Innate immuntity - Receptors
10 important questions on Innate immuntity - Receptors
Which TLRs are only known in mouse?
What is a broad name for all the ligands recognised by TLRs?
What is the main component of the extracellular region of a TLR?
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Describe the activation of NFkB through TLR signalling
2. TRAF-6 is polyubiquitinated, creating a scaffold for activation of TAK1
3. TAK1 associates with IKK and phosphorylates IKKb, which phosphorylates IkB
4. IkB is degraded, releasing NFkB into the nucleus to induce expression of cytokine genes
Which proteins contain TIR?
Which proteins contain a DD (death domain)?
Which proteins contain DED (death effector domain)?
What does binding of bacterial ligands to NOD induce?
2. RIP2 associates with E3 ligases (XIAP, cIAP1 and cIAP2)
3. E3 ligase activity produces a polyubiquitin scaffold which associates with TAK1 and the IKK complex
4. NFkB activation
Describe the stimulation of type 1 interferon production through activation of RIG-I-like receptors
2 Conformational chage of the CARD domains, to become free to interact with the amino-terminal CARD domain of MAVS.
3. Generation of K63-linked polyubiquitin from E3 ligases (TRIM25 or Riplet).
4. Aggregation induces a proline-rich region of MAVS to interact with TRAFs and leads to the generation of additional K63-linked polyubiquitin scaffold
5. Scaffold recruits TBK1 and IKK complexes that activate IRF and NFkB, producing type I interferons and pro-inflammatory cytokines
Describe the activation of type 1 interferon production through cGAS
2. Stimulation of the enzymatic activity of cGAS leading to production of cyclic GMP-AMP (cGAMP)
3. Bacteria that infect cells produce second messengers like c-di-GMP and c-di-AMP
4. cGAMP and these bacterial cyclic dinucleotides bind and activate STING dimer present on the ER membane
5. STING activates TBK1
6. Active TBK1 activates IRF3 through phosphorylation, which enters the nucleus and induces expression of type I interferon genes
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