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Module 2 > Inflammasomes and antimicrobial immunity > Flashcards

Inflammasomes and antimicrobial immunity Flashcards

1
Q

Give examples of extracellular bacteria?

A

staph; strep; klebsiella

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2
Q

Give an example of cell surface bacteria

A

E.coli

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3
Q

Give eamples of intra-vacuolar bacteria?

A

salmonella; legionella; mycobacterium

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4
Q

Give examples of cytosolic bacteria?

A

listeria; shigella

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5
Q

What type of protein are injectisomes related to?

A

flagellar rotors

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6
Q

What is the gram stain of salmonella?

A

gram neg

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7
Q

Why is the injectisome useful for the innate immune system to recognise?

A

highly conserved

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8
Q

What type of pathogen is listeria?

A

gram pos cytosolic pathogen

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9
Q

How does listeria move wtihin the cell and spread to adjacent cells?

A

host actin machinery and produce listeriolyin O

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10
Q

What is the function of listeriolyin O?

A

pore forming toxin

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11
Q

What cells does TB live and replicate inside?

A

alveolar macrophages

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12
Q

What is essential for the virulence of TB?

A

ESX secretion system

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13
Q

What cytokines protect against M.tb?

A

IL-12; IFNy and IL-1b

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14
Q

What do AIM2 receptors recognise?

A

cytosolic dsDNA

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15
Q

Describe the PYHIN family proteins?

A

can activate inflammasomes; sontain can N-terminal pyrin domain but lack the LRR domain of NLRs instead have HIN domain

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16
Q

Name a member of the PYHIN family?

A

AIM2

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17
Q

What cells does IL-18 act upon?

A

NK cells and T cells

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18
Q

What cytokine does IL-18 induce NK cells and T cells to make?

A

IFNy

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19
Q

What is the result of IFN-induced cell autonomous defensce?

A

iNOS; NADPH oxidase; autophagy; GBP

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20
Q

What is an inflammasome?

A

a large multiprotein complex that activates caspase-1 via the adaptor protein Asc

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21
Q

How is pro-caspase 1 activated?

A

self-proteolytic cleavage into p20 and p10 active subunits

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22
Q

What are the inflammatory outcomes of inflammasome activation?

A

IL-1b and IL18 release; alarmin release; pyroptosis

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23
Q

What alarmins does inflammasome activation result in the release of?

A

IL-1a and HMGB1

24
Q

What domain is responsible for recruiting Asc to the receptor?

A

pyrin domain

25
Q

What domain links Asc to caspase -1?

A

CARD domains

26
Q

What happens when there is a gain of function in caspase-1?

A

autonimmune/inflammatory diseases; fever syndromes

27
Q

Why does gain of function in caspase-1 result in fever syndromes?

A

IL-1b acts on hypothalamus to cause fever

28
Q

What does inflammasome pathways require?

A

priming of cells- expression of receptors and substrates

29
Q

How does AIM2 cause inflammasome assembly?

A

HIN domains oligomerise around DNA leaving PYD open for binding to Asc which then polymerises and binds caspase1

30
Q

What do NAIPs recognise?

A

T3SS rod or needle or bacterial flagellin

31
Q

What do ligand bound NAIPs bind?

32
Q

happens when NLRC4 is activated by NAIP?

A

able to activate caspase-1 by ASc or sometimes directly by its N-terminal CARD domain

33
Q

What is the inflammasome assembly described as being like?

A

Prion-like

34
Q

What type of bacteria do not have T3SS?

A

gram positive

35
Q

How does listeria activate NLRP3?

A

produces toxin which produces pore resulting in K efflux and dissociation of NLrp3 chaperone proteins allowing its LRR domsns to join and bind Asc

36
Q

What inflammasomes are activated by M.tb?

A

NLRP3 and AIM2

37
Q

What are the features of pyroptosis?

A

osmotic swelling and bursting of cells; spillage of cellular contents and enhanced infalmmation

38
Q

What protien is essential in pyroptosis?

A

gasdermin-D

39
Q

What is the function of gasdermin-D?

A

forms pores in membranes

40
Q

What cleaves gasdermin-D?

A

caspases 1,4,5

41
Q

What is the functions of caspases 4 and 5?

A

cytosolic receptors for LPS

42
Q

What is the mechanism of inflammasome activation by caspases 4 and 5?

A

non-canonical

43
Q

How do caspase 4 and 5 result in inflammasome activation?

A

cleave gasdermin D which makes pores in membrane or by processing pannexin1 resulting K effluc and NLRP3 activation

44
Q

What is the equivalent of caspases 4 and 5 in mice?

A

caspase 11

45
Q

Why do cytosolic gram negative bacteria trigger pyroptosis?

A

result of direct activation of capse 4 by LPS

46
Q

What 2 death domains does ASC consist of?

A

pyrin domain and CARD domain

47
Q

What viral infections is AIM2 important in?

A

CMV vaccinia

48
Q

What domain on caspases 4 and 5 binds to LPS?

49
Q

What domain in NLRs mediates self-oligomerisation?

A

NOD domain

50
Q

By what mechanism are IL-1b and IL18 released from the cell?

A

unconventional secretion- independent of the ER and golgi

51
Q

What are the regultors of inflammasome assembly that modulate the interactions of death fold domains?

A

CARD-only proteins- COPs and PYD-only proteins (POPs)

52
Q

How are COPs thought to work?

A

sequester caspase 1 thereby negative regulating inflammasomes

53
Q

What is thought to be the function of caspase-12?

A

interacts with caspase 1 resulting in reduced caspase 1

54
Q

What is the function of POPs?

A

binds ASC with its pyrin domain preventing its binding to other pyrin domains

55
Q

What can induce POP1 expression?

A

TLR and IL-1R signalling

Module 2 (38 decks)

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