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Medical Immunology.Pdf Page i Introduction to Medical Immunology Fourth Edition Edited by Gabriel Virella Medical University of South Carolina Charleston, South Carolina MARCEL DEKKER, INC. NEW YORK • BASEL • HONG KONG Page ii Library of Congress Cataloging-in-Publication Data Introduction to medical immunology / edited by Gabriel Virella. — 4th ed. p. cm. Includes bibliographical references and index. ISBN 0-8247-9897-X (hardcover : alk. paper) 1. Clinical immunology. 2. Immunology. I. Virella, Gabriel. [DNLM: 1. Immunity. 2. Immunologic Diseases. QW 504 I6286 1997] RC582.I59 1997 616.07'9—dc21 DNLM/DLC for Library of Congress 97-22373 CIP The publisher offers discounts on this book when ordered in bulk quantities. For more information, write to Special Sales/Professional Marketing at the address below. This book is printed on acid-free paper. Copyright © 1998 by MARCEL DEKKER, INC. All Rights Reserved. Neither this book nor any part may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, microfilming, and recording, or by any information storage and retrieval system, without permission in writing from the publisher. MARCEL DEKKER, INC. 270 Madison Avenue, New York, New York 10016 http://www.dekker.com Current printing (last digit): 10 9 8 7 6 5 4 3 2 1 PRINTED IN THE UNITED STATES OF AMERICA Page iii PREFACE Ten years after the publication of the first edition of Introduction to Medical Immunology, the ideal immunology textbook continues to be a very elusive target. The discipline continues to grow at a brisk pace, and the concepts tend to become obsolete as quickly as we put them in writing. It is very true of immunology that the more we know, the greater our ignorance. This represents the challenge that makes teaching immunology so exceptional and writing immunology textbooks such a daunting task. The fourth edition of Introduction to Medical Immunology retains the features that make this textbook unique— particularly, its emphasis on the clinical application of immunology—but represents a significant departure from the earlier editions. Most changes have resulted from our strong conviction that this textbook is not written to impress our peers with extraordinary insights or revolutionary knowledge, but rather to be helpful to medical students and young professionals who need an introduction to the field. The requirements that we tried to fulfill were sometimes difficult to conciliate. The text needs to be updated and relatively complete, but not overwhelming. The scientific basis of immunology needs to be clearly conveyed without allowing the detail to obscure the concept. The application to medicine needs to be transparently obvious, but without unnecessary exaggeration. The text must present a reasonably general and succinct overview, while covering areas that appear likely to have a strong impact in the foreseeable future. The book needs to stimulate students to seek more information and to develop their own “thinking” without being merely a model of theoretical dreams (and nightmares). In what is probably not an entirely successful attempt to fulfill some of these goals, we have extensively revised the book, added significant new concepts, and deleted areas that were clearly obsolete. The clinical sections are peppered with cases in order to provide a solid link between the discussion of concrete problems presented by patients with diseases of immunological basis and the relevant immunological principles. More significantly, the book has been rewritten in an outline format. This format allows us to keep the conceptual approach while facilitating the understanding of a reader facing the complexities of immunology with very little background. Of necessity, the book emphasizes that which is well understood, as clearly as we can present it, and we try to promote a general understanding of the discipline at the end of the twentieth century. It is not, and never will be, a finished work. We are certain that we will always wish we could add here and revise there. But we hope that this new edition will be even more successful in focusing the Page iv attention of our readers toward an intrinsically fascinating discipline that seeks understanding of fundamental biological knowledge that has direct impact on the diagnosis and treatment of a variety of conditions in which the immune system plays a key role. GABRIEL VIRELLA, M.D., PH.D. Page v CONTENTS Preface iii Contributors ix Part I. Basic Immunology 1. Introduction 1 Gabriel Virella 2. Cells and Tissues Involved in the Immune Response 11 Gabriel Virella and Jean-Michel Goust 3. Major Histocompatibility Complex 31 Jean-Michel Goust 4. The Induction of an Immune Response: Antigens, Lymphocytes, and Accessory 49 Cells Gabriel Virella and Barbara E. Bierer 5. Immunoglobulin Structure 75 Gabriel Virella and An-Chuan Wang 6. Biosynthesis, Metabolism, and Biological Properties of Immunoglobulins 91 Gabriel Virella and An-Chuan Wang 7. Genetics of Immunoglobulins 105 Janardan P. Pandey 8. Antigen-Antibody Reactions 121 Gabriel Virella 9. The Complement System 137 Robert J. Boackle 10. Lymphocyte Ontogeny and Membrane Markers 163 Jean-Michel Goust and Anne L. Jackson 11. Cell-Mediated Immunity 187 Jean-Michel Goust and Barbara E. Bierer Page vi 12. The Humoral Immune Response and Its Induction by Active Immunization 217 Gabriel Virella 13. Infections and Immunity 239 Gabriel Virella Part II. Diagnostic Immunology 14. Immunoserology 259 Gabriel Virella 15. Diagnostic Evaluation of Humoral Immunity 283 Gabriel Virella 16. Diagnostic Evaluation of Lymphocyte Functions and Cell-Mediated Immunity 297 Gabriel Virella and Jean-Michel Goust 17. Diagnostic Evaluation of Phagocytic Function 317 Gabriel Virella Part III. Clinical Immunology 18. Tolerance and Autoimmunity 335 Jean-Michel Goust, George C. Tsokos, and Gabriel Virella 19. Organ-Specific Autoimmune Diseases 363 Christian C. Patrick, Jean-Michel Goust, and Gabriel Virella 20. Systemic Lupus Erythematosus 383 Jean-Michel Goust and George C. Tsokos 21. Rheumatoid Arthritis 399 Jean-Michel Goust 22. Hypersensitivity Reactions 417 Gabriel Virella 23. IgE-Mediated (Immediate) Hypersensitivity 433 Jean-Michel Goust and Albert F. Finn, Jr. 24. Immunohematology 453 Gabriel Virella and Mary Ann Spivey 25. Immune Complex Diseases 475 Gabriel Virella and George C. Tsokos 26. Immune System Modulators 495 Jean-Michel Goust, Henry C. Stevenson-Perez, and Gabriel Virella 27. Transplantation Immunology 517 Gabriel Virella and Jonathan S. Bromberg Page vii 28. Tumor Immunology 535 Henry C. Stevenson-Perez and Kwong-Y. Tsang 29. Malignancies of the Immune System 553 Gabriel Virella and Jean-Michel Goust 30. Immunodeficiency Diseases 579 Gabriel Virella Index 621 Page ix CONTRIBUTORS Barbara E. Bierer, M.D. Associate Professor of Medicine, Department of Pediatric Oncology, Dana Farber Cancer Institute, Boston, Massachusetts Robert J. Boackle, Ph.D. Professor and Director of Oral Biology and Professor of Immunology, Division of Stomatology, Medical University of South Carolina, Charleston, South Carolina Jonathan S. Bromberg, M.D., Ph.D. Associate Professor of Surgery, Microbiology, and Immunology, Department of General Surgery, Transplant Division, University of Michigan Hospitals, Ann Arbor, Michigan Albert F. Finn, Jr., M.D. Clinical Assistant Professor, Departments of Medicine, Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina Jean-Michel Goust, M.D. Professor of Immunology, Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina Anne L. Jackson, Ph.D. Consultant, Ridgefield, Washington Janardan P. Pandey, Ph.D. Professor, Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina Christian C. Patrick, M.D., Ph.D. Director of Academic Programs and Associate Member, Department of Infectious Diseases and Pathology and Laboratory Medicine, St. Jude Children's Research Hospital, Memphis, Tennessee Mary Ann Spivey, M.H.S., M.T. (A.S.C.P.), S.B.B. Department of Pathology-Laboratory Medicine, Transfusion Medicine Section, Medical University of South Carolina, Charleston, South Carolina Henry C. Stevenson-Perez, M.D. Senior Investigator, Biologics Evaluation Section, Investigational Drug Branch, National Cancer Institute, National Institutes of Health, Rockville, Maryland Page x Kwong-Y. Tsang, Ph.D. Senior Scientist, Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland George C. Tsokos, M.D. Professor, Department of Medicine, Uniformed Services University of Health Sciences, Bethesda, Maryland, and Department of Clinical Investigations, Walter Reed Army Medical Center, Washington, D.C. Gabriel Virella, M.D., Ph.D. Professor and Vice Chairman of Education, Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina. An-Chuan Wang, Ph.D. Professor, Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina Page 1 1 Introduction Gabriel Virella I. Introduction A. The fundamental observation that led to the development of immunology as a scientific discipline was that an individual can become resistant for life to a certain disease after having contracted it only once. The term immunity, derived from the Latin “immunis” (exempt), was adopted to designate this naturally acquired protection against diseases such as measles
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