IMMUNOLOGY A Short Course To Lisa, Jonathan, and Jennifer R.C. To Ilene, Caroline, Alex, and Pearl G.S. This title is also available as an e-book. 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No warranty may be created or extended by any promotional statements for this work. Neither the publisher nor the author shall be liable for any damages arising herefrom. Library of Congress Cataloging-in-Publication Data Coico, Richard, author. Immunology : a short course / Richard Coico, Geoffrey Sunshine. – Seventh edition. p. ; cm. Includes bibliographical references and index. ISBN 978-1-118-39691-9 (pbk.) I. Sunshine, Geoffrey, author. II. Title. [DNLM: 1. Allergy and Immunology. 2. Immune System Diseases. 3. Immune System Processes. 4. Immunity. QW 504] QR181 616.07′9–dc23 2014023101 A catalogue record for this book is available from the British Library. Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic books. Cover image: Russell Kightley Set in 10/12 pt Times by Toppan Best-set Premedia Limited 1 2015 CONTENTS IN BRIEF 1 11 OVERVIEW OF THE IMMUNE SYSTEM, 1 ACTIVATION AND FUNCTION OF T CELLS, 153 2 12 INNATE IMMUNITY, 11 CYTOKINES, 176 3 13 ADAPTIVE IMMUNITY, 26 TOLERANCE AND AUTOIMMUNITY, 194 4 14 IMMUNOGENS AND ANTIGENS, 35 COMPLEMENT, 217 15 5 HYPERSENSITIVITY: TYPE I, 233 ANTIBODY STRUCTURE AND FUNCTION, 47 16 6 HYPERSENSITIVITY: TYPES II AND III, 249 ANTIGEN–ANTIBODY INTERACTIONS, IMMUNE ASSAYS, AND EXPERIMENTAL SYSTEMS, 67 17 HYPERSENSITIVITY: TYPE IV, 259 7 THE GENETIC BASIS OF ANTIBODY 18 STRUCTURE, 88 IMMUNODEFICIENCY DISORDERS AND NEOPLASIAS OF THE LYMPHOID SYSTEM, 268 8 BIOLOGY OF THE B LYMPHOCYTE, 100 19 TRANSPLANTATION, 298 9 HOW T CELLS RECOGNIZE ANTIGEN: 20 THE ROLE OF THE MAJOR HISTOCOMPATIBILITY TUMOR IMMUNOLOGY, 312 COMPLEX, 117 21 RESISTANCE AND IMMUNIZATION TO 10 BIOLOGY OF THE T LYMPHOCYTE, 137 INFECTIOUS DISEASES, 328 v CONTENTS About the Authors, xv Inflammation, 20 Hallmark Signs of Inflammation, 20 Contributors, xvi Localized Inflammatory Responses, 21 Preface and Acknowledgments, xvii Chronic Inflammation, 23 How to Use Your Textbook, xix Fever, 23 References and Bibliography, 24 About the Companion Website, xxiii Review Questions, 24 Answers to Review Questions, 25 1 OVERVIEW OF THE IMMUNE SYSTEM, 1 3 Introduction, 1 ADAPTIVE IMMUNITY, 26 Innate and Adaptive Immunity, 2 Cells and Organs Involved in Adaptive Immunity, 26 Innate Immunity, 2 The Lymphatic Organs, 27 Adaptive Immunity, 2 Lymphocyte Migration and Recirculation, 29 Clonal Selection Theory, 3 The Fate of Antigen after Penetration, 31 Active, Passive, and Adoptive Immunization, 5 Frequency of Antigen-Specific Naïve Major Characteristics of the Adaptive Immune Lymphocytes, 32 Response, 5 Interrelationship between Innate and Adaptive Cells Involved in the Adaptive Immunity, 33 Immune Response, 5 Review Questions, 34 Humoral and Cellular Immunity, 6 Answers to Review Questions, 34 Humoral Immunity, 6 Cell-Mediated Immunity, 7 4 IMMUNOGENS AND ANTIGENS, 35 Generation of Diversity in the Immune Response, 8 Introduction, 35 Benefits of Immunology, 8 Requirements for Immunogenicity, 35 Damaging Effects of the Foreignness, 35 Immune Response, 9 High Molecular Weight, 36 The Future of Immunology, 9 Chemical Complexity, 36 The Short Course Begins Here, 10 Degradability, 36 References and Bibliography 10 Haptens, 36 Further Requirements for Immunogenicity, 37 2 INNATE IMMUNITY, 11 Primary and Secondary Responses, 38 Introduction, 11 Antigenicity and Antigen-Binding Site, 38 Physical and Chemical Barriers of Innate Immunity, 11 Epitopes Recognized by B Cells and T Cells, 39 Origin, Differentiation, and Characterization of Cells Major Classes of Antigens, 40 of the Innate Immune System, 12 Binding of Antigen with Antigen-Specific Antibodies or Pattern Recognition: The Hallmark of Innate Immune T Cells, 41 Responses, 15 Cross-Reactivity, 41 Pattern Recognition Receptors, 15 Adjuvants, 42 Complement, 18 References and Bibliography, 44 Intracellular and Extracellular Killing of Review Questions, 45 Microorganisms, 19 Answers to Review Questions, 45 vii viii CONTENTS 5 Primary Interactions between Antibody and Antigen, 68 ANTIBODY STRUCTURE AND FUNCTION, 47 Association Constant, 68 Introduction, 47 Affinity and Avidity, 70 Isolation and Characterization of Immunoglobulins, 48 Secondary Interactions between Antibody and Structure of Light and Heavy Chains, 48 Antigen, 70 Domains, 51 Agglutination Reactions, 70 Hinge Region, 51 Precipitation Reactions, 72 Variable Region, 51 Immunoassays, 74 Immunoglobulin Variants, 53 Direct-Binding Immunoassays, 74 Isotypes, 53 Solid-Phase Immunoassays, 75 Allotypes, 54 Immunofluorescence, 76 Idiotypes, 54 Direct Immunofluorescence, 76 Structural Features of IgG, 55 Indirect Immunofluorescence, 76 Biologic Properties of IgG, 55 Flow Cytometry, 76 Agglutination and Formation of Precipitate, 56 Immunoabsorption and Immunoadsorption, 78 Passage through the Placenta and Absorption in Cellular Assays, 78 Neonates, 56 Assays of Lymphocyte Function, 78 Opsonization, 57 B-Cell and T-Cell Proliferation Assays, 78 Antibody-Dependent Cell-Mediated Cytotoxicity, 58 Antibody Production by B Cells, 78 Activation of Complement, 58 Effector Cell Assays for T Cells and Natural Killer Neutralization of Toxins, 58 Cells, 79 Immobilization of Bacteria, 58 Cell Culture, 79 Neutralization of Viruses, 58 Primary Cell Cultures and Cloned Lymphoid Cell Structural Features of IgM, 59 Lines, 79 Biologic Properties of IgM, 59 B-Cell Hybridomas and Monoclonal Antibodies, 80 Complement Fixation, 59 T-Cell Hybridomas, 80 Neonatal Immunity and First Line of Humoral Genetically Engineered Molecules and Defense, 59 Receptors, 80 Agglutination, 60 Experimental Animal Models, 81 Isohemagglutinins, 60 Inbred Strains, 81 Structural and Biologic Properties of IgA, 60 Adoptive Transfer, 82 Biologic Properties of IgA, 60 SCID Mice, 82 Role in Mucosal Infections, 60 Thymectomized and Congenitally Athymic (Nude) Bactericidal Activity, 61 Mice, 82 Antiviral Activity, 61 Transgenic Mice and Gene Targeting, 82 Structural and Biologic Properties of IgD, 61 Transgenic Mice, 82 Structural and Biologic Properties of IgE, 62 Knockout and Knock-in Mice, 83 Importance of IgE in Parasitic Infections and Analysis of Gene Expression, 83 Hypersensitivity Reactions, 62 Microarrays to Assess Gene Expression, 83 Kinetics of the Antibody Response Following References and Bibliography, 85 Immunization, 62 Review Questions, 86 Primary Response, 62 Answers to Review Questions, 86 Secondary Response, 62 The Immunoglobulin Superfamily, 63 References and Bibliography, 65 7 THE GENETIC BASIS OF ANTIBODY Review Questions, 65 STRUCTURE, 88 Answers to Review Questions, 66 Introduction, 88 A Brief Review of Nonimmunoglobulin Gene Structure 6 ANTIGEN–ANTIBODY INTERACTIONS, IMMUNE and Gene Expression, 88 ASSAYS, AND EXPERIMENTAL SYSTEMS, 67 Genetic Events in Synthesis of Ig Chains, 90 Introduction, 67 Organization and Rearrangement of Antigen–Antibody Interactions, 67 Light-Chain Genes, 90