Inflammatory Bowel Disease and Celiac Disease Flashcards
What is a particular type of epithelial cell in the gut mucosa that promotes host defense against bacteria via anti-microbial enzymes and defensin proteins?
Paneth cells; implicated in IBD
What are the two main susceptibility loci within epithelial cells that confer risk for IBD?
NOD2 and ATG16L1
What is the role of NOD2 in gut immunity?
Intracellular sensor of bacterial antigens
What types of mutations are there in NOD2 in IBD?
The mutations appear to attenuate NOD2 signaling. 30-40% of Crohn’s patients have NOD2 polymorphisms
What is the postulated role of ATG16L1?
Role in autophagy. If mutated in Paneth cells, there is abnormal granule exocytosis and altered inflammatory gene expression prolifes
What drug targets TNF-alpha that is used in IBD?
Infliximab
What co-receptor do gut macrophages not express in order to maintain an attenuated state?
Do not express a co-receptor CD14 for TLR-4 to detect LPS
What drug targets the alpha4beta7 integrin for IBD treatment, and how does it work?
Vedolizumab targets this. It works because alpha4beta7 is a gut homing integrin that brings activated lymphocytes that are destined for GALT to their location.
What is the predominant lymphocyte and Ig isotype present in the gut?
B cells are predominant, and the IgA plasma B cell is the most dominant. 30 - 40% of mucosal cells.
In IBD, what transition of isotypes for antibodies takes place?
In IBD, transition from IgA predominance to IgG predominance
What are the main IBD associated antibodies?
ASCA antibodies (Anti-saccharomyces cerevisiae) more specific for Crohn's atypical P-ANCA antibodies, more specific for ulcerative colitis
Celiac disease is due to enhanced gluten protein translocation across epithelia into lamina propria. What makes the gluten more immunogenic in the lamina propria?
Enzyme tissue transglutaminase (TTG) which deamidates gliadin proteins at glutamine residues
What are two ways that TTG increases immunogenicity in celiac disease?
Antibodies may form against TTG, and IgA anti-TTG is a diagnostic test for celiac. Also, TTG makes gluten more immunogenic by deamidation at glutamine residues.
What are the two key MHC class II mutations that are found in celiac disease? What is their mechanism of how they cause disease?
HLA-DQ 2 and/or HLA-DQ8. Over 95% of celiac patients have these genes. Class II presentation of gliadin proteins activate Th1 which release proinflammatory cytokines like IFN-gamma
What are intraepithelial lymphocytes (IEL) and how do they contribute to celiac disease?
IELs are a subset of CD8+ lymphocytes that have some NK cell properties. In celiac disease, they have an NK phenotype and kill intestinal epithelial cells
