L13-14: Inflammation

Question 1

Pyroptosis mechanism in Salmonella infections

Answer 1

Flagellin is recognised by DC through NLRC4 inflammasomes in the spleen and cleaves pro-IL-18 into its active form.
IL-18 activates memory CD8+ T cells and elicits the IFN-γ response.
CD8+ T cells provide IFNγ irrespective of their TCR

Question 2

Two mechanisms by which inflammasome contributes to Salmonella immunity

Answer 2

1. Enabling recognition of pathogens that hide within phagocytes by eliciting pyroptosis of those cells. This exposes the pathogens from the intracellular hiding site to the extracellular space, where neutrophils elicit an immune response.
2. Flagellin-activation of the NLCR4 inflammasome by DC in the spleen leads to activation of IL-18 which can bind to NK cells as well as memory CD8+ T cells which provide protective IFN-γ.

Question 3

5 cardinal signs of inflammation

Answer 3

Tumor, Calor, Rubor, Dolor, and Loss of function

Question 4

Swelling in inflammation is due to

Answer 4

increase in fluid - oedema

Question 5

Redness and heat in inflammation are due to

Answer 5

increased vasodilation

Question 6

Pain in inflammation is due to

Answer 6

activation of free nerve endings by some of the mediators elicited by the immune response

Question 7

IL-1 production by inflammasome activation

Answer 7

NLR stimulation converts pro-caspase I to caspase I. Caspase I converts the inactive pro-IL-1-β to IL-1.
This requires the stimulation through TLR as pro-IL-1β transcription only occurs after stimulation of the TLR.

Question 8

Signal 1 + 2 of inflammation

Answer 8

Signal 1: Signalling through the TLR induces NFκB activation which leads to gene transcription producing pro-IL-1β, as well as upregulating NLRP3.
Signal 2: NLR stimulation leads to conversion of pro-caspase I to caspase I. Caspase I is then able to cleave pro-IL-1-β to IL-1.

Question 9

Ligands and factors that activate inflammasomes

Answer 9

K+ efflux, pore-forming toxins, CT, candida

Question 10

AIM2 inflammasome responds exclusively to

Answer 10

nucleases (DNA sensor) - cytosolic pathway of recognising dsDNA (from viruses and bacteria)

Question 11

NLRC4 inflammasome exclusively responsive to

Answer 11

proteins; two types of ligands: flagellin and T3SS.

Question 12

Which molecule is required for recognition of flagellin

Answer 12

Naip5