PAMPs Flashcards
Membrane PRR expression: TLR4
Complex of TLR4, MD2, CD14 and LPS
TIR domain of TLR4 binds to MyD88
MyD88 activates IRAK4, which phosphorylates TRAF6 -> phosphorylates IKK (Activates) -> phosphorylates I kappa B
-> I kappa B degrades, NF kappa B releases
NF kappa B activates -> allowing cytokines to be transcribed, translated and secreted
Endosomal membrane PRR expression: TLR3
TLR3 binds to dsRNA driving production of TRIF
Either produces NK kappa B or signals transcription factor IRF3
initiates transcription of type 1 interferons
Release of IFN-alpha/beta
Inhibits viral protein synthesis
Degrades viral RNA
Inhibits of virus assembly
Activates other cells of the innate response (e.g., APCs, NK cells)
Increases antigen presentation and expression of MHC-I
Dimerization of TLR4
MD-2 and CD14 are accessory proteins that are essential to TLR4s recognition of LPS
LPS has multiple fatty acyl chains
Five can bind to MD-2
One can bind to the outer TLR4
makes a dimer and triggers intercellular signalling
RLRs
cytosol
RIG-I-like receptors (RLR) recognise viral RNA present in the cytosol
Presence changes confirmation which allows it to bind to MAV (mitochondrial antiviral signal)
aggregated MAVs recruits TRAFs and induces the activation of IRF3 and NF kappa B
Induce secretion of inflammatory cytokines and IFN-a/b
cGAS-STING
sensor of dsDNA that leads to the production of cyclic GMP-AMP
cGAMP bind to STING dimer present on the ER membrane
STING activates the kinase TBK1 to phosphorylate IRF3, which enters the nucleus and induces expression of type 1 interferon genes
Inflammasome
Multiple NLRs join together to kill cell!
Needs TWO signals (danger + stranger signal)
Activates caspase-1
Cleaves pro-IL-1beta, pro-IL-18 (leaves cell pro-inflammatory), and gasdermin D (forms a pore)
NLRs
NOD proteins activated by dimerising, certain peptides produced by intracellular bacteria bring the domains together
- Lead to the recruitment RIP2
- Activating TAK1 leading to NF kappa B activation
