Magor-2 Flashcards
Function of TLR
- detect PAMPs and DAMPs
- produce antimicrobials, antivirals, cytokines; inflammation
3 parts of TLR
- has ligand-binding exterior domain
- membrane spanning domain
- interior Toll/IL-1R domain
Function of TLR Interior Toll/IL-1R domain (TIR)
- Interacts with TIR domains of other members of TLR signal transductions
- adaptor proteins bind here
What is the ligand-binding end of TLR made of?
- Leucine rich repeats (LRRs) (20-40 aa per repeat)
- has alpha helix and beta strand
What does TLR1 recognize?
- lipopeptides microbe (Gram -)
What does TLR2 recognize?
- Gram + bacteria
- parasite and fungus
What does TLR3 recognize?
dsRNA = virus
What does TLR4 recognize?
- LPS –> Gram -ve
- fungus
What does TLR5 recognize?
flagellin –> microbe
Example of TLR that binds directly to PAMPs
TLR5
What does TLR4 need to indirectly bind a PAMP?
CD14, MD-2 and LBP
What directs what type of cytokines made?
Adaptor molecules that bind the TIR domain
What do NLRs detect?
peptidoglycan and flagellin
What do RLRs detect?
ssRNA (-ve sense)
What can NLRs and RLRs do? (broadly)
amplify or block TLR signalling
What doe C-type lectin receptors (CLR) detect?
Carbohydrate PAMPs using CLR
4 types of pattern recognition families
TLR, CLR, RLR, and NLR
What molecules are normally on cell surface in healthy cells?
CD47 and CD31
2 major DAMPs
mitochondrial membrane and DNA
Who developed clonal selection theory?
Sir Macfarlane Burnet
Who proposed the idea of PAMPs and DAMPs?
- Charlie Janeway
- Polly Matzinger
What can TLR2 be paired with?
TLR1 and TLR6
What does TLR1/TLR2 recognize?
triacyl lipopeptide
What does TLR1/TLR6 recognize?
diacyl lipopetide
What is the TIR domain?
Toll and Interleukin-1 Receptor
What does SIGIRR doe?
negatively regulate TLRs
- blocks signalling
Structure of CLR signalling domain
has ITAM motif
What does ITAM stand for?
Immune Tyrosine Activating Motif
Where are PRRs found?
pAPCs, barrier cells (epithelial and mucosal cells), and endothelial cells
5 reasons for redundancy in pattern recognition
- makes sure host recognizes something in the pathogen
- reduce chances of autoimmune damage by cross-signalling
- better control of the type of response via cross-talk
- better control of the resolution of a response via cross-talk
- redundancy probably resulted from gene duplication events
Function of NLRs?
produce antimicrobials and cytokines, inflammation
Function of RLRs?
produce interferons and cytokines
Functions of CLRs?
produce antimicrobials and cytokines, inflammation and phagocytosis