Term
| How is IBD hypothesized to arise? |
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Definition
1) Induced by aberrant innate immune response against intestinal flora secondary to environmental change in genetically pre-disposed individuals
2) Adaptive immune response propagates the response |
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Term
| What is one explanation for the fact that IBD tends to originate in the distal illeum and the colon? |
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Definition
| These areas have the greatest floral diversity in the gut (# of bacteria) |
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Term
| Is the different population of bacteria seen in the gut of patients with IBD the "cause" or "effect" of IBD? |
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Definition
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Term
| What "non-immunologic" factors enhance host defense in the gut by limiting pathogen growth? |
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Definition
1) Gut secretions
2) Peristalsis
3) Epithelial tight junctions
** the normal flora prevent growth of Clostridium difficle** |
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Term
| How does the innate immune system defend again pathogens in the gut? |
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Definition
1) Epithelial borders
2) DCs and macrophages
3) Paneth cells (epithelia) release anti-microbial and defensin proteins
4) TLR and NOD2 (IL-1 and other cytokines) |
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Term
| What is the relationship between Paneth cells in the innate immune system and the development of IBD? |
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Definition
Paneth cells (epithelia) release anti-microbial and defensin proteins
GWAS identified polymorphisms in NOD2 (intracellular sensor for bacterial peptidoglycan-30/40% of Chron's) and ATG16L (Autophagy-altered granules and secretions) as predictors of IBD |
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Term
| What is the important of Peyer's patches in IBD? |
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Definition
They "educate" naive lymphocytes, which utilize a4b7 integrin (interacting with MadCAM-1 on endothelial cells) to migrate back to the gut.
PPs are adaptive immune regions in the terminal ileum that are overlaid with microfold epithelioid cells (M cells) which sample pathogens from the lumen. |
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Term
| How does the mAb natalizumab work to treat IBD? |
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Definition
| Inhibitor of alpha4-beta7 (lymphocyte):MadCAM-1 (endothelial) complex which allows lymphocytes "educated" in Peyer's Patches to migrate back to targets in the gut. |
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Term
| Why is TNF-a a target in IBD and how is it targeted? |
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Definition
| Infliximab (mAb) is given in Crohn's and UC to prevent immune-mediated inflammation by Th1 cells |
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Term
| What is the relationship between Th17 cell differentiation and IBD? |
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Definition
GWAS has implicated IL-23 axis in development of colitis (also in Th17 development), and polymorphisms have been linked to susceptibility
**CCR6 and EP4 (E2 prostaglandin receptor) have also been implicated** |
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Term
| What might the role of Tregs be in IBD? |
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Definition
| They suppress inflammation, so if they are not differentiating, you may get abberant inflammation. |
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Term
| How can you use the IBD humoral response to differentially diagnose UC and Crohn's? |
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Definition
Remember, there is a general IgA to IgG transition in both!
ASCA= Crohn's
atypical P-ANCA= UC
1) Anti-Saccharomyces cerevisiae (ASCA) in 40-80% of Crohn's, in terminal ileum and cemum, but unusual in UC
2) Atypical perinuclear antineutrophil cytoplasmic (atypical P-ANCA) Ab found in 60-80% of UC but <27% of Crohns. |
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