Immune system intestinal barrier

The leading hypothesis for the development of chronic intestinal inflammation is that an abnormal immune response to normal flora might be crucial. This loss of tolerance might be due to a lack of regulatory mediators or cells, or a breakdown in barrier function which makes possible the access of inflammatory bacterial products to the local immune system, thereby overwhelming the normal regulation [3], These possibilities were supported by... 

Abstract This chapter attempts to give an overview on the properties of the intestinal epithelium with regard to both, barriers to transcellular (transporter and efflux systems) and paracellular (tight junctional complex) drug absorption and transport systems and tight junction modulation. A short introduction into the relation between the innate immune system and modulation of paracellular permeability is equally given. 

Once Salmonella invade the intestinal barrier, the bacteria encounter host immune cells such as neutrophils, lymphocytes and macrophages, which engulf the bacteria (Fields et al., 1986 McCormick et al., 1993) (Fig. 5.1). Salmonella serotypes capable of causing gastroenteritis are killed by host macrophages, and effectively cleared by the immune system. Invasion of M cells and intestinal epithelial cells induces a pro-inflammatory response in the intestinal mucosa (Fig. 5.1a). A combination of inflammatory cytokine production, neutrophil infiltration and fluid and electrolyte secretion by the epithelium results in the diarrhea associated with gastrointestinal enteritis (Fig. 5.1a). 

There is accumulating evidence that the interaction between the intestinal microbiota and the gut plays an important role for the postnatal development of the immune system. However, the interactions between the intestinal epithehal and immune cells and the different species of the intestinal microbiota are very complex and not fully understood. The complexity of these interactions is based on the fact that on the one hand the human defense system consists of several layers, for example, of mechanical and chemical barriers (first line of defence) as well as innate and adaptive immunity (67) all of which can be influenced by microbiota (68). 

Regarding the well-described toxic activity of DON against the immune system, alterations of the immune cells could affect the intestinal and brain functions, as recently desciibed. In particular, the intestinal and systemic production of cytokines could participate in the growth retardation, feed refusal and emesis caused by DON on account of the effects on the neuroendocrine system. The consequent inflammation could lead to an increased permeability of the intestinal and blood barriers, thus affecting the xenobiotic absorption. 

Catheter-related sepsis is the most fire-quent complication in patients receiving home parenteral nutrition for short bowel syndrome. A low-grade systemic inflammatory state and an altered mucosal immune response, as well as diminished intestinal barrier function have been characterized in these patients. The possibility of systemic immunocompromise has only recently been suggested. 

The balance and composition of microbiota is extremely important to modulate the immune system and to influence the development and physiology of the host (Brestoff and Artis 2013). During stress, permeability and the intestinal barrier function are altered. Probiotics are able to reinforce the epithelial barrier, as was demonstrated by different studies (Zareie et al. 2006 Ait-Belgnaoui et al. 

Bacterial translocation is defined as the passage of viable indigenous bacteria from the GI tract to extraintesti-nal sites, such as the mesenteric lymph node complex, liver, spleen and bloodstream [183], Three major mechanisms promote bacterial translocation intestinal bacterial overgrowth, deficiencies in host immune defenses and increased permeability or damage to the intestinal mucosal barrier [184], These mechanisms can act in concert to promote synergistically the systemic spread of indigenous translocating bacteria to cause lethal sepsis. 

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