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Pathogenic mechanism of exotoxin release
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Secreted by bacteria in extracellular space- Toxins hit cell- Kill cell
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Endotoxin release
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With bacteria, trigger cell to secrete inappropriate cytokines that cause local and systemic symptoms.
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How do inflammatory cytokines work in innate protection?
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Raise body temperature and induce acute phase proteins
iL-1 Temperature iL-6 acute phase proteins |
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Two baceterial evasion mechanisms
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Pseudomonus
and streptococcus pneumoniae |
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Pseudomonus- bacterial evasion
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produces a protein that inactivates C3a and C5a that blocks recruitment of other immune cells
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Streptococcus PNEUMONIAE
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capsule prevents phagocytosis
Prevents large amount of binding C' proteins on surface BigMAC can't penetrate this capsule So you need particular Antibody to control streptococcus pneumoniae |
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Mechanism of Bacterial infection
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1) attaches
2) proliferates 3) invasion of host tissue 4) Toxins damage host cells APIT APIT APIT |
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How can A of APIT be stopped?
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attaches via adhesion molecules
Host defense IgA blocks so prevents bacterial attachement, can't colonize, can't proliferate. |
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How can P of APIT be stopped?
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Phagocytosis/C' lysis
Innate immunity via C3b |
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how can I of APIT be stopped?
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Antibody aggutination
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How do you stop toxins in APIT?
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Antibodies neutralize these toxins.
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Neisseria gonorrhoeae as evasion mechanism
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produce proteases that cleave igA (that usually work to prevent bacteria adhesion) to Fab fragments
Cleave igA blocks its ability to AGGULTINATE pathogens for clearance |
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Extracellular @ interstitial space, blood lymph
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Viruses, bacteria, worms require
Ab C' Phagocytosis Neutralization |
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Extracellular @ epithelial surfaces
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Neisseria gonorrhoeae
Antibodies,especially igA antimicrobial peptides |
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Two types of intracelllar sites of infection
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Cytoplasmic vs. Vesicular
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Cytoplasmic intracellular organism
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chlamydia spp.
Fight with CTLs and NK cells |
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Vesicular Intracellular
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Salmonella typhimurium
Myobacteria T cell and NK cell dependent MACROPHAGE activation |
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What cytokines stimulate th2 response?
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Primarily iL4
iL 13 iL 5 Antibody production Eosinophil production |
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13 and 5 are important for what?
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recruitment, growth, survival factors for eosinophils
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5 helps with what
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"shift to different isotypes"
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Eosinophiles are important for
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Parasite killing. They secrete superoxide and other proteases
Inducible Nitric Oxide |
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Oxidative killing involves
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NADPH oxidase
Superoxide O2 Hydrogen perioxide Radical and oxidized chloride (bleach) |
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iNos
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nitric oxide
INDUCIBLE Nitric Oxide Synthase Enzyme that generate nitric oxide EXTREMELY toxic to bacteria |
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NO (nitric oxide) and bacteria
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NO is EXTREMELY toxin to bacteria
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Perioxynitrate
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mas toxic to pathogens
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What stimulates th1
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IFN gamma (virus infected)
so generates CD8 T cell activation activation of macrohages to kill intracellular organisms |
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What determines th1 or th2
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The cytokine environment at the time
place of Ag presentation to the naive CD4 by the dendritic cell |
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T cell receives signal from APC and cytokines present at the time.
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Cytokines of dendritic cell or the epithelial cells of secondary lymph node.
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il4 and 5 generate
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Antibody response
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il 12 generate what
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CTL and inflammation
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What determines cytokine MILIEU that determines kind of response
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1) nature of pathogen
2) route of infection 3) amount of antigen/microbes |
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Nature of the pathogen
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TLR or NOD engagement
entracellular or intracellular |
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Toll Like Receptors
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membrane bound one location or at endosomes
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NOD
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Intracellular pattern recognition receptor
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Route of infection as a factor that determines cytokine concentration
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Where does the Ag traffic to?
What cells are present? |
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Amount of antigen/microbes as a factor the influences cytokines
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peptide: MHC complexes
The dnesity and affinity of these antigens/microbes. |
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The nature of the pathogen is intracelllular
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Viruses and some bacteria induce dendritic to secrete iL 12 that activate NK cells
NK cells produce IFN gamma Naive CD4 T Cells with iL12 and IFN gamma are comitted to th1 |
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Intracellular nature of the pathogen
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CTLS
Macrophage activation because iL12 is inducing NK cells produce IFN gamma Gamma interacts with CD4 drive naive to th1 |
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Extracellular pathogen
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Worms, bacteria, viruses do not induce dC iL12 but induce NK1.1+ T cells to synthesize and secrete iL 4
Naive plus iL 4 differentiate into th2 Producing 13 and 5 |
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Extracellular pathogen that makes dC's make cytokines
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Seeing worm antigens
Present to naïve cd4 cell Il-4 producing Th2 cell Secrete more 4, 13, 5 |
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Peyer's patch DC produce higher levels of what cytokine? compared to what other location?
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il10 ---- Ab production
Compared to spleen |
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iL 10 is inhibitory to what response
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th1
Blocks adherence and cohesion Neutralizes toxins |
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Mechanism of Peyers patches
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Polymeric igA is transported to gut through epithelial cells
igA binds to mucus layer overlying epithelium IgA in gut neutralizes pathogens and bacterial toxins |
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Peyer's Patches and iGA
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Th2
Allows plasma cells to generate and secrete igA F c alpha receptors Transported through epithelial cells Line epithelial cell layer (within mucus membrane) Prevent colonization of bacteria in gut (adherence to walls) Neutralize toxins in the gut |
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Recap what are the three factors that determine cytokine milleus
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1) nature of pathogen
2) location 3) amount or concentration |
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Amounts and concentrations of antigen or microbes help determine cytokines
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Low abundance/affinity vs. high abbudance/high affinity
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Low abundance/ low affinity
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APC presents peptide with weak binding to TCR
Naive CD4T cell differentiates into th2 iL 4 and 5 |
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High affinity and high abundance
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APC presents peptide that binds strongly to TCR
Naive differentiates into th1 makes 2, gamma, TNF Beta |
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th1 cytokines again
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il2, ifn gamma, tnf beta
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th2 secretes TGF- beta and iL 10
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These inhibit activation and growth of Th1 cells
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Th1 cells secrete ifN gamma
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inhibits proliferation of th2 cells
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T reg's
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T reg control th1 response
Turn off production of T cells whne there is no longer pathogen. T reg are CD4 Cd25+ Rediscovered Aka suppressor cells Type of Cd4, function to inhibit th1 By Secreting beta and 10 Lack these regS- autoimmune disorders |
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Disease progression depend on th1 or th2 balance
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1) Leprosy:
Tuberculoid vs. Lepromatous 2) Leishmania major: requires th1 protection high affinity, high abundance il2, TGF beta, IFN gamma |
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TUBERCULOID LEPROSY
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growth well controlled by th1 like cells that activate infected macrophages
Lesion contains granulomas and is inflammed Local inflammation- local effects (Peripheral nerve damage) |
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Tuberculoid leprosy granuloma
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Granuloma: large number of infiltrating cells (dark brown stain)
Low numbers of organisms that are present, undetectable levels Low activity as a result Growth of microbacteria Limited in Tuberculoid leprosy Because you generated a th1 type of cell Local inflammation Don't have large systemic effects No local nerve damage |
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Lepromatous leprosy
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Widely disseminated
Not so many cells infiltrating Don't wall off High activity bc of organisms Can go beyond local environment Didn't generate cytokines that drove th1 response to kill intracellular pathogens 4, 13, 5? Are made (wrong cytokines) these generate th2 response ( Antibody production) |
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What cytokines dominate in the tuberculoid form
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th1 cytokines
iL2 IFN gamma TNF betta |
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What cytokines dominate in LEPROMATOUS FORM
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th2 cytokines
iL 4 iL 5 iL 10 dominate |
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IFN gamma would be expected to actiave macrophages
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Enhances killing of M. leprae
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iL4
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actually inhibits induction of bactericidal activity in macrophages
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Modifying the immune response to Leishmania (intracellular)
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Treat with anti-iL 4 antibody at time of infection allows normally susceptible mice to clear infection
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Leishmania and anti-4 antibody
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Scarf up all il 4
Allow th1 response to become visible and propogate Ifn gamma, tnf, inos generation Allows normally susceptible mouse to fight it |
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Leishmania and Balb/c
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Very susceptible to Leishmania by generating a lot of iL 4
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C57/BL6 and not Balb/c
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doesn't kill them, considered a th1 mouse, totally resistant to Leishmania
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