Lec 32 Immune Response to Infectious Pathogens Flashcards
What is host response to extracellular bacteria [innate and adaptive]?
innate: phagocytosis, alternative complement activation, inflammation
adaptive: same effector mech as innate but initiated by antibodies that also neutralize microbes/toxins
What is the body’s response to superantigen? What are examples of these antigens?
- systemic inflammatory response
- superantigens bind to Class II MHC randomly on any APC and bind T cell, trigger T cells to respond as if were interacting with their specific antigen even though they aren’t, get polyclonal activation of T cells and cytokine storm
- examples: exotoxins like SEA [staph aureus], SEB [staph aureus], TSST [staph aureus], TSLS [strep pyogenes]
What is the local and systemic protective response of the immune system to LPS [on gram neg] or lipoteichoic acid [on gram pos]?
local: microbe comes along, triggers endothelial cells to release cytokines [TNF, IL-1, IL-6] which cause inflammatory response, increased blood flow, changed in vascular permeability, etc
cytokines then recruit other leukocytes to site of infection
systemic:
- trigger fever
- acute phase proteins release from liver [C reacitve protein, mannan binding lectin, serum amyloid protein]
- leukocyte production in bone marrow
what are the potential pathologic effects of endotoxin LPS [on gram -] or lipoteichoic acids [on gram +]?
- can cause septic shock
- lead to release of acute phase cytokines which have some protective and some pathologic effects
- ex. the pathologic effects of TNF
- — decrease cardiac function
- — increased vascular leakage and potential thrombus formation
- — metabolic abnormalities –> insulin resistance, wasting syndrome
What are the pathologic effects of TNF that we talked about?
- — decrease cardiac function
- — increased vascular leakage and potential thrombus formation
- — metabolic abnormalities –> insulin resistance, wasting syndrome
What are 3 examples of acute phase proteins released from liver in response to IL-1/IL-6 in infection
- C reactive protein
- mannan binding lectin
- serum amyloid protein
N. gonorrhoeae: what is mech of immune evasion?
- antigenic variation
Strep pyogenes: what is mech of immune evasion?
- M protein resists phagocytosis
- resists alternative path of complement
Strep aureus: what is mech of immune evasion?
- catalase: inhibits ROS from phagosome so avoids digestion
- coagulase: causes clot formation
Strep epidermidis: what is mech of immune evasion?
- biofilm formation
Where do intracellular bacteria replicate? Why is this beneficial for them?
- survive or replicate in phagocytes
- means they are not susceptible to circulating antibodies –> thus recovery depends solely on cellular immunity and cytokine production
What is host response to intracellular bacteria [adaptive and innate]?
innate: first response, NK cells and phagocytes control bacterial growth in absence of adaptive
adaptive: starts at 7 days, T cells release cytokines [IL-12] trigger Th1 response that activates phagocytes
What are 3 examples of intracellular bacteria?
- mycobacteria
- listeria
- legionella
How do intracellular microbes survive in phagocytes?
- some survive within phagolysosomes
- some escape from phagolysosome into cytoplasm
What is immune mech for killing microbes located within vesicles [phagolysosomes]?
- cytokines [mainly IFN gamma] secreted form TH1 and TH17 act on cells that have phagocytosed microbes
this: - upregulates their ROS activity so they kill ingested microbes
- causes them to secrete TNF, IL-1, IL-12 [inflammation, TH1 differentiation]
- causes them to increase expn MHC and costimulators [so more susceptible targets of killer cells, amplify T cell response]
What is immune mech for killing microbes located in cytoplasm?
- CD8 T cells kill phagocytes that are expressing MHC and costimulators
Is TB in phagolysosome or in cytoplasm?
phagolysosome
Is listeria in phagolysosome or cytoplasm?
cytoplasm
What is mech by which TB evades immune response?
- inhibition of phagolysosome fusion
What is mech by which legionella evades immune response?
- inhibits phagolysosome fusion
What is mech by which listeria evades immune response?
inactivates ROS
What is mech by which M. leprae evades immune response?
- destroys phagosome membrane, escapes to cytoplasm
What is the pathogenesis of intracellular bacteria infection?
- delayed type hypersensitivity rxn may cause tissue damage
- chronic stimulation of phagocytes leads to walling off of bacteria [granuloma formation]
- resistance to phagocytic destruction [inhibition phagolyso fusion] leads to chronic infection
- non-sterile immunity-reactivation possible
What is typical response to reactivation of Tb? two cells typically found in this?
- formation of granulomas –> epithelioid cells, langhan cells
What is mech of immunity [innate and adaptive] against viruses?
- viruses are intracellular = dependent on host for replication
innate: IFN-a/B [upregulates MHC so exposes infected cell and protects uninfected cells, prevents cell-cell transmission], NK cells [kill virus infected cell]
adaptive: virus specific CTLs and antibodies
What is mech of type 1 interferon induction?
in endosome: virus taken up into endosome –> pattern recognition receptor recognizes and triggers TLRs to turn on transcription factor to produce IFN-a/B
in cytosol: proteins in cytosol lke DAI sense viral nuclei acids and trigger to turn on transcription factors that produce IFN-a/B
What happens to virus titers during innate immunity phase? adaptive?
innate = continue to rise, during adaptive starts to fall
What is mech by which innate protects against infection? adaptive?
innate: type 1 IFN acts on cells to make them refractory to infection [can’t become infected]
adaptive: B cells produce antibodies that prevent viruses from infecting cells
What is mech by which innate eradicated established infection? adaptive?
innate: NK cells kill infected cell
adaptive: CD8 CTL kill infected cell [most imp]
What are examples of viruses that cannot be cleared [persist or are latent]?
- herpes
- HIV
- hepatitis
What is mech by which RSV evades host immunity?
ails to stimulate effective immunity [especially early in life]
What is mech by which influenza evades host immunity?
evolves and changes antigenic structure
What is mech by which rhinovirus evades immunity?
it has multiple serotypes so –> you can get infected with multiple different types over course of lifetime so don’t develop humoral immunity that covers all the types
What are classic ways of viruses evaiding host immunity?
- antigenic variation
- inhibition of antigen processing
What are mechs of inhibition of antigen processing [and which pathogens?]
- inhibit proteasomal activity
- block MHC synthesis or ER retention
- block in TAP transport
- remove class 1 from ER
- interfere with CTL recognition by producing “decoy” viral class 1-like molecules
what are 4 mechs of CMV inhibiting antigen processing?
- inhibit proteasomal activity [human]
- block MHC synthesis or ER retention [human]
- remove class 1 from ER
- interfere with CTL recognition by producing “decoy” viral class 1-like molecules [murine]
Which two viruses are known to inhibit proteasomal activity?
- EBV
- human CMV
Which two viruses are known to inhibit MHC synthesis and/or ER retention?
- adenovirus
- human CMV
Which virus is known to block in TAP transport?
HSV
Which viruses block type 1 interferon pathway?
ALL!
Which virus kills immune cells?
HIV
Which virus produces immunosuppressive cytokines like IL-10?
EBV
Which virus produces cytokine receptor decoys?
poxviruses
What is mech of immunity against parasites?
- TH2 cells secrete IL13/IL-5 that activates eosinophils, trigger production IgE that bind surface of parasite, IgE receptor binds IgE and then releases cytotoxic granules
- kills helminth
What is the major adaptive effector against virus infection?
CD8
What prevents reinfection?
antibodies
What is primary adaptive resposne against bacteria that evaded innate immunity?
- antibodies
- complement activation
- phagocytosis
- toxin neutralization
