Lec 32 Immune Response to Infectious Pathogens Flashcards

1
Q

What is host response to extracellular bacteria [innate and adaptive]?

A

innate: phagocytosis, alternative complement activation, inflammation
adaptive: same effector mech as innate but initiated by antibodies that also neutralize microbes/toxins

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2
Q

What is the body’s response to superantigen? What are examples of these antigens?

A
  • 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]
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3
Q

What is the local and systemic protective response of the immune system to LPS [on gram neg] or lipoteichoic acid [on gram pos]?

A

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

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4
Q

what are the potential pathologic effects of endotoxin LPS [on gram -] or lipoteichoic acids [on gram +]?

A
  • 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
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5
Q

What are the pathologic effects of TNF that we talked about?

A
  • — decrease cardiac function
  • — increased vascular leakage and potential thrombus formation
  • — metabolic abnormalities –> insulin resistance, wasting syndrome
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6
Q

What are 3 examples of acute phase proteins released from liver in response to IL-1/IL-6 in infection

A
  • C reactive protein
  • mannan binding lectin
  • serum amyloid protein
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7
Q

N. gonorrhoeae: what is mech of immune evasion?

A
  • antigenic variation
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8
Q

Strep pyogenes: what is mech of immune evasion?

A
  • M protein resists phagocytosis

- resists alternative path of complement

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9
Q

Strep aureus: what is mech of immune evasion?

A
  • catalase: inhibits ROS from phagosome so avoids digestion

- coagulase: causes clot formation

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10
Q

Strep epidermidis: what is mech of immune evasion?

A
  • biofilm formation
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11
Q

Where do intracellular bacteria replicate? Why is this beneficial for them?

A
  • survive or replicate in phagocytes
  • means they are not susceptible to circulating antibodies –> thus recovery depends solely on cellular immunity and cytokine production
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12
Q

What is host response to intracellular bacteria [adaptive and innate]?

A

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

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13
Q

What are 3 examples of intracellular bacteria?

A
  • mycobacteria
  • listeria
  • legionella
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14
Q

How do intracellular microbes survive in phagocytes?

A
  • some survive within phagolysosomes

- some escape from phagolysosome into cytoplasm

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15
Q

What is immune mech for killing microbes located within vesicles [phagolysosomes]?

A
  • 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]
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16
Q

What is immune mech for killing microbes located in cytoplasm?

A
  • CD8 T cells kill phagocytes that are expressing MHC and costimulators
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17
Q

Is TB in phagolysosome or in cytoplasm?

A

phagolysosome

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18
Q

Is listeria in phagolysosome or cytoplasm?

A

cytoplasm

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19
Q

What is mech by which TB evades immune response?

A
  • inhibition of phagolysosome fusion
20
Q

What is mech by which legionella evades immune response?

A
  • inhibits phagolysosome fusion
21
Q

What is mech by which listeria evades immune response?

A

inactivates ROS

22
Q

What is mech by which M. leprae evades immune response?

A
  • destroys phagosome membrane, escapes to cytoplasm
23
Q

What is the pathogenesis of intracellular bacteria infection?

A
  • 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
24
Q

What is typical response to reactivation of Tb? two cells typically found in this?

A
  • formation of granulomas –> epithelioid cells, langhan cells
25
Q

What is mech of immunity [innate and adaptive] against viruses?

A
  • 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

26
Q

What is mech of type 1 interferon induction?

A

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

27
Q

What happens to virus titers during innate immunity phase? adaptive?

A

innate = continue to rise, during adaptive starts to fall

28
Q

What is mech by which innate protects against infection? adaptive?

A

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

29
Q

What is mech by which innate eradicated established infection? adaptive?

A

innate: NK cells kill infected cell
adaptive: CD8 CTL kill infected cell [most imp]

30
Q

What are examples of viruses that cannot be cleared [persist or are latent]?

A
  • herpes
  • HIV
  • hepatitis
31
Q

What is mech by which RSV evades host immunity?

A

ails to stimulate effective immunity [especially early in life]

32
Q

What is mech by which influenza evades host immunity?

A

evolves and changes antigenic structure

33
Q

What is mech by which rhinovirus evades immunity?

A

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

34
Q

What are classic ways of viruses evaiding host immunity?

A
  • antigenic variation

- inhibition of antigen processing

35
Q

What are mechs of inhibition of antigen processing [and which pathogens?]

A
  • 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
36
Q

what are 4 mechs of CMV inhibiting antigen processing?

A
  • 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]
37
Q

Which two viruses are known to inhibit proteasomal activity?

A
  • EBV

- human CMV

38
Q

Which two viruses are known to inhibit MHC synthesis and/or ER retention?

A
  • adenovirus

- human CMV

39
Q

Which virus is known to block in TAP transport?

A

HSV

40
Q

Which viruses block type 1 interferon pathway?

A

ALL!

41
Q

Which virus kills immune cells?

A

HIV

42
Q

Which virus produces immunosuppressive cytokines like IL-10?

A

EBV

43
Q

Which virus produces cytokine receptor decoys?

A

poxviruses

44
Q

What is mech of immunity against parasites?

A
  • 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
45
Q

What is the major adaptive effector against virus infection?

A

CD8

46
Q

What prevents reinfection?

A

antibodies

47
Q

What is primary adaptive resposne against bacteria that evaded innate immunity?

A
  • antibodies
  • complement activation
  • phagocytosis
  • toxin neutralization