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Innate Immune System Flashcards

1
Q

GIve some examples of pentraxins.

A

CRP, serum amyloid P (SAP), and PTX3

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2
Q

What is the function of pentraxins?

A

Soluble pattern recognition molecules that trigger complement activation and/or phagocytosis

CRP activates complement through the classical pathway by binding C1q

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3
Q

Which ligand(s) do pentraxins bind?

A

Ligands found on bacterial membranes and/or exposed on apoptotic cells
CRP binds microbial phosphorylcholine
SAP binds phosphatidylethanolamine

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4
Q

Give some examples of collectins

A

MBL and surfactant proteins SP-A and SP-D

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5
Q

What are the two function(s) of MBL?

A
  1. Activate complement through the lectin pathway
  2. Act as an opsonin
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6
Q

What are the four function(s) of SP-A and SP-D?

A
  1. Maintain the ability of alveoli to expand by reducing surface tension
  2. Act as opsonins
  3. Activate macrophages
  4. Inhibit bacterial growth
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7
Q

Which ligand(s) does MBL recognize?

A

Carbohydrates with terminal mannose and fucose

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8
Q

Which ligand(s) do surfactants recognize?

A

Various microbial structures

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9
Q

What are the two functions of ficolins?

A
  1. Opsonize bacteria
  2. Activate complement in a similar way to MBL
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10
Q

Which ligand(s) do ficolins bind?

A

N-acetylglucosamine and lipoteichoic acid components of gram positive bacterial cell walls

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11
Q

What are the three functions of complement?

A
  1. Opsonize microbes
  2. Recruit phagocytes to sites of inflammation
  3. Directly kill microbes
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12
Q

What triggers the classical complement pathway?

A

Binding of C1q to either pentraxins or the Fc portion of antibodies bound to the surfaces of other microbes

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13
Q

What triggers the alternative complement pathway?

A

Binding of C3 to microbial surfaces, such as LPS

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14
Q

What triggers the lectin complement pathway?

A

Binding of MBL to terminal mannose residues on microbial glycoproteins and glycolipids

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15
Q

Which TLRs are located in the plasma membrane?

A

TLR1, TLR2, TLR4, TLR5, TLR6

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16
Q

Which TLRs are located in endosomes?

A

TLR3, TLR7, TLR8, TLR9

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17
Q

Which TLR(s) bind gram positive bacteria?

A

TLR1:TLR2
TLR2
TLR2:TLR6

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18
Q

Which TLR(s) bind gram-negative bacteria?

A

TLR4

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19
Q

Which TLR(s) bind all flagellated bacteria?

A

TLR5

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20
Q

Which TLR(s) binds dsRNA?

A

TLR3

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21
Q

Which TLR(s) binds ssRNA?

A

TLR7
TLR8

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22
Q

Which TLR(s) binds CpG DNA?

A

TLR9

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23
Q

Which TLR(s) bind bacterial lipopeptides?

A

TLR1:TLR2
TLR2:TLR6

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24
Q

Which TLR(s) bind bacterial peptidoglycan?

A

TLR2

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25
Q

Which TLR(s) bind bacterial flagellin?

A

TLR5

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26
Q

Which TLR ligand(s) are produced by viruses only?

A

dsRNA
ssRNA in endosomes

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27
Q

Which TLR ligand(s) are produced by viruses, bacteria and fungi?

A

CpG DNA

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28
Q

Deficiency in the encoded protein for which gene results in increased susceptibility to herpes simplex encephalitis?

A

UNC93B1

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29
Q

What is the function of the protein encoded by the UNC93B1 gene?

A

Trafficking nucleotide sensing toll-like receptors to the endolysosome from the endoplasmic reticulum

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30
Q

Which protein is encoded by IRAK4?

A

A kinase that activates NF-kappaB in both the Toll-like receptor (TLR) and T-cell receptor (TCR) signaling pathways

IRAK4 = interleukin 1 receptor associated kinase 4

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31
Q

Which TLR sigaling pathways are affected by IRAK4 deficiency?

A

All but TLR3, which signals only through the TRIF pathway

32
Q

What are the adaptor proteins used by TLRs?

A

MyD88 and TRIF

33
Q

Which TLR(s) use the adaptor protein MyD88?

A

TLR1, TLR2, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9

34
Q

Which TLR(s) use the adaptor protein TRIF?

A

TLR3, TLR4

35
Q

Which transcription factor is activated by MyD88/IRAK4?

36
Q

Which transcription factor(s) are activated by TRIF?

A

Interferon response factors (IRFs)

37
Q

What are the downstream results of MyD88 signaling?

A

Expression of inflammatory genes to produce:
- Proinflammatory cytokines (TNF, IL-1, IL-6)
- Chemokines (CCL2, CXCL8)
- Endothelial adhesion molecules (E-selectin)
- Costimulatory molecules (CD80, CD86)

38
Q

What are the downstream results of TRIF signaling?

A

Expression of type 1 interferon (IFN-alpha, IFN-beta) genes, secretion of type 1 IFNs

39
Q

What is an inflammasome?

A

A multiprotein enzymatic complex that forms in the cytosol in response to infections or cell injury and produces active caspase-1, thereby generating active forms of IL-1 and IL-18.

40
Q

What are the three components of most inflammasomes?

A

Sensor (TLR, NLR), caspase-1, and an adaptor linking the two

41
Q

How is IL-1B gene transcription induced?

A

TLR, NLR, and RLR pathways that activate NF-kB

42
Q

How is active IL-1B generated?

A

Pro-IL-1B is cleaved by caspase-1, which is activated by inflammasomes

43
Q

Which family of diseases is related to errors in inflammasome pathways?

A

Dysregulated activation of inflammasomes, most often due to gain-of-function mutations leads to inflammasomopathies (IL-1B-activation syndromes), autoinflammatory syndromes characterized by recurrent attacks of fever and inflammation

44
Q

Give two examples of inflammasomopathies

A
  1. Familial Mediterranean fever, which is caused by a mutation in the gene encoding pyrin
  2. Cryopyrin-associated periodic syndromes, which are caused by mutations in the gene encoding NLRP3 (cryopyrin)
45
Q

Which class of medications can be used to treat inflammasomopathies?

A

IL-1 antagonists (Anakinra, canakinumab)

46
Q

Which cytokine produced by macrophages activates NK cells?

47
Q

Which cytokine secreted by NK cells activates macrophages to phagocytose microbes?

48
Q

Which subunits distinguish activating and inhibiting NK cell receptors?

A

Activating receptors have immunoreceptor tryrosine-based activation motifs (ITAMs).
Inhibiting receptors have immunoreceptor tyrosine-based inhibition motifs (ITIMs).

49
Q

Give three examples of NK cell-activating receptors.

A
  1. NKG2D, which binds class I MHC-like proteins that are upregulated by infected cells
  2. CD16, which binds Fc regions of IgG bound to microbial antigens expressed on surface of infected cells
  3. KIR2DS, KIR3DS
50
Q

Give 3 examples of NK cell-inhibitory receptors.

A
  1. KIR2DL
  2. KIR3DL, which bind a variety of different class 1 MHC molecules expressed on normal cells
  3. CD94/NKG2A
51
Q

What are the major cytokines of the innate immune system that stimulate NK cell function?

A

IL-12, IL-15, IL-18 and type 1 IFNs

52
Q

Which cytokine is an important growth factor for NK cells?

53
Q

Which cell(s) are the main source(s) of TNF?

A

Macrophages and T cells

54
Q

What are the effects of TNF on endothelial cells, neutrophils, the hypothalamaus, the liver, and muscle and fat?

A

Endothelial cells: activation
Neutrophils: activation
Hypothalamus: fever
Liver: synthesis of acute phase proteins
Muscle, fat: catabolism

55
Q

Which cytokines are important mediators of septic shock?

A

TNF, IL-1, IL-6

56
Q

What are the effects of IL-1 on endothelial cells, the hypothalamus, the liver, muscle and fat, and T cells?

A

Endothelial cells: activation
Hypothalamus: fever
Liver: synthesis of acute phase proteins
Muscle, fat: catabolism
T cells: Th17 differentiation, enhanced cytotoxic activity

57
Q

What are the effects of IL-6 on the liver, T cells, and B cells?

A

Liver: synthesis of acute phase proteins
T-cells: Th17 differentiation
B-cells: proliferation of antibody-producing cells

58
Q

Which cytokine is an important activator of transcription factor STAT3?

59
Q

Which cytokine is an important contributor to inflammation in rheumatoid arthritis?

60
Q

What is the pathogenesis of Castleman disease?

A

Excess IL-6, which induces lymphadenopathy

Can be caused by HHV-8, which encodes a homolog of IL-6

61
Q

What are the effects of IL-10 on macrophages and dendritic cells?

A

Inhibits production of inflammatory cytokines, including TNF, IL-1 and IL-12

62
Q

What are the three main functions of IL-12?

A
  1. Stimulation of IFN-y production by NK cells, ILC1s, and T cells
  2. Enhances NK-cell and CTL-mediated cytotoxicity
  3. Promotes differentiation of Th1 cells
63
Q

Which cytokine is an important stimulator of production of IFN-y by NK cells and T cells?

64
Q

Mutations in which cytokine receptor are associated with increased susceptibility to intracellular bacteria, such as Salmonella and mycobacteria?

A

IL-12 receptor

65
Q

Production of which cytokines is dependent on inflammasomes?

A

IL-1 and IL-18

66
Q

What is the function of IL-18?

A

Activates NK cells and T cells, thereby stimulating IFN-γ production, a key cytokine in Th1 immune responses

67
Q

Which cytokines are produced by epithelial barrier cells?

A

IL-25, thymic stromal lymphopoietin (TSLP), and IL-33

68
Q

What is the main function of IL-25, TSLP, and IL-33?

A

Stimulating ILC2s, Th2 cells and mast cells to produce IL-4, IL-5 and IL-13

69
Q

What are the main effects of IL-12 on T cells?

A

Th1 differentiation, IFN-y synthesis, increased cytotoxic activity

70
Q

What are the main effects of IL-12 on NK cells?

A

IFN-Y synthesis, increased cytotoxic activity

71
Q

What is the main effect of IL-15 on NK cells and T cells?

A

Proliferation

72
Q

What is the main effect of IL-18 on NK cells and T cells?

A

IFN-y synthesis

73
Q

What is the main effect of IL-23 on T cells?

A

Development and maintenance of IL-17 producing T cells

74
Q

What is the main effect of IL-27 on T cells?

A

Th1 differentiation, inhibition of Th17 cells

75
Q

What is the main effect of IL-27 on NK cells?

A

IFN-y snthesis

75
Q

Which cell(s) are the main source(s) of IL-27?

A

Macrophages and dendritic cells

Immunology (10 decks)

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