Inflammasome

Question 1

What is interleukin-1B? (2)

Answer 1

A central mediator of innate immunity and inflammation

Question 2

Regulation of Interleukin-1 signalling (3)

Answer 2

Receptor binding is negatively regulated via:
- Receptor antagonist
- Soluble receptors
- Decoy receptors

Question 3

Regulation of IL-1 beta activity (3)

Answer 3

IL-1beta undergoes precise proteolytic cleavage
This converts the inactive precursor into its active receptor-binding form

IL-1B ubiquitinated and degraded via the proteasomal pathway to control its levels and prevent excessive inflammation

Question 4

How is cleavage of IL-1B regulated? (1)

Answer 4

Cleavage of IL-1β is mediated via macromolecular complexes known
as inflammasomes

Question 5

What are the stages of inflammasome activation? (3)

Answer 5

Priming- causes increases in inflammasome components

Second signal- assembly of NLRPs, procaspase-1 and pro IL-1/18

Generation and release of active IL-1/18

Question 6

How does priming of the inflammasome occur? (1)

Answer 6

Priming of the inflammasome occurs via PAMPs/DAMPs

Question 7

What are NLRP proteins? (2)

Answer 7

Involved in danger sensing and inflammasome assembly
Lead to activation of cascade -1

Question 8

What triggers inflammasome activity? (3)

Answer 8

Reactive oxygen species
K+ efflux
mtDNA release
Lysosomal damage

Question 9

How does inflammasome activation lead to pyroptosis? (3)

Answer 9

Caspase-1/11 dependent cell death (via activation and assembly of Gasdermin D)

Ultimately leads to membrane rupture and release of intracellular contents (including alarmins)

Question 10

In pyroptosis pore formation and membrane rupture requires what? (2)

Answer 10

Cleavage of the Gasdermin D - Release of IL-1β, other “small” proteins and ionic flux

Cleavage of ninjurin-1 - Release of larger cytosolic components

Question 11

What do Pyroptotic cells release? (1)

Answer 11

Alarmins

Question 12

Immune evasion of the inflammasome by bacteria (3)

Answer 12

Bacterial effector molecules inhibit the NLRC4 inflammasome
Intracellular bacteria evade AIM2
mediated signalling
Mtb inhibit ROS production
- therefore inflammasome activation

Question 13

Evasion of inflammasomes by pathogen decoy proteins (4)

Answer 13

KSHV- codes an NLRP1 homolog that lacks PYD and CARD, interacts with host NLRP1, NLRP3, and NOD2

Poxvirus-encoded PYD-containing protein, M13L, which interacted with ASC, prevent inflammasome activation

Rabbit poxivirus encodes serine protease inhibit (Serp2)-inhibit caspase-1

Vaccinia virus : IL-1β/IL-18 BPs