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 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
gratified 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 first 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 difficult ing field 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 find 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 filled 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 difficult 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 confidence, 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 find 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 field shepherded the book through the production process
has evolved and how it continues to be relevant to with a calm efficiency 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

Innate and Adaptive Immunity 3 Immunity is defined as resistance to disease, specifi-

Types of Adaptive Immunity 4
cally infectious disease. The collection of cells, tissues,
and molecules that mediate resistance to infections is
Properties of Adaptive Immune Responses 5 called the immune system, and the coordinated reac-
Specificity and Diversity 6 tion of these cells and molecules to infectious microbes
Memory 6
is the immune response. Immunology is the study of
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
Lymphocytes 8
established infections, and this is the principal
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
Tissues of the Immune System 13
is dramatically illustrated by the frequent observation
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
Overview of Immune Responses to Microbes 18 the most effective method for protecting individuals
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-
Decline of Immune Responses and Immunological ficiency syndrome (AIDS) since the 1980s has tragi-
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
2 Basic Immunology: Functions and Disorders of the Immune System

Role of the immune system Implications

Defense against infections Deficient immunity results in increased
susceptibility to infections; exemplified by AIDS
Vaccination boosts immune defenses
and protects against infections

The immune system recognizes Immune responses are barriers to

and responds to tissue grafts transplantation and gene therapy
and newly introduced proteins
Defense against tumors Potential for immunotherapy of cancer
FIGURE 1-1 The importance of the immune system in health and disease. This table summarizes some of the physiologic functions of the
immune system. Note that immune responses are also the causes of diseases. AIDS, acquired immunodeficiency syndrome.

human malignancies. Furthermore, abnormal immune laboratory testing in clinical medicine and research.
responses are the causes of many inflammatory dis- Antibodies designed to block or eliminate potentially
eases with serious morbidity and mortality. Antibod- harmful molecules and cells are in widespread use for
ies, one of the products of immune responses, are the treatment of immunologic diseases, cancers, and
highly specific reagents for detecting a wide variety of other types of disorders. For all of these reasons, the
molecules in the circulation and in cells and tissues field of immunology has captured the attention of cli-
and have therefore become invaluable reagents for nicians, scientists, and the lay public.

Disease Maximum number Number of Percent

of cases (year) cases in 2004 change
Diphtheria 206,939 (1921) 0 -99.99
Measles 894,134 (1941) 37 -99.99
Mumps 152,209 (1968) 236 -99.90
Pertussis 265,269 (1934) 18,957 -96.84
Polio (paralytic) 21,269 (1952) 0 -100.0
Rubella 57,686 (1969) 12 -99.98
Tetanus 1,560 (1923) 26 -98.33
Haemophilus ~20,000 (1984) 16 -99.92
influenzae type b
infection
Hepatitis B 26,611 (1985) 6,632 -75.08
FIGURE 1-2 The effectiveness of vaccination for some common infectious diseases. This table illustrates the striking decrease in the inci-
dence of selected infectious diseases for which effective vaccines have been developed. In some cases, such as with hepatitis B, a vaccine has
become available recently, and the incidence of the disease is continuing to decrease. (Adapted from Orenstein WA, Hinman AR, Bart KJ, Hadler SC:
Immunization. In Mandell GL, Bennett JE, Dolin R (eds): Principles and Practices of Infectious Diseases, 4th ed. New York, Churchill Livingstone, 1995; and
Morbidity and Mortality Weekly Report 53:1213-1221, 2005.)
 1 Introduction to the Immune System 3

In this opening chapter of the book, we introduce Innate and Adaptive Immunity
the nomenclature of immunology, some of the impor-
tant general properties of all immune responses, and Host defense mechanisms consist of innate immu-
the cells and tissues that are the principal components nity, which mediates the initial protection against
of the immune system. In particular, the following infections, and adaptive immunity, which develops
questions are addressed: more slowly and mediates the later, even more
• What types of immune responses protect indi- effective, defense against infections (Fig. 1-3). The
viduals from infections? term innate immunity (also called natural or native
• What are the important characteristics of immu- immunity) refers to the fact that this type of host
nity, and what mechanisms are responsible for defense is always present in healthy individuals, pre-
these characteristics? pared to block the entry of microbes and to rapidly
• How are the cells and tissues of the immune eliminate microbes that do succeed in entering host
system organized to find microbes and respond tissues. Adaptive immunity (also called specific or
to them in ways that lead to their elimination? acquired immunity) is the type of host defense that is
We conclude the chapter with a brief overview of stimulated by microbes that invade tissues, that is, it
immune responses against microbes. The basic prin- adapts to the presence of microbial invaders.
ciples that are introduced in this chapter set the The first line of defense in innate immunity is pro-
stage for more detailed discussions of immune vided by epithelial barriers and by specialized cells
responses in the remainder of the book. A glossary of and natural antibiotics present in epithelia, all of
the important terms used in the book is provided in which function to block the entry of microbes. If
Appendix I. microbes do breach epithelia and enter the tissues or

Microbe
Innate immunity Adaptive immunity

Epithelial B lymphocytes Antibodies

barriers

Phagocytes Dendritic Effector T cells

cells T lymphocytes

NK
Complement cells
Hours Days
0 6 12 1 3 5
Time after infection
FIGURE 1-3 The principal mechanisms of innate and adaptive immunity. The mechanisms of innate immunity provide the initial defense
against infections. Some of the mechanisms prevent infections (e.g., epithelial barriers) and others eliminate microbes (e.g., phagocytes, natural
killer [NK] cells, the complement system). Adaptive immune responses develop later and are mediated by lymphocytes and their products.
Antibodies block infections and eliminate microbes, and T lymphocytes eradicate intracellular microbes. The kinetics of the innate and adaptive
immune responses are approximations and may vary in different infections.
4 Basic Immunology: Functions and Disorders of the Immune System

circulation, they are attacked by phagocytes, special- between innate and adaptive immunity are referred to
ized lymphocytes called natural killer cells, and several in later chapters. By convention, the terms immune
plasma proteins, including the proteins of the com- system and immune response refer to adaptive immu-
plement system. All of these agents of innate immunity nity, unless stated otherwise.
specifically recognize and react against microbes but
do not react against noninfectious foreign substances.
Types of Adaptive Immunity
Different components of innate immunity may be spe-
cific for molecules produced by different classes of The two types of adaptive immunity, humoral
microbes. In addition to providing early defense immunity and cell-mediated immunity, are mediated
against infections, innate immune responses enhance by different cells and molecules and are designed
adaptive immune responses against the infectious to provide defense against extracellular microbes
agents. The components and mechanisms of innate and intracellular microbes, respectively (Fig. 1-4).
immunity are discussed in detail in Chapter 2. Humoral immunity is mediated by proteins called
Although innate immunity can effectively combat antibodies, which are produced by cells called B lym-
infections, many microbes that are pathogenic for phocytes. Antibodies are secreted into the circulation
humans (i.e., capable of causing disease) have evolved and mucosal fluids, and they neutralize and eliminate
to resist innate immunity. Defense against these infec- microbes and microbial toxins that are present outside
tious agents is the task of the adaptive immune of host cells, in the blood and in the lumens of mucosal
response, and this is why defects in the adaptive organs, such as the gastrointestinal and respiratory
immune system result in increased susceptibility to tracts. One of the most important functions of anti-
infections. The adaptive immune system consists bodies is to stop microbes that are present at mucosal
of lymphocytes and their products, such as anti- surfaces and in the blood from gaining access to and
bodies. Whereas the mechanisms of innate immunity colonizing host cells and connective tissues. In this
recognize structures shared by classes of microbes, the way, antibodies prevent infections from ever getting
cells of adaptive immunity, namely, lymphocytes, established. Antibodies cannot gain access to microbes
express receptors that specifically recognize different that live and divide inside infected cells. Defense
substances produced by microbes as well as noninfec- against such intracellular microbes is called cell-
tious molecules. These substances are called antigens. mediated immunity because it is mediated by cells
Adaptive immune responses are triggered only if called T lymphocytes. Some T lymphocytes activate
microbes or their antigens pass through epithelial bar- phagocytes to destroy microbes that have been ingested
riers and are delivered to lymphoid organs where they by the phagocytes into intracellular vesicles. Other T
can be recognized by lymphocytes. Adaptive immune lymphocytes kill any type of host cells that are harbor-
responses are specialized to combat different types of ing infectious microbes in the cytoplasm. Thus, the
infections. For example, antibodies function to elimi- antibodies produced by B lymphocytes recognize
nate microbes in extracellular fluids, and activated T extracellular microbial antigens, whereas T lympho-
lymphocytes eliminate microbes living inside cells. cytes recognize antigens produced by intracellular
These specialized mechanisms of adaptive immunity microbes. Another important difference between B
are described throughout the book. Adaptive immune and T lymphocytes is that most T cells recognize only
responses often use the cells and molecules of the protein antigens, whereas antibodies are able to rec-
innate immune system to eliminate microbes, and ognize many different types of molecules, including
adaptive immunity functions to greatly enhance these proteins, carbohydrates, and lipids.
antimicrobial mechanisms of innate immunity. For Immunity may be induced in an individual by
instance, antibodies (a component of adaptive immu- infection or vaccination (active immunity) or con-
nity) bind to microbes, and these coated microbes ferred on an individual by transfer of antibodies or
avidly bind to and activate phagocytes (a component lymphocytes from an actively immunized individ-
of innate immunity), which ingest and destroy the ual (passive immunity). An individual exposed to the
microbes. Many similar examples of the cooperation antigens of a microbe mounts an active response to
 1 Introduction to the Immune System 5

Humoral Cell-mediated
immunity immunity

Microbe
Intracellular
Extracellular Phagocytosed microbes
microbes microbes in (e.g., viruses)
macrophage replicating within
infected cell

Responding
lymphocytes
Helper Cytotoxic
B lymphocyte T lymphocyte T lymphocyte

Secreted
antibody
Effector
mechanism

Block Activate Kill

infections and macrophages infected cells
Functions eliminate to kill and eliminate
extracellular phagocytosed reservoirs
microbes microbes of infection

FIGURE 1-4 Types of adaptive immunity. In humoral immunity, B lymphocytes secrete antibodies that eliminate extracellular microbes.
In cell-mediated immunity, T lymphocytes either activate macrophages to destroy phagocytosed microbes or kill infected cells.

eradicate the infection and develops resistance to later does not induce long-lived resistance to the infection.
infection by that microbe. Such an individual is said An excellent example of passive immunity is seen in
to be immune to that microbe, in contrast with a naive newborns, whose immune systems are not mature
individual, not previously exposed to that microbe’s enough to respond to many pathogens but who are
antigens. We shall be concerned mainly with the protected against infections by acquiring antibodies
mechanisms of active immunity. In passive immunity, from their mothers through the placenta and in
a naive individual receives cells (e.g., lymphocytes, milk.
feasible only in genetically identical [inbred] animals)
or molecules (e.g., antibodies) from another individ- Properties of Adaptive
ual already immune to an infection; for the lifetime of
the transferred antibodies or cells, the recipient is able
Immune Responses
to combat the infection. Passive immunity is therefore Several properties of adaptive immune responses are
useful for rapidly conferring immunity even before the crucial for the effectiveness of these responses in com-
individual is able to mount an active response, but it bating infections (Fig. 1-5).
6 Basic Immunology: Functions and Disorders of the Immune System

ferent antigens arise before encounter with these anti-

Feature Functional significance
gens, and each antigen elicits an immune response by
Specificity Ensures that distinct antigens selecting and activating the lymphocytes of a specific
elicit specific responses clone (Fig. 1-6). We now know how the specificity
Diversity Enables immune system and diversity of lymphocytes are generated (see
to respond to a large Chapter 4).
variety of antigens
The diversity of lymphocyte means that very few
Memory Leads to enhanced responses cells, perhaps as few as one in 100,000 lymphocytes,
to repeated exposures to the
same antigens are specific for any one antigen. In order to mount
effective defense against microbes, these few cells have
Clonal Increases number of to proliferate to generate a large number of cells
expansion antigen-specific lymphocytes
to keep pace with microbes capable of combating the microbes. The remarkable
effectiveness of immune responses is possible because
Specialization Generates responses that are
of several features of adaptive immunity–marked
optimal for defense against
different types of microbes expansion of the pool of lymphocytes specific for any
antigen subsequent to exposure to that antigen, posi-
Contraction and Allows immune system
homeostasis to respond to newly tive feedback loops that amplify immune responses,
encountered antigens and selection mechanisms that preserve the most
Nonreactivity Prevents injury to the useful lymphocytes. We will describe these charac-
to self host during responses to teristics of the adaptive immune system in later
foreign antigens chapters.
FIGURE 1-5 Properties of adaptive immune responses. The
important properties of adaptive immune responses, and how each
feature contributes to host defense against microbes, are
summarized. MEMORY
The immune system mounts larger and more effective
responses to repeated exposures to the same antigen.
The response to the first exposure to antigen, called
the primary immune response, is mediated by lym-
phocytes, called naive lymphocytes, that are seeing
SPECIFICITY AND DIVERSITY
antigen for the first time (Fig. 1-7). The term naive
The adaptive immune system is capable of distin- refers to the fact that these cells are “immunologically
guishing among millions of different antigens or inexperienced,” not having previously recognized and
portions of antigens. Specificity for many different responded to antigens. Subsequent encounters with
antigens implies that the total collection of lympho- the same antigen lead to responses, called secondary
cyte specificities, sometimes called the lymphocyte immune responses, that usually are more rapid,
repertoire, is extremely diverse. The basis of this larger, and better able to eliminate the antigen than
remarkable specificity and diversity is that lympho- are the primary responses (see Fig. 1-7). Secondary
cytes express clonally distributed receptors for anti- responses are the result of the activation of memory
gens, meaning that the total population of lymphocytes lymphocytes, which are long-lived cells that were
consists of many different clones (each of which induced during the primary immune response. Immu-
is made up of one cell and its progeny), and each nologic memory optimizes the ability of the immune
clone expresses an antigen receptor that is different system to combat persistent and recurrent infections,
from the receptors of all other clones. The clonal selec- because each encounter with a microbe generates
tion hypothesis, formulated in the 1950s, correctly more memory cells and activates previously generated
predicted that clones of lymphocytes specific for dif- memory cells. Memory also is one of the reasons
 1 Introduction to the Immune System 7

Lymphocyte Mature
precursor lymphocyte
Lymphocyte
clones with
diverse receptors
arise in generative
lymphoid organs

Clones of mature
lymphocytes
specific for many
antigens enter
FIGURE 1-6 Clonal selection. Mature lymphoid tissues Antigen X Antigen Y
lymphocytes with receptors for many anti-
gens develop before encounter with these
antigens. A clone refers to a population of
Antigen-specific
lymphocytes with identical antigen recep- clones are
tors and, therefore, specificities; all these activated
cells are presumably derived from one pre- ("selected")
cursor cell. Each antigen (e.g., the exam- by antigens
ples X and Y) selects a preexisting clone of
specific lymphocytes and stimulates the
proliferation and differentiation of that
clone. The diagram shows only B lympho- Antigen-specific
cytes giving rise to antibody-secreting immune
effector cells, but the same principle applies
to T lymphocytes. The antigens shown are
responses occur
Anti-X Anti-Y
surface molecules of microbes, but clonal antibody antibody
selection also is true for soluble antigens.

why vaccines confer long-lasting protection against that adaptive immunity keeps pace with rapidly pro-
infections. liferating microbes. Immune responses are special-
ized, and different responses are designed to best
defend against different classes of microbes. All
immune responses are self-limited and decline as the
OTHER FEATURES OF ADAPTIVE IMMUNITY
infection is eliminated, allowing the system to return
Adaptive immune responses have other characteristics to a resting state, prepared to respond to another
that are important for their functions (see Fig. 1-5). infection. The immune system is able to react against
When lymphocytes are activated by antigens, they an enormous number and variety of microbes and
undergo proliferation, generating many thousands of other foreign antigens, but it normally does not react
clonal progeny cells, all with the same antigen speci- against the host’s own potentially antigenic sub-
ficity. This process, called clonal expansion, ensures stances—so-called self antigens.
8 Basic Immunology: Functions and Disorders of the Immune System

Antigen X +
Antigen X Antigen Y
Activated
Anti-X B cell B cells
Anti-Y B cell
Serum antibody titer

Secondary
Activated anti-X
B cells response
Memory
B cells Activated FIGURE 1-7 Primary and secondary
Naive
Naive B cell B cells immune responses. Antigens X and Y
B cells Primary Primary induce the production of different anti-
anti-X anti-Y bodies (a reflection of specificity). The
response response secondary response to antigen X is
more rapid and larger than the primary
response (illustrating memory) and is
different from the primary response to
2 4 6 8 10 12 antigen Y (again reflecting specificity).
Weeks Antibody levels decline with time after
each immunization.

Cells of the Immune System using panels of monoclonal antibodies. The standard
nomenclature for these proteins is the CD (cluster of
The cells of the immune system consist of lympho- differentiation) numerical designation, which is used
cytes, specialized cells that capture and display to delineate surface proteins that define a particular
microbial antigens, and effector cells that eliminate cell type or stage of cell differentiation and are recog-
microbes (Fig. 1-8). In the following section the nized by a cluster or group of antibodies. (A list of CD
important functional properties of the major cell molecules mentioned in the book is provided in
populations are discussed; the details of the morphol- Appendix II.)
ogy of these cells may be found in histology As alluded to earlier, B lymphocytes are the only
textbooks. cells capable of producing antibodies; therefore, they
are the cells that mediate humoral immunity. B cells
LYMPHOCYTES
express membrane forms of antibodies that serve as
Lymphocytes are the only cells that produce the receptors that recognize antigens and initiate
specific receptors for antigens and are thus the key the process of activation of the cells. Soluble antigens
mediators of adaptive immunity. Although all and antigens on the surface of microbes and other
lymphocytes are morphologically similar and rather cells may bind to these B lymphocyte antigen
unremarkable in appearance, they are extremely receptors and elicit humoral immune responses. T
heterogeneous in lineage, function, and phenotype lymphocytes are the cells of cell-mediated immunity.
and are capable of complex biologic responses and The antigen receptors of most T lymphocytes only
activities (Fig. 1-9). These cells often are distin- recognize peptide fragments of protein antigens that
guishable by surface proteins that may be identified are bound to specialized peptide display molecules
 1 Introduction to the Immune System 9

Cell type Principal function(s)

Lymphocytes: B lymphocytes; Specific recognition of antigens:
T lymphocytes; natural B lymphocytes: mediators of humoral
killer cells immunity
T lymphocytes: mediators of cell-mediated
immunity
Natural killer cells: cells of innate immunity

Blood lymphocyte

Antigen-presenting cells: Capture of antigens for display

dendritic cells; macrophages; to lymphocytes:
follicular dendritic cells Dendritic cells: initiation of T cell responses
Macrophages: initiation and effector phase
of cell-mediated immunity
Follicular dendritic cells: display of antigens
to B lymphocytes in humoral immune
responses
Dendritic cell Blood monocyte

Effector cells: T lymphocytes; Elimination of antigens:

macrophages; granulocytes T lymphocytes: helper T cells and cytotoxic
T lymphocytes
Macrophages and monocytes: cells of the
mononuclear-phagocyte system
Granulocytes: neutrophils, eosinophils

Neutrophil

FIGURE 1-8 The principal cells of the immune system. The major cell types involved in immune responses, and their functions, are shown.
Micrographs in the left panels illustrate the morphology of some of the cells of each type. Note that tissue macrophages are derived from blood
monocytes.

called major histocompatibility complex (MHC) mol- (“lyse”) cells harboring intracellular microbes. A third
ecules, on the surface of specialized cells called class of lymphocytes is called natural killer (NK)
antigen-presenting cells (APCs) (see Chapter 3). cells; these cells also kill infected host cells, but they
Among T lymphocytes, CD4+ T cells are called helper do not express the kinds of clonally distributed antigen
T cells because they help B lymphocytes to produce receptors that B cells and T cells do and are compo-
antibodies and help phagocytes to destroy ingested nents of innate immunity, capable of rapidly attacking
microbes. Some CD4+ T cells belong to a special infected cells.
subset that functions to prevent or limit immune All lymphocytes arise from stem cells in the bone
responses; these are called regulatory T lympho- marrow (Fig. 1-10). B lymphocytes mature in the
cytes. CD8+ T lymphocytes are called cytotoxic, or bone marrow, and T lymphocytes mature in an
cytolytic, T lymphocytes (CTLs) because they kill organ called the thymus; these sites in which mature
10 Basic Immunology: Functions and Disorders of the Immune System

Antigen recognition Effector functions

Neutralization
B of microbe,
lymphocyte + phagocytosis,
complement
Microbe activation
Antibody

Cytokines Activation of
macrophages
+
Inflammation

Helper T Microbial antigen

presented
lymphocyte by antigen- Activation
presenting cell (proliferation and
differentiation)
of T and B
lymphocytes

+ Killing of
Cytotoxic T infected cell
lymphocyte
(CTL) Infected cell
expressing
microbial antigen

Natural Killing of
killer infected cell
(NK) cell Target cell
FIGURE 1-9 Classes of lymphocytes. Different classes of lymphocytes recognize distinct types of antigens and differentiate into effector cells
whose function is to eliminate the antigens. B lymphocytes recognize soluble or cell surface antigens and differentiate into antibody-secreting
cells. Helper T lymphocytes recognize antigens on the surfaces of antigen-presenting cells and secrete cytokines, which stimulate different
mechanisms of immunity and inflammation. Cytotoxic (cytolytic) T lymphocytes recognize antigens on infected cells and kill these cells. (Note
that T lymphocytes recognize peptides that are displayed by major histocompatibility complex (MHC) molecules; this process is discussed in
Chapter 3.) Natural killer cells recognize changes on the surface of infected cells and kill these cells. Regulatory T cells are not shown in the
figure.

lymphocytes are produced are called the generative receptors. A normal adult contains approximately
lymphoid organs. Mature lymphocytes leave the gen- 1012 lymphocytes in the circulation and lymphoid
erative lymphoid organs and enter the circulation and tissues.
the peripheral lymphoid organs, where they may When naive lymphocytes recognize microbial
encounter antigen for which they express specific antigens and also receive additional signals