Intact, antigenic proteins are thus prevented from reaching the L

Intact, antigenic proteins are thus prevented from reaching the LP [16,17]. Tight junctions between the apical pole of enterocytes are another factor that contributes to shielding LP against the intestinal lumen content [18]. These junctions are formed of transmembrane proteins – claudins, occludins and junction-associated molecules, connected to the cytoskeleton by another protein structure, zonula occludens. The tight junctional complexes allow only small molecules, less than 500 Daltons in molecular mass, to cross Caspase phosphorylation between cells [19]. These

types of small molecules are usually not immunogenic. Tight junctions differ in permeability along the intestine, being more permeable in the large bowel than in the jejunum. They are also sensitive to the immune medium in the intestinal mucosa, manifesting an increased leakiness after check details prolonged exposure

of epithelial cells to high levels of tumour necrosis factor (TNF)-α, interleukin (IL)-13 or low levels of IL-10 [20]. An increased transcytosis of intact proteins was found in animal models of allergic diseases, which supports the importance of the intestinal epithelium as a mechanical barrier [21]. In these animals, epithelial permeability of allergens seems to be mediated by CD23/FcεRII and is antigen-specific, given the involvement of immunoglobulin (Ig)E [22]. CD23 is a molecule normally present on the surface of enterocytes, GPX6 both in humans and in rodents [23]. A high rate of CD23-mediated IgE transfer from the basal to the

apical pole of the enterocyte was found in allergic individuals, followed by intraluminal allergen binding and return of the antigen–antibody complex in LP, with the possibility of mast cell activation [24]. The epithelial barrier protects the internal medium not only from food antigens, but also from bacteria. The distal small bowel, caecum and colon have higher bacterial colonization levels than the proximal regions, reaching 1012 colony-forming units per gram of intestinal content in the colon. Sixty per cent of the faecal matter mass in humans is due to bacteria. The small intestine contains lower numbers of commensal bacteria as a result of stomach acid, pancreatic enzymes and motility patterns [25]. Instead, the small intestine contains higher levels of nutrients, available for absorption. The distribution of the immune structures is correlated inversely with the density of luminal bacteria. The small intestine has higher numbers of intraepithelial T cells than the colon; it also harbours lymphoid structures such as Peyer’s patches, which are absent in the large intestine. Paneth cells, which produce anti-microbial peptides, are almost confined to the small intestine, being only marginally encountered in the caecum and appendix.

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