Lecture 29 - Innate Immunity II Flashcards

1
Q

Janeway’s proposed mechanism of innate immunity

A

Presence of PAMPS and PRRs

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2
Q

Deficiency with Janeway’s proposed model

A

Didn’t account for sterile inflammation (inflammation without a pathogen)
EG: Crohn’s disease

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3
Q

Solution to problem of sterile inflammation

A

DAMPS

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4
Q

Example of a DAMP

A

DNA when it is outside the nucleus

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5
Q

Fungi PAMPs
1)
2)
3)

A

1) Zymosan
2) Mannan
3) Beta-glycan

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6
Q

TLRs
1)
2)
3)

A

1) Germline-encoded PRRs
2) Always associated with membranes
3) Stimulation results in cytokine and chemokine release

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7
Q

MyD88
1)
2)
3)

A

1) Secondary messenger (intracellular) that all TLRs signal through
2) Exception to this is TLR3, which signals through TRIF
3) TLR4 can use either MyD88 or TRIF

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8
Q

Which secondary messenger to all TLRs except TLR3 signal through?

A

MyD88

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9
Q

Which secondary messenger does TLR3 use?

A

TRIF

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10
Q

TRIF

A

Secondary messenger used by TLR3.

TLR4 goes through either MyD88 or TRIF

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11
Q

Transcription factor used by TLRs

A

NF-kB

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12
Q
Generic TLR signal transduction
1)
2)
3)
4)
5)
A

1) TLR binds ligand
2) Intracellular TIR domain of TLR binds to MyD88 (except for TLR3, or sometimes TLR4)
3) Death domain of MyD88 stimulates other factors, which lead to a kinase cascade
4) IkB is phosphorylated, which makes it release NF-kB
5) NF-kB enters nucleus, acts as a transcription factor

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13
Q
TLRs expressed on the cell membrane
1)
2)
3)
4)
A

1) TLR2
2) TLR4
3) TLR5
4) TLR11

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14
Q

TLRs expressed in phagosomes or endosomes
1)
2)
3)

A

1) TLR3
2) TLR7
3) TLR9

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15
Q

TLR4 MyD88 dependent response

A

1) Release of IL-6

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16
Q
IL6 effects
1)
2)
3)
4)
5)
A

1) Liver releases acute phase proteins (C- reactive protein)
2) Contributes to Th17 differentiation
3) B cell differentiation
4) Increased costimulatory molecule expression
5) Systemic inflammatory responses (fever, fatigue)

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17
Q

TLR4 MyD88-independent response

A

IFN alpha and beta release

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18
Q
IFN alpha and beta effects
1)
2)
3)
4)
A

1) Inhibition of viral protein synthesis
2) Degradation of viral RNA
3) Inhibition of virus assembly
4) Increased costimulatory molecule expression

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19
Q

Useful clinical marker for bacterial infections

A

C reactive protein

Only bacteria stimulate CRP release

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20
Q

How does IL-6 stimulate fever?

A

Enters the brain, stimulates the thalamus

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21
Q

IRF

A

Interferon-releasing factor

22
Q

Number of genes transcribed as a result of IFNa/b release

A

Over 1000

23
Q

Effect of IFN deficiency

A

Herpes simplex becomes lethal

24
Q
RLR
1)
2)
3)
4)
5)
A

1) Rig-I like receptors
2) Recognise viral RNA in the cytosol
3) Associate with mitochondria
4) Require MAVS as an adaptor molecule
5) Induce secretion of IFNa/b

25
Q

Transcription factors activated by rig-I like receptor stimulation

A

IRF (interferon-releasing factor)

26
Q
Examples of self-derived factors that can stimulate NLR/inflammasomes
1)
2)
3)
4)
5)
A

1) Amyloid-b
2) ATP
3) Glucose
4) Hyaluronan
5) Cholesterol crystals

27
Q
Environmentally-derived factors that can stimulate NLR/inflammasomes
1)
2)
3)
4)
A

1) Alum
2) Silica
3) Asbestos
4) UV radiation

28
Q

Sources of factors that can result in NLR/inflammasome stimulation
1)
2)
3)

A

1) Environmentally-derived
2) Self-derived
3) Pathogen-derived

29
Q

Factors that can stimulate NLRP3
1)
2)
3)

A

1) Damaged mitochondria
2) Potassium efflux from cell (alterations in membrane potential can indicate membrane damage, DAMP)
3) Lysosome destabilisation

30
Q

Factor that can stimulate NLRP4

A

Flagellin (when intracellular)

31
Q

What in gout can stimulate inflammasomes?

A

Uric acid crystals in joints

32
Q

How does an inflammasome activate pro-caspase 1?

A

Sterically

Shape of assembled inflammasome activates pro-caspase 1

33
Q

TLR3 ligand

A

dsRNA

34
Q

TLR3 ligand source

A

Virus, bacteria

35
Q

TLR3 activation effects

A

IFNa/b

36
Q

TLR5 ligand

A

Flagellin

37
Q

TLR5 activation effects

A

IL-6 release (from NF-kB)

38
Q

TLR9 ligand

A

cPg DNA

39
Q

cPg DNA source

A

Viruses, bacteria

40
Q

TLR9 activation effect

A

IL-12

IFNa/b

41
Q

TLR11 ligand

A

Flagellin

42
Q

TLR11 activation effect

A

IL-6 (NF-kB)

43
Q
Membrane-associated TLRs
1)
2)
3)
4)
A

1) TLR3
2) TLR5
3) TLR9
4) TLR11

44
Q

RIG-like receptor location

A

Cytosolic

45
Q

RIG-like receptors
1)
2)

A

1) RIG-1

2) MDA-5

46
Q

RIG-1/MDA5 ligands

A

dsRNA

47
Q

RIG-1/MDA5 stimulation effect

A

IL-6

IFNa/b

48
Q

NLRC4 stimulation effect

A

IL-1b
IL-18
IL-33

49
Q

Receptors that detect flagellin

A

1) TLR5
2) TLR11
3) NLRC4

50
Q

PRRs that lead to NF-kB-mediated IL-6 release when stimulated

A

TLR-5, TLR-11