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Roitt’s EssentialImmunology
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Thirteenth editionRoitt’s EssentialImmunologyPeter J. DelvesPhDDivision of Infection and ImmunityUCLLondon, UKSeamus J. MartinPhD, FTCD, MRIAThe Smurfit Institute of GeneticsTrinity CollegeDublin, IrelandDennis R. BurtonPhDDepartment of Immunology and Microbial ScienceThe Scripps Research InstituteLa Jolla, California, USAIvan M. RoittMA, DSc (Oxon), FRCPath, Hon FRCP (Lond), FRSCentre for Investigative and Diagnostic OncologyMiddlesex UniversityLondon, UK
This edition first published 2017 2017 by John Wiley and Sons, Ltd. 1971, 1974, 1977, 1980,1984, 1988, 1991, 1994, 1997, 2001, 2006, 2011 by Peter J. Delves,Seamus J. Martin, Dennis R. Burton, Ivan M. RoittRegistered OfficeJohn Wiley & Sons, Ltd, The Atrium, Southern Gate, Chichester, West Sussex, PO19 8SQ, UKEditorial Offices9600 Garsington Road, Oxford, OX4 2DQ, UKThe Atrium, Southern Gate, Chichester, West Sussex, PO19 8SQ, UKFor details of our global editorial offices, for customer services and for information about howto apply for permission to reuse the copyright material in this book please see our website atwww.wiley.com/wiley‐blackwellThe right of the author to be identified as the author of this work has been asserted in accordance withthe UK Copyright, Designs and Patents Act 1988.All rights reserved. No part of this publication may be reproduced, stored in a retrieval system,or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording orotherwise, except as permitted by the UK Copyright, Designs and Patents Act 1988, without the priorpermission of the publisher.Designations used by companies to distinguish their products are often claimed as trademarks. Allbrand names and product names used in this book are trade names, service marks, trademarks orregistered trademarks of their respective owners. The publisher is not associated with any product orvendor mentioned in this book. It is sold on the understanding that the publisher is not engaged inrendering professional services. If professional advice or other expert assistance is required, the servicesof a competent professional should be sought.The contents of this work are intended to further general scientific research, understanding, anddiscussion only and are not intended and should not be relied upon as recommending or promotinga specific method, diagnosis, or treatment by health science practitioners for any particular patient.The publisher and the author make no representations or warranties with respect to the accuracy orcompleteness of the contents of this work and specifically disclaim all warranties, including withoutlimitation any implied warranties of fitness for a particular purpose. In view of ongoing research,equipment modifications, changes in governmental regulations, and the constant flow of informationrelating to the use of medicines, equipment, and devices, the reader is urged to review and evaluate theinformation provided in the package insert or instructions for each medicine, equipment, or device for,among other things, any changes in the instructions or indication of usage and for added warnings andprecautions. Readers should consult with a specialist where appropriate. The fact that an organizationor Website is referred to in this work as a citation and/or a potential source of further information doesnot mean that the author or the publisher endorses the information the organization or Website mayprovide or recommendations it may make. Further, readers should be aware that Internet Websiteslisted in this work may have changed or disappeared between when this work was written and when itis read. No warranty may be created or extended by any promotional statements for this work. Neitherthe publisher nor the author shall be liable for any damages arising herefrom.Library of Congress Cataloging‐in‐Publication DataNames: Delves, Peter J., author. Martin, Seamus J., 1966– author. Burton, Dennis R., author. Roitt, Ivan M. (Ivan Maurice), author.Title: Roitt’s essential immunology / Peter J. Delves, Seamus J. Martin, Dennis R. Burton,Ivan M. Roitt.Other titles: Essential immunologyDescription: 13th edition. Chichester, West Sussex ; Hoboken, [NJ] : John Wiley & Sons, Inc., 2017. Preceded by Roitt’s essential immunology / Peter J. Delves . [et al.]. 12th ed. 2011. Includes bibliographical references and index.Identifiers: LCCN 2016022210 (print) LCCN 2016022856 (ebook) ISBN 9781118415771 (pbk.) ISBN 9781118416068 (pdf ) ISBN 9781118416044 (epub)Subjects: MESH: Immune System ImmunityClassification: LCC QR181 (print) LCC QR181 (ebook) NLM QW 504 DDC 616.07/9–dc23LC record available at https://lccn.loc.gov/2016022210A 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 maynot be available in electronic books.Cover image: Getty Images / Science Photo Library - STEVE GSCHMEISSNERSet in 10/12pt Adobe Garamond by SPi Global, Pondicherry, India12017
ContentsAbout the authors viAcknowledgments viiiPreface ixAbbreviations xHow to use your textbook xviAbout the companion website xviiPart 1: Fundamentals of immunology 1 Innate immunity 132 Specific acquired immunity 523 Antibodies 694 Membrane receptors for antigen 975 Antigen‐specific recognition 1396 The anatomy of the immune response 1677 Lymphocyte activation 1878 The production of effectors 2189 The regulation of the immune response 27210 Development and evolution of the immune response 291Part 2: Applied immunology 31911 Adversarial strategies during infection 32112 Vaccines 35313 Immunodeficiency 37814 Allergy and other hypersensitivities 40515 Transplantation 43516 Tumor immunology 45817 Autoimmune diseases 499Glossary 529Index 541Don’t forget to visit the companion website for this book:www.roitt.com
About the authorsPeter J. DelvesProfessor Delves obtained his PhD from the University of Londonin 1986 and is a Professor of Immunology at UCL (UniversityCollege London). His research has focused on molecular aspectsof antigen recognition. He has authored and edited a number ofimmunology books, and teaches the subject worldwide at a broadrange of levels.Seamus J. MartinProfessor Martin received his PhD from The National Universityof Ireland in 1990 and trained as a post‐doctoral fellow atUniversity College London (with Ivan Roitt) and The La JollaInstitute for Allergy and Immunology, California, USA (withDoug Green). Since 1999, he is the holder of the Smurfit Chair ofMedical Genetics at Trinity College Dublin and is also a ScienceFoundation Ireland Principal Investigator. His research is focusedon various aspects of programmed cell death (apoptosis) in theimmune system and in cancer and he has received several awardsfor his work in this area. He has previously edited two books onapoptosis and was elected as a Member of The Royal Irish Academyin 2006 and as a member of The European Molecular BiologyOrganisation (EMBO) in 2009.Dennis R. BurtonProfessor Burton obtained his BA in Chemistry from theUniversity of Oxford in 1974 and his PhD in Physical Biochemistryfrom the University of Lund in Sweden in 1978. After a period atthe University of Sheffield, he moved to the Scripps ResearchInstitute in La Jolla, California in 1989 where he is Professor ofImmunology and Microbial Science. His research interests includeantibodies, antibody responses to pathogens and rational vaccinedesign, particularly in relation to HIV.
About the authors / viiIvan M. RoittProfessor Roitt was born in 1927 and educated at King Edward’sSchool, Birmingham and Balliol College, Oxford. In 1956,together with Deborah Doniach and Peter Campbell, he made theclassic discovery of thyroglobulin autoantibodies in Hashimoto’sthyroiditis which helped to open the whole concept of a relationship between autoimmunity and human disease. The work wasextended to an intensive study of autoimmune phenomena in pernicious anaemia and primary biliary cirrhosis. In 1983 he waselected a Fellow of The Royal Society, and has been elected toHonorary Membership of the Royal College of Physicians andappointed Honorary Fellow of The Royal Society of Medicine.His current research is focused on cancer.
AcknowledgmentsPeter Delves would like to acknowledge the enormous help provided by Biljana Nikolic in the delivery ofeducation by the UCL Division of Infection & Immunity, and the huge support of his wife Jane andc hildren Joe, Tom, and Jess.Dennis Burton acknowledges funding for his research from the NIH, the Bill and Melinda GatesFoundation, the International AIDS Vaccine Initiative and the Ragon Institute of MGH, MIT andHarvard. I also thank my wife Carole and children Damian, Scott, and Julia for their support.Ivan Roitt is eternally grateful to his wife Margaret and PA Christine and the uncontrolled events in hisbody which have sustained his mojo!
PrefaceGreetings, dear reader! In the exciting world of scientific progress, immunology plays a prominent role andwe have aimed to bring this edition to the cutting edge of the latest discoveries. Highlights of the newupdates include: Tailoring of the adaptive immune response to pathogens, particularly in the skin by pattern recognitionreceptors New insights into the interaction between antibodies and Fc receptors, and immunoglobulin genetics Epigenetic control of T‐cell activation T‐cell recognition of lipid antigens and beautiful high‐resolution images of interactions with other cellsof the immune system Expanded discussion of novel events in cytokine biology Revised section on antibody interaction with viral proteins Recent developments in vaccinology including RNA vaccines Induction of cells suppressing a protective immune response by tumors, and recent breakthroughs intumor immunotherapy Induction and maintenance of immunosuppression to curb graft rejection The role of inflammasomes in autoinflammatory disease and much more!We try to maintain the chatty style characteristic of all earlier editions, imagining that you and theauthors are on either side of a fireplace discussing the issues informally, which we hope makes the processof assimilation less painful and quite probably enjoyable.Peter J. DelvesSeamus J. MartinDennis R. BurtonIvan M. Roitt
naadeno‐associated virusantibodyacetylcholine receptoradoptive cell transferadrenocorticotropic hormoneadenosine deaminaseantibody‐dependent cellular cytotoxicityasparagine endopeptidaseantigenactivation‐induced cytidine deaminaseacquired immunodeficiency syndromeautoimmune regulatoraddressable laser bead assayantineutrophil cytoplasmic antibodiesantigen‐presenting cellantigen receptor response element‐1antigen receptor response element‐2antiretroviral therapyAfrican swine fever viruszidovudine ctivating factor of the tumor necrosis factor familylymphocyte which matures in bone marrowbacille Calmette–Guérin attenuated form of tuberculosisB‐cell receptorbone marrowbovine serum albuminbovine spongiform encephalopathyBruton’s tyrosine kinasebromodeoxyuridinecomplementconstant part of TCR α(β/γ/δ) chaincommon acute lymphoblastic leukemia antigencyclic adenosine monophosphatecomplement control protein repeatcluster of differentiationcomplementarity determining regions of Ig or TCR variable portioncarcinoembryonic antigencomplete Freund’s adjuvantcyclic guanosine monophosphatechromatin immunoprecipitationchemotaxis inhibitory proteinconstant part of Ig heavy (light) chaincutaneous lymphocyte antigenclass II‐associated invariant chain peptidecell‐mediated immunitycell‐mediated lympholysiscytomegaloviruscomplement component “n”activated complement component “n”inactivated complement component “n”small peptide derived by proteolytic activation of Cn
Abbreviations / xiCpGCR(n)CRPCSFCSRCTLRDAFDAGDAMPDCD DQ/DR)cytosine phosphate‐guanosine dinucleotide motifcomplement receptor “n”C‐reactive proteincerebrospinal fluidclass switch recombinationC‐type lectin receptordecay accelerating factordiacylglyceroldanger‐associated molecular patterndendritic cellsdiversity minigene joining V and J segments to form variable regiondisease‐modifying antirheumatic drugdinitrophenyldelayed‐type hypersensitivitydiphtheria, tetanus, pertussis triple vaccineexperimental autoimmune (allergic) encephalomyelitisEpstein–Barr virusenzyme‐linked immunosorbent assayelectron microscopeeosinophilerythropoietinendoplasmic reticulumembryonic stem (cell)exfoliative toxinsfactor (B, etc.)monovalent Ig antigen‐binding fragment after papain digestiondivalent antigen‐binding fragment after pepsin digestionfluorescence‐activated cell sorterFas‐ligandIg crystallizable‐fragment originally; now non‐Fab part of Igreceptor for IgG Fc fragmentfollicular dendritic cellflk‐2 ligand(single chain) VH–VL antigen binding fragmentGRB2‐related adaptor proteinglomerular basement membranegranulocyte colony‐stimulating factorguanine‐nucleotide exchange factorsgranulocyte–macrophage colony‐stimulating factorn kDa glycoproteingrowth factor receptor‐binding protein 2glycogen synthase kinase 3graft versus hostthe mouse major histocompatibility complexmain loci for classical class I (class II) murine MHC moleculeshuman antimouse antibodieshuman antitoxin antibodyhepatitis B surface antigenhuman chorionic gonadotropinhuman cytomegalovirushen egg lysozymehigh‐walled endothelium of postcapillary venulehuman immunodeficiency virushuman major histocompatibility complexmain loci for classical class I (class II) human MHC molecules
xii / ��1Id IgSFIL‐1iNOSIP3ISCOMITAMITIMITPIVIgJAKJ chainJ �1LGLLHRHLIFLPSLRRLT(B)mAbMACMAdCAMhigh mobility grouphypersensitive responsehomologous restriction factorheat‐stable antigenhematopoietic stem cellheat‐shock protein5‐hydroxytryptaminehuman T‐cell leukemia virusmale transplantation antigeninflammatory bowel diseaseintercellular adhesion molecule‐1idiotype (anti‐idiotype)interdigitating dendritic cellsinsulin‐dependent diabetes mellitusindoleamine 2,3‐dioxygenaseintraepithelial lymphocyteα‐interferon (also IFNβ, IFNγ)interferon‐regulated factorimmunoglobulinimmunoglobulin G (also IgM, IgA, IgD, IgE)surface immunoglobulinmembrane peptide chains associated with sIg B‐cell receptorimmunoglobulin superfamilyinterleukin‐1 (also IL‐2, IL‐3, etc.)inducible nitric oxide synthaseinositol trisphosphateimmunostimulating compleximmunoreceptor tyrosine‐based activation motifimmunoreceptor tyrosine‐based inhibitory motifidiopathic thrombocytopenic purpuraintravenous immunoglobulinJanus kinasespolypeptide chain in IgA dimer and IgM pentamerjoining gene linking V or D segment to constant regionassociation (dissociation) affinity constant (usually Ag–Ab reactions)units of molecular mass in kilodaltonskiller immunoglobulin‐like receptorskeyhole limpet hemocyaninlymphokine‐activated killer celllysosomal‐associated membrane proteinslinker for activation of T‐cellslong‐acting thyroid stimulatorLPS‐binding proteinlymphocytic choriomeningitis virusLewisa/b/x blood group antigenslymphocyte function‐associated antigen‐1large granular lymphocyteluteinizing hormone releasing hormoneleukemia inhibiting factorlipopolysaccharide (endotoxin)leucine‐rich repeatleukotriene (B etc.)monoclonal antibodymembrane attack complexmucosal addressin cell adhesion molecule
Abbreviations / xiiiMALTMAMMAP CFNFATNFkBNKNLRNONODNZBNZB VPG(E)PHAphoxPI3KPIASpIgRmucosa‐associated lymphoid tissueMycoplasma arthritidis mitogenmitogen‐activated protein kinasemitogen‐associated protein kinase kinase kinasemannose binding lectinmajor basic protein of eosinophils (also myelin basic protein)membrane cofactor protein (complement regulation)monocyte chemotactic protein‐1macrophage colony‐stimulating factormuramyl dipeptidemajor histocompatibility complexMHC class I chain‐related A chainmetal ion‐dependent adhesion sitemacrophage migration inhibitory factorMHC class II‐enriched compartmentsmonophosphoryl lipid Amixed lymphocyte reactionmouse mammary tumor virusmacrophagemethicillin‐resistant Staphylococcus aureusmultiple sclerosismesenchymal stem cellmelanocyte stimulating hormonemicrosomal triglyceride‐transfer proteinmurine leukemia virusnicotinamide adenine dinucleotide phosphateneutrophil activating peptidenitroblue tetrazoliumneutrophil chemotactic factornuclear factor of activated T‐cellsnuclear transcription factornatural killer cellNOD‐like receptornitric oxidenonobese diabetic mouseNew Zealand Black mouseNew Zealand Black mouse NZ White F1 hybridsuperoxide anionoptical densityopen reading frameobese strain chickenovalbuminplatelet activating factor (‐receptor)polyacrylamide gel electrophoresispathogen‐associated molecular patternperipheral blood stem cellspassive cutaneous anaphylaxispolymerase chain reactionporcine endogenous retrovirusesprostaglandin (E etc.)phytohemagglutininphagocyte oxidasephosphatidylinositol 3‐kinaseprotein inhibitor of activated STATpoly‐Ig receptor
xiv / ESEA (B TTACIT‐ALLTAPTBTcphosphatidylinositol diphosphateprotein kinase CRNA‐dependent protein kinasephospholipase Cphospholipase Cγ2polymorphonuclear neutrophilphotomultiplier tubeparoxysmal nocturnal hemoglobinuriaperoxisome proliferator‐activated receptorpurified protein derivative from Mycobacterium tuberculosispattern recognition receptorpolytetrafluoroethyleneprotein tyrosine kinasepokeweed mitogenrheumatoid arthritisregulated upon activation normal T‐cell expressed and secreted chemokineradioallergosorbent testrheumatoid factorrhesus blood group (D)rat insulin promoterRIG‐like helicase receptorRNA interferencereactive oxygen intermediatesrecombination signal sequenceserum amyloid Psphingolipid activator proteinsystemic acquired resistancesevere acute respiratory syndromeSARS‐associated coronavirusIg secretory componentstem cell factorsingle‐chain variable region antibody fragment (VH VL joined by a flexible linker)sodium cromoglycatesevere combined immunodeficiencystromal‐derived factorsodium dodecyl sulfatesodium dodecyl sulfate–polyacrylamide gel electrophoresisStaphylococcus aureus enterotoxin A (B etc.)serological analysis of recombinant cDNA expression librariesshort‐interfering RNASimian immunodeficiency virussystemic lupus erythematosussublingual allergen immunotherapySH2‐domain containing leukocyte protein of 76 kDasuppressor of cytokine signalingstreptococcal pyogenic exotoxinssingle radial immunodiffusionstreptococcal superantigensignal transducer and activator of transcriptiontransmembrane activator and calcium modulator and cyclophilin ligand [CAML]interactorT‐acute lymphoblastic leukemiatransporter associated with antigen processingtubercle bacilluscytotoxic T‐cell
Abbreviations / VLVLAVLPVNTRVP1XLZAP‐70thymus‐derived lymphocyteT‐cell factorT‐cell receptor with γ/δ chains (with
Roitt’s Essential Immunology Peter J. Delves PhD Division of Infection and Immunity UCL London, UK Seamus J. Martin PhD, FTCD, MRIA The Smurfit Institute of Genetics Trinity College Dublin, Ireland Dennis R. Burton PhD Department of Immunology and Microbial Science The Scripps Research Institute La Jolla, California, USA Ivan M. Roitt
Roitt’s Essential Immunology Peter J. Delves PhD Division of Infection and Immunity UCL London, UK Seamus J. Martin PhD, FTCD, MRIA Th e Smurfi t Institute of Genetics Trinity College Dublin, Ireland Dennis R. Burton PhD Department of Immunology and Molecular Biology Th e Scripps Research Institute La Jolla, California, USA Ivan M. Roitt
ROITT’S ESSENTIAL IMMUNOLOGY PETER J. DELVES SEAMUS J. MARTIN DENNIS R. BURTON IVAN M. ROITT 12TH EDITION w i t h w e bsit e with Wiley DESKTOP EDITION Medical Pharmacology at a Glance Seventh Edition Michael J. Neal Medical Pharmacology at a Glance (BO617) Australian Medicines Hand-book 2012, Book format (BO706) Roitt’s Essential .
Roitt IM. Roitt’s Essential Immunology 10th ed. Blackwell Science 2001 3. Hochburg et al. Rheumatology 3rd ed. Mosby 2003 4. UpToDate 12.3 5. Kalla AA. Rheumatology Handbook. Rheumatic Diseases Unit Univrersity of Cape Town. 2003 References (cont) 6. Parkin J, Cohen B. An overview of the immune system. Lancet 2001;357: 1777-1789. 7. Mackay IR .
5. Roitt’s Essential Immunology 11th ed– Delves P, Martin S, Burton D, Roitt I. Blackwell Publishing 6. Immunology 2ed – C.V.Rao. Narosa Publication 7. Molecular Biology of the Cell – Alberts et al. Garland Science 8. Molecular cell Biology – Lodish et al. Freeman Publishers 9.
Roitt’s Essential Immunology. Ivan M. Roitt and Peter J. Delves. 10 th Ed. Blackwell Publishing Ltd. 2001. 4. Fundamental Immunology. William E. Paul. 6 th edition. Lippincott Williams & Wilkins, a Wolters Kluwer business. 2008. DAV UNIVERSITY, JALANDHAR Page 11 of 55
Roitt’s Essential Immunology Roitt 13/2017 978-1118415771 Wiley-Blackwell 100.00 (print) 80.00 (rent) 60.00 (ebook) BIOL 3503 Ecología Elements of Ecology Smith, Smith 9/2015 978-1292077406 Pearson 150.00 (print) 40.00 (rent) 60.00 (ebook) BIOL 4604 Biología Celular y .
Jawetz, Melnick and Adelberg’s Publication Medical Microbiology. 26th edition. McGraw Hill Delves P, Martin S, Burton D, Roitt IM. (2006). Roitt’s Essential Immunology.11th edition Wiley-Blackwell Scientific Publication, Oxford. Goering R., Dockrell H., Zuckerman M. and Wakelin D. (2007) Mims’ Medical Microbiology. 4th edition.
Introduction Origami is the art of folding 2D materials, such as a flat sheet of paper, into 3D objects with desired shapes. Since early 1980s, origami has evolved into a fertile scientific field connecting diverse disciplines, creating an
