Previous chapters have focused on the immune response against pathogens, primarily examining responses in peripheral lymph nodes that drain infected tissues. Although most internal tissues are normally free of microbes, the barrier tissues of the body—the skin and various mucosal tissues, such as the gastrointestinal, respiratory, and urogenital tracts—are in continual contact with the external world and have ongoing encounters with microbes beginning immediately after birth and persisting throughout life. In addition to providing the greatest surface area across which pathogens can invade, these tissues are normally populated by a diverse community of resident microorganisms—the commensal microbiota. The requirement to contend with the commensal microbiota while performing physiological functions that expose these tissues to a wide range of environmental antigens (for example, ingestion of dietary antigens in the gastrointestinal tract; inspiration of airborne antigens in the respiratory tract) presents unique challenges to the maintenance of immune homeostasis at these sites; immune cells in barrier tissues must tolerate the commensal microbiota while maintaining the ability to mount robust responses against pathogenic microbes. In this chapter we consider specialized features of the immune system at these barrier tissues, with primary emphasis on those features invested by the mucosae—the mucosal immune system.
The mucosal immune system—in particular, that of the gut—may well have been the first part of the adaptive immune system to arise in evolution, possibly developing to contend with the vast populations of commensal microorganisms that coevolved with vertebrates to provide nutrient and nonnutrient benefits: primarily bacteria, but also fungi, viruses, and parasites, particularly worms (helminths). Organized lymphoid tissues and antibodies are first found in vertebrates in the gut of primitive cartilaginous fishes, and two important central lymphoid organs—the thymus and the avian bursa of Fabricius—have developmental origins related to the gut. It has therefore been suggested that the mucosal immune system of the gut represents the original vertebrate immune system, and that the spleen and lymph nodes are later specializations. Here we consider the unique features of the barrier immune system, focusing primarily on the gastrointestinal tract but also considering other barrier tissues such as the pulmonary tract and the nonmucosal barrier tissue, skin.