Integrative immunophysiology in the intestinal mucosa

Over the past ten years, it has become evident that intestinal epithelial functions such as ion secretion are a host defense response to the presence of antigens, microbes, and other noxious substances in the gut lumen. Such responses are mediated by the activation of immune cells in the mucosa causing release of chemical mediators that act directly or indirectly on the epithelium. Frequently, immune cell products stimulate enteric nerves resulting in amplification. Thus immune cells and nerves form interactive units that can recognize various stimuli both specifically and nonspecifically and initiate mechanisms to eliminate offending material. Here, we review the current state of knowledge regarding immune regulation of epithelial physiology with particular emphasis on the ability of immune cells and their products (biogenic amines, cytokines, arachidonic acid metabolites, oxidants) to alter electrolyte transport. The mast cell will be highlighted in this scheme as this cell has been, and continues to be, the focus of extensive research efforts. However, recently it has become apparent that cells such as lymphocytes, macrophages, and polymorphonuclear leukocytes also play important roles in immunophysiology. The effect of immune cell activation on epithelial functions other than transport, such as permeability, proliferation, and antigen presentation, will be described where appropriate. Finally, we will present evidence that the enterocyte can express an "activated" phenotype and thus participate directly in mucosal immune responses.