Inflammatory Bowel Disease: Mucosal Immune Dysregulation

Inflammatory bowel disease (IBD) encompasses Crohn's disease (CD) and ulcerative colitis (UC), both characterized by chronic relapsing mucosal inflammation driven by dysregulated immune responses to gut microbiota in genetically susceptible individuals. In Crohn's disease, the immune dysregulation is primarily Th1/Th17-mediated with excessive TNF-alpha, IFN-gamma, IL-12, and IL-23 production. The inflammation is transmural (involving all bowel wall layers), skip lesions (discontinuous), and can affect any GI segment from mouth to anus (most commonly terminal ileum and proximal colon). Transmural inflammation leads to complications: strictures (fibrosis), fistulae (abnormal connections between bowel and adjacent structures), and abscesses. Pathognomonic findings include non-caseating granulomas (present in 30-50% of biopsies) and cobblestone mucosa (alternating deep ulcers with edematous mucosa). In ulcerative colitis, the immune response is Th2-mediated with prominent IL-5, IL-13, and NKT cell activation. Inflammation is limited to the mucosa and submucosa (superficial, not transmural), continuous (no skip lesions), and always involves the rectum with variable proximal extension (proctitis → left-sided colitis → pancolitis). UC features crypt abscesses (neutrophilic infiltration of colonic crypts), pseudopolyps (islands of regenerating mucosa), and continuous mucosal inflammation. The critical distinction...