Inflammasomes and antimicrobial immunity

Question 1

Give examples of extracellular bacteria?

Answer 1

staph; strep; klebsiella

Question 2

Give an example of cell surface bacteria

Answer 2

E.coli

Question 3

Give eamples of intra-vacuolar bacteria?

Answer 3

salmonella; legionella; mycobacterium

Question 4

Give examples of cytosolic bacteria?

Answer 4

listeria; shigella

Question 5

What type of protein are injectisomes related to?

Answer 5

flagellar rotors

Question 6

What is the gram stain of salmonella?

Answer 6

gram neg

Question 7

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

Answer 7

highly conserved

Question 8

What type of pathogen is listeria?

Answer 8

gram pos cytosolic pathogen

Question 9

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

Answer 9

host actin machinery and produce listeriolyin O

Question 10

What is the function of listeriolyin O?

Answer 10

pore forming toxin

Question 11

What cells does TB live and replicate inside?

Answer 11

alveolar macrophages

Question 12

What is essential for the virulence of TB?

Answer 12

ESX secretion system

Question 13

What cytokines protect against M.tb?

Answer 13

IL-12; IFNy and IL-1b

Question 14

What do AIM2 receptors recognise?

Answer 14

cytosolic dsDNA

Question 15

Describe the PYHIN family proteins?

Answer 15

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

Question 16

Name a member of the PYHIN family?

Answer 16

AIM2

Question 17

What cells does IL-18 act upon?

Answer 17

NK cells and T cells

Question 18

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

Answer 18

IFNy

Question 19

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

Answer 19

iNOS; NADPH oxidase; autophagy; GBP

Question 20

What is an inflammasome?

Answer 20

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

Question 21

How is pro-caspase 1 activated?

Answer 21

self-proteolytic cleavage into p20 and p10 active subunits

Question 22

What are the inflammatory outcomes of inflammasome activation?

Answer 22

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

Question 23

What alarmins does inflammasome activation result in the release of?

Answer 23

IL-1a and HMGB1

Question 24

What domain is responsible for recruiting Asc to the receptor?

Answer 24

pyrin domain

Question 25

What domain links Asc to caspase -1?

Answer 25

CARD domains

Question 26

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

Answer 26

autonimmune/inflammatory diseases; fever syndromes

Question 27

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

Answer 27

IL-1b acts on hypothalamus to cause fever

Question 28

What does inflammasome pathways require?

Answer 28

priming of cells- expression of receptors and substrates

Question 29

How does AIM2 cause inflammasome assembly?

Answer 29

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

Question 30

What do NAIPs recognise?

Answer 30

T3SS rod or needle or bacterial flagellin

Question 31

What do ligand bound NAIPs bind?

Answer 31

NLCR4

Question 32

happens when NLRC4 is activated by NAIP?

Answer 32

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

Question 33

What is the inflammasome assembly described as being like?

Answer 33

Prion-like

Question 34

What type of bacteria do not have T3SS?

Answer 34

gram positive

Question 35

How does listeria activate NLRP3?

Answer 35

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

Question 36

What inflammasomes are activated by M.tb?

Answer 36

NLRP3 and AIM2

Question 37

What are the features of pyroptosis?

Answer 37

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

Question 38

What protien is essential in pyroptosis?

Answer 38

gasdermin-D

Question 39

What is the function of gasdermin-D?

Answer 39

forms pores in membranes

Question 40

What cleaves gasdermin-D?

Answer 40

caspases 1,4,5

Question 41

What is the functions of caspases 4 and 5?

Answer 41

cytosolic receptors for LPS

Question 42

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

Answer 42

non-canonical

Question 43

How do caspase 4 and 5 result in inflammasome activation?

Answer 43

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

Question 44

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

Answer 44

caspase 11

Question 45

Why do cytosolic gram negative bacteria trigger pyroptosis?

Answer 45

result of direct activation of capse 4 by LPS

Question 46

What 2 death domains does ASC consist of?

Answer 46

pyrin domain and CARD domain

Question 47

What viral infections is AIM2 important in?

Answer 47

CMV vaccinia

Question 48

What domain on caspases 4 and 5 binds to LPS?

Answer 48

CARD

Question 49

What domain in NLRs mediates self-oligomerisation?

Answer 49

NOD domain

Question 50

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

Answer 50

unconventional secretion- independent of the ER and golgi

Question 51

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

Answer 51

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

Question 52

How are COPs thought to work?

Answer 52

sequester caspase 1 thereby negative regulating inflammasomes

Question 53

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

Answer 53

interacts with caspase 1 resulting in reduced caspase 1

Question 54

What is the function of POPs?

Answer 54

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

Question 55

What can induce POP1 expression?

Answer 55

TLR and IL-1R signalling