Gastrointestinal tract cell-mediated responses

As mentioned earlier, an understanding of the role of the mucosal response is critical, especially for protection via the respiratory or gastrointestinal tracts, as well as the importance of the humoral versus the cell-mediated response. Antimicrobial drug supplementation may also provide added benefit for immediate or short-term protection. 

PARs are coupled to multiple G-proteins and mediate a number of well-defined cellular responses via classical second messenger and kinase pathways. PARs are differentially expressed in cells of the vasculature as well in the brain, lung, gastrointestinal tract, skin as well as other highly vascularised tissues and evidence suggests distinct physiological functions and roles in disease states [2]. 

Histamine plays a central role in immunologic and anti-inflammatory responses, particularly in the immediate hypersensitivity response. Three subclasses of histamine receptors have been identified Hj, Hj, and Hj receptors. Hj receptors are involved in mediating increased vascular permeability, pruritus, coutraction of smooth muscle in the respiratory and gastrointestinal tracts, release of mediators of inflammation, and recruitment of inflammatory cells. Among other effects, Hj receptors mediate the negative feedback control of histamine synthesis and release and may play some defensive role against excess bronchoconstriction. H, and Hj receptors are both found primarily in bronchial smooth muscle in the human respiratory tract (40). 

Sensitized cells release specific cytokine and chemokine mediators that can be quantified. These include substances such as histamine and tryptase, as well as markers of inflammation in the gastrointestinal tract. The latter may be of value in the evaluation of allergic response since inflammation is a risk factor for increased sensitization. Markers of intestinal inflammation include eosinophil cationic protein in serum and feces, a-1 antitrypsin, and tumor necrosis factor alpha (Majamaa et ak, 1996). Skin prick and patch tests have good negative predictive value, but poor positive predictive value, and therefore are of more limited use in clinical testing. 

The physiological and pharmacological effects of histamine are mediated through four different receptors Hi, Hj, Hj, and Ht, all members of the 7-transmembrane g protein-coupled receptor (GPCR) family with amino terminal glycosylation sites and phosphorylation sites for protein kinases A and C. The receptors are widely expressed on different tissues that are responsive to histamine. For the Hi receptor these tissues include smooth muscle cells of the airways and vasculature, the gastrointestinal tract, cardiovascular system, neutrophils, endothelial cells, T and B cells, hepatocy tes, nerve... 

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