Summary: L7-8 Ii: Intestinal Immunity Ii | Jerry Wells
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Read the summary and the most important questions on L7-8 II: Intestinal Immunity II | Jerry Wells
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1 TLR
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Why do TLR1-2 and TLR2-6 bind to each other?
It will yield the highest affinity in binding the lipid chain of microbes.
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What does TLR2-6 bind?
Lipoteichoic acid (LTA), in cell wall of Gram+ bact.
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How does TLR2-6 bind?
Lipid chains in LTA bind to TLR2, the head group contacts TLR6 to form an active heterodimer.
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How is LPS build up?
Variable O-specific chain: used for identification
Conserved core region
Conserved Lipid A, which binds to TLR4 -
What is the cascade of LPS binding to TLR4?
LPS binds to LBP (LPS-binding protein)
Interacts with CD14
LPS binds to TLR4 monomer with MD2 co-receptor
TLR4 receptor dimerization: MyD88 -> early NF-kB
Internalization: late NF-kB and type I IFNs -
What is the signalling pathway for extracellular TLR4/5/9?
MyD88 --> phosphorylation of IKB (degradation of NF-kB inhibitor)
NF-kB into nucleus -> Type 1 IFN/infl. cytokines en chemokines -
What is the signalling pathway of endosomal TLR3/4?
Via TRIF, two ways:
Type 1 IFN in nucleus
via NF-kB into nucleus: inflammation cytokines and chemokines -
2 Epithelial cells
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What is the polarisation of eptihelial cells, and how is it maintained?
Due to tight junctions, different receptors/structures are either present on the basolateral or apical surface.
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How does polarization aid epithelial function?
It allows the gut to be permeable, yet still forms a barrier vs. pathogens.
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How is TLR9 distributed over an epithelial cell, and where will it lead to IL-8 production?
TLR9 (CpG DNA) is present both apical and basolateral, but it only activates IL-8 production on the BL side.
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