Chapter 26 - Gut Barrier: Adaptive Immunity

Abstract

The adaptive immune system occurs is present in only the 1% of multicellular organisms that have a longer life span and the ability to supply the high cost of the energy demands of an adaptive immune response. A prime directive of the immune system is to recognize self versus nonself in order to distinguish harmless versus harmful signals. Thus, adaptive immune cells provide the host with the ability to recognize a near infinite number of different antigens. In addition, the adaptive immune effector lymphocytes (T and B cells) develop immunological memory that allows the elimination of pathogens more quickly upon a subsequent exposure. Memory responses shorten the subsequent duration of associated functional changes such as reduced mucosal barrier function. The mucosal barrier in the gastrointestinal (GI) tract is a complex and highly integrated functional system. As an interface, the mucosa can be thought of as an extension of self with the epithelial cells forming a self-aware and selective barrier to the unrestricted passage of luminal contents. Regulation of barrier function involves a cross talk among epithelial cells and luminal factors as well as the immune cells in the lamina propria. In response to tissue injury, inflammation or infection, the coordination of the transcription factors and signaling pathways is critical for the regulation of epithelial cell renewal that is modulated by the adaptive immune system. In addition, changes in differentiation and maturation of epithelial cells exert a major effect on mucosal barrier integrity. The number and proportion of each of the cell types that compose the epithelium are regulated by the immune environment, as each cell expresses receptors for both pathogens as well as for immune cell mediators. The diversity of function along the GI tract is reinforced by regional differences in the number and type of resident immune cells. Tissue injury, inflammation, or infection also increases the number of innate immune cells, many of which actively participate in the adaptive immune response. The resulting profile of recruited immune cells leads to a release of mediators that affect epithelial cell permeability by direct or by indirect effects. The targets of the adaptive immune mediators include epithelial self-renewal, tight junction complexes, host receptors such as protease-activated receptor-2, and transcriptional networks such as the signal transducers and activators of transcription that program the expression of specific gene profiles that can impact mucosal barrier function. The immune regulation of intestinal permeability has acquired a new status with the recognition of its importance in the pathogenesis of a variety of diseases that affect the GI tract including celiac disease, inflammatory bowel diseases, food allergies, and functional GI disorders such as the irritable bowel syndrome. Persistent changes in mucosal barrier function are often a defining feature of chronic inflammatory GI pathologies with a building consensus that a permeability defect is an initiating factor. The list of pathologies that impact the gut barrier function has fostered consideration of restoration of barrier integrity as a major therapeutic target.