Table Of ContentOtto G. Bier Wilmar Dias da Silva
Dietrich Gotze Ivan Mota
Fundamentals
of Immunology
Completely Revised Second Edition
With a Contribution by
Reinhard Burger
With 173 Figures
Springer -Verlag
Berlin Heidelberg New York
London Paris Tokyo
DR. OTTO G. BIER t
Laborat6rio Especial de Imunologia Aplicada
Instituto Butantan, Sao Pau1o, SP., Brazil
Dr. WILMAR DIAS DA SILVA
Instituto de Biociencias, Departamento de Microbiologia e Imunologia
Cidade Universitaria, Sao Pau1o, SP., Brazil
Formerly Center for Blood Research, Boston, MA, USA
Dr. med. habil. DIETRICH GOTZE
University Medical School, Heidelberg, FRG
Formerly Associate Professor of Immunology
The Wistar Institute - The University of Pennsylvania
Philadelphia, P A, USA
Dr. IVAN MOTA
Centro de Imunologia da OMSjOPS, Instituto Butantan
CPo 65, Sao Pau1o, SP., Brazil
Contributor:
Dr. med. habil. REINHARD BURGER
University Medical School Heidelberg
Institut fiir Immunologie und Serologie
1m Neuenheimer Feld 305, Heidelberg, FRG
Cover page figure: schematic representation of the T cell antigen receptor (TAR) C( and f3
chains in the cell membrane associated with the CD3 ("I, f>, 8) molecule
ISBN -13: 978-3-540-15332-0 e-ISBN -13: 978-3-642-70393-5
DOl: 10.1007/978-3-642-70393-5
Library of Congress Cataloging-in-Publication Data. Fundamentals of immunology. Includes
bibliographies and indexes. 1. Immunology. I. Bier, Otto, 1906--.
QRI81.F851986 616.07'9 86-17881
ISBN-13:978-3-540-15332-0 (U.S.)
This work is subject to copyright. All rights are reserved, whether the whole or part of the
material is concerned, specifically those of translation, reprinting, re-use of illustrations,
broadcasting, reproduction by photocopying machine or similar means, and storage in data
banks.
Under § 54 of the German Copyright Law, where copies are made for other than private use, a fee
is payable to "Verwertungsgesellschaft Wort", Munich.
© 1981by Springer-Verlag New York Inc.
© Springer-Verlag Berlin Heidelberg 1986
The use of registered names, trademarks, etc. in this publication does not imply, even in the
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regulations and therefore free for general use.
Product Liability: The publisher can give no guarantee for information about drug dosage and
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2127/3130-543210
Preface to the Second Edition
The good acceptance of this textbook is an indication that it has served
its purpose. The present edition has been prepared in order to cover the
main progress achieved in the five years that have elapsed since the first
edition.
The structure of the book remains essentially the same but a con
siderable amount of new material has been introduced, particularly in
certain areas such as the genetics of immunoglobulins and T cell
receptor, the regulation of the immune response, hypersensitivity
reactions, and cellular immunology.
Today, immunology is essential for biologists in general and in
particular for physicians, veterinarians, and pathologists. The great
progress and diversification that has taken place in the last few years is
due to its enormous value both for the understanding of theoretical
biology and for the practical resolution of biochemical, genetic,
pathological, and biological problems. Greatly contributing to this
progress have been relatively sophisticated techniques, such as
immunofluorescence, radioimmune assay, transmission electron micro
scopy, scanning electron microscopy, isoelectric focusing, quantitative
cytofluorimetry, affinity chromatography, and techniques that allow
separation of the different lymphocyte subpopulations. A potentially
fabulous field was recently opened with the development of techniques
for obtaining monoclonal antibodies by fusion of immunologically
active lymphocytes with myeloma cells. These hybrid cells produce
large amounts of monoclonal antibodies or other lymphocyte factors.
The establishment of this hybridoma technology, that is already routine
in most laboratories, is being used in the resolution of general biology
problems, particularly in the study of the various cell surface molecules.
The production of monoclonal antibodies against cancer cell antigens,
parasite antigens, virus antigens, or numerous clinically important
antigens, like interferon, will have a large application in the near future.
As a consequence of all these advances, immunology is today a science
developing at the speed of a jet, or to be more accurate, at the speed of a
rocket. All this makes it very hard to write an up-to-date immunology
book. In the latent period between handing the manuscript to the
editors and the selling of the book, symptoms of thymic involution
already start appearing, as is particularly true for subjects like cellular
immunology, where the acquisition of new knowledge is extremely
fast.
VI Preface to the Second Edition
This book is particularly dedicated to the young students, and we will
be satisfied if it helps them in their way to immunocompetence.
June 1986 WILMAR DIAS DA SILVA
DIETRICH GOTZE
IVAN MOTA
Preface to the First Edition
This textbook of basic and clinical immunology has been written
primarily for medical and biology students who are receiving their first
introduction to this fascinating field. Although we have presumed
some knowledge of basic biology (particularly physiology and bio
chemistry), our primary intent has not been to cover in depth the latest
research findings. Rather, we have sought to lay a firm foundation for
subsequent reading in the laboratory and clinical sciences: internal
medicine, pediatrics, microbiology, serology, physiology, cell biology,
and genetics. Hence the first part of the text presents the various
components of basic immunology, while the second shows how these
elements interact under both normal physiologic and pathologic
conditions.
To facilitate comprehension of the relationship between basic and
clinical immunology, we have introduced cross-references throughout
the book. A glossary of important terms has also been included.
Selected references are provided with each chapter to guide the student
to additional information on topics of special interest.
Throughout the book we have attempted to convey to new students
of immunology some of the excitement which the subject has long held
for us. If we have succeeded, the task of writing will have been
worthwhile.
December 1980 OTTO G. BIER
WILMAR DIAS DA SILVA
DIETRICH GOTZE
IVAN MOTA
Contents
Chapter 1 Tissue and Cells of the Immune System
IVAN MOTA. With 18 Figures . . . .
Chapter 2 Activity of Immune Cells
IVAN MOTA. With 9 Figures . . . . . . . . . . 35
Chapter 3 Antigens
IVAN MOTA. With 4 Figures. . . . . . . . . . 63
Chapter 4 Antibodies
OTTO G. BIER. With 23 Figures . . . . . . . . 73
Chapter 5 Complement
WILMAR DIAS DA SILVA. With 9 Figures. . . . . 115
Chapter 6 The Major Histocompatibility Complex
DIETRICH GOTZE and REINHARD BURGER.
With 16 Figures . . . . . . . . . . . . . . . 139
Chapter 7 Antigen-Antibody Interaction
OTTO G. BIER. With 37 Figures . . . . . . . . 179
Chapter 8 Blood Groups
OTTO G. BIER. With 5 Figures . . . . . . . . . 227
Chapter 9 Hypersensitivity
IVAN MOTA. With 19 Figures ......... 243
Chapter 10 Transplantation
DIETRICH GOTZE and IVAN MOTA.
With 4 Figures. . . . . . . . . . . . . . . . 297
Chapter 11 Immunity
DIETRICH GOTZE and WILMAR DIAS DA SILVA
With 9 Figures. . . . . . . . . . . . . . . . 317
Chapter 12 Immunodeficiencies
WILMAR DIAS DA SILVA and DIETRICH GOTZE.
With 5 Figures. . . . . . . . . . . . . . . . 359
x
Contents
Chapter 13 Autoimmunity
WILMAR DIAS DA SILVA and DIETRICH GOTZE.
With 11 Figures . . . . . . . . . . . . . . . 383
Chapter 14 Immunomodulation
WILMAR DIAS DA SILVA. With 4 Figures ..... 415
Brief History of Important Immunologic Discoveries
and Developments. . . . . . . .439
Glossary of Immunologic Terms . .445
Subject and Author Index. . . . .457
Chapter 1 Tissue and Cells of the Immune System
IVAN MOTA
Contents lymphocytes are part of a complex network
of cells interacting with each other through
Histology and Histogenesis
of Lymphoid Tissue . . . . . . . . . 1 recognition molecules (receptors) in order
Lymph and Lymph Vessels . . . . . .. 2 to keep the system in homeostasis. This au
Primary and Secondary Lymphoid Organs 3 toreactivity seems to be essential for the
Origin of the Lymphoid Cells
function of the immune system. The intro
of the Primary Lymphoid Organs 3
duction of a foreign substance or antigen
Immunologic Dichotomy
of the Lymphoid System 4 (that must have some similarity with self
Cells of the Immune System. 5 molecules) into the organism pertubates the
Polymorphonuclear Cells 5 lymphocyte network homeostasis resulting
Mast Cells . 8
in a transitory increase in the lymphocytes
Monocytes . . . . . . 9
Lymphocytes . . . . . 9 whose receptors fit the antigenic determi
Platelets . . . . . . . 13 nants (epitopes) of the foreign substance.
Immunologic Activity of the Primary Since these lymphocytes are part of the
Lymphoid Organs . . . . . . . 15
chain of interacting cells the whole system is
Thymus . . . . . . . . . . . . 15
pertubated. The assemblage of changes
Bursa of Fabricius. . . . . . . . 22
Immunology Activity of the Secondary caused by the antigen constitutes the so-cal
Lymphoid Organs . . . . 23 led immune response.
Lymph Node System. . . . 23 Lymphoid tissue is constructed of fibrillar
Spleen . . . . . . . . . . 27
reticulum whose networks contain free
Other Lymphoid Structures . 30
Localization of the Antigen cells. This fibrillar reticulum is composed of
in the Lymphoid Organs . 30 reticular fibers, reticular cells, and fixed
Phylogenic and Ontogenic Development macrophages that are integral to the reticu
of Immunologic Capacity . 32
loendothelial system. The majority of free
References . . . . . . . . . . . . . 33
cells are lymphocytes in different stages of
differentiation plasma cells and macro
phages. Two types of lymphoid tissues are
recognized -loose lymphoid tissue in which
Histology and Histogenesis reticulum cells predominate, and dense
of Lymphoid Tissue lymphoid tissue in which lymph cells pre
dominate. The dense lymphoid tissue is ca
The immune system is formed by antigen pable of organizing nodular formations
specific cells represented by thymus-depen that constitute nodular lymphoid tissue.
dent or T lymphocytes and by thymus inde Once localized in the primary lymphoid or
pendent or B lymphocytes (B from bursa in gans the primordial immature cells are sub
birds or bone marrow in mammals). Func jected to the action of a number of differ
tionally closely associated with these cells entiation and growth factors present in the
are antigen non-specific cells such as mac hemopoietic-inducing microenvironment
rophages, dendritic cells, and the epithelial (HIM) of these organs. T lymphocytes dif
cells of the primary lymphoid organs. The ferentiate in the HIM of the bursa of Fab-
2 Ivan Mota
Undifferentiated immature cell
existing in the blood-forming
islets of the embryo, in the
fetal liver, and in the bone
marrow of the adult
Bcells Tcells
Induction and
Bone proliferation
Thymus
marrow in the HIM of
these organs
\
(Bursa of
Fabricius
In birds)
Secondary lymphoid organs
Activation of the
cellular clones by
(j+
~ the antigen
\~+ Ag Ag
• •
~~
/\ 1\ /\ /\
• •
®i)~(j (f)~
Fig. 1.1. Origin and differentiation
Effector and Effector and of the lymphoid cells in the prima
memory B cells memory T cells ry lymphoid organs
nclUs in birds and probably in the bone with each other and then anastomose, form
marrow HIM in mammals. After differenti ing networks. These capillaries are of vary
ation, the lymphocytes migrate to the sec ing diameter and develop into the major
ondary lymphoid organs where they com lymphatic vessels. Their walls are composed
plete their differentiation. It is believed that of a layer of endothelial cells, outwardly sur
after a few days in these organs the lympho rounded by a loose reticular fibrous lattice.
cytes die unless they contact antigens. In Lymphatic capillaries, unlike blood capil
meeting antigen these cells are activated laries, do not possess basement membranes.
and proliferate resulting in effector cells This fact is probably responsible for the ca
and memory cells (Fig. 1.1). Most of these pacity exhibited by lymphatic capillaries to
cells then leave the secondary lymphoid or absorb macromolecules present in intersti
gans and enter the circulatory pool of lym tial liquid and in inflammatory exudates.
phocytes. Lymph results from interstitial liquid that
passes through the walls of lymphatic capil
laries and is directed via these capillaries to
Lymph and Lymph Vessels
the lymph nodes. The passage of lymph
Lymph vessels originate in tissue as extreme through the interstices of the meshwork of
ly fine lymph capillaries that communicate these organs allows intimate contact be-
