Mucosal immunity and diseases (Paul de Vos)
12 important questions on Mucosal immunity and diseases (Paul de Vos)
How does IgA cause the neutralizing and immunization of toxins?
2) IgA is able to bind and neutralize antigens internalized in endosomes.
3) IgA can export toxins and pathogens from the lamina propria while being secreted.
When it goes wrong and bacteria come in: describe the neutrophil extracellular trap (NETosis)
NET formation is associated with bacterial clearance, but also with thrombosis, sepsis and SLE.
We cannot live without commensals. What are the 4 uses of commensals?
- produce small chain fatty acids (SCFA)
- stimulates mucus production.
2) Inhibit pathogenic bacteria
- by decreasing luminal pH, bacteriocidal proteins, blocking epithelial binding
3) Immunoregulatory
- Stimulates anti-inflammatory cytokines (IL10 and TGF-b)
- Stimulates IgA production
4) Mandatory for our metabolism
- primary source vitamins
- digestion of complex diet components (cellulose)
- source for SCFA
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Behind the epithelium lies GALT (Gut associated lymphoid tissue). What kind of receptor keep the balance between immunity versus tolerance?
What is the physiological role of zonulin?
What is the pathophysiological role of zonulin in celiac disease?
2) Release of zonulin.
3) Zonulin causes claudin modification in the tight junction and causes a increase of permeability, gliadin now passes the lamina propria.
4) After deamination gliadin binds to MHC or HLA on APC or on CXCR3 expressing cells such as APCs, NK cells and T cells.
5) Cytokines are released by APCs and gliadin is presented to T cells.
6) The final outcome entails a huge activation of both humoral and cellular nature.
How can leaky gut be related to type 1 diabetes?
Which molecule causes the blockage in tight junctions for molecules > 3.5 kDa?
Which receptors and cytokines differ in APC to differentiate a CD4/CD8 or Treg cell?
Th# -> TLRs
What is the normal processing of macromolecules (< 3.5 kDa) through epithelial cells from intenstinal lumen?
Naive T cells that enter Peyer's patches from blood vessels directed by the homing receptor CCR7 and L-selectin. Describe how the homing progresses further, and how different chemokine receptors determine homing in the small and large intestines.
2) Activated T cells drain via mesenteric lymph nodes to the thoracic duct and return to the gut via the bloodstream.
3) Gut-homing effector T cells bind MAdCAM-1 on endothelium.
4) Activated T cells expressing alpha-4B7 integrin and CCR9 home into the small intestine.
T cells expressing CCR10 home into the large intestine.
In the lamina propria it is decided whether the mature T cells differentiate into intra-epithelial lymphocytes. How is this organized and what does this allow?
This allows binding to E-cadherin on epithelium.
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