• Different genetic abnormalities can lead to similar disease phenotypes. • Genes associated with Crohn's disease are not implicated in Ulcerative Colitis • There is similar chromosomal susceptibility in CD and UC.
Mutant CARD15 causes;
Decreased antimicrobial peptide secretions
from Paneth cells of the small intestine
Defective down-regulation of innate immune
response to bacterial adjuvants
Ineffective clearance of intra- cellular
bacteria infections Proliferation of luminal and mucosally
adherent commensal bacteria
Anti TNF (tumour necrosis factor) may
also cause inflammation
• Innate and acquired immune systems are activated
• Loss of tolerance to enteric commensal bacteria
• Cells of Innate immune system response are similarly activated • Proinflammatory cytokine and chemokine expression is upregulated • Expression of adhesion molecules and costimulatory molecules is increased
• Enteric microflora stimulate
immune responses either by
functioning as adjuvants or antigens.
o Adjuvants activate innate immune responses, including dendritic cells and other APCs o Antigens stimulate the clonal expansion of T cells that selectively recognize the antigen through their T-cell receptor leading to aggravated T-cell response • There is both bacterial and host specificity to each disease
Luminal Microbial Antigens and Adjuvants
• Infection and NSAIDS -Initiate non-specific inflammation and break mucosal barrier • Diet - Implicated by...
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