INTRODUCTION TO PSYCHONEUROIMMUNOLOGY ThisPageIntentionallyLeftBlank. INTRODUCTION TO PSYCHONEUROIMMUNOLOGY Jorge H. Daruna Department of Psychiatry and Neurology Tulane University School of Medicine AMSTERDAM • BOSTON • HEIDELBERG • LONDON NEW YORK • OXFORD • PARIS • SAN DIEGO SAN FRANCISCO • SINGAPORE • SYDNEY • TOKYO Elsevier Academic Press 200 Wheeler Road, 6th Floor, Burlington, MA 01803, USA 525 B Street, Suite 1900, San Diego, California 92101-4495, USA 84 Theobald’s Road, London WC1X 8RR, UK This book is printed on acid-free paper. Copyright ß 2004, Elsevier Inc. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without permission in writing from the publisher. Permissions may be sought directly from Elsevier’s Science & Technology Rights Department in Oxford, UK: phone: (þ44) 1865 843830, fax: (þ44) 1865 853333, e-mail: [email protected]. You may also complete your request on-line via the Elsevier homepage (http://elsevier.com), by selecting ‘‘Customer Support’’ and then ‘‘Obtaining Permissions.’’ Library of Congress Cataloging-in-Publication Data Application submitted. British Library Cataloguing in Publication Data A catalogue record for this book is available from the British Library. ISBN: 0-12-203456-2 For all information on all Academic Press publications visit our Web site at www.books.elsevier.com Printed in the United States of America 04 05 06 07 08 09 9 8 7 6 5 4 3 2 1 For Brandon and Caroline ThisPageIntentionallyLeftBlank. PREFACE This book presents an introduction to psychoneuroimmunology, which is the scientiWc discipline best poised to elucidate the complex processes that underlie health. It is intended for students planning careers in medicine, nursing, psych- ology, public health, social work, or for anyone interested in the scientiWc basis for an integrative approach to healthcare. The book covers a vast territory, touching on various disciplines, including endocrinology, genetics, immunology, medicine, neuroscience, psychology, and sociology. The aim has been to capture the big picture with respect to how bodily systems intercommunicate to sustain health. The book most distinguishes itself from other books on the topic of psychoneur- oimmunology by the breadth of coverage, by highlighting the complexity that is evident at all levels of analysis without becoming excessively entangled in the Wne detail of speciWc topics, and by drawing implications for health science research and healthcare. The book begins with an overview in Chapter 1 of the topics that will be covered in each subsequent chapter. Chapter 2 proceeds to deWne psychoneuro- immunology within the context of historical ideas about health and disease. The immune system is the topic of Chapter 3. It is described in some detail to highlight that its function is multifaceted and has evolved to protect the organism from diverse microscopic adversaries. However, the immune system does not operate with autonomy. This is made clear in Chapters 4 and 5, which describe how the hormones released by the endocrine system and the activity of the peripheral nervous system modulate immune function. These chapters further underscore that communication between the systems is bidirectional, in other words, the immune system is able to inXuence the release of hormones as well as the activity of the nervous system. Stress is discussed in Chapter 6 as a broad concept denoting the organism’s response to contextual change. Disease is regarded as a form of stress with both physical and psychosocial aspects. Beginning with Chapter 7, the coverage focuses on psychosocial stress and its eVects on endocrine, neural, and immune activity. This evidence demonstrates that psychosocial stress can indeed modify the activity of the systems that operate to sustain health. The impact of psychosocial stress on infectious disease, allergy, cancer, and autoimmune disorders is examined in Chapters 8 and 9. It is evident that psychosocial stress interacts with factors such as disease pathophysiology and characteristics of the individual. Its eVect is further dependent on temporal factors. Psychiatric disorders are given consideration in Chapter 10, where the role of immune activity in the viii Preface modiWcation of brain function is discussed. Chapter 11 shifts the focus to factors that appear beneWcial with respect to immune function and may serve to safeguard health. The topics covered include the role of suggestion, beliefs and expectations, the inXuence of social involvement and emotional expression, and the impact of sleep, relaxation, exercise, and diet. Finally, Chapter 12 examines the implications of psychoneuroimmunology and underscores the need for much more integrative approaches to both research and healthcare. ACKNOWLEDGMENTS The book has been made possible by the work of numerous scientists and scholars, whose names appear throughout the text. However, my exploration of their work owes directly to the inXuence of Robert Ader’s seminal volume, Psychoneuroimmunology. The idea for the book grew out of my experience teaching a course on psychoneuroimmunology at the Tulane University School of Medi- cine. The course was encouraged by Don Gallant and became possible with the collaboration of Carolyn Daul, Jane Morgan, and Darrenn Hart. Our students reinforced the idea that an introductory book on the topic was needed. I am especially grateful to Martha Ciattei for the inspiration and encouragement, which helped transform the idea into what is now an actual book. Darrenn Hart was involved in the original planning for the book and Mary Watson helped by conducting literature searches. I have enjoyed the support of colleagues, in par- ticular, Richard Dalton, Betty Muller, Dan Winstead, and Charley Zeanah. Paul Rodenhauser oVered wise counsel. Patricia Barnes shared her medical knowledge and provided incisive commentary on some of the chapters. I further beneWted from the thoughtful comments of anonymous reviewers. I have been most fortu- nate to receive the superb assistance of Sherry Juul, Julie Aguilar, and Linzi Conners. Julie has been responsible for the majority of the work and has done a magniWcent job preparing the manuscript. Arden Nelson provided expert tech- nical assistance. I proudly acknowledge my daughter, Caroline Daruna, for her help with the illustrations. I am greatly indebted to my publisher, Nikki Levy, for her guidance during the unfolding of this project. She and Barbara Makinster have been simply wonderful. ThisPageIntentionallyLeftBlank. CONTENTS Preface vii Acknowledgements ix CHAPTER 1 Introduction I. Aim and Organization 1 II. Source 5 CHAPTER 2 Historical Antecedents I. Introduction 7 II. Health 8 III. Social Organization, Health, and Healing 9 IV. Early Ideas about Health and Disease 10 A. Magic and Religion 10 B. Natural Philosophy 11 V. Empirical Approaches to Health 14 VI. Science and Health 15 A. Microbes and Innate Defenses 15 B. Regulation of Life-sustaining Activities 16 C. Psychoneuroimmunology 18 VII. Concluding Comments 19 VIII. Sources 20 CHAPTER 3 Immune System Basics I. Introduction 23 II. Molecular Self/Nonself Discrimination 24 III. Cell Types, Proteins, and Genes 24 xii Contents IV. Immune System Cell Types and Complement 25 V. Immune Cell Functions and Inflammation 28 VI. Human Leukocyte Antigen System 31 VII. Antigen Presentation 32 VIII. Natural Killer Cells 34 IX. B Lymphocytes, Antibody Structure, and Diversity 35 X. T Lymphocytes 37 A. T-Cell Receptor Diversity and CD Markers 37 B. Helper TLymphocytes (CD4þ)38 C. T-Cell Help of Antibody Production 40 D. T-Cell Help of Cytotoxicity 41 XI. Cytokines, Chemokines, and Cell Adhesion Molecules 42 XII. Lymphoid Organs and Leukocyte Traffic 46 XIII. Immune Activation/Deactivation and Memory 49 XIV. Development of Immune Functions 50 XV. Measures of Immune Function 51 XVI. Concluding Comments 53 XVII. Sources 55 CHAPTER 4 Endocrine-Immune Modulation I. Introduction 58 II. Endocrine System 59 A. Hypothalamus 59 B. Pituitary Gland 60 C. Other Glands 62 III. Cytokines, Hormones, and Their Receptors 63 IV. Anterior Pituitary Hormones and Immune Function 64 A. Growth Hormone 64 B. Prolactin 66 C. The Pituitary–Adrenal Axis: POMC Peptides (ACTH, b-Endorphin) and Glucocorticoids 67 D. The Pituitary–Gonadal Axis:Gonadotropins and Gonadal Steroids 70 E. The Pituitary–Thyroid Axis:Thyrotropin and Thyroid Hormones 72 Contents xiii V. Posterior Pituitary Gland Hormones and Immune Function 73 A. Arginine Vasopressin 73 B. Oxytocin 73 VI. Other Hormones and Immune Function 74 A. Insulin 74 B. Parathyroid Hormone 74 C. Melatonin 75 VII. Thymus Gland 76 A. Pituitary Regulation of Thymus 76 B. Thymus Regulation of Pituitary 76 C. Hormones and Thymocyte Development 77 VIII. Concluding Comments 77 IX. Sources 79 CHAPTER 5 Neuroimmune Modulation I. Introduction 82 II. Peripheral Nervous System 82 A. Somatosensory Pathways 83 B. Visceral Sensory Pathways 84 C. Autonomic Nervous System 84 D. Enteric Nervous System 85 III. Peripheral Nervous System Innervation of Lymphoid Organs 86 A. Bone Marrow and Thymus 86 B. Spleen,Lymph Nodes, and Mucosa-Associated Lymphoid Tissue 86 IV. Chemical Signaling in the Periphery 87 A. Classical Neurotransmitters 87 B. Neuropeptides 88 C. Cytokines 88 D. Other Mediators 89 V. Functional Effects of Peripheral Neuroimmune Interactions 89 VI. Central Nervous System 92 VII. Bidirectional Central