Immunophysiology of the Gut

W. Allan Walker, Paul R. Harmatz, Barry K. Wershil, W. Allan Walker, Paul R. Harmatz, Barry K. Wershil

• Publisher: Academic Press
• Year: 2013
• Print ISBN: 9780127320854
• eBook ISBN: 9781483273495
• Topic: Medicine
• Subtopic: Clinical Medicine

Bristol-Myers Squibb/Mead Johnson Nutrition Symposia, Volume 11: Immunophysiology of the Gut represents a comprehensive and systematic coverage of the immunophysiology of the gut, compiling research that integrates the mucosal immune system and intestinal physiology. This book discusses the immunological regulation of epithelial function, fibroblastic sheath, pathways of arachidonic acid metabolism, and gastric response to mucosal anaphylaxis. The implications for inflammatory diarrhea, role of breast milk in neonatal host defense, and milk-borne peptide growth factors in human and bovine milk are also elaborated. This publication likewise covers the immunopathologic features of celiac disease, immune responses in protein-energy malnutrition, and bacterial translocation. This volume is suitable for experts and clinicians from the disciplines of mucosal immunology, intestinal physiology, and enteric neurophysiology.

Part I

Immunophysiology of the Gut

Outline

Chapter 1: Introduction to Immunophysiology of the Gut

Chapter 2: Immunological Regulation of Epithelial Function

Chapter 3: Mesenchymal-Epithelial Interactions: The Subepithelial Fibroblastic Sheath as a Paracrine Modulator of Inflammation-Induced Intestinal Secretion

Chapter 4: Immune Regulation of Intestinal Arachidonic Acid Metabolism: Effects on Intestinal Water and Electrolyte Transport

Chapter 5: Gastrointestinal Anaphylaxis: Effect on Gastric and Intestinal Function

Chapter 6: Acute and Chronic Control of Colonic Chloride Secretion by Mast Cell Mediators

Introduction to Immunophysiology of the Gut

W. Allan Walker, Mucosal Immunology Laboratory, Combined Program in Pediatric Gastroenterology and Nutrition, Children’s Hospital and Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts

As mentioned in the preface of this book, an important new area of research in mucosal immunology has developed over the last two decades that provides evidence that mucosal immune responses modulate gastrointestinal epithelial functions and provide a collective host defense against microorganisms and antigens crossing the intestinal epithelium from the luminal cavity. Gilbert Castro, the author of the first chapter in this section, was the first investigator to coin the term “immunophysiology of the gut.” His original work in this area involved the interaction of parasites infesting the intestine with increased numbers of mucosal mast cells that occur as a result of infection (Harai et al., 1987). He postulated that mediators released from these activated mast cells contributed to the epithelial changes associated with parasitic infestation (fluid secretion, mucus release, and increased peristalsis). Since this observation was made, others made by investigators such as Bloch and Walker (Walker et al., 1975; Lake et al., 1979), Bienenstock (Stead et al., 1989), Gall (Perdue and Gall, 1986; Scott et al., 1988), and Barrett (Wasserman et al., 1988) have further demonstrated an association between immunologic responses and intestinal function such as mucus secretion, myenteric plexus stimulus (enhanced peristalsis), and fluid and electrolyte secretion. In addition, a much clearer understanding of mucosal immune responses at the intestinal surface has evolved. For example, lymphoid cells (T cells and B cells) have been characterized and their specific function determined. The distribution of such cells within the lamina propria and intraepithelial spaces has been determined and the presumed function of these cells in the mucosal immune response demonstrated (Kagnoff, 1989), and factors affecting the migration of lymphoid and inflammatory cells to the gut have been identified. Furthermore, the roles of lymphokines in these processes are now better understood (Strober and James, 1987). In addition, a better understanding of antigen uptake across the specialized follicular intestinal epithelium (microfold cell) and of antigen processing by lymphoid cells within Peyer’s patches has explained the specific secretory immunoglobulin A (IgA) response by plasma cells in the lamina propria of the small and large intestine to luminal antigens. These advances in our understanding of mucosal immune responses at the cellular and molecular level have been matched by major advances in intestinal epithelial cell biology and a better understanding of mechanisms of intestinal secretion and fluid absorption (Sullivan and Field, 1991). We also have a better appreciation for the enterocyte’s interaction with external stimuli mediated by membrane receptors and signal transduction interactions (Brown, 1991). With the simultaneous expansion of our knowledge of gut immunology and epithelial cell biology came the realization that these two processes are intimately connected and each may have a reciprocal effect on the other. This section of the monograph is devoted to an in-depth analysis of exactly how that interrelationship between intestinal immunologic/inflammatory processes and epithelial cell function works. The individual chapters further refine our knowledge of immunophysiology of the gut (Powell, 1991).

In the first chapter, entitled “Immunological Regulation of Epithelial Function,” Professor Castro brings his background in parasitology to consider a general approach to the subject, which supports the notion that this phenomenon is an interdisciplinary and integrative process. He develops general concepts that “demonstrates, unambiguously, that the immune system regulates epithelial function in the gut.” The collective evidence for this theme is considered in order to develop generalities and concepts that contribute to our understanding of homeostasis and of disease processes as well as to consider “potential applications of [this] new found knowledge.” He considers the approaches that have been taken to arrive at these conclusions, including (1) determining the functional effect of “inflammatory mediators” on gastrointestinal (GI) tissues and (2) determining, in a multiple-step procedure, the effect of antigen applied to immune-sensitized GI tissues on physiologic and pathophysiologic responses that are evoked. These results provide evidence that soluble mediators of activated and stimulated mast cells can affect enterocyte fluid secretion and can also augment neuroendocrine effects on epithelial cell function. Mast cell mediator release can occur with parasitic infestation of the gut or with intestinal anaphylaxis caused by oral exposure of allergen to a presensitized gut. These models have helped define the role of type I, and to some extent types II–IV, hypersensitivity reactions in causing epithelial cell responses.

In the second chapter, entitled “Mesenchymal–Epithelial Interactions: The Subepithelial Fibroblastic Sheath as a Paracrine Modulator of Inflammation-Induced Intestinal Secretion,” Professor Don W. Powell, an intestinal epithelial cell biologist, with Dr. Helen M. Berschneider, examines the role of prostaglandins (a product of inflammation) on the subepithelial fibroblastic sheath–enterocyte interaction. His approach to this process is that of the physiologist with an acquired interest in mucosal immunology, and therefore he provides a unique insight into immunophysiology of intestinal electrolyte transport. Using Ussing chamber studies to measure electrolyte transport across the colon of experimental animals, Dr. Powell provides evidence that products of the cyclooxygenase pathway can increase net fluid secretion. These effects can be blocked by cyclooxygenase inhibitors, such as indomethacin. The stimulus for increased secretion may be mediated via (1) a receptor-effector (cAMP-mediated) response as with prostaglandin E₂ (PGE₂), or (2) by activation of enteric nerves (PGI₂). He further refines the observation by citing recently generated data that suggest the phenomenon may be a two-step process invo...

Table of contents

• Cover image
• Title page
• Table of Contents
• Bristol-Myers Squibb/Mead Johnson Nutrition Symposia
• Copyright
• Dedication
• Contributors
• Sponsor’s Foreword
• Foreword
• Preface
• Part I: Immunophysiology of the Gut
• Part II: Lymphokines and Mucosal Immune Function
• Part III: Endocrine Effects on Mucosal Immune Function
• Part IV: Nutrition and Mucosal Host Defense
• Part V: Effects of Nutritional Factors and the Microenvironment on Mucosal Immune Function
• Summary, Conclusions, and Future Projections
• Index