Lecture 16: Immune response to bacteria/fungi Flashcards

1
Q

opportunistic pathogen

A

a bacterium, virus or other microorganism that can cause disease in animals w/ IMPAIRED immunity but not in healthy individuals

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2
Q

most E.coli strains are…

A

non-pathogen = harmless and frequent resident of mammalian microbe

ex: E.coli K12

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3
Q

what are common strains of pathogenic E.coli

A
  • Enteropathogenic and Enterotoxigenic E.coli (EPEC and ETEC)
  • can cause diarrheal diseases
  • ETEC has multiple toxins
  • EPEC has virulence factors for colonization of host
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4
Q

about how many bacterial cells are in the colon

A

10^12

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5
Q

pathogens cause direct damage to tissues by…

A
  • killing host cells
  • releasing toxins
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6
Q

how does the immune system respond to non-pathogens

A
  • complement
  • phagocytosis
  • adaptive response to microbiota
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7
Q

how do pathogens evade immune response

A
  • antigenic or phase variation
  • antigenic drift
  • molecular mimicry
  • virulence factors
  • capsule
  • SIgA proteases
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8
Q

antigenic or phase variation

A
  • ability of bacteria to change the expression of critical proteins on its surface

ex: differential expression of flagellin protein in salmonella

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9
Q

explain how Neisseria uses antigenic variation evade immune system

A
  • pili function to attach to host cells
  • made of protein call pilin that should be highly antigentic
  • however it has 10-20 silent copies of pilS
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10
Q

what is antigenic drift

A
  • natural mutations over time result in structural changes of proteins
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11
Q

what is molecular mimicry

A
  • bacteria tries to make itself look like host cell so antibodies won’t be made against it
  • ex: Campylobacter jejuni
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12
Q

explain the virulence factors used by Borrelia burgdorferi (Lyme disease)

A
  • resists complement mediated phagocytosus by producing Osp proteins that binds complement protein factor H
  • when C3b binds to factor H, it inactivates it
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13
Q

what are the main defenses against intracellular bacteria

A
  • macrophage activation —> phagocytosis
  • NK cells
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14
Q

activated NK cells secrete ______ to activate macrophages

A

INF-y

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15
Q

macrophages secrete _____ in response to ingested microorganisms that they cannot kill intracellularly

A

IL-12, which activates NK cells

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16
Q

IL-12 from phagocytes stimulates helper cells _____

A

Th1

16
Q

Th1 response results in the secretion of ______ and the expression of ____ to activate macrophages

A

INF-y + expression of CD40L

16
Q

how does a capsule help pathogens evade immune system

A
  • prevents phagocytosis, esp. important for extracellular bacteria
17
Q

what does SIgA protease do

A

cleaves IgA making it no longer able to bind to bacteria - bacteria is able to go through mucus and reach the epithelial cells

18
Q

Fungal pathogens immune evasion tactics

A
  • Biofilm - facilitates colonization, resists phagocytosis
  • cell wall organization - masks antigens from immune system
  • synthesis of structures that hinder immune system (fungal dimorphism, capsules)
  • ability to obtain nutrients
  • secretion of proteins that inactivate antimicrobial peptides
19
Q

innate response to fungal pathogens

A
  • neutrophils, macrophages, dendritic cells
  • sentinel macrophages + DCs secrete PRRs that recognize fungal cell wall components
  • neutrphils can phagocytose fungal cells, release ROIs, NETs, lysosomal enzymes
20
Q

Adaptive response to fungal pathogens

A
  • stimulated by cytokines from DC
  • intracellular fungi -** Th1** + CTLs (Th1 activates macrophages)
  • extracellular fungi - **Th17 **(stimulates inflammation and recuitment of neutrophils)
  • antibodies -neutralization, opsonization, activation of complement, ADCC
21
Q

Extracellular bacteria mechanisms of pathogenesis

A
  • release of toxins
  • endotoxins (LPS) - gram negative bacteria cell walls (causes activation of macrophages, release of cytokines, activates complement)
  • Exotoxins - gram positive bacteria (stimulate cytokine release or are cytotoxic)
22
Q

activated NK cells respond to intracellular bacteria in what 2 ways

A
  • secreting INF-y to activate macrophages (increases production of ROS and lysosomal enzymes)
  • directly killing infected cells if the bacterium caused a downregulation of MHC class I
23
Q

CD8 (cytotoxic T cell) response to intracellular bacteria

A
  • activated CTLs kill cells displaying bacterial antigens on class I MHC molecules
  • CTLs kill infected cells via perforin and granzymes
24
Q

role of antibodies against intracellular bacteria

A
  • minor role
  • binding to bacterial antigens displayed on the surface of infected cells can initiate ADCC
25
Q

what intracellular bacteria escape phagosomes

A
  • Listeria monocytogenes
  • they poke holes in the phagosome so they can get out and replicate in the cytoplasm
26
Q

what intracellular bacteria prevent phagosome-lysosome fusion

A
  • Mycobacterium tuberculosis
27
Q

what intracellular bacteria are resistant to lysosomal enzymes

A
  • Corynebacterium pseudotuberculosis
28
Q

Exotoxin that causes atrophic rhinitis in pigs

A
  • *Bordatella brontisceptica
  • Pasteruella multocida*
29
Q

innate immune response to extracellular bacteria

A
  • physical barriers (skin, mucosal membranes)
  • antimicrobial peptides (lysozyme, defensins)
  • If invasion of tissues occurs…
    - Inflammation, activation of complement, phagocytosis
    - Inflammation promoted by anaphylatoxins and pro-inflammatory cytokines
30
Q

adaptive immune response to extracellular bacteria

A
  • Antibodies are primary response - protective against bacterial cells and the proteins (toxins) they produce
31
Q

Fungal pathogens mechanism of pathogenesis

A

* Persistence w/in phagocytes - survival or organisms within phagocytes leads to increased replication and potential spread
* Inflammation - results in tissue destruction
CTL cell activity - damages tissues