Innate Immune System Flashcards
1
Q
GIve some examples of pentraxins.
A
CRP, serum amyloid P (SAP), and PTX3
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
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
4
Q
Give some examples of collectins
A
MBL and surfactant proteins SP-A and SP-D
5
Q
What are the two function(s) of MBL?
A
- Activate complement through the lectin pathway
- Act as an opsonin
6
Q
What are the four function(s) of SP-A and SP-D?
A
- Maintain the ability of alveoli to expand by reducing surface tension
- Act as opsonins
- Activate macrophages
- Inhibit bacterial growth
7
Q
Which ligand(s) does MBL recognize?
A
Carbohydrates with terminal mannose and fucose
8
Q
Which ligand(s) do surfactants recognize?
A
Various microbial structures
9
Q
What are the two functions of ficolins?
A
- Opsonize bacteria
- Activate complement in a similar way to MBL
10
Q
Which ligand(s) do ficolins bind?
A
N-acetylglucosamine and lipoteichoic acid components of gram positive bacterial cell walls
11
Q
What are the three functions of complement?
A
- Opsonize microbes
- Recruit phagocytes to sites of inflammation
- Directly kill microbes
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
13
Q
What triggers the alternative complement pathway?
A
Binding of C3 to microbial surfaces, such as LPS
14
Q
What triggers the lectin complement pathway?
A
Binding of MBL to terminal mannose residues on microbial glycoproteins and glycolipids
15
Q
Which TLRs are located in the plasma membrane?
A
TLR1, TLR2, TLR4, TLR5, TLR6
16
Q
Which TLRs are located in endosomes?
A
TLR3, TLR7, TLR8, TLR9
17
Q
Which TLR(s) bind gram positive bacteria?
A
TLR1:TLR2
TLR2
TLR2:TLR6
18
Q
Which TLR(s) bind gram-negative bacteria?
A
TLR4
19
Q
Which TLR(s) bind all flagellated bacteria?
A
TLR5
20
Q
Which TLR(s) binds dsRNA?
A
TLR3
21
Q
Which TLR(s) binds ssRNA?
A
TLR7
TLR8
22
Q
Which TLR(s) binds CpG DNA?
A
TLR9
23
Q
Which TLR(s) bind bacterial lipopeptides?
A
TLR1:TLR2
TLR2:TLR6
24
Q
Which TLR(s) bind bacterial peptidoglycan?
A
TLR2
25
Which TLR(s) bind bacterial flagellin?
TLR5
26
Which TLR ligand(s) are produced by viruses only?
dsRNA
ssRNA in endosomes
27
Which TLR ligand(s) are produced by viruses, bacteria and fungi?
CpG DNA
28
Deficiency in the encoded protein for which gene results in increased susceptibility to herpes simplex encephalitis?
UNC93B1
29
What is the function of the protein encoded by the UNC93B1 gene?
Trafficking nucleotide sensing toll-like receptors to the endolysosome from the endoplasmic reticulum
30
Which protein is encoded by IRAK4?
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
31
Which TLR sigaling pathways are affected by IRAK4 deficiency?
All but TLR3, which signals only through the TRIF pathway
32
What are the adaptor proteins used by TLRs?
MyD88 and TRIF
33
Which TLR(s) use the adaptor protein MyD88?
TLR1, TLR2, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9
34
Which TLR(s) use the adaptor protein TRIF?
TLR3, TLR4
35
Which transcription factor is activated by MyD88/IRAK4?
NF-kB
36
Which transcription factor(s) are activated by TRIF?
Interferon response factors (IRFs)
37
What are the downstream results of MyD88 signaling?
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
What are the downstream results of TRIF signaling?
Expression of type 1 interferon (IFN-alpha, IFN-beta) genes, secretion of type 1 IFNs
39
What is an inflammasome?
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
What are the three components of most inflammasomes?
Sensor (TLR, NLR), caspase-1, and an adaptor linking the two
41
How is IL-1B gene transcription induced?
TLR, NLR, and RLR pathways that activate NF-kB
42
How is active IL-1B generated?
Pro-IL-1B is cleaved by caspase-1, which is activated by inflammasomes
43
Which family of diseases is related to errors in inflammasome pathways?
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
Give two examples of inflammasomopathies
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
Which class of medications can be used to treat inflammasomopathies?
IL-1 antagonists (Anakinra, canakinumab)
46
Which cytokine produced by macrophages activates NK cells?
IL-12
47
Which cytokine secreted by NK cells activates macrophages to phagocytose microbes?
IFN-y
48
Which subunits distinguish activating and inhibiting NK cell receptors?
Activating receptors have immunoreceptor tryrosine-based activation motifs (ITAMs).
Inhibiting receptors have immunoreceptor tyrosine-based inhibition motifs (ITIMs).
49
Give three examples of NK cell-activating receptors.
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
Give 3 examples of NK cell-inhibitory receptors.
1. KIR2DL
2. KIR3DL, which bind a variety of different class 1 MHC molecules expressed on normal cells
3. CD94/NKG2A
51
What are the major cytokines of the innate immune system that stimulate NK cell function?
IL-12, IL-15, IL-18 and type 1 IFNs
52
Which cytokine is an important growth factor for NK cells?
IL-15
53
Which cell(s) are the main source(s) of TNF?
Macrophages and T cells
54
What are the effects of TNF on endothelial cells, neutrophils, the hypothalamaus, the liver, and muscle and fat?
Endothelial cells: activation
Neutrophils: activation
Hypothalamus: fever
Liver: synthesis of acute phase proteins
Muscle, fat: catabolism
55
Which cytokines are important mediators of septic shock?
TNF, IL-1, IL-6
56
What are the effects of IL-1 on endothelial cells, the hypothalamus, the liver, muscle and fat, and T cells?
Endothelial cells: activation
Hypothalamus: fever
Liver: synthesis of acute phase proteins
Muscle, fat: catabolism
T cells: Th17 differentiation, enhanced cytotoxic activity
57
What are the effects of IL-6 on the liver, T cells, and B cells?
Liver: synthesis of acute phase proteins
T-cells: Th17 differentiation
B-cells: proliferation of antibody-producing cells
58
Which cytokine is an important activator of transcription factor STAT3?
IL-6
59
Which cytokine is an important contributor to inflammation in rheumatoid arthritis?
IL-6
60
What is the pathogenesis of Castleman disease?
Excess IL-6, which induces lymphadenopathy
Can be caused by HHV-8, which encodes a homolog of IL-6
61
What are the effects of IL-10 on macrophages and dendritic cells?
Inhibits production of inflammatory cytokines, including TNF, IL-1 and IL-12
62
What are the three main functions of IL-12?
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
Which cytokine is an important stimulator of production of IFN-y by NK cells and T cells?
IL-12
64
Mutations in which cytokine receptor are associated with increased susceptibility to intracellular bacteria, such as Salmonella and mycobacteria?
IL-12 receptor
65
Production of which cytokines is dependent on inflammasomes?
IL-1 and IL-18
66
What is the function of IL-18?
Activates NK cells and T cells, thereby stimulating IFN-γ production, a key cytokine in Th1 immune responses
67
Which cytokines are produced by epithelial barrier cells?
IL-25, thymic stromal lymphopoietin (TSLP), and IL-33
68
What is the main function of IL-25, TSLP, and IL-33?
Stimulating ILC2s, Th2 cells and mast cells to produce IL-4, IL-5 and IL-13
69
What are the main effects of IL-12 on T cells?
Th1 differentiation, IFN-y synthesis, increased cytotoxic activity
70
What are the main effects of IL-12 on NK cells?
IFN-Y synthesis, increased cytotoxic activity
71
What is the main effect of IL-15 on NK cells and T cells?
Proliferation
72
What is the main effect of IL-18 on NK cells and T cells?
IFN-y synthesis
73
What is the main effect of IL-23 on T cells?
Development and maintenance of IL-17 producing T cells
74
What is the main effect of IL-27 on T cells?
Th1 differentiation, inhibition of Th17 cells
75
What is the main effect of IL-27 on NK cells?
IFN-y snthesis
75
Which cell(s) are the main source(s) of IL-27?
Macrophages and dendritic cells
