Term
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Definition
Gluten-sensitive enteropathy and nontropical sprue
Chronic, malabsorptive disorder triggered by exposure to gluten-derived gliadin peptides in wheat, barley and rye. |
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Term
| What is the basic cause of Celiac disease? |
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Definition
Short- Infection causes loss of gliadin tolerance
Loss of immune tolerance to gliadin (nontoxic food antigen) manifested in proximal small bowel, likely after an environmental stress such as infection.
Like IBD, CD induced by aberrant innate response in genetically predisposed individuals propagated by adaptive. |
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Term
| What are the 3 postulated mechanisms of oral tolerance? |
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Definition
All occur in the absence of inflammation
1 & 2 involve high-dose of antigen
3 involves low-dose of antigen
1) Down-regulation of TCR followed by apoptosis-mediated clonal deletion of antigen-specific cells (true in animals overfed with particular antigens)
2) Anergy because of lack of co-stimulation (resulting from overfeeding with antigens)
3) Low doses of antigens results in Treg-mediated suppression of inflammation (can mediate tolerance in transplanted naive animals) |
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Term
| What is the proposed pathogenesis of CD? |
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Definition
Gliadin peptides are resistant to proteolysis (P and Q) and arrive at mucosa in high concentrations
In pre-disposed patients (HLA-DQ2 and DQ8 alleles that bind tightly and present really well), T cells are overactivated in lamina propria
1) During inflammation, gliadin is released into lamina propria and transglutaminase deamidates it at Q to E, increasing its affinity for DQ-2/DQ-8
2) Propagated by dysregulated CD4+ T/B/yd-T response |
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Term
| What is the link between MHC-II HLA phenotype and susceptibility to CD? |
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Definition
| DQ-2 and DQ-8 bind gliadin particularly well, and EVEN BETTER if transglutaminase deamidates Q to E in gliadin. |
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Term
| Why is tissue glutaminase used to diagnose Celiac disease? |
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Definition
This enzyme is induced by inflammation to deamidate gliadin (Q to E), increasing its affinity for DQ-2/DQ-8 and increasing the T-cell response.
High levels of this enzyme mean that more gliadin is being presented to T-cells and a greater inflammatory response is likely to ensue. |
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