Lecture 29 - Innate Immunity II

Question 1

Janeway’s proposed mechanism of innate immunity

Answer 1

Presence of PAMPS and PRRs

Question 2

Deficiency with Janeway’s proposed model

Answer 2

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

Question 3

Solution to problem of sterile inflammation

Answer 3

DAMPS

Question 4

Example of a DAMP

Answer 4

DNA when it is outside the nucleus

Question 5

Fungi PAMPs
1)
2)
3)

Answer 5

1) Zymosan
2) Mannan
3) Beta-glycan

Question 6

TLRs
1)
2)
3)

Answer 6

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

Question 7

MyD88
1)
2)
3)

Answer 7

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

Question 8

Which secondary messenger to all TLRs except TLR3 signal through?

Answer 8

MyD88

Question 9

Which secondary messenger does TLR3 use?

Answer 9

TRIF

Question 10

TRIF

Answer 10

Secondary messenger used by TLR3.

TLR4 goes through either MyD88 or TRIF

Question 11

Transcription factor used by TLRs

Answer 11

NF-kB

Question 12

Generic TLR signal transduction
1)
2)
3)
4)
5)

Answer 12

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

Question 13

TLRs expressed on the cell membrane
1)
2)
3)
4)

Answer 13

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

Question 14

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

Answer 14

1) TLR3
2) TLR7
3) TLR9

Question 15

TLR4 MyD88 dependent response

Answer 15

1) Release of IL-6

Question 16

IL6 effects
1)
2)
3)
4)
5)

Answer 16

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)

Question 17

TLR4 MyD88-independent response

Answer 17

IFN alpha and beta release

Question 18

IFN alpha and beta effects
1)
2)
3)
4)

Answer 18

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

Question 19

Useful clinical marker for bacterial infections

Answer 19

C reactive protein

Only bacteria stimulate CRP release

Question 20

How does IL-6 stimulate fever?

Answer 20

Enters the brain, stimulates the thalamus

Question 21

IRF

Answer 21

Interferon-releasing factor

Question 22

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

Answer 22

Over 1000

Question 23

Effect of IFN deficiency

Answer 23

Herpes simplex becomes lethal

Question 24

RLR
1)
2)
3)
4)
5)

Answer 24

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

Question 25

Transcription factors activated by rig-I like receptor stimulation

Answer 25

IRF (interferon-releasing factor)

Question 26

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

Answer 26

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

Question 27

``` Environmentally-derived factors that can stimulate NLR/inflammasomes 1) 2) 3) 4) ```

Answer 27

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

Question 28

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

Answer 28

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

Question 29

Factors that can stimulate NLRP3 1) 2) 3)

Answer 29

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

Question 30

Factor that can stimulate NLRP4

Answer 30

Flagellin (when intracellular)

Question 31

What in gout can stimulate inflammasomes?

Answer 31

Uric acid crystals in joints

Question 32

How does an inflammasome activate pro-caspase 1?

Answer 32

Sterically | Shape of assembled inflammasome activates pro-caspase 1

Question 33

TLR3 ligand

Answer 33

dsRNA

Question 34

TLR3 ligand source

Answer 34

Virus, bacteria

Question 35

TLR3 activation effects

Answer 35

IFNa/b

Question 36

TLR5 ligand

Answer 36

Flagellin

Question 37

TLR5 activation effects

Answer 37

IL-6 release (from NF-kB)

Question 38

TLR9 ligand

Answer 38

cPg DNA

Question 39

cPg DNA source

Answer 39

Viruses, bacteria

Question 40

TLR9 activation effect

Answer 40

IL-12 | IFNa/b

Question 41

TLR11 ligand

Answer 41

Flagellin

Question 42

TLR11 activation effect

Answer 42

IL-6 (NF-kB)

Question 43

``` Membrane-associated TLRs 1) 2) 3) 4) ```

Answer 43

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

Question 44

RIG-like receptor location

Answer 44

Cytosolic

Question 45

RIG-like receptors 1) 2)

Answer 45

1) RIG-1 | 2) MDA-5

Question 46

RIG-1/MDA5 ligands

Answer 46

dsRNA

Question 47

RIG-1/MDA5 stimulation effect

Answer 47

IL-6 | IFNa/b

Question 48

NLRC4 stimulation effect

Answer 48

IL-1b IL-18 IL-33

Question 49

Receptors that detect flagellin

Answer 49

1) TLR5 2) TLR11 3) NLRC4

Question 50

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

Answer 50

TLR-5, TLR-11