Immunobiology -- A healthy enteric immune state has, at its foundation, the capacity to prevent inflammatory cytokine release and mediate damage. The gut is an exernal environment assaulted with high loads of antigens but also harbors the largest and most diverse microbiota of over 500 species of bacteria. In a healthy immune state, no inflammatory response is activated, whereas the pathophysiology of IBD results in a hyperactive immune state and subsequent alignment of histamine and neurokinin and leads to mesenteric pain. Commensal bacteria modulate gene expression in nutrient absorption, mucosal barrier reinforcement and postnatal intestinal maturation. The symbiotic relationship is established during the first two to three years of life. During colonization, the mucosal immune system matures and oral tolerance is established. Intestinal epithelium serves as a defensive barrier. Defective mucus production is part of the pathophysiology of people with Crohn's and UC.
Specialized Paneth cells produce antimicrobial proteins against gram positive and gram negative baceteria which regulate microbial density and protects nearby stem cells. Pattern-recognition receptors identify microbe-associated molecular patterns. NOD proteins are located in the cytoplasm of antigen-presenting cells that have been exposed to peptidoglycans. They are usually little present in intestinal epithelium but NOD 1 and 2 rise upon insult by inflammation and inflammatory cytokines. NOD 2 is found in Paneth cells and stimulate NF Kappa B.
Mucosal lymphoid tissues contain T cells, B cells, granulocytes, mast cells, NKCs and NK T cells. Highly-specialized enterocytes reside between the epithelium and lymphoid tissue. By their structure and function, villi cells channel antigens to Peyers patches, lymphocyte clusters where antigen-presenting cells are present. Of these, dendritic cells open tight junctions between epithelial cells and directly sample bacteria without compromising the barrier. In this way, immunity is maintained against pathogens and tolerance toward commensals.
Pathophysiology -- IBD results from inappropriate response of a defective mucosal immune system to normally-existing flora and antigens. Several interacting pathways may trigger inflammatory cascades. Seven system malfunctions are identified in the pathophysiology of IBD:
- People with IBD have leaky epithelial barriers and these precede disease onset. The mechanism is hypothesized to be a result of T cell disruption of tight junction proteins to enteric neuron dysfunction.
- The innate immune mechanism of the epithelial layer is also disturbed, with different TLR expression patterns than those in healthy subjects.
- Dendritic cells may not recognize commensal bacteria and thereby cause a proinflammatory response.
- Non-professional antigen-presenting cells which normally produce inaction become potent effector T cell activators in people with IBD.
- Activated T cells persist rather than undergo apoptosis.
- The balance of regulatory and effector T cells is disturbed in IBD to the favor of effector T cells.
- Psychological stress triggers through the vagus nerve an inflammatory response that induces cytokine production. In UC, stress causes paracellular permeability.
The article is very well written, provides excellent and fine detail in special blocks, pros and cons, hypothetical information and clearly understood figures. I do hope you will take the time to look into the article. I look forward to your questions and comments.
Baumgart, Daniel C., and Simon R. Carding. "Inflammatory bowel disease: cause and immunobiology." The Lancet 369.9573 (2007): 1627-1640.
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