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Immune and microbial mechanisms in the pathogenesis of inflammatory bowel disease

Scott B Snapper, MD, PhD
Clara Abraham, MD
Section Editors
Paul Rutgeerts, MD, PhD, FRCP
E Richard Stiehm, MD
Deputy Editor
Kristen M Robson, MD, MBA, FACG


The immune response has long been implicated in the pathogenesis of inflammatory bowel disease (IBD), including both ulcerative colitis and Crohn disease. A vast body of literature has identified roles for both host and microbial factors in the pathogenesis of IBD, ultimately leading to inappropriate immune responses to microbes residing in the intestinal lumen [1].

This topic review will focus on our expanding understanding of the immune, microbial, and genetic factors involved in both the initiation and maintenance of IBD. The epidemiology, risk factors, clinical manifestations, diagnosis and management of IBD is discussed in detail separately. (See "Definition, epidemiology, and risk factors in inflammatory bowel disease" and "Clinical manifestations, diagnosis and prognosis of Crohn disease in adults" and "Overview of the medical management of mild to moderate Crohn disease in adults" and "Overview of the medical management of severe or refractory Crohn disease in adults" and "Clinical manifestations, diagnosis, and prognosis of ulcerative colitis in adults" and "Management of mild to moderate ulcerative colitis in adults" and "Management of severe ulcerative colitis in adults".)


In the process of carrying out the absorption of essential nutrients, the human intestine must discriminate between innocuous food antigens and infectious or toxic agents. To protect the host from the latter, the intestine relies upon an effective barrier and an innate and an acquired immune system (figure 1):

The effective barrier depends upon an intact intestinal epithelium, with its overlying surface mucus secreted by goblet cells, normal peristalsis, and the secretion of numerous protective factors (eg, antimicrobial proteins, growth factors). Studies have shown that, in addition to their role in producing mucus, goblet cells actively participate in the delivery of antigens from the intestinal lumen to cells in the intestinal lamina propria [2].

The innate immune system is comprised of myeloid-derived cells (neutrophils, monocytes, dendritic cells, and macrophages), natural killer cells, and innate lymphoid cells. These cells, in addition to epithelial cells, endothelial cells, and stromal cells, express so-called pattern recognition receptors, which bind stereotypic microbial products. In combination, these cells provide the initial response to either pathogenic or commensal micro-organisms.

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