Immunology Second Edition The INSTANT NOTES series Series Editor: B.D. Hames School of Biochemistry and Molecular Biology, University of Leeds, Leeds, UK Animal Biology 2nd edition Biochemistry 2nd edition Bioinformatics Chemistry for Biologists 2nd edition Developmental Biology Ecology 2nd edition Immunology 2nd edition Genetics 2nd edition Microbiology 2nd edition Molecular Biology 2nd edition Neuroscience Plant Biology Chemistry series Consulting Editor: Howard Stanbury Analytical Chemistry Inorganic Chemistry 2nd edition Medicinal Chemistry Organic Chemistry 2nd edition Physical Chemistry Psychology series Sub-series Editor: Hugh Wagner Dept of Psychology, University of Central Lancashire, Preston, UK Psychology Cognitive Psychology Forthcoming title Physiological Psychology Immunology Second Edition P.M. Lydyard Department of Immunology and Molecular Pathology, Royal Free and University College Medical School, University College London, London, UK A. Whelan Department of Immunology, Trinity College and St James’ Hospital, Dublin, Ireland and M.W. Fanger Department of Microbiology and Immunology, Dartmouth Medical School, Lebanon, New Hampshire, USA © Garland Science/BIOS Scientific Publishers Limited, 2004 First published 2000 This edition published in the Taylor & Francis e-Library, 2005. “To purchase your own copy of this or any of Taylor & Francis or Routledge’s collection of thousands of eBooks please go to www.eBookstore.tandf.co.uk.” Second edition published 2004 All rights reserved. No part of this book may be reproduced or transmitted, in any form or by any means, without permission. A CIP catalogue record for this book is available from the British Library. ISBN 0-203-48828-8 Master e-book ISBN ISBN 0-203-59723-0 (Adobe eReader Format) ISBN 1 85996 039 1 (Print Edition) Garland Science/BIOS Scientific Publishers 4 Park Square, Milton Park, Abingdon, Oxon OX14 4RN, UK and 29 West 35th Street, New York, NY 10001–2299, USA Tel: (+1) 2122167800, Fax: (+1) 2125647854 World Wide Web home page: www.bios.co.uk Garland Science/BIOS Scientific Publishers is a member of the Taylor & Francis Group Distributed in the USA by Fulfilment Center Taylor & Francis 10650 Toebben Drive Independence, KY 41051, USA Toll Free Tel.: +1 800 634 7064; E-mail: [email protected] Distributed in Canada by Taylor & Francis 74 Rolark Drive Scarborough, Ontario M1R 4G2, Canada Toll Free Tel.: +1 877 226 2237; E-mail: [email protected] Distributed in the rest of the world by LibraryThomson of Publishing Congress Cataloging-in-PublicationServices Data Cheriton House North Way Andover, Hampshire SP10 5BE, UK Tel.:Patrick, +44 Graham (0)1264 L.332424; E-mail: [email protected] Production Editor: Andrew Watts Front cover: Confocal images of human dendritic cells stained by immunofluorescence for mannose receptors (green), HLA Class 1 (red) and colocalisation (yellow). Image kindly supplied by John Connolly, PhD. CONTENTS Abbreviations viii Preface x Key to cell symbols xi Section A – Overview of the immune system A1 The need 1 A2 External defenses 2 A3 Immune defense 5 A4 Antigens 9 A5 Hemopoiesis – development of blood cells 12 Section B – Cells and molecules of the innate immune system B1 Cells of the innate immune system 15 B2 Molecules of the innate immune system 23 B3 Recognition of microbes by the innate immune system 33 B4 Innate immunity and inflammation 36 Section C – The adaptive immune system C1 Lymphocytes 41 C2 Lymphoid organs and tissues 48 C3 Mucosa-associated lymphoid tissues 53 C4 Lymphocyte traffic and recirculation 56 C5 Adaptive immunity at birth 59 Section D – Antibodies D1 Antibody structure 61 D2 Antibody classes 65 D3 Generation of diversity 68 D4 Allotypes and idiotypes 78 D5 Monoclonal antibodies 80 D6 Antigen/antibody complexes (immune complexes) 83 D7 Immunoassay 87 D8 Antibody functions 93 Section E – The antibody response E1 The B cell receptor complex, co-receptors and signaling 99 E2 B cell activation 102 E3 The cellular basis of the antibody response 108 E4 Antibody responses in different tissues 112 Section F – The T cell response – cell-mediated immunity F1 The role of T cells in immune responses 115 F2 T cell recognition of antigen 117 F3 Shaping the T cell repertoire 124 F4 T cell activation 127 vi Contents F5 Clonal expansion and development of effector function 132 F6 Cell-mediated immunity in context 138 Section G – Regulation of the immune response G1 Overview 141 G2 Central and peripheral tolerance 145 G3 Acquired tolerance 149 G4 Regulation by antigen and antibody 152 G5 Genes, T helper cells, cytokines and the neuroendocrine system 155 Section H – Immunity to infection H1 The microbial cosmos 159 H2 Immunity to different organisms 162 H3 Pathogen defense strategies 167 Section I – Vaccination I1 Principles of vaccination 171 I2 Immunization 174 I3 Antigen preparations 177 I4 Vaccines to pathogens and tumors 181 Section J – Immunodeficiency – when the immune system fails J1 Deficiencies in the immune system 183 J2 Primary/congenital (inherited) immunodeficiency 185 J3 Secondary (acquired) immunodeficiency 189 J4 Diagnosis and treatment of immunodeficiency 192 Section K – Hypersensitivity – when the immune system overreacts K1 Definition and classification 197 K2 IgE-mediated (type I) hypersensitivity: allergy 199 K3 IgG and IgM-mediated (type II) hypersensitivity 204 K4 Immune-complex-mediated (type III) hypersensitivity 208 K5 Delayed (type IV) hypersensitivity 210 Section L – Autoimmunity and autoimmune diseases L1 The spectrum and prevalence of autoimmunity 215 L2 Factors contributing to the development of autoimmune disease 217 L3 Autoimmune diseases – mechanisms of development 222 L4 Disease pathogenesis – effector mechanisms 227 L5 Diagnosis and treatment of autoimmune disease 231 Section M – Transplantation M1 The transplantation problem 235 M2 Transplantation antigens 237 M3 Rejection mechanisms 240 M4 Prevention of graft rejection 243 Section N – Tumor immunology N1 Origin and host defense against tumors 249 Contents vii N2 Tumor antigens 250 N3 Immune responses to tumors 253 N4 Immunodiagnosis 256 N5 Cytokine and cellular immunotherapy of tumors 259 N6 Immunotherapy of tumors with antibodies 262 N7 Tumor vaccines 266 Section O – Gender and the immune system O1 Overview 269 O2 Immune cells and molecules associated with the reproductive tracts 271 O3 Functional effects of sex hormones on the immune system 279 Section P – Aging and the immune system (immunosenescence) P1 Overview 283 P2 Developmental changes in primary lymphoid tissue and lymphocytes with age 285 P3 Effects of aging on innate immunity 288 P4 The effects of aging on T cell immunity 290 P5 The effects of aging on humoral immunity 292 P6 Immunosenescence and morbidity, mortality and longevity 294 Further reading 297 Multiple Choice Questions 299 Appendix I – Selected CD molecules 315 Appendix II – The principal cytokines 317 Glossary 319 Index 325 ABBREVIATIONS 5HT 5′hydroxytryptamine HPA hypothalamus/pituitary/adrenal ADA adenosine deaminase HPV human papilloma virus ADCC antibody-dependent cell/cellular HSC hemopoietic stem cell cytotoxicity HTLV human T cell leukemia virus AFP alpha-fetoprotein IDC interdigitating cell AICD activation-induced cell death IEL intraepithelial lymphocyte AIDS acquired immune deficiency IF immunofluorescence syndrome IFN interferon AIHA autoimmune hemolytic anemia IL interleukin BALT bronchus-associated lymphoid ITAM immunoreceptor tyrosine-based tissue activation motif BCR B cell receptor ITIM immunoreceptor tyrosine-based CEA carcinoembryonic antigen inhibitory motif CGD chronic granulomatous disease ITP immune thrombocytopenic purpura CMV cytomegalovirus KAR killer activation receptor CRD carbohydrate recognition domain KIR killer inhibitory receptor CRH corticotrophin-releasing hormone LAK lymphokine-activated killer CRP C-reactive protein LCMV lymphocytic choriomeningitis virus CTL cytolytic/cytotoxic T lymphocyte LFA leukocyte function antigen CVID common variable LGL large granular lymphocyte immunodeficiency LH Langerhans cell DAF decay-accelerating factor LP late proliferative DAG diacyl glycerol LPS lipopolysaccharide DC dendritic cell LRR leucine-rich repeat DHEA dehydroepiandrosterone LS late secretory DHEAS dehydroepiandrosterone sulfate LSC lymphoid stem cells DTH delayed-type hypersensitivity MAC membrane attack complex EAE experimental allergic MALT mucosa-associated lymphoid tissue encephalomyelitis MBP mannose-binding protein EBV Epstein–Barr virus MCP membrane co-factor protein ELISA enzyme-linked immunosorbent M-CSF monocyte/macrophage colony- assay stimulating factor ER endoplasmic reticulum MDP muramyl dipeptide FDC follicular dendritic cell MHC major histocompatibility complex FRT female reproductive tract MØ macrophage GALT gut-associated lymphoid tissue MS multiple sclerosis GC germinal center MZ marginal zone G-CSF granulocyte colony-stimulating NALT nasal-associated lymphoid tissue factor NBT nitroblue tetrazolium test GI gastrointestinal NK natural killer GOD generation of diversity NO nitric oxide HAMA human anti-mouse antibody NSAID nonsteroidal anti-inflammatory HBV hepatitis B virus drugs HEV high endothelial venules PAF platelet-activating factor HHV8 human herpes virus 8 PALS periarteriolar lymphoid sheath HIV human immunodeficiency virus PCR polymerase chain reaction HLA human leukocyte antigen PMN polymorphonuclear cell Abbreviations ix PRR pattern recognition receptor SV splenic vein PS phosphatidyl serine TAA tumor-associated antigens