The mucosal tissues of the body such as the intestine and respiratory tract are continuously exposed to enormous amounts of different antigens, which can be either pathogenic invaders or harmless materials such as foods and commensal organisms. Potential immune responses to this antigen load are controlled by a distinct compartment of the immune system, the mucosal immune system, which is the largest in the body. Its unique features include distinctive routes and processes for the uptake and presentation of antigens, exploitation of M cells to transport antigens across the epithelium of Peyer’s patches, and retinoic acid-producing dendritic cells that imprint the T and B cells they activate with gut-homing properties. Dendritic cells also favor the generation of FoxP3-positive Treg cells in the normal gut. Tissue-resident intestinal macrophages contribute to these regulatory processes by phagocytosing antigens without causing inflammation, due to their production of IL-10. Lymphocytes primed in the mucosa-associated lymphoid tissues acquire specific homing receptors, allowing them to redistribute preferentially back to mucosal surfaces as effector cells. The adaptive immune response in mucosal tissues is characterized by the production of secretory dimeric IgA, and by the presence of distinct populations of memory/effector T cells in the epithelium and lamina propria. CD4 T cells in the lamina propria produce pro-inflammatory cytokines such as IL-17 and IFN-γ even in the absence of overt infection, but this is normally balanced by the presence of IL-10-producing Treg cells. IELs exhibit cytolytic activity and other innate functions that help maintain a healthy epithelial barrier.
The mucosal response to infection and regulation of mucosal immune responses.
The major role of the mucosal immune response is defense against infectious agents, which include all forms of microorganisms from viruses to multicellular parasites. This means that the host must be able to generate a wide spectrum of immune responses tailored to meet the challenge of individual pathogens; unsurprisingly, many microbes have evolved means of adapting to and subverting the host response. To ensure an adequate response to pathogens, the mucosal immune system needs to be able to recognize and respond to any foreign antigen, but it must not produce the same effector response to a harmless antigen (from food or commensals) as it would to a pathogen. A major role of the mucosal immune system is to balance these competing demands, and how it does this will be the focus of this part of the chapter.
12-15 Enteric pathogens cause a local inflammatory response and the development of protective immunity.
Despite the array of innate immune mechanisms in the gut, and stiff competition from the indigenous microbiota, the gut is a frequent site of infection by a wide variety of pathogenic organisms. These include many viruses; enteric bacteria such as Vibrio, Salmonella, and Shigella species; protozoans such as Entamoeba histolytica; and multicellular helminth parasites such as tapeworms and pinworms. These pathogens cause disease in many ways, and as elsewhere in the body, the key to generating protective immunity is the activation of appropriate aspects of the innate immune system.
The effector mechanisms of the innate immune system can themselves eliminate most intestinal infections rapidly and without significant spread of the infection beyond the intestine. The essential features of these responses in epithelial surfaces are discussed in Section 2-2 and here we highlight only aspects that are unique or unusual to the intestine. Of these, the most important involve the epithelial cells themselves (Fig. 12.15). The tight junctions between