Immunobiology of the Macrophage

David S. Nelson

• Publisher: Academic Press
• Year: 2014
• Print ISBN: 9780125145503
• eBook ISBN: 9781483274775
• Topic: Biological Sciences
• Subtopic: Zoology
• Index: Biological Sciences

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.

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

A Methodology

B Advantages and Disadvantages of Tissue Culture Systems

III Introductory Immunogenetics

IV Requirements for Macrophages in Antibody Responses in Vitro

A Separation and Purification

B Characteristics of Macrophages

C Antibody Responses to T Cell-Dependent Antigens

D Antibody Responses to T Cell-Independent Antigens

V Functions of Macrophages in Antibody Responses in Vitro

A Promotion of Lymphoid Cell Viability

B Antigen Presentation

C Relationship of Viability-Promoting and Antigen Presentation Functions of Macrophages

D The Macrophage as a Focus for T Cell–B Cell Interaction?

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 developed by Marbrook (1967), the cells and antigen are placed in a glass tube closed at the bottom with dialysis membrane. The bottom portion of the tube is immersed in culture medium contained in a larger vessel, and the apparatus is incubated stationary at 37°C in the humidified atmosphere used in the Mishell–Dutton system. The density of cells on the dialysis membrane is sufficient for required cell interactions, and the cultures do not require the daily supplementation with nutritional cocktail and fetal calf serum. After the desired incubation period, the cells are harvested and assayed for plaque-forming cells (PFC) to the stimulating antigen by one of the variations of the hemolytic plaque technique of Jerne et al. (1974). By employing appropriate modifications of this assay procedure (Pierce et al., 1971), IgM, IgG, and IgA PFC responses can readily be measured.

In addition to heterologous erythrocytes [usually sheep erythrocytes (SRBC)], hapten–protein conjugates, bacterial proteins, polysaccharides, lipopolysaccharides, serum proteins, viruses, and synthetic polypeptide antigens, such as the random terpolymer of l-glutamic acid⁶⁰-l-alanine³⁰-l-tyrosine¹⁰ (GAT), stimulate both primary and secondary antibody respon...

Table of contents

• Cover image
• Title page
• Table of Contents
• CONTRIBUTORS
• Copyright
• List of Contributors
• Preface
• Introduction
• Chapter 1: The Role of Macrophages in Antibody Responses in Vitro
• Chapter 2: The Role of Macrophages in the Specific Determination of Immunogenicity and Tolerogenicity
• Chapter 3: Role of Macrophages in T Cell–B Cell Collaboration in Antibody Production
• Chapter 4: Functional Heterogeneity of Macrophages
• Chapter 5: The Role of Macrophages in the Induction of Cell-Mediated Immunity in Vivo
• Chapter 6: Macrophage Function in Antigen Recognition by T Lymphocytes
• Chapter 7: The Role of Macrophages in the Activation of T and B Lymphocytes in Vitro
• 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
• Chapter 9: Nonspecific Immunoregulation by Macrophages and Their Products
• Chapter 10: Macrophage Membranes
• Chapter 11: Macrophage Cell Lines and Their Uses in Immunobiology
• Chapter 12: Monocyte Kinetics and Their Changes in Infection
• Chapter 13: Chemotaxis of Macrophages
• Chapter 14: Cellular and Molecular Aspects of Chemotaxis of Macrophages and Monocytes
• Chapter 15: Lymphocyte–Macrophage Interactions and Macrophage Activation in the Expression of Antimicrobial Immunity in Vivo
• Chapter 16: Macrophage Activation by Lymphocyte Mediators and Studies on the Interaction of Macrophage Inhibitory Factor (MIF) with Its Target Cell
• Chapter 17: Secretion of Macrophage Enzymes in Relation to the Pathogenesis of Chronic Inflammation
• Chapter 18: Induction of Macrophage-Mediated Cytotoxicity
• Chapter 19: Cytostatic and Cytocidal Effects of Activated Macrophages
• Chapter 20: Macrophages and the Destruction of Syngeneic Virus-Induced Tumors
• Chapter 21: Mechanisms of Extracellular Killing of Nucleated Mammalian Cells by Macrophages
• Chapter 22: Immunotherapeutic Approaches to Tumors Involving the Skin
• Chapter 23: Macrophages and Their Disorders in Man
• Chapter 24: Macrophages: Perspectives and Prospects
• Index