Roitt's essential immunology

562 Pages·2011·41.73 MB·English

by  Peter J Delves

Roitt’s
Essential
Immunology
Peter J. Delves
Professor Delves obtained his PhD from the University of
London in 1986 and is a Professor of Immunology at UCL
(University College London). His research has focused on
molecular aspects of antigen recognition. He has authored and
edited a number of immunology books, and teaches the subject
at a broad range of levels.
Seamus J. Martin
Professor Martin received his PhD from Th e National University
of Ireland in 1990 and trained as a post - doctoral fellow at
University College London (with Ivan Roitt) and Th e La Jolla
Institute for Allergy and Immunology, California, USA (with
Doug Green). Since 1999, he is the holder of the Smurfi t Chair
of Medical Genetics at Trinity College Dublin and is also a
Science Foundation Ireland Principal Investigator. His research is
focused on various aspects of programmed cell death (apoptosis)
in the immune system and in cancer and he has received several
awards for his work in this area. He has previously edited two
books on apoptosis and was elected as a Member of Th e Royal
Irish Academy in 2006 and as a member of Th e European
Molecular Biology Organisation (EMBO) in 2009.
Dennis R. Burton
Professor Burton obtained his BA in Chemistry from the
University of Oxford in 1974 and his PhD in Physical
Biochemistry from the University of Lund in Sweden in 1978.
After a period at the University of Sheffi eld, he moved to the
Scripps Research Institute in La Jolla, California in 1989 where
he is Professor of Immunology and Molecular Biology. His
research interests include antibodies, antibody responses to
pathogens and vaccine design, particularly in relation to HIV.

Ivan M. Roitt
Professor Roitt was born in 1927 and educated at King Edward ’ s
School, Birmingham and Balliol College, Oxford. In 1956,
together with Deborah Doniach and Peter Campbell, he made
the classic discovery of thyroglobulin autoantibodies in
Hashimoto ’ s thyroiditis which helped to open the whole concept
of a relationship between autoimmunity and human disease. Th e
work was extended to an intensive study of autoimmune
phenomena in pernicious anaemia and primary biliary cirrhosis.
In 1983 he was elected a Fellow of Th e Royal Society, and has
been elected to Honorary Membership of the Royal College of
Physicians and appointed Honorary Fellow of Th e Royal Society
of Medicine.
TWELFTH EDITION
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
MA, DSc(Oxon), FRCPath, Hon FRCP (Lond), FRS
Centre for Investigative and Diagnostic Oncology
Middlesex University
London, UK
A John Wiley & Sons, Ltd., Publication
Th is edition fi rst published 2011 © 1971, 1974, 1977, 1980, 1984, 1988, 1991, 1994,
1997, 2001, 2006 by Peter J Delves, Seamus J. Martin, Dennis R. Burton, Ivan M. Roitt
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Library of Congress Cataloging-in-Publication Data
Roitt’s essential immunology / Peter J. Delves ... [et al.]. – 12th ed.
p. cm. – (Essentials ; 16)
Rev. ed. of: Roitt’s essential immunology / Ivan M. Roitt, Peter J. Delves.
Includes bibliographical references and index.
ISBN 978-1-4051-9683-3 (pbk.)
1. Immunology. I. Delves, Peter J. II. Roitt, Ivan M. (Ivan Maurice) Roitt’s essential
immunology. III. Title: Essential immunology.
QR181.R57 2011
616.07'9–dc22
2010047392
A catalogue record for this book is available from the British Library.
Set in 10/12 pt Adobe Garamond Pro by Toppan Best-set Premedia Limited
1 2011
Contents
Acknowledgments vi
Preface vii
Abbreviations viii
How to get the best out of your textbook xii
PART 1: Fundamentals of Immunology
1. Innate immunity 3
2. Specifi c acquired immunity 35
3. Antibodies 53
4. Membrane receptors for antigen 79
5. The primary interaction with antigen 113
6. Immunological methods and applications 141
7. The anatomy of the immune response 188
8. Lymphocyte activation 205
9. The production of effectors 226
10. Control mechanisms 263
11. Ontogeny and phylogeny 283
PART 2: Applied Immunology
12. Adversarial strategies during infection 313
13. Vaccines 345

14. Immunodefi ciency 369
15. Allergy and other hypersensitivities 394
16. Transplantation 423
17. Tumor immunology 445
18. Autoimmune diseases 475
Glossary 511
Index 522
Companion website www.roitt.com
Acknowledgments
Th e input of the editorial team of Elizabeth Johnston, Laura Murphy and Cathryn Gates at Wiley - Blackwell and the project
management of Ruth Swan is warmly acknowledged. We are much indebted to the co - editors of Immunology, J. Brostoff , D.
Roth and D. Male, together with the publishers, Mosby, and the following individuals for permission to utilize or modify their
fi gures: J. Brostoff and A. Hall for fi gure 15.11 ; J. Horton for figure 11.19 ; a nd J. Taverne for fi gures 12.23 and 12.24 .
I MR would like to acknowledge the indefatigable secretarial assistance of Christine Griffi n. DRB wishes to particularly
acknowledge the invaluable contributions of Amandeep Gakhal, Erin Scherer, Rena Astronomo and Wendelien Oswald. He is
grateful to Jenny Woof, Ann Feeney, Beatrice Hahn, Jim Marks, Don Mosier, Paul Sharp, Robyn Stanfi eld, James Stevens and
Mario Stevenson for many very helpful comments. PJD would particularly like to thank Per Brandtzaeg, Volker Brinkmann,
Greg Campbell, Peter Lydyard, Rand Swenson and Ulrich Wahn. SJM is indebted to Ed Lavelle, Sean Cullen, Cristina
Munoz - Pinedo and all of the members of his laboratory for comments, suggestions and support. He would also like to thank
Mia, Madeleine and Jamie for their support and indulgence.
Every eff ort has been made by the authors and the publisher to contact all the copyright holders to obtain their permission
to reproduce copyright material. However, if any have been inadvertently overlooked, the publisher will be pleased to make the
necessary arrangements at the fi rst opportunity.
A number of scientists very generously provided illustrations for inclusion in this edition, and we have acknowledged our
gratitude to them in the relevant fi gure legends.
Companion website
Th is book is accompanied by a companion website:
w ww.roitt.com
Th e website includes:
• Interactive MCQs and SBA questions for each chapter, with feedback on all answers selected
• Animations and videos showing key concepts
• Fully downloadable fi gures and illustrations, further reading and useful links
• Extracts from the Encyclopaedia of Life Sciences
• Podcasts to reinforce the key principles explained in the text: ideal for revision ‘ o n the go ’
Preface
W elcome to this new edition! When Ivan wrote the fi rst edition some 40 years ago, he wanted to feel that he was chatting to
the reader almost informally, rather than preaching, and it has been our intention to maintain this style. As a subject, immunol-
ogy is exciting and dynamic and to persuade you that it is absolutely worthwhile for you to tackle this new edition we have
made very extensive changes to update the previous edition. Accordingly, apart from the introduction of numerous new illustra-
tions, we have:
■ Expanded discussion of pathogen - and danger - associated molecular patterns (PAMPs & DAMPs)
■ Introduced a new section on dendritic cells and their role in antigen processing including cross - presentation
■ Updated sections on B - cell and NK receptors
■ Enhanced discussion of lymphocyte traffi cking
■ Incorporated the latest fi ndings on T - cell subsets, particularly Th 17 and the diversity of regulatory T - cells
■ Recorded newer information on NK and cytotoxic T - cell killing mechanisms
■ Given more insight into the eff ects of aging on immune responses
■ Carried out a major rewrite of the vaccine chapter with new emphasis on mechanisms of action of conventional and carbo-
hydrate vaccines, and new approaches to vaccine development including reverse vaccinology, together with progress in malaria
vaccines and adjuvant action
■ P rovided new information on novel genetic immunodefi ciency defects, on the origin of AIDS and the ever- e xpanding plethora
of AIDS drugs plus results from the latest HIV vaccine trials
■ Clarifi ed the recent fi ndings on the cellular transformations leading to cancer, the manipulation of the immune system by
tumors and the links between infection, infl ammation and cancer
■ Substantially rewritten the chapter on autoimmune diseases.
It is our fond expectation that you will enjoy and benefi t from a reading of our off ering.
Peter J. Delves
Seamus J. Martin
Dennis R. Burton
Ivan M. Roitt
Abbreviations
AAV adeno - associated virus CMV cytomegalovirus
Ab antibody Cn complement component “ n ”
AChR acetylcholine receptor Cn activated complement component “ n ”
ACT adoptive cell transfer iCn inactivated complement component “ n ”
ACTH adrenocorticotropic hormone Cna small peptide derived by proteolytic
ADA adenosine deaminase activation of Cn
ADCC antibody - dependent cellular cytotoxicity CpG cytosine phosphate - guanosine dinucleotide
AEP asparagine endopeptidase motif
Ag antigen CR(n) complement receptor “ n ”
AID activation- induced cytidine deaminase CRP C - reactive protein
AIDS acquired immunodefi ciency syndrome CSF cerebrospinal fl uid
AIRE autoimmune regulator CSR class switch recombination
ALBA addressable laser bead assay CTLR C - type lectin receptor
ANCA antineutrophil cytoplasmic antibodies D gene diversity minigene joining V and J
APC antigen - presenting cell segments to form variable region
ARRE - 1 antigen receptor response element - 1 DAF decay accelerating factor
ARRE - 2 antigen receptor response element - 2 DAG diacylglycerol
ART antiretroviral therapy DAMP danger - associated molecular pattern
ASFV African swine fever virus DC dendritic cells
AZT zidovudine (3 ′ - azido - 3 ′ - deoxythymidine) DMARD disease - modifying antirheumatic drug
BAFF B - cell - activating factor of the tumor DNP dinitrophenyl
necrosis factor family DTH delayed - type hypersensitivity
B - cell lymphocyte which matures in bone DTP diphtheria, tetanus, pertussis triple
marrow vaccine
BCG bacille Calmette – Gu é rin attenuated form EAE experimental autoimmune (allergic)
of tuberculosis encephalomyelitis
BCR B - cell receptor EBV Epstein – Barr virus
BM bone marrow ELISA enzyme - linked immunosorbent assay
BSA bovine serum albumin EM electron microscope
BSE bovine spongiform encephalopathy E ø eosinophil
Btk Bruton ’ s tyrosine kinase EPO erythropoietin
BUDR bromodeoxyuridine ER endoplasmic reticulum
C complement ES embryonic stem (cell)
C α ( β / γ / δ ) constant part of TCR α ( β / γ / δ ) chain ET exfoliative toxins
CALLA common acute lymphoblastic leukemia F(B) factor (B, etc.)
antigen Fab monovalent Ig antigen - binding fragment
cAMP cyclic adenosine mono phosphate after papain digestion
CCP complement control protein repeat F(ab ′ ) divalent antigen - binding fragment after
2
CD cluster of diff erentiation pepsin digestion
CDR complementarity determining regions of Ig FasL Fas - ligand
or TCR variable portion FACS fl uorescence - activated cell sorter
CEA carcinoembryonic antigen Fc Ig crystallisable - fragment originally; now
CFA complete Freund ’ s adjuvant non - Fab part of Ig
cGMP cyclic guanosine monophosphate Fc γ R receptor for IgG Fc fragment
ChIP chromatin immunoprecipitation FDC follicular dendritic cell
CHIP chemotaxis inhibitory protein fl t - 3 fl k - 2 ligand
C constant part of Ig heavy (light) chain (sc)Fv (single chain) V – V antigen binding
H(L) H L
CLA cutaneous lymphocyte antigen fragment
CLIP class II - associated invariant chain peptide GADS GRB2 - related adapter protein
CMI cell - mediated immunity g.b.m. glomerular basement membrane
CML cell - mediated lympholysis G - CSF granulocyte colony - stimulating factor