Flashcards in PRRs and inflammation Deck (43)
What are teh 2 steps in production of IL-1b?
expression of pro-IL-1b and then cleavage by a protease
What is expression og pro-IL-1b regulated by?
syntehsis of its mRNA in a TLR dependent manner
what protease cleaves IL-1b?
What complex activates caspase-1?
How do type I IFNs play a central role in antiviral reponses?
induce apoptotic cell death in virally infected cells, render cells resistant to virus infection; activate acquired immunity; stimulate haemotpoietic stem cell turnover and proliferation
What happens when type I IFN receptors are activated?
phorphsorylation and nuclear translocation of ISGF3 (IFN stimulated gene factor 3)
What is the function of ISGF3?
induces expression og protein kinase R and OAS
What is the function of protein kinase R?
suppresses the proliferation of virus infected cells
What is the function of OAS?
activates RNAse L which cleaves viral nucleotides to inhibit virus replication
What suggests that cellular responses to TLR2 ligands differs depending on the cell type involved?
stimulation of TLR2 produces proinflammatory cytokines- not type I IFNs in macropahges in DCs however in inflammatory monocytes TLR2 activation did induce type I IFNs
As well as LPS, what else does TLR4 bind to?
viral envelope proteins
Which cells highly express TLR5?
DCs of the lamina propria in the small intensine
what happens to LPDCs in resposne to flagellin?
induces B cells to differentiate into IgA plasma cels and differentiation of naive T cells into Th17 and Th1 cells
Aside from DNA, what else does TLR9 response to?
hemozoin- produced by malaria parasite
Which cells highly express TLR7 and TLR9?
What must happen to TLR9 when it is recruited from the ER to the endolysosome?
processing by proteases such as cathepsins B, K and L in order to recognise CpG DNA
What is required fro the TLR7 recognition in the endosome?
What induces trafficking of TLR7 and TLR9 from the ER to the endolysosome?
stimulation with ligands or infection by viruses
What happens to ciruses that have entered the cytoplasm and delivers nucleic acids to the endolysosome?
engulfed by autophagosomes
What is autophagy?
self-proteins and damaged organelles are degraded in double-membraned vesicles called autophagosomes
What suggests that autophagy is important in TLR7 and TLR9 recognition?
absence of ATG5- a protein essential for autophagosome formation results in pDCs failing to produce type I IFNs
What links the polyubiquitin chain created by TRAF6?
lysine 63 (K63)
What happens to phosphorylated IkB?
degradation by the ubiquitin-proteasome system
What is the difference between signalling of TLR7 and TLR9 in cDCs vs pDCs?
in pDCs actiavte IRF and type I IFNs whereas in cDCs, IRF1 is activated resulting in IFN-b gene expression
What does TLR4 require for activating TRIF?
What are RLRs composed of?
2 N-temrinal CARDs; a central DEAD box helicase/ATPase domain and a C-terminal regulatory domain
What is the difference between the dsRNA recognised by RIG-I and MDA5?
MDA5 detects long dsRNA
Which part of hte RLR is responsible for binding to dsRNAs?
C-terminal regulatory domain
Where does STING translocate from and to in response to dsDNA?
from the ER to the golgi apparatus