Preface to the First Edition

Only 25 years ago, a multidisciplinary group of some three dozen individuals met for the first time in Vero Beach, Florida, under the auspices of the National Institute of Child Health and Human Development (NICHHD) to discuss a recently identified immunoglobulin, secretory IgA. Since that historic workshop, seven international congresses have been held to discuss secretory immunoglobulins and mucosal immunology, and there have been a number of scientific meetings on immunological mechanisms in such mucosal sites as respiratory tract, gut, genital tract, mammary glands, and periodontal tissues. The last International Congress of Mucosal Immunology, held in 1992 in Prague, Czechoslovakia, was attended by nearly 1000 participants.

The recognition that defenses are mediated via mucosal barriers dates back several thousand years. Ingestion of Rhus leaves to modify the severity of reactions to poison ivy is a centuries old practice among native North Americans. The modern concepts of local immunity, however, were developed by Besredka in the early 1900s, followed by the discovery of IgA in 1953 and its isolation and characterization in 1959. Studies in the early 1960s demonstrated the presence of IgA in a unique form in milk and, shortly thereafter, in other external secretions. These studies were followed by the discovery of the secretory component and the identification of the J chain. These remarkable observations were soon complemented by the characterization of the bronchus-associated lymphoid tissue (BALT) and the gut-associated lymphoid tissue (GALT), the observation of circulation of antigen-sensitized or reactive IgA B cells from BALT and GALT to other mucosal surfaces such as the genital tract and the mammary glands, and the definition of mucosal T cells. In the past decade, our concept of the mucosal immune system has been expanded to include M cells and mechanisms of mucosal antigen processing, regulatory T lymphocytes and other effector cell mechanisms, neuropeptides, and the network of interleukins and other cytokines. Finally, the biological significance of the mucosal immune system increasingly is being realized in the context of human infections acquired via mucosal portals of entry, including conventional infections as well as new syndromes such as acquired immune deficiency associated with infection by HIV.

Despite the tremendous progress made in the acquisition of new knowledge concerning the common mucosal immune system, mucosal infections, and oral immunization, no single text covering the entire spectrum of mucosal immunity was available. Therefore, this handbook was organized to develop a perspective of the basic biology of the components that constitute the framework of the common mucosal immune system, as well as of the infectious and immunologically mediated disease processes of the mucosae. Virtually all chapters have been authored by original investigators responsible for key observations on which current concepts are based.

Part I, Cellular Basis of Mucosal Immunity, provides an introductory overview and a historical perspective of the mucosal immune system (Chapter 1), followed by 10 comprehensive chapters (Section A) on development and physiology of mucosal defense (Chapters 2-11). These chapters address structure and function of mucosal epithelium, cellular basis of antigen transport, mucosal barrier, innate humoral factors, bacterial adherence, development and function of mucosal immunoglobulin, and epithelial and hepatobiliary transport. Section B (Chapters 12-19) focuses on cells, regulation, and specificity in inductive and effector sites. The inductive site chapters discuss characteristics of mucosa-associated lymphoid tissue (MALT), Peyer's patches, regulation of IgA B cell development, diversity and function of mucosal antigen-presenting cells, oral tolerance, peptidergic circuits, role of B-1 cells, and lymphocyte homing.The chapters on effector sites (Section C) present information about cytokines, mucosal Ig-producing cells, regulatory T cells, intraepithelial cells, mucosal IgE, inflammation and mast cells, cytokines in liver, cytotoxic T cells in mucosal effector sites, and immunity to viruses (Chapters 20-29). Section D addresses mucosal immunization and the concepts of mucosal vaccines. These chapters discuss passive immunization, vaccine development for mucosal surfaces, antigen delivery systems, mucosal adjuvants, and approaches for generating specific secretory IgA antibodies (Chapters 30-34).

Part II, Mucosal Diseases, addresses the secretory immune system with special reference to mucosal diseases. Section E consists of chapters on the stomach, intestine, and liver, and includes diseases of GALT and intestinal tract, a chain and related lymphoproliferative disorders, gastritis and peptic ulcer, malabsorption syndrome, food allergy, intestinal infections, and diseases of the liver and biliary tract (Chapters 35-42). Section F covers selected areas of lung and lower airway and includes chapters on BALT and pulmonary diseases, mucosal immunity in asthma, respiratory infections, and inhalant allergy (Chapters 43-46). Section G presents information on the oral cavity, upper airway, and mucosal regions in the head and neck (Chapters 47-50), as well as ocular immunity, tonsils and adenoids, and middle ear. Sections H and I are devoted to mammary glands and genitourinary tract, respectively. These sections consist of chapters on milk, immunological effects of breast feeding (Chapters 51 and 52), IgA nephropathy, immunology of female and male reproductive tracts, endocrine regulation of genital immunity, mucosal immunopathophysiol-ogy of HIV infection, and genital infections relative to maternal and infant disease (Chapters 53-58).

The information reviewed in the different chapters in this handbook will be of considerable interest to diverse groups of clinicians, basic and clinical immunologists, biologists, veterinarians, and public health workers interested in understanding the application of basic biology to virtually all immunological or infection-mediated disease processes of external mucosal surfaces. This handbook will be of particular importance to students of medicine and pediatrics, including individuals studying gastroenterology and pul-monology, ophthalmology, gynecology, infectious disease, otolaryngology, periodontal disease, sexually transmitted disease, and especially mucosal immunology.

Pearay L. Ogra Jiri Mestecky Michael E. Lamm Warren Strober Jerry R. McGhee John Bienenstock

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