Basic Immunology Functions and Disorders of the Immune System

321 Pages·2011·23.563 MB·English

by  Abul K. Abbas, Andrew H. Lichtman

Basic
Updated
Immunology
Functions and Disorders
of the Immune System
Abul K. Abbas, MBBS
Professor and Chair
Department of Pathology
University of California San Francisco, School of Medicine
San Francisco, California
Andrew H. Lichtman, MD, PhD
Professor of Pathology
Harvard Medical School
Brigham and Women’s Hospital
Boston, Massachusetts
Illustrated by David L. Baker, MA, and Alexandra Baker, MS, CMI
1600 John F. Kennedy Blvd. Ste 1800
Philadelphia, PA 19103-2899
BASIC IMMUNOLOGY: FUNCTIONS AND DISORDERS ISBN: 978-1-4160-5569-3
OF THE IMMUNE SYSTEM
Copyright © 2011 by Saunders, an imprint of Elsevier Inc.
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Previous editions copyrighted 2009, 2006, 2004, 2001
Library of Congress Cataloging-in-Publication Data
Abbas, Abul K.
Basic immunology: functions and disorders of the immune system / Abul
K. Abbas, Andrew H. Lichtman. – 3rd ed.
p. ; cm.
Includes bibliographical references and index.
ISBN 978-1-4160-5569-3
1. Immunology. 2. Immunity. I. Lichtman, Andrew H. II. Title.
[DNLM: 1. Immunity. 2. Hypersensitivity. 3. Immune System–physiology. 4. Immunologic Defi ciency
Syndromes. QW 504 A122b 2009]
QR181.A28 2009
616.07’9–dc22
2007030085
Acquisitions Editor: William Schmitt
Developmental Editor: Rebecca Gruliow
Editorial Assistant: Laura Stingelin Working together to grow
Design Direction: Gene Harris
libraries in developing countries
www.elsevier.com | www.bookaid.org | www.sabre.org
Printed in China.
Last digit is the print number: 9 8 7 6 5 4 3 2
To Ann, Jonathan, Rehana,
Sheila, Eben, Ariella, Amos, Ezra
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PREFACE
T
he third edition of Basic Immunology has been ologically relevant, issue of host defense against infec-
revised to incorporate recent advances in our under- tious pathogens.
standing of the immune system and to improve upon This book has been written to address the per-
how we present information to maximize its useful- ceived needs of both medical school and undergradu-
ness to students and teachers. We have been extremely ate curricula and to take advantage of the new
gratifi ed with how well the previous two editions of understanding of immunology. We have tried to
Basic Immunology have been received by students in achieve several goals. First, we have presented the
the courses that we teach, and the guiding principles most important principles governing the function of
on which the book is based have not changed from the immune system. Our principal objective has been
the fi rst edition. As teachers of immunology, we are to synthesize the key concepts from the vast amount
becoming increasingly aware that assimilating detailed of experimental data that emerge in the rapidly advanc-
information and experimental approaches is diffi cult ing fi eld of immunology. The choice of what is most
in many medical school and undergraduate courses. important is based largely on what is most clearly
The problem of how much detail is appropriate has established by experimentation, what our students
become a pressing one because of the continuous and fi nd puzzling, and what explains the wonderful effi -
rapid increase in the amount of information in all the ciency and economy of the immune system. Inevita-
biomedical sciences. This problem is compounded by bly, however, such a choice will have an element of
the development of integrated curricula in many bias, and our bias is toward emphasizing the cellular
medical schools, with reduced time for didactic teach- interactions in immune responses and limiting the
ing and an increasing emphasis on social and behav- description of many of the underlying biochemical
ioral sciences and primary health care. For all these and molecular mechanisms to the essential facts. We
reasons, we have realized the value for many medical also have realized that in any concise discussion of
students of presenting the principles of immunology complex phenomena, it is inevitable that exceptions
in a concise and clear manner. and caveats will fall by the wayside. We have avoided
It is our view that several developments have come such exceptions and caveats without hesitation, but
together to make the goal of a concise and modern we continue to modify conclusions as new informa-
consideration of immunology a realistic goal. Most tion emerges. Second, we have focused on immune
importantly, immunology has matured as a discipline, responses against infectious microbes, and most of our
so that it has now reached the stage when the essential discussions of the immune system are in this context.
components of the immune system, and how they Third, we have emphasized immune responses in
interact in immune responses, are understood quite humans (rather than experimental animals), drawing
well. There are, of course, many details to be fi lled upon parallels with experimental situations whenever
in, and the longstanding challenge of applying basic necessary. Fourth, we have made liberal use of illustra-
principles to human diseases remains a diffi cult task. tions to highlight important principles but have
Nevertheless, we can now teach our students, with reduced factual details that may be found in more
reasonable confi dence, how the immune system comprehensive textbooks. Fifth, we have discussed
works. The second important development has been immunologic diseases also from the perspective of
an increasing emphasis on the roots of immunology, principles, emphasizing their relation to normal
which lie in its role in defense against infections. As a immune responses and avoiding details of clinical
result, we are better able to relate experimental results, syndromes and treatments. We have added selected
using simple models, to the more complex, but physi- clinical cases in an Appendix, to illustrate how the
v
vi Preface
principles of immunology may be applied to common encourage them to delve even more deeply into
human diseases. Finally, in order to make each chapter immunology.
readable on its own, we have repeated key ideas in Several individuals played key roles in the writing
different places in the book. We feel such repetition of this book. Our editor, Bill Schmitt, has been a con-
will help students to grasp the most important stant source of encouragement and advice. We have
concepts. been fortunate to again work with two wonderful illus-
It is our hope that students will fi nd this book clear, trators, David and Alexandra Baker of DNA Illustra-
cogent, and manageable. Most importantly, we hope tions, who have translated ideas into pictures that are
the book will convey our sense of wonder about the informative and aesthetically pleasing. Ellen Sklar has
immune system and excitement about how the fi eld shepherded the book through the production process
has evolved and how it continues to be relevant to with a calm effi ciency and wonderful organization. Our
human health and disease. Finally, although we were development editor, Rebecca Gruliow, kept the project
spurred to tackle this project because of our associa- organized and on track despite pressures of time and
tions with medical school courses, we hope the book logistics. To all of them we owe our many thanks.
will be valued more widely by students of allied health
and biology as well. We will have succeeded if the
Abul K. Abbas
book can answer many of the questions these students
have about the immune system and, at the same time, Andrew H. Lichtman
CONTENTS
1 INTRODUCTION TO THE IMMUNE SYSTEM ........................................................................1
The Nomenclature, General Properties, and Components of the
Immune System
2 INNATE IMMUNITY ..........................................................................................................23
The Early Defense Against Infections
3 ANTIGEN CAPTURE AND PRESENTATION TO LYMPHOCYTES ..........................................45
What Lymphocytes See
4 ANTIGEN RECOGNITION IN THE ADAPTIVE IMMUNE SYSTEM.........................................67
Structure of Lymphocyte Antigen Receptors and the Development of
Immune Repertoires
5 CELL-MEDIATED IMMUNE RESPONSES ...........................................................................89
Activation of T Lymphocytes by Cell-Associated Microbes
6 EFFECTOR MECHANISMS OF CELL-MEDIATED IMMUNITY ...........................................113
Eradication of Intracellular Microbes
7 HUMORAL IMMUNE RESPONSES ...................................................................................131
Activation of B Lymphocytes and Production of Antibodies
8 EFFECTOR MECHANISMS OF HUMORAL IMMUNITY .....................................................153
The Elimination of Extracellular Microbes and Toxins
9 IMMUNOLOGICAL TOLERANCE AND AUTOIMMUNITY ....................................................173
Self–Nonself Discrimination in the Immune System and Its Failure
10 IMMUNE RESPONSES AGAINST TUMORS AND TRANSPLANTS ......................................189
Immunity to Noninfectious Transformed and Foreign Cells
11 HYPERSENSITIVITY........................................................................................................205
Disorders Caused by Immune Responses
12 CONGENITAL AND ACQUIRED IMMUNODEFICIENCIES ...................................................223
Diseases Caused by Defective Immune Responses
vii
viii Contents
SUGGESTED READINGS ............................................................................................................239
APPENDIX I
GLOSSARY ................................................................................................................................245
APPENDIX II
PRINCIPAL FEATURES OF CD MOLECULES ..............................................................................273
APPENDIX III
CLINICAL CASES ......................................................................................................................283
INDEX .......................................................................................................................................293
Chapter 1
INTRODUCTION TO THE IMMUNE SYSTEM
The Nomenclature, General Properties, and
Components of the Immune System
I
Innate and Adaptive Immunity 3 mmunity is defi ned as resistance to disease, specifi -
cally infectious disease. The collection of cells, tissues,
Types of Adaptive Immunity 4
and molecules that mediate resistance to infections is
Properties of Adaptive Immune Responses 5
called the immune system, and the coordinated reac-
Specifi city and Diversity 6 tion of these cells and molecules to infectious microbes
is the immune response. Immunology is the study of
Memory 6
the immune system and its responses to invading
Other Features of Adaptive Immunity 7
pathogens. The physiologic function of the immune
Cells of the Immune System 8 system is to prevent infections and to eradicate
established infections, and this is the principal
Lymphocytes 8
context in which immune responses are discussed
Antigen-Presenting Cells 13
throughout this book.
Effector Cells 13 The importance of the immune system for health
is dramatically illustrated by the frequent observation
Tissues of the Immune System 13
that individuals with defective immune responses are
Peripheral Lymphoid Organs 14
susceptible to serious, often life-threatening infections
Lymphocyte Recirculation and Migration into (Fig. 1-1). Conversely, stimulating immune responses
Tissues 16 against microbes by the process of vaccination is
the most effective method for protecting individuals
Overview of Immune Responses to Microbes 18
against infections and is, for example, the approach
The Early Innate Immune Response to Microbes 18
that has led to the worldwide eradication of smallpox
The Adaptive Immune Response 18 (Fig. 1-2). The emergence of the acquired immunode-
fi ciency syndrome (AIDS) since the 1980s has tragi-
Decline of Immune Responses and Immunological
Memory 21 cally emphasized the importance of the immune
system for defending individuals against infection.
Summary 21
The impact of immunology, however, goes beyond
infectious disease (see Fig. 1-1). The immune response
is the major barrier to successful organ transplanta-
tion, an increasingly used therapy for organ failure.
Attempts to treat cancers by stimulating immune
responses against cancer cells are being tried for many
1