Crohn’s disease Ulcerative Colitis • 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 Crohn’s disease Ulcerative Colitis.
Luminal Microbial Antigens and Adjuvants • Infection and NSAIDS -Initiate non-specific inflammation and break mucosal barrier • Diet – Implicated by patients but mechanisms poorly understood • Aluminium and Iron may have adjuvant activity and stimulate bacterial virulence and dysbiosis • Stress – alters mucosal permeability and blood flow • Smoking – Contributor to Crohn’s but preventative to Ulcerative Colitis. • Appendectomy – Preventative against Ulcerative colitis • Persistent pathological infection.
o Mycobacterium Avium Paratuberculosis – Contributor to Crohn’s o Enteroadherent and Invasive E. Coli – likely cause of Crohn’s Environmental Triggers Mucosal Barrier Integrity – Breaks more easily Immunoregulation – Exaggerated response Homeostasis of Pathogenic:Beneficial Enteric Bacteria – Dysbiosis Implicated genes regulate several biological functions that affect: Weaker genetic link No gene specifically linked HLA factors (determine blood groups) can predict behaviour of pathogenesis.
T-helper type 1 and 17 cytokine mediated process, with deficient innate immune response An atypical T-Helper type 2 disorder showing natural killer cell and IL-13 activity More strongly implicated to commensal Increased numbers of enteric Bacteroides s. p. p and Enterobacteriaceae s. p. p shown in infected areas Persistent luminal antigen stimulation is required for transfer of Colitis Environmental triggers influence susceptibility to inflammation, increases uptake of commensal bacterial antigens and adjuvants and improves luminal microenvironment.