Lymphocyte Differentiation, Recognition, and Regulation (eBook)

David H. Katz (Autor)

F. J. Dixon, Henry G. Kunkel (Herausgeber)

eBook Download: PDF | EPUB

2014 | 1. Auflage
772 Seiten
Elsevier Science (Verlag)
978-1-4832-7407-2 (ISBN)

Infos

Lymphocyte Differentiation, Recognition, and Regulation provides an overview of the state of knowledge on cellular immunology. The focus is on animal work than on studies in man, although in certain areas human lymphocyte biology has been discussed in some detail. The book attempts to integrate information from diverse areas of cellular immunology, immunogenetics, and immunochemistry to form some cohesive concepts that can be perhaps utilized as a working foundation for students and investigators in various areas of immunology. The book begins with a general description of some of techniques and principles underlying the systems frequently employed in cellular immunology. This is followed by detailed analyses of lymphocyte differentiation, receptor function, and regulatory processes. The main points that emerge from such analyses are that the immune system is an infinitely complex and finely tuned network of cells, receptors, and molecules which interact with one another in a genetically controlled manner that is manifested ultimately in the process known as differentiation.

Inhalt

Front Cover 1
Lymphocyte Differentiation, Recognition, and Regulation 4
Copyright Page 5
Table of Contents 8
Dedication 6
Preface 12
Chapter I. Introduction 14
THE TWO MAJOR CLASSES OF IMMUNOCOMPETENT LYMPHOCYTES 15
Chapter II. Surface Antigens and Markers on T Lymphocytes 22
A. ANTIGENS FOUND EXCLUSIVELY ON T CELLS 23
B. ANTIGENS ON T LYMPHOCYTES AND ON OTHER NONLYMPHOID CELLS, BUT NOT PRESENT ON B LYMPHOCYTES 39
Chapter III. Surface Antigens and Markers on B Lymphocytes 53
A. ANTIGENS FOUND EXCLUSIVELY ON CELLS OF THE B LYMPHOCYTE LINEAGE 54
B. ANTIGENS ON B LYMPHOCYTES AND ON OTHER NONLYMPHOID CELLS, BUT NOT PRESENT ON T LYMPHOCYTES 80
Chapter IV. Surface Antigens Present on T Lymphocytes and Also on B Lymphocytes 83
A. THE MAJOR HISTOCOMPATIBILITY ANTIGENS 84
B. THE I-REGION-ASSOCIATED (la) ANTIGENS 91
C. THE Fc RECEPTOR (FcR) 102
D. THE THYMUS–B CELL COMMON ANTIGEN (Th–B) 129
E. THE LY-8 ANTIGEN 131
Chapter V. Ontogeny of the Two Major Classes of Lymphocytes 132
A. GENERAL CONSIDERATIONS 133
B. ONTOGENY OF T LYMPHOCYTES 134
C. ONTOGENY OF B LYMPHOCYTES 142
Chapter VI. Surface Immunoglobulin on Lymphocytes 165
A. INTRODUCTION 166
B. DETECTION OF SURFACE IMMUNOGLOBULIN 167
C. QUANTITATION OF SURFACE IG 171
D. TISSUE DISTRIBUTION OF SURFACE IG+ LYMPHOCYTES 174
E. ONTOGENY OF IG+ LYMPHOCYTES 178
F. IMMUNOGLOBULIN CLASS EXPRESSION OF SURFACE IG ON LYMPHOCYTES 178
G. MOVEMENT AND REDISTRIBUTION OF SURFACE IMMUNOGLOBULIN MOLECULES ON B LYMPHOCYTES 194
H. SURFACE IMMUNOGLOBULIN ON T LYMPHOCYTES 195
I. PROPERTIES OF SURFACE IMMUNOGLOBULIN ISOLATED FROM B LYMPHOCYTES 199
Chapter VII. Immunological Specificity of Immunocompetent Lymphocytes 201
A. FUNCTIONAL EVIDENCE FOR SPECIFICITY IN T AND B LYMPHOCYTES 202
B. COMPARATIVE SPECIFICITIES OF THE T AND B CELL REPERTOIRES 208
C. DETERMINANT SPECIFICITY OF T AND B CELL RECEPTORS 213
D. ANTIGEN RECEPTORS ON B LYMPHOCYTES 229
E. ANTIGEN RECEPTORS ON T LYMPHOCYTES 231
Chapter VIII. Functional Properties of T Lymphocytes 260
A. REGULATORY T LYMPHOCYTES 262
B. EFFECTOR T LYMPHOCYTES 278
C. DIFFERENTIAL SENSITIVITIES OF T CELL SUBPOPULATIONS TO CHEMICAL AND PHYSICAL MANIPULATIONS 324
Chapter IX. Functional Properties of B Lymphocytes 356
A. ANTIBODY-FORMING CELL PRECURSORS (AFCP) 357
B. FUNCTIONAL SUBPOPULATIONS OF B LYMPHOCYTES DISTINGUISHED BY RELATIVE DEPENDENCE ON T CELLS 360
C. OTHER CRITERIA FOR FUNCTIONAL SUBPOPULATIONS OF B LYMPHOCYTES 379
D. GENETIC DEFECTS IN B LYMPHOCYTE FUNCTION 390
Chapter X. Regulatory Cellular Interactions in Immune Responses 395
A. BASIC MODELS OF T–B CELL INTERACTIONS 397
B. NATURE OF THE REGULATORY INFLUENCE OF ACTIVATED T CELLS ON ANTIBODY PRODUCTION 422
C. SUPPRESSIVE EFFECTS OF T LYMPHOCYTES ON ANTIBODY PRODUCTION 430
D. T CELL REGULATION OF IgE ANTIBODY SYNTHESIS 442
E. BASIC MODELS OF T–T CELL INTERACTIONS 474
F. SUPPRESSIVE EFFECTS OF T CELLS ON CELL-MEDIATED IMMUNE RESPONSES 483
Chapter XI. The Allogeneic Effect on Immune Responses 495
A. ESSENTIAL FEATURES OF THE ALLOGENEIC EFFECT ON ANTIBODY RESPONSES 498
B. MEDIATION OF THE ALLOGENEIC EFFECT VIA DEVELOPMENT OF THE GRAFT-VERSUS-HOST REACTION 503
C. THE ALLOGENEIC EFFECT IN VITRO 513
D. RELEVANCE OF THE ALLOGENEIC EFFECT TO THE MECHANISM OF REGULATORY PHYSIOLOGICAL INTERACTIONS BETWEEN T AND B LYMPHOCYTES IN IMMUNE RESPONSES 515
E. PATHOPHYSIOLOGICAL SIGNIFICANCE OF THE ALLOGENEIC EFFECT 537
F. CONCLUSIONS 542
Chapter XII. Genetic Control of Immune Responses and Cellular Interactions 543
A. HISTOCOMPATIBILITY-LINKED Ir GENES 545
B. HISTOCOMPATIBILITY-LINKED IMMUNE SUPPRESSION (Is) GENES 558
C. THE ROLE OF PRODUCTS OF THE MAJOR HISTOCOMPATIBILITY COMPLEX IN CELLULAR INTERACTIONS WHICH REGULATE IMMUNE RESPONSES 563
D. RELATIONSHIP OF HISTOCOMPATIBILITY GENE PRODUCTS TO EACH OTHER IN NATURE AND FUNCTION 607
E. GENERAL CONCLUSIONS 609
Chapter XIII. Mechanisms of Regulatory Cellular Interactions 611
A. GENERAL CONSIDERATIONS 611
B. PROPERTIES OF BIOLOGICALLY ACTIVE PRODUCTS OF ACTIVATED T CELLS AND MACROPHAGES MEDIATING HELPER OR SUPPRESSOR ACTIVITIES 613
C. HYPOTHETICAL MODELS FOR CELLULAR INTERACTIONS 640
Chapter XIV. Immunological Tolerance 644
A. HISTORICAL PERSPECTIVE 646
B. TARGET CELLS FOR TOLERANCE INDUCTION 647
C. MECHANISMS OF TOLERANCE INDUCTION IN EITHER T OR B LYMPHOCYTES 649
D. INTERRELATIONSHIPS AMONG THE ALTERNATIVE PATHWAYS TO UNRESPONSIVENESS 685
E. RELATIONSHIPS OF THE ALTERNATIVE PATHWAYS TO INDUCTION AND MAINTENANCE OF SELF-TOLERANCE 687
F. CONCLUDING REMARKS 688
Chapter XV. Concluding Remarks 689
Glossary 692
Bibliography 697
Index 754

Textauszug

I

Introduction

Publisher Summary

It is generally accepted that a class of bone marrow lymphocytes migrates to the thymus where the small lymphocytes adapt to certain specific immune functions by virtue of some crucial influence of the thymus. These thymus-derived lymphocytes, referred to as T cells, are responsible for the various phenomena of cell-mediated immunity, such as delayed hypersensitivity, transplantation reactivity, including cell-mediated cytotoxicity and mixed lymphocyte reactions, and cell-mediated resistance to infection; T cells are also the predominant cell type concerned with regulation of other lymphoid cells in the immune system. The second lymphocyte cell type, referred to as B cells, arises also in the bone marrow and settles ultimately in distinct anatomical sites in peripheral lymphoid tissues where they give rise to the precursors of antibody-secreting cells. Among the more helpful tools available to the cellular immunologist are experimental systems in which analyses can be made of the respective functions of T cells and B cells, either independently of one another or in an interdependent manner.

For the past 7 to 8 years, the phenomena of cell interactions in the development and regulation of immune responses have been extensively investigated. During this time, much has been learned about the importance of such cell interactions in regulating the immune system, and also about the possible mechanisms by which these interactions take place. During this same period, remarkable advances have been made in furthering our knowledge and understanding of cell surface membrane molecules, some of which perform receptor functions, either clonally restricted or nonclonal, and others which appear to be integrally associated with activation and differentiation events in lymphoid cells. Although it is true that much has yet to be determined, particularly at the molecular level, about the precise pathways involved in the development of immunocompetent cell functions and interactions, it seems fair to state that our insights on these events, derived to a great extent from phenomenological observations, have led to various working hypothetical models on which to proceed, eventually, and hopefully, to some concrete solutions.

Nearly five years ago, we undertook the task of reviewing the areas concerned with T cell regulation of antibody responses and the significance of cell interaction phenomena for the regulatory processes of the immune system (1051). Since then, there has continued to be an avalanche of new and exciting observations by many active investigators resulting in increasingly provocative modifications in certain basic concepts, and the strong indications that much of what is being analyzed in immunological systems may have considerably broader implications for developmental and molecular biology. Thus, the knowledge obtained about the fundamental regulatory control of lymphocyte and macrophage functions and the events initiating and perpetuating differentiation of such cells may now, or very shortly, be appropriately interpreted in the context of developmental functions of eukaryotic cells in general.

This monograph was prepared in an attempt to provide some insight on the systems and data on which the above statements are based. In so doing, I hope to integrate information from diverse areas of cellular immunology, immunogenetics, and immunochemistry to form some cohesive concepts that can be perhaps utilized as a working foundation for students and investigators in various areas of immunology. The main points that emerge from such analyses to be presented herein are, in my view, that the immune system is an infinitely complex and finely tuned network of cells, receptors, and molecules which interact with one another in a genetically controlled manner that is manifested ultimately in the process known as differentiation.

In order to develop meaningful insights into the immense complexity of the integrated systems governing immune defenses of the individual, it seems appropriate to consider in some detail certain aspects of lymphocyte differentiation, mechanisms underlying specific recognition by such cells and the processes concerned with regulation of lymphocyte function. The following chapters in this monograph are directed to these aspects of cellular immunology and are not intended to represent the entire spectrum of present day immunology. Notably absent, for example, are discussions of the complement system or details of immunoglobulin structure, various aspects of immunopathological processes or tumor immunology, among other things.

Before going into any detailed analysis of our current knowledge of lymphocyte differentiation, receptor function, and regulatory processes, it may be helpful to those readers who are not very familiar with some of the systems frequently employed in cellular immunology to provide at the outset a general description of these techniques and the principles underlying them. I will return to them in greater detail in appropriate subsequent chapters.

THE TWO MAJOR CLASSES OF IMMUNOCOMPETENT LYMPHOCYTES

One of the major advances in immunobiology in the past two decades has been the recognition of two pathways for the differentiation of antigen-reactive cells. It is generally accepted that a class of bone marrow lymphocytes migrates to the thymus where these small lymphocytes adapt to certain specific immune functions by virtue of some crucial influence of the thymus. These thymus-derived lymphocytes, referred to as T cells, are responsible for the various phenomena of cell-mediated immunity, such as delayed hypersensitivity, transplantation reactivity, including cell-mediated cytotoxicity and mixed lymphocyte reactions, and cell-mediated resistance to infection; T cells are also perhaps the predominant cell type concerned with regulation of other lymphoid cells in the immune system. The second lymphocyte cell type, referred to as B cells, arises also in the bone marrow and settles ultimately in distinct anatomical sites in peripheral lymphoid tissues where they give rise to the precursors of antibody-secreting cells (339, 448, 1051, 1381).

Among the more helpful tools available to the cellular immunologist are experimental systems in which analyses can be made of the respective functions of T cells and B cells, either independently of one another or in an interdependent manner. The introduction of defined haptenic determinants onto immunogenic carriers by Landsteiner (1201) has provided a most convenient method for the analysis of specific interactions between antigens and specific cells of the immune system. For many years it has been known that immunization with a hapten elicits anti-hapten antibody responses only when the hapten is coupled to a carrier substance which is itself immunogenic; nonimmunogenic substances serve only poorly, or not at all, as functional carriers for haptens. Moreover, as mentioned above, optimal hapten-specific secondary responses require challenge with the hapten–carrier conjugate used for primary immunization (i.e., the “carrier effect”). Since the anti-hapten antibodies produced by such immunizations were highly specific for the haptenic determinant employed (e.g., little, if any, contribution to binding energy was attributable to determinants on the carrier) and since the assumption was made that the specificity of antibody accurately expresses the specificity of the antigen-binding receptor molecules on the precursors of antibody-forming cells, then these observations suggested the operation of an additional recognition mechanism for the carrier molecule. Indeed, the demonstration that cooperative interactions between distinct lymphocytes respectively specific for carrier and haptenic determinants are essential for the development of anti-hapten immune responses validated this interpretation (reviewed in 1051; see Chapter X). Two basic in vivo experimental models have been employed to establish the latter point:

1. The adoptive secondary anti-hapten response following transfer of hapten-primed and carrier-primed cells into irradiated recipient mice.

2. The use of preimmunization or supplemental immunization with free carrier to enhance primary and secondary anti-hapten antibody responses in guinea pigs and rabbits.

The adoptive transfer experimental system is based on the use of a lethally or sublethally irradiated animal as a relatively immunologically inert recipient of primed or unprimed lymphoid cells whose functions is under analysis. Under usual circumstances inbred animals are employed in this technique, and the cell donors and recipients are syngeneic at the major histocompatibility locus. Modifications from this usual approach will be discussed in Chapters X and XII.

A schematic illustration of the basic approach for studying cooperative lymphocyte interactions in responses to hapten-protein (carrier) conjugates in mice is shown in Fig. I.1. In such systems, two types of donor syngeneic spleen cell populations are employed: One of these is obtained from donors previously immunized with a hapten–carrier conjugate, in this case, 2,4-dinitrophenyl (DNP)-keyhole limpet hemocyanin (KLH); the second donor population is obtained from donors previously immunized with an unrelated carrier alone, in this case bovine γ-globulin (BGG), or from normal unprimed donors as a control. Appropriate numbers of the...

Produkt-Details

• Erscheint lt. Verlag: 28.6.2014
• Sprache: englisch
• Themenwelt: Sachbuch/Ratgeber ► Natur / Technik ► Naturführer
• Themenwelt: Studium ► Querschnittsbereiche ► Infektiologie / Immunologie
• Themenwelt: Naturwissenschaften ► Biologie ► Zoologie
• Themenwelt: Technik
• ISBN-10: 1-4832-7407-1 / 1483274071
• ISBN-13: 978-1-4832-7407-2 / 9781483274072