Tolerance is key in the gut
9 important questions on Tolerance is key in the gut
Name some immunomodulatory products of intestinal microbiota.
Polysaccharide A
Short chain fatty acids
PTGN
How can short chain fatty acids affect health?
They regulate inflammation via GPR43 and GPR120 and affect ROS formation negatively. They also regulate cytokine production
What effect does butyrate have on the epithelial cells of the intestine?
They act as main food resource for the cells and are actively transported.
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What immunomodulatory effect do omega 3 fatty acids have?
anti-inflammatory and anti-diabetic effects via the GPR120 receptor on macrophages.
How does mucosal immune defence work?
Secretory components (a polymery Ig receptor) actively transport IgA and IgM into the lumen. This is stimulation by the uptake of antigens via M cells. Some non-adherent soluble antigens as well as local microbiota on the other hand side supress pro-inflammatory Th2 responses, namely IgE, Th1 dependent delayed hypersensitivity and Th17 dependent granulocytic reactions.
Which sites of the intestinal immune system are there and what is their function?
The inductive site is the GALT, namely Peyer's Patches. Here, exogenous antigens are actively transportet to reach APCs like macrophages, Bcells, DCs and follicular DCs. Here, B and T cells are primed and then wander via lymph to mesenteric lymph and then via thoraic duct to peripheral blood for extravasation at mucosal effector sites, which is the second site of the intestinal immune system. The endothelial cells here express a gatekeeper function by expressing adhesion molecules and cytokines.
Which paths to oral tolerance are there?
- antigens can be processed by epithelial cells and presented on MHC
- they can cross the epithelium and then be transported into the liver
- they can be captured by macrophages and transported into the lymph
- DCs can capture them in the gut lumen and transport them into the lymph
all of the pathways finally lead into the spleen
What is important about gut DCs?
They express retinoid acid which they make from vitamin A
they can drive Treg differentiation from Foxp3
How are Tregs in the gut inducted?
by DCs
by CD11p monocytes via the CCR7 and CCR9 receptors
by co-stimulation by PDL1 programmed cell death ligand
possibily by the liver via antigen uptake by plasmacytoid DCs
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