Inflammasomes

Question 1

Outline of what inflammasomes do

Answer 1

Inflammasomes trigger capsases that triggers the release of cytokines

Question 2

What are inflammasomes?

Answer 2

Wheel-like supramolecular complexes formed in the cytosol

Question 3

What do inflammasomes do?

Answer 3

Elicit immune responses in response to PAMPs or DAMPs

Question 4

What are the three parts of an inflammasome?

Answer 4

Upstream sensor
Adaptor molecule
Downstream effector

Question 5

What are inflammasomes named after?

Answer 5

Their upstream sensors

Question 6

What are the names of common inflammasomes?

Answer 6

NLRP1
NLRP2
NLRP3
NLRC4

Question 7

What is an example of an adaptor molecule?

Answer 7

ASC

Question 8

What does an adaptor molecule do?

Answer 8

Links the upstream sensor to the downstream effector

Question 9

What is binding of the domains governed by?

Answer 9

Protein-protein interactions between shared binding domains

Question 10

What is the main goal of an inflammasome?

Answer 10

To increase production of IL-1b and IL-18 which mounts an inflammatory response

Question 11

What is the net result of inflammasome assembly?

Answer 11

Cleavage of caspases into active forms to increase the production of cytokines

Question 12

What is the main cytokine produced by inflammasomes?

Answer 12

IL-1b

Question 13

What do the cytokines accomplish?

Answer 13

Pyroptosis

Question 14

What is pyroptosis?

Answer 14

Messy cell death

Combination between apoptosis and necrosis

DNA is cleaved and contents of the cell spill out

Question 15

How can pyroptosis be beneficial?

Answer 15

Pyroptosis of macrophages for example can lead to the spilling of pro-inflammatory cytokines which induce inflammation in damaged area

Question 16

How can inflammasomes become activated?

Answer 16

Via changes in the environment - membrane potential in response to damage to cell membrane causing leakage of potassium and ATP

Oxidative stress

Protease activity

Question 17

How are inflammasomes and crystal diseases related?

Answer 17

When macrophages ingest crystals, this activates NLRP3 inflammasomes

Causes IL-1b release

Question 18

What mutations in the inflammasomes has been linked to autoinflammatory diseases?

Answer 18

CAPS

Mutation to the NLRP3 gene

Leads to excessive IL-1b secretion

Question 19

How does the CAPS mutation lead to autoinflammation?

Answer 19

Mutations lower the threshold of inflammasome activation in the presence of other soluble factors

Question 20

What is the role of inflammasome in development of rheumatoid arthiritis?

Answer 20

Not well established

Question 21

What mutations in the inflammasome have been linked to rheumatoid arthiritis?

Answer 21

Homozygous carriers of RA have shown loss of function of a component of NLRP3 - CARD8

Polymorphisms in NLRP3 and CARD8 have increased susceptibility to develop RA

Question 22

What proof is there that inflammasomes are related to RA development?

Answer 22

Synovial tissue of RA patients have increased IL-1b concentrations

Question 23

What is the A20 gene?

Answer 23

RA susceptibility gene

Question 24

How is the A20 gene related to inflammasomes?

Answer 24

Absence of A20 show increased IL-1b and NLRP3

Question 25

What is the link between inflammasomes and SLE?

Answer 25

Inhibition of NLRP3, caspase-1 and IL-18 have shown to benefit nephritis in murine models of lupus

Question 26

How can we use inflammasomes as therapeutic solutions for diseases?

Answer 26

Anti-IL1 therapies have been successful in diabetes type II and juvenile arthritis