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Immunology > 3. Cellular mechanisms of innate immunity > Flashcards

3. Cellular mechanisms of innate immunity Flashcards

1
Q

what are PAMPs

A

conserved molecular features shared by related groups of microorganisms
recognized by PRRs

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2
Q

what are PRRs

A

receptors that recognize PAMPs (and DAMPs) - foreign material that appears on microorganisms but are lacking in host cells
genetically encoded and inherited through germ line

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3
Q

what is non-clonal expansion of PRRs

A

immune cells express multiple PRRs

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4
Q

macrophages express receptors that enable them to…

A

take up microbes by phagocytosis

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5
Q

phagolysosomes of macrophages

A

contains a lysosome and AMPs
become acidified
produces superoxide and NO radicals to kill pathogens

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6
Q

what are the 5 families of PRRs

A

TLRs
lectin receptor
scavenger receptor
cytosolic innate receptor
opsonin receptor

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7
Q

characteristics of the lectin receptor

A

bind carbohydrates: sulfated sugars and polysaccharides
prompts phagocytosis
e.g. mannose receptor (CD206)

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8
Q

characteristics of the scavenger receptor

A

binds negative charged ligands: sulphated polysaccharides and LTA (G+) and LPS (G-)
prompts phagocytosis
e.g. SR-A and SR-B

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9
Q

characteristics of the cytosolic innate receptor

A

binds intracellular PAMPs: DNA, dsDNA, cyclic dinucleotides
inhibits pathogen growth
prompts WBC recruitment to kill infected cells
e.g. RIG-1 (viral RNA) and cGAS (DNA)

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10
Q

characteristics of the opsonin receptor

A

binds pathogens or foreign molecules tagged with opsonins
prompts phagocytosis
e.g. complement receptors (CR3, CR4) and Fc receptor

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11
Q

what happens when cytokines cause blood vessels to dilate and alter endothelial cells

A

neutrophils and monocytes are guided by chemokines to enter the infected tissues

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12
Q

characteristics of TLRs

A

vital roll in the innate immune response
induce key signalling events for mounting robust defense against pathogens
evolutionarily conserved
ligands are specific to hosts and are not expressed on human cells

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13
Q

which TLRs are intracellular and participate in antiviral immunity

A

TLR 3, 7, 8 and 9

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14
Q

which TLRs are extracellular and participate in antibacterial immunity

A

TLR 1-2, 2-6, 4, 5,

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15
Q

what are the 3 characteristics all TLRs share

A

leucine rich repeats
ITRs
the overall C form

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16
Q

TLR-4 signalling pathway to produce pro-inflammatory cytokines (apply to most TLRs)

A

TLRs dimerize*
recruit IRAK 1 and 4 which activate TRAF6
TRAF6 is polyubiquitinated which activates TAK1
TAK1 associates with IKK which leads to the phosphorylation of IkB
IkB is degraded, releasing NFkB into the nucleus as a TF for cytokine gene expression

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17
Q

what does the TF KFkB induce?

A

the expression of pro-inflammatory cytokines

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18
Q

TLR signalling to produce interferons: TLR3 pathway

A

TLR3 in endosome binds dsRNA and signals TRIF and TRAF3 to induce IFN gene expression via IRF3

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19
Q

TLR signalling to produce interferons: TLR7 pathway

A

TLR7 in endosome binds ssRNA and signals via MyD88 to induce IFN gene expression via IRF7

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20
Q

what are DAMPs

A

Damage-associated molecular patterns
derived from host cells (including tumor or dying cells)
recognized by PRRs

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21
Q

cytosolic innate immune receptors recognize different ligands by different strategies, match the ligands to their recognition strategy (RIG1, MDA5, cGAS, NOD1, NOD2)

A

RIG1 - triphosphate dsRNA
MDA5 - dsRNA
cGAS - DNA
NOD1 - iE-DAP
NOD2 - MDP

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22
Q

what are cytokines and their functions

A

signalling molecules which promote immune cell activation
bind to cytokine receptors on immune and non-immune cells
activate innate and adaptive immunity
involved in inflammation
many are members of the Interleukin (IL) family

23
Q

which cytokines are inflammatory

A

TNF-a
IL-1

24
Q

which cells secrete inflammatory cytokines

A

macrophages

25
Q

which cytokines are signalling

A

IL-2, IL-4, IL-10
IL-12
IL-17
IFN-y
IFN-a/-B
TGF-B

26
Q

which molecule is a chemokine

A

CXCL8 (IL-8)

27
Q

which cytokines function in T and B cell activation

A

T = IL-2
B = IL-4

28
Q

which cytokine is anti-inflammatory

A

IL-10

29
Q

What is the function of INF-a and INF-B

A

NK cell activation, prevention of viral replication
(remember how NK cells are most important innate cells in anti-viral immunity)

30
Q

which cytokine functions in peripheral tolerance

A

TGF-B

31
Q

what is the JAK-STAT pathway

A

a pathway which cytokine receptors use for rapid signalling to induce gene transcription

32
Q

basis of the JAK-STAT pathway

A
  • cytokine receptors contain JAK on their cytoplasmic domain
  • cytokine binding dimerizes the receptors bringing together the cytoplasmic JAKs, they activate each other and phosphorylate the receptor
  • STATs bind to receptors and are phosphorylated by JAKs
  • STATs form dimers, these dimers translocate to the nucleus to initiate cytokine gene transcription
33
Q

what are some important cytokines produced by macrophages (and DCs) in response to bacterial products

A

IL-1B: increase vascular permeability (inflammation)
TNF-a: increase vascular permeability (inflammation)
IL-6: increase antibody production
CXCL8 (IL8): recruit neutrophils
IL-12: activate NK cells

34
Q

which cytokines increase vascular permeability so that neutrophils can enter the endothelium

A

IL-1B and TNF-a

35
Q

what are the 4 steps leukocytes must undergo to accumulate in a blood vessel

A

tethering
rolling
activation
firm adhesion

36
Q

what are cell adhesion molecules

A

proteins that hold cells together
exists as a pair of complementary receptors: one is present on the neutrophil and its partner on the tissue

37
Q

4 types of cell adhesion molecules

A

selectins: bind carbohydrate groups on neutrophils
glycoproteins: bind to selectins
integrins: bind to other proteins
iCAMs: bind to integrins

38
Q

adhesion molecules involved in leukocyte interactions: selectins

A

bind to carbohydrate groups on neutrophils
bound by glycoproteins - sialyl-lewis-x and PSGL-1
tissue distribution = activated endothelium
weak adhesion allows leukocyte rolling

39
Q

adhesion molecules involved in leukocyte interactions: integrins

A

bind to cell-adhesion molecules and extracellular matrix
bound by iCAMs, iC3b and fibronectin
wide tissue distribution
strong adhesion allows diapedesis

40
Q

steps in leukocyte migration into tissues

A

rolling adhesion
tight binding
diapedesis
migration

41
Q

3 proteins affected in the interferon response to viral infection and their protective mechanisms

A

PKR: inhibits protein synthesis
RNase L: destroys RNA in the cell (RNA is in many viral genomes)
p53: induce apoptosis

42
Q

autocrine response of interferons from a virus infected cell

A
  • interferon response by IFN-B (PKr, RNase L, p53) when it binds to type-1 interferon receptor on same cell
  • causes IRF7 tp enter cell and allow transcription of IFN-a genes to produce other effects
43
Q

paracrine response of interferons from a virus infected cell

A

interferon response on uninfected cell AND induce NK response from NK cells (release perforins and granzymes)

44
Q

what components of NK cells are responsible for cell death and how?

A

perforin: punches holes in the membrane of cells
granzymes: induce apoptosis

45
Q

what are the 2 kinds of receptors on the surface of NK cells

A
  1. activating: NKG2D, 2B4
  2. inhibitory: CD94:NKG2A
46
Q

what are some malfunctions in innate immune cells and what they lead to

A

macrophages = persistent infections
neutrophils = granulomas
recurring viral infection = NK cells

47
Q

systemic vs local release of TNF-a

A

same activity but different outcomes
local = removal of infection by adaptive immunity
systemic = death

48
Q

which PRRs work in extracellular recognition

A

TLRs and lectin receptor

49
Q

PRRs in cytosolic recognition

A

NLRs (anti-bacterial)
RLRs (anti-viral)

50
Q

PRRs in endosomal recognition

A

TLR-3, 7, 8 and 9

51
Q

what is the difference in outcome of intra and extra cellular TLRS

A

intracellular: mostly leads to interferon production
extracellular: mostly leads to cytokine production

52
Q

what do each of the extracellular TLRs bind

A

2-6: lipopeptides
1-2: lipopeptides
5: flagellin
4: LPS

53
Q

what do each of the intracellular TLRs bind

A

3: dsRNA
7: ssRNA
8: ssRNA
9: CpG DNA

Immunology (20 decks)

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