Inflammasome Flashcards
What cell types does autoinflammatory rely on
B cells and T cells
What receptors recognise non-self antigens
TLRs and NLRs
Whats an NLR
NOD-like receptor
What do NLRs detect
DAMPs within the cytosol
What does cellular activation via PRRs like TLR and NLR lead to
ISER7 (IFN), NfkB (cytokines), IRE3(IFN) and API production (cytokines)
MD5A recgonised what nucleic acid
dsDNA
IL-1 via NfkB can lead to…..
Acute inflammation, cellular recruitement and affect the liver
How does IL-1 affect the liver
Liver will switch on acute phase proteins, these are massively upregulated: CRP (binds to phospholipids on bacteria), MBLs (complement system), phospholipases destroy cell membranes. Haptoglobin binds to toxic haem molecules when RBCs burst.
What is the central mediator of innate immunity and inflammation
IL-1beta
Why does IL-1beta need tight regulation
Affects from cell to system
How is IL-1 singalling mediated
Negatively regulated via receptor antagonist, soluble receptors and decoy receptors
How is IL-1beta activated regulated (to with its activity)
As it begins as an inactive precursor induced by PAMPs/DAMPs which undergoes proteolytic digestion. Can be degraded
Cleavage of IL-1beta is mediated by what?
Inflammasome
What does cleavage of IL-1beta lead to cleavage of,,,,, by what enzyme
proIL-1/pro-IL18 by Capsase-1 into their active forms
Stages of inflammasome activation
- Priming: causes increases in inflammasome components ( pro-IL 1/18, NLRPs). This occurs via PAMPs and DAMPs. Priming induces inflammasome component expression but not assembly. NLPR3 is regulated by miR-223 and EBV miRNA. Binding to TLR (MyD88pathway) or TNFR.
- Second signal- assembly of NLRPs, procaspase 1 and pro IL-1/18. Influx of ions, phagocytosis of parasites inflammasome assembly/
- Generation and release of active IL-1/18 (caspase 1 dependent manner).
Pyroptosis (caspasd-1 or caspase 11 dependent cell death) – cell death characterised by cell rupture, continuous cell expansion.
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What domain are caspases recruited by
CARD
What nuclear protein family regulated caspase activation and what cytokine induces them
HIN-200 by IFN
Name three types of receptors that trigger inflammasome activity
RIG-1, NLRP3, IFI-16
What stimulates NLRP activation
ROS production, release of mtDNA, translocation to mitochondria
K+ efflux
Lysosomal damage
What does inflammasome activation lead to and how
pyroptosis. Memrbane swelling and rupture, this is mediated by pores and gasdermin D which makes then up.
Cleavage of what two molecules is required for pore formation and membrane rupture
Cleavage of Gasdermin D and ninjurin-1 are required for pore formation and membrane rupture:
Release of IL-1beta and other small proteins and ionic flux via GSDMD-NTD.
NINJ1 filament formation causes membrane rupture –> release of larger cytosolic components.
What molecule class is released from pyroptotic cells (hint: wee woo)
Alarmins
What is CAPS
Crypyrin associated autoinflammatory syndrome
What is CAPS caused by
Overactivation of inflammasome
Famililal cold autoinflammatory syndome FCAS: Trigger and MOA
Cold, conformational change of NLRP3
Is gout an aquired CAPS, what triggers the NLRP3
Yes, uric acid
Familial mediterranean fever patients are more resistant to what bacterial infection
Y. pestis
What could be a potential mechanism behind atherosclerosis
NLRP3 inflammasome activation via cholesterol crystals maybe mechanism behind atherosclerosis.
What is the therapy of resistant gout
Anakinra (IL-1 blocker)
What is DIRA
Deficiency of IL-1RA
What is IL-1RA
IL_1 receptor antagonist
DIRA leads to the lack of regulation of
IL-1R
Generalised pustural psiorasis is mediated by what interleukin being mutated or having a lack of
IL-36
DITRA
Deficiency of IL-36RA
IL-36 is in what cells
Gut and epithelial cells
What type of inflammasome do bacteria effector molecules inhibit
NLRC4
Examples of bacteria that inhibit the NLRC4 inflammasome
P. aerguniosa and Yersinia spp.
Mtb (macrophage infected with TB) inhibit what thus activtating inflammasome
ROS production
KSHV encodes what homogue with interacts with host NLRP1,3 and NOD2
NLRP1 homolog that lacks PYD and CARD
M13L is a PYD-contain protein of what virus
Poxvirus
M13L interacts with what proteins preventing inflammasome activation
ASC
Rabbit poxivirus encodoes what enzyme which inhibits caspase-1
Serine protease
Vaccinia virus encodes whar type of binding proteins against inflammasomes
IL-1beta/IL-18 BPs
