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Immunobiology of the Macrophage -

Immunobiology of the Macrophage (eBook)

David S. Nelson (Herausgeber)

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2014 | 1. Auflage
652 Seiten
Elsevier Science (Verlag)
978-1-4832-7477-5 (ISBN)
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Immunobiology of the Macrophage
Immunobiology of the Macrophage presents an account of the state of knowledge of the immunobiology of the macrophage. The book's contributors-immunologists of diverse scientific and geographic backgrounds-have been encouraged to give personal accounts of developments in their special fields of interest as well as critical surveys of the backgrounds leading to these developments. The book begins with a study on the functions of macrophages in the initiation and regulation of antibody responses in vitro. This is followed by separate chapters on topics such as the role of macrophages in making antigen more immunogenic and less tolerogenic; functional distinctions between macrophages at different sites; and the role of the macrophage in antigen recognition by T lymphocytes. Subsequent chapters examine interactions between macrophages and lymphocytes in the production of interferon and other mediators of cellular immunity; macrophage cell lines and their uses in immunobiology; and cytotoxic macrophages in allograft rejection.

Front Cover 1
Immunobiology of the Macrophage 4
Copyright Page 5
Table of Contents 6
List of Contributors 12
Preface 16
Introduction 18
Chapter 1. The Role of Macrophages in Antibody Responses in Vitro 20
I. INTRODUCTION 21
II. ANTIBODY RESPONSES IN VITRO 23
III. INTRODUCTORY IMMUNOGENETICS 25
IV. REQUIREMENTS FOR MACROPHAGES IN ANTIBODY RESPONSES IN VITRO 26
V. FUNCTIONS OF MACROPHAGES IN ANTIBODY RESPONSES IN VITRO 32
VI. IMMUNOGENETIC CONSIDERATIONS OF MACROPHAGE FUNCTIONS IN ANTIBODY RESPONSES IN VITRO 41
VII. CONCLUSIONS, PRESENT STATE OF THE ART, 
46 
VIII. NOTE ADDED IN PROOF 48
ACKNOWLEDGMENTS 49
REFERENCES 49
Chapter 2. The Role of Macrophages in the Specific Determination of Immunogenicity and Tolerogenicity 54
I. INTRODUCTION 54
II. IN VITRO REQUIREMENTS FOR CELL ACTIVATION BY DNP-D-GL 57
III. CHARACTERISTICS OF AN ANTIGEN WHICH DOES NOT REQUIRE MACROPHAGE PROCESSING 60
IV. MACROPHAGE ROLES IN CELL ACTIVATION 61
V. NOTE ADDED IN PROOF 62
REFERENCES 63
Chapter 3. Role of Macrophages in T Cell–B Cell Collaboration in Antibody Production 64
I. INTRODUCTION 64
II. IMMUNOBIOLOGY OF T CELL–B CELL COLLABORATION 65
III. ROLE OF MACROPHAGES IN T CELL–B CELL COLLABORATION 71
IV. MECHANISMS OF T CELL–B CELL COLLABORATION 79
V. T CELL-B CELL COLLABORATION IN VIVO 92
ACKNOWLEDGMENTS 104
REFERENCES 104
Chapter 4. Functional Heterogeneity of Macrophages 110
I. INTRODUCTION 110
II. FUNCTIONAL HETEROGENEITY OF MACROPHAGES FROM DIFFERENT TISSUES 111
III. FUNCTIONAL HETEROGENEITY OF MACROPHAGES FROM THE SAME TISSUE 116
IV. CONCLUSIONS 125
ACKNOWLEDGMENTS 126
REFERENCES 127
Chapter 5. The Role of Macrophages in the Induction of Cell-Mediated Immunity in Vivo 130
I. INTRODUCTION 131
II. CONTRIBUTION OF MACROPHAGES TO INDUCTION OF DELAYED HYPERSENSITIVITY REACTIONS AND IN PRIMING HELPER T CELLS FOR ANTIBODY PRODUCTION 131
III. RELATIONSHIP OF MACROPHAGE PRESENTATION AND PROCESSING OF ANTIGENS TO INDUCTION OF CELL-MEDIATED IMMUNITY 136
IV. REGULATION OF IMMUNOGENICITY MACROPHAGE-ASSOCIATED ANTIGENS 142
V. SUMMARY AND CONCLUSIONS 146
ACKNOWLEDGMENT 148
REFERENCES 148
Chapter 6. Macrophage Function in Antigen Recognition by T Lymphocytes 150
I. INTRODUCTION 150
II. MACROPHAGES ARE REQUIRED FOR ANTIGEN RECOGNITION BY T LYMPHOCYTES 151
III. INTERACTION BETWEEN MACROPHAGE AND SOLUBLE ANTIGEN IN THE IMMUNE RESPONSE 153
IV. GENETIC REGULATION OF FUNCTIONAL MACROPHAGE–LYMPHOCYTE INTERACTION 160
V. PHYSICAL INTERACTIONS BETWEEN MACROPHAGES AND LYMPHOCYTES 163
VI. ROLE OF MACROPHAGES IN NONANTIGENIC STIMULATION OF T LYMPHOCYTES 171
VII. MODEL BUILDING FOR THE CELLULAR AND MOLECULAR EVENTS IN ANTIGEN RECOGNITION BY T LYMPHOCYTES 174
ACKNOWLEDGMENTS 177
REFERENCES 177
Chapter 7. The Role of Macrophages in the Activation of T and B Lymphocytes in Vitro 180
I. INTRODUCTION 181
II. MECHANISMS OF ACTION OF MACROPHAGES 181
III. THE ROLE OF MACROPHAGES IN ANTIGEN-INDUCED LYMPHOCYTE PROLIFERATIVE RESPONSES IN VITRO 186
IV. THE ROLE OF MACROPHAGES IN THE RESPONSE OF B AND T LYMPHOCYTES TO MITOGENS IN VITRO 197
V. THE ROLE OF MACROPHAGES IN THE ACTIVATION OF LYMPHOCYTES BY ALLOGENEIC CELLS (MLR) 206
VI. THE ROLE OF MACROPHAGES IN THE ACTIVATION OF B LYMPHOCYTES BY SHEEP ERYTHROCYTES 208
VII. THE ROLE OF MACROPHAGES IN THE INDUCTION OF LYMPHOKINE SYNTHESIS BY B AND T LYMPHOCYTES 209
VIII. SUMMARY AND CONCLUSIONS 213
ACKNOWLEDGMENTS 215
REFERENCES 216
Chapter 8. The Ability of Macrophages to Augment in Vitro Mitogen- and Antigen-Stimulated Production of Interferon and Other Mediators of Cellular Immunity by Lymphocytes 220
I. INTRODUCTION 221
II. THE ABILITY OF MACROPHAGES TO AUGMENT MITOGEN-STIMULATED PRODUCTION OF INTERFERON BY LYMPHOCYTES 222
III. THE ABILITY OF MACROPHAGES TO AUGMENT BACTERIAL AND VIRAL ANTIGEN-STIMULATED PRODUCTION OF INTERFERON BY LYMPHOCYTES 233
IV. MACROPHAGES AND THEIR RELATIONSHIP TO THE PRODUCTION OF OTHER MEDIATORS OF CELLULAR IMMUNITY BY LYMPHOCYTES 238
V. MACROPHAGES AND THEIR ROLE IN AFFECTING THE PRODUCTION OF VIRAL-INDUCED INTERFERON BY LEUKOCYTES 244
VI. SUMMARY 248
ACKNOWLEDGMENTS 250
REFERENCES 250
Chapter 9. Nonspecific Immunoregulation by Macrophages and Their Products 254
I. INTRODUCTION 254
II. POTENTIATION OF LYMPHOID CELL RESPONSES 255
III. INHIBITION OF LYMPHOID CELL RESPONSES 258
IV. MODE OF ACTION OF MACROPHAGES IN DEPRESSING LYMPHOCYTE RESPONSES 262
V. SIGNIFICANCE OF LYMPHOID CELL STIMULATION AND INHIBITION BY MACROPHAGES AND THEIR PRODUCTS 269
ACKNOWLEDGMENTS 272
REFERENCES 272
Chapter 10. Macrophage Membranes 278
I. INTRODUCTION 278
II. PROBES OF MACROPHAGE SURFACE ORGANIZATION 280
III. RANDOM MOBILITY OF MACROPHAGE SURFACE PROTEINS 281
IV. ORGANIZED MOVEMENT OF MACROPHAGE SURFACE ELEMENTS 283
V. CONTROL OF TRANSLATIONAL MOVEMENTS OF RECEPTORS AND TRANSPORT PROTEINS WITHIN THE PLANE OF THE MEMBRANE 285
VI. SUMMARY 290
REFERENCES 291
Chapter 11. Macrophage Cell Lines and Their Uses in Immunobiology 294
I. INTRODUCTION 294
II. GROWTH OF PRIMARY MACROPHAGES IN VITRO 295
III. PERMANENT LINES WITH PROPERTIES OF MACROPHAGES 302
IV. CONCLUSION 307
REFERENCES 308
Chapter 12. Monocyte Kinetics and Their Changes in Infection 310
I. INTRODUCTION 310
II. THEORETICAL AND METHODOLOGICAL BACKGROUND 312
III. CELL KINETICS OF THE MONOCYTES 314
IV. CELL KINETICS OF MONOCYTES IN INFECTION 330
V. CONCLUDING REMARKS 338
ACKNOWLEDGMENTS 339
REFERENCES 339
Chapter 13. 
342 
I. INTRODUCTION 342
II. METHODS FOR QUANTIFYING MACROPHAGE CHEMOTAXIS 343
III. HUMORAL FACTORS CHEMOTACTIC FOR MACROPHAGES 348
IV. LYMPHOCYTE-DERIVED CHEMOTACTIC FACTORS 352
V. CHEMOTACTIC FACTORS FROM BACTERIA 356
VI. FACTORS WHICH ALTER MONOCYTE CHEMOTACTIC FUNCTION 356
VII. ABNORMALITIES OF MONOCYTE CHEMOTAXIS IN HUMAN DISEASES 359
VIII. SUMMARY AND CONCLUSIONS 364
ACKNOWLEDGMENTS 365
REFERENCES 365
Chapter 14. Cellular and Molecular Aspects of Chemotaxis of Macrophages and Monocytes 368
I. INTRODUCTION 369
II. LOCOMOTION OF DIFFERENT TYPES OF MACROPHAGE 369
III. MODES OF MACROPHAGE MIGRATION 370
IV. RECOGNITION OF CHEMOTACTIC FACTORS AT THE CELL MEMBRANE 372
V. INTRACELLULAR EVENTS FOLLOWING INTERACTION OF THE CHEMOTACTIC FACTOR WITH THE CELL MEMBRANE 375
VI. DIFFERENTIAL EFFECTS OF BACTERIAL TOXINS ON LOCOMOTION OF NEUTROPHILS AND MACROPHAGES 377
VII. RECOGNITION IN CHEMOTAXIS, PHAGOCYTOSIS, AND OTHER MACROPHAGE FUNCTIONS 379
VIII. ANTIGEN-SPECIFIC CHEMOTAXIS 380
IX. CONCLUSIONS 382
ACKNOWLEDGMENT 382
REFERENCES 382
Chapter 15. Lymphocyte–Macrophage Interactions and Macrophage Activation in the Expression of Antimicrobial Immunity in Vivo 386
I. INTRODUCTION 386
II. GENERATION OF EFFECTOR T CELLS 388
III. MECHANISMS OF T CELL- AND MACROPHAGE-MEDIATED IMMUNITY TO INFECTION 394
IV. CONCLUSIONS 414
REFERENCES 416
Chapter 16. Macrophage Activation by Lymphocyte Mediators and Studies on the Interaction of Macrophage Inhibitory Factor (MIF) with Its Target Cell 420
I. INTRODUCTION 420
II. MACROPHAGE ACTIVATION BY LYMPHOCYTE MEDIATORS 422
III. INTERACTION OF MIF WITH THE MACROPHAGE 433
IV. BIOLOGICALLY ACTIVE SUBSTANCES PRODUCED BY MACROPHAGES 440
V. CONCLUSION 442
ACKNOWLEDGMENT 442
REFERENCES 442
Chapter 17. Secretion of Macrophage Enzymes in Relation to the Pathogenesis of Chronic Inflammation 446
I. INTRODUCTION 447
II. THE ORIGIN AND TURNOVER OF CELLS IN SITES OF CHRONIC INFLAMMATION 447
III. IN VITRO STUDIES ON THE ROLE OF MACROPHAGES IN CHRONIC INFLAMMATION 449
IV. WHAT IS THE CONTRIBUTION OF HYDROLYTIC ENZYME SECRETION TO CHRONIC INFLAMMATION? 467
V. OTHER PRODUCTS OF MACROPHAGES 470
VI. INTERACTIONS AND MODULATING FACTORS 473
REFERENCES 476
Chapter 18. Induction of Macrophage-Mediated Cytotoxicity 482
I. INTRODUCTION 483
II. MACROPHAGE-MEDIATED CYTOTOXICITY IN ALLOGRAFT REJECTION 483
III. CYTOTOXIC MACROPHAGES IN SYNGENEIC TUMOR SYSTEMS 488
IV. MACROPHAGE-MEDIATED CYTOTOXICITY INDUCED BY INFECTION WITH VARIOUS MICROORGANISMS 491
V. IN VITRO INDUCTION OF MACROPHAGE-MEDIATED CYTOTOXICITY 492
VI. SUMMARY AND IMPLICATIONS 500
ACKNOWLEDGMENTS 503
REFERENCES 503
Chapter 19. Cytostatic and Cytocidal Effects of Activated Macrophages 506
I. INTRODUCTION 506
II. NOMENCLATURE 507
III. CYTOSTATIC EFFECTS OF ACTIVATED MACROPHAGES 508
IV. CYTOCIDAL EFFECTS OF MACROPHAGES 518
V. THE BIOLOGIC RELEVANCE OF THE IN VITRO FINDINGS 522
VI. CRITICAL OUTLOOK 524
ACKNOWLEDGMENTS 526
REFERENCES 526
Chapter 20. Macrophages and the Destruction of Syngeneic Virus-Induced Tumors 528
I. INTRODUCTION 528
II. ANTIGENICITY OF CELLS TRANSFORMED BY ONCOGENIC VIRUSES 529
III. IMMUNE RESPONSE OF SYNGENEIC HOST TO VIRUS-INDUCED TUMORS 531
IV. ROLE OF MACROPHAGES IN REJECTION OF VIRUS-INDUCED TUMORS 537
V. STEPS IN THE DEVELOPMENT OF CELL-MEDIATED IMMUNITY AND THE MECHANISMS OF REJECTION OF DNA VIRUS-INDUCED TUMORS 546
ACKNOWLEDGMENTS 550
REFERENCES 550
Chapter 21. Mechanisms of Extracellular Killing of Nucleated Mammalian Cells by Macrophages 554
I. INTRODUCTION 555
II. SPECIFIC MACROPHAGE CYTOTOXICITY 556
III. NONSPECIFIC MACROPHAGE CYTOTOXICITY 574
IV. CYTOTOXIC MACROPHAGES AND THE TUMOR BEARING HOST 586
V. IN VIVO SIGNIFICANCE OF THE NONSPECIFICALLY CYTOTOXIC MACROPHAGE 589
VI. ROLE OF MACROPHAGES IN SURVEILLANCE 590
VII. CONCLUSION 591
REFERENCES 592
Chapter 22. Immunotherapeutic Approaches to Tumors Involving the Skin 596
I. INTRODUCTION 596
II. CLINICAL INVESTIGATIONS 598
III. A PRIMITIVE SURVEILLANCE MECHANISM? 603
IV. SUMMARY 606
ACKNOWLEDGMENTS 607
REFERENCES 608
Chapter 23. Macrophages and Their Disorders in Man 612
I. METABOLISM 613
II. FUNCTIONS 615
III. DISORDERS OF THE MONOCYTE–MACROPHAGE SYSTEM 621
IV. SUMMARY AND FUTURE PERSPECTIVES 630
REFERENCES 631
Chapter 24. Macrophages: Perspectives and Prospects 636
Index 642

1

The Role of Macrophages in Antibody Responses in Vitro


Carl W. Pierce and Judith A. Kapp

Publisher Summary


This chapter discusses immunogenetics, requirements for macrophages in antibody responses in vitro, and the mechanisms involved in the development and the regulation of antibody responses. Distinct pathways for the differentiation of two classes of clonally restricted, antigen-specific, immunocompetent lymphocytes from hemopoietic stem cells are well recognized, as are the distinctive properties and functions of these lymphocytes. B cells, after interaction with antigen via membrane immunoglobulin receptors specific for that antigen, and under appropriate regulatory influences of thymus-derived lymphocytes, develop into plasma cells that secrete antibody molecules uniquely capable of combining with the antigenic moiety that initially stimulated the B cells. The antigens that stimulate antibody responses may be divided into two broad and probably artificial classes, T cell-dependent and T cell-independent antigens. T cell-dependent antigens are complex multi-determinant antigens, such as heterologous erythrocytes and hapten–protein conjugates. The development of antibody responses to these antigens by B cells is strictly dependent on the concomitant positive regulatory influence, or helper effect, of T cells.

I Introduction

II Antibody Responses in Vitro

III Introductory Immunogenetics

IV Requirements for Macrophages in Antibody Responses in Vitro

V Functions of Macrophages in Antibody Responses in Vitro

VI Immunogenetic Considerations of Macrophage Functions in Antibody Responses in Vitro

A The Role of Macrophages in Antibody Responses to Antigens Controlled by H-2-Linked Ir Genes

B Lack of Genetic Restrictions for Interactions among Macrophages and Lymphoid Cells in Antibody Responses

C Role of Macrophages in Suppression of Antibody Responses by Alloantisera against Leukocyte Alloantigens

VII Conclusions, Present State of the Art, and the Future

VIII Note Added in Proof

References

I INTRODUCTION


During the last decade, our understanding of the cells and mechanisms involved in the development and the regulation of antibody responses has increased at an astonishing pace. Distinct pathways for the differentiation of two classes of clonally restricted, antigen-specific, immunocompetent lymphocytes from hemopoietic stem cells are now well recognized, as are the distinctive properties and functions of these lymphocytes. Although the precise pathway (s) of differentiation of the precursors of antibody-producing cells, or B cells, in mammals is still the subject of intensive investigation, the immunologic function of B cells is incontrovertible. B cells, after interaction with antigen via membrane immunoglobulin (Ig) receptors specific for that antigen, and under appropriate regulatory influences of thymus-derived lymphocytes, develop into plasma cells that secrete antibody molecules uniquely capable of combining with the antigenic moiety which initially stimulated the B cells. Thymus-derived lymphocytes, or T cells, after interaction with antigen via a still undefined membrane receptor, do not synthesize nor secrete antibody. T cells, however, are responsible for the various phenomena of cell-mediated immunity including the tissue rejection phenomena, such as graft versus host reactions and allograft and tumor rejection, and the production of a variety of biologically active molecules, “lymphokines,” which are responsible for the inflammatory response and the tissue damage characteristic of delayed hypersensitivity reactions. T cell function is also critical for immunity and resistance to certain infectious microorganisms. Furthermore, from the experiments of numerous investigators, it is now clear that T cells, in addition to their function as effector cells for cell-mediated immune reactions, are the critical regulators of both B cell and T cell responses to antigen. T cells mediating positive regulatory functions are referred to as “helper cells” in antibody responses and “amplifier cells” in cell-mediated immune responses. Negative regulatory functions in both T cell and B cell responses are ascribed to “suppressor T cells.” The relationships between and the mechanisms of action of the T cells mediating these opposing regulatory functions are currently under intensive investigation in numerous laboratories.

The antigens that stimulate antibody responses may be divided into two broad and probably artificial classes: T cell-dependent and T cell-independent antigens. T cell-dependent antigens are complex multideterminant antigens, such as heterologous erythrocytes and hapten–protein conjugates. The development of antibody responses to these antigens by B cells is strictly dependent on the concomitant positive regulatory influence, or helper effect, of T cells. T cell-independent antigens are generally polymeric molecules with repeating chemical subunits, such as pneumococcal polysaccharides, lipopolysaccharides, flagellin, and polyvinylpyrrolidone. These antigens are capable of stimulating antibody responses without the helper effect of T cells and thus derive their classification as T cell-independent antigens. However, in antibody responses to these types of antigens, the suppressive effects of T cells are most easily demonstrated and their classification as T cell-independent antigens becomes considerably less meaningful and valid. Several review articles are available which delve into this background material in greater detail (Katz and Benacerraf, 1972; Claman and Mosier, 1972; Gershon, 1974; Warner, 1974; Pierce and Benacerraf, 1975; Coutinho and Möller, 1975; Nossal and Schrader, 1975).

The macrophage is a third type of cell that is intimately involved in the development and expression of humoral and cell-mediated immune responses. In contrast to T cells and B cells, macrophages are neither clonally restricted nor antigen specific, but function as nonspecific accessory cells. Their functions in antigen uptake, catabolism, and presentation to T and B cells in the initiation of immune responses have been reviewed (Unanue, 1972), as have their roles as accessory effector cells in both cellular and humoral immune responses (Benacerraf and Green, 1969). Considerable attention has also been devoted to the physiology of macrophages, the mechanisms of phagocytosis and pinocytosis, and their functions in the inflammatory response (Cohn, 1968; Nelson, 1969; van Furth, 1970; Gordon and Cohn, 1973; Steinman and Cohn, 1974a; Ebert and Grant, 1974). The reader is referred to these articles and appropriate chapters of this book for detailed information on these aspects of macrophage function.

In this chapter, we will attempt to present a cogent overview of the functions of macrophages in the initiation and regulation of antibody responses in vitro. We realize some of our views may be controversial and biased by our experiences. However, if we succeed in acquainting the uninitiated reader with the complexities of these macrophage functions, and, at the same time, stimulate others to perform experiments to clarify those areas where controversy exists, we will have accomplished our goals.

II ANTIBODY RESPONSES IN VITRO


A Methodology


Two similar culture systems are used to study antibody responses in vitro. In both culture systems, dispersed, single spleen cells, or appropriate combinations of “purified” T cells, B cells, and macrophages are suspended in a completely supplemented culture medium containing selected fetal calf serum at a cell density between 10 × 106 and 20 × 106 cells/ml. In the system developed by Mishell and Dutton (1967), the cells are incubated with antigen in small plastic petri dishes at 37°C in a humidified atmosphere of 7% O2, 10% CO2, and 83% N2 on a slowly rocking platform to facilitate interactions among the cells. Each culture is supplemented daily with a nutritional “cocktail” and fetal calf serum. In the system...

Erscheint lt. Verlag 28.6.2014
Sprache englisch
Themenwelt Sachbuch/Ratgeber Natur / Technik Naturführer
Studium Querschnittsbereiche Infektiologie / Immunologie
Naturwissenschaften
ISBN-10 1-4832-7477-2 / 1483274772
ISBN-13 978-1-4832-7477-5 / 9781483274775
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