Immunology An Illustrated Outline Immunology An Illustrated Outline Sixth Edition David Male CRC Press Boca Raton and London Sixth edition published 2021 by CRC Press 6000 Broken Sound Parkway NW, Suite 300, Boca Raton, FL 33487-2742 and by CRC Press 2 Park Square, Milton Park, Abingdon, Oxon, OX14 4RN © 2021 Taylor & Francis Group, LLC CRC Press is an imprint of Taylor & Francis Group, LLC The right of David Male to be identified as author of this work has been asserted by him in accordance with sections 77 and 78 of the Copyright, Designs and Patents Act 1988. Reasonable efforts have been made to publish reliable data and information, but the author and publisher cannot assume responsibility for the validity of all materials or the consequences of their use. The authors and publishers have attempted to trace the copyright holders of all material reproduced in this publication and apologize to copyright holders if permission to publish in this form has not been obtained. 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ISBN: [978-0-367-68464-8] (hbk) ISBN: [978-0-367-68139-5] (pbk) ISBN: [978-1-003-13765-8] (ebk) Typeset in Helvetica by KnowledgeWorks Global Ltd. Preface This book serves three different functions. It provides a concise overview of basic immunology for readers who have not studied the subject previously, but need an understanding of the subject to support undergraduate or postgraduate work. It can also be used as a reference for science and medical students who have studied immunology, but require a refresher on specific content or to aid revision for exams. Finally, the book can be used as a dictionary of immunological terms. Readers who already know some immunology and require a sum- mary of particular aspects should consult the contents pages. The book is divided into five sections, each of which contains a number of related topics that are generally set out on double-page spreads. These topics are arranged in a logical sequence, so that Sections 1–3 are a short course in basic immunology, Section 4 provides the basis for clinical immunology, and Section 5 outlines important immunological techniques. To use the book as a dictionary, look up the word or abbreviation in the “Index of Terms.” This gives a single page number where a definition of the word will be found; associated terms can be found on the same page. Page references to particular topics set out over several pages are indicated in bold. Items found as entries in tables are given in italics. This edition of the book has been fully revised to highlight the latest understanding of the subject, particularly in the areas of therapeu- tic antibodies, innate immune defenses, and control of immune responses. Naturally, a book of this kind cannot include everything of interest to immunologists. I have tried to cover all essential areas of the subject, but I should be pleased to know when readers con- sider that particular subjects deserve further coverage. I am most grateful to colleagues, acknowledged in the figure leg- ends, who have allowed me to use micrographs or photographs. For this edition, I am very pleased to have worked with a new edito- rial team, including Jo Koster and Jordan Wearing at CRC Press/ Taylor & Francis and I also thank the illustrator, Nigel Orme. Contents Index of Terms ix Chapter 1 The Immune System Introduction 2 Lymphocytes 4 Innate lymphoid cells 8 Markers 9 Antigen-presenting cells 12 Phagocytes and auxiliary cells 14 Lymphoid system 16 Leukocyte development 18 Thymus and T-cell development 20 Lymph nodes 22 Spleen 24 Gut-associated lymphoid tissue (GALT) 25 Chapter 2 Immune Recognition Antigen receptors 26 Antibody structure 28 Antibody-structural variations 30 Antibody functions 32 Antibody genes 34 Antibody biotechnology 38 Immunotherapeutic agents 39 Antigen-antibody interactions 40 T-cell antigen receptor (TCR) 42 T-cell receptor genes 43 MHC molecules 44 MHC genes 46 Immune recognition by NK cells 48 Innate immune recognition 50 Chapter 3 Immune Responses Adaptive and innate immunity 54 Antibody response 56 Cell cooperation 58 Antigen presentation 60 T-cell activation 64 viii B-cell activation 67 Cytokines and cytokine receptors 70 Phagocytosis 76 Complement receptors 78 Fc receptors 79 Phagocyte microbicidal systems 80 Intracellular receptors for pathogens 83 Cytotoxicity 84 Inflammation 87 Mechanisms of cell migration 90 Chemokines and chemokine receptors 94 Complement 96 Immunoregulation 100 Neuroendocrine regulation 103 Tolerance 104 Genetic polymorphism in the immune response 106 Immunosuppression 108 Immunopotentiation 110 Vaccines 111 Chapter 4 Immunopathology Immunodeficiency 112 Transplantation 116 MHC disease associations 118 MHC typing 120 Autoimmune disease 121 Animal models and mutant strains 124 Hypersensitivity 126 Type I (immediate) hypersensitivity 128 Type II (antibody-mediated) hypersensitivity 130 Type III (immune-complex-mediated) hypersensitivity 132 Type IV (delayed) hypersensitivity (DTH) 134 Chapter 5 Immunological Techniques Antibodies and antigens 136 Clones and cell lines 146 Isolation of cells 148 Cellular functions 150 Index of Terms Note: Bold page numbers identify topics set out on several pages; roman page numbers identify entries in the text, including definitions; italic page numbers indicate additional information in tables or figures. 12/23 rule 34 Angiotensin-converting enzyme (CD143) 11 A Animal models 124–125 Ab (antibodies) 27 Ankylosing spondylitis 119 Abatercept 39 Antibodies (Ab) 27 ABO blood group system 130 assays for/using 136–145 Accessory cells 3 biotechnology 38 Acquired immune deficiency classes and subclasses 30, 33 syndrome (AIDS) 115 fragments 38 Acquired (adaptive) immunity 54 functions 32–33 Activation-induced cytidine generation of diversity 34 deaminase (AID) 37 structural variations 30–31 Active immunization 57 structure 28–29 Acute-phase proteins 54 synthesis 37 Acute rejection 117 therapeutic 109 ADAMs 82 see also Immunoglobulins Adaptive immunity 54–55 Antibody affinity 40 ADCC (antibody-dependent cell Antibody avidity 41 mediated cytotoxicity) 85 Antibody/complement Addison’s disease 119 depletion 148 Adenoids 17 Antibody-dependent cell-mediated Adherence 148 cytotoxicity (ADCC) 85 Adhesion 58 Antibody-drug conjugates 39 Adhesion assays 151 Antibody-forming cells (AFC) 6 Adhesion molecules 91, 93 Antibody genes 34–37 Adjuvants 110 Antibody-mediated (type II) AFC (antibody-forming cells) 6 hypersensitivity 127, Afferent lymphatics 23 130–131 Affinity, antibody 40 Antibody-mediated Affinity chromatography 142 immunoregulation 101 Affinity maturation 56–57 Antibody response 56–57 Aflibercept 39 Antibody therapy 39 AID (activation-induced cytidine Antibody valency 41 deaminase) 37 Antigen(s) 26 AIDS (acquired immune deficiency assays for/using 136–145 syndrome) 115 Antigen-antibody bond 40 AIRE (autoimmune regulator) 21 Antigen-antibody Allelic exclusion 30 interactions 40–41 Allergens 128 Antigen presentation 58, 60–63 Allergy 128 class I (internal) pathway 62 Allotypes 31 class II (external) pathway 61 Alternative pathway, cross-presentation 63 complement 96 Antigen-presenting cells Amplification loop, complement 96 (APCs) 12–13, 13 Amyloid-P, serum (SAP) 53 antigen processing and Anaphylatoxins 98 presentation 60 Anaphylaxis 129 facultative 13 Anchor residues 62 Antigen processing 60 Angioedema, hereditary 98 Antigen receptors 26–27 x Antigen suicide 149 Biological response modifiers Antigenic determinants (BRMs) 110 (epitopes) 26 Biotechnology, antibody 38 Antigenic peptides 61 Biotin reagents 138 Antiviral proteins 55 Biozzi ABH mouse 125 APCs (antigen-presenting Biozzi mice 107 cells) 12–13, 13 Bispecific antibodies 39 APRIL 69 Blood groups 130 Arthus reaction 133 Bone marrow 18 Atacicept 39 Bordetella pertussis toxin/toxoid Ataxia telangiectasia 113 (PTx) 110 Atopy 129 Bradykinin 88 Attenuated live vaccines 111 BRMs (biological response Autoimmune activation 122 modifiers) 110 Autoimmune disease 121–123 Bronchus-associated lymphoid Autoimmune hemolytic tissue (BALT) 17 anemia 131 Bruton’s disease 114 Autoimmune regulator (AIRE) 21 Buffalo rat 125 Autoimmunity, genetic risk factors BXSB mouse 125 for, 122 Bystander lysis 98 Autoreactive cells 122 Autoregulatory failure 123 C Auxiliary cells 14–15 C genes 37 Avidity, antibody 41 C-reactive protein (CRP) 53 Azathioprine 108 C (constant) regions 29 C1inh 99 B C1q/C1r/C1s 99 BAFF (B-cell activating factor) 69 C2 99 B (complement factor) 99 C3 99 B cell(s) 6 C3 convertases 96 antigen presentation 13 C3a 88, 98 development 23 C3bina (I) 99 B-cell activation 67–69 C3H/HeJ mouse 125 B-cell activating factor (BAFF) 69