Main description:

Immunopharmacology: A New Discipline of Immense Potential Among the looming triumphs of the biologic revolution is the rapidly developing understanding of the mechanisms of bodily defense. In the short span of 35 years, knowledge of immunologic machinery has progressed from crudest description to major understanding in cellular and molecular terms. Antibodies, immunoglobulins, and the complement system have been almost completely defined in detailed molecular terms. Organs, like thymus, spleen and lymph nodes-so long enigmatic black boxes-are beginning to be understood not only in cellular terms but in molecular, physiologic, and endocrinologic terms. With this surging new information about the immune system comes the possi bility of developing a pharmacology which can modulate and control immunologic functions. Immunopharmacology most broadly conceived must address (1) control of development and function of the cellular components of the immunologic appara tus; (2) facilitation and suppression of function of the immunologically competent cells of the several subclasses, like T helpers, suppressors, and effectors, and B effectors and suppressors; (3) manipulation and repair of the major biologic amplifi cation systems, e. g. , the complement system and kinin-kallikrein system, and (4) utilization, modulation, and inhibition of the galaxy of molecules generated by T lymphocytes, the lymphokines. This new pharmacology must deal with the funda mental effector mechanisms of immunity, namely inflammation, phagocytosis, vascular reactivity, and blood coagulation. Furthermore, immunopharmacology must address and manipulate cell-cell communication and interaction, so vital to control of the immunological apparatus.

Contents:

1 Cyclic Nucleotides in Lymphocyte Proliferation and Differentiation.- 1. Introduction.- 2. Cyclic Nucleotide Biochemistry.- 3. Hormonal and Pharmacological Modulation of Lymphocyte Proliferation.- 4. Cyclic Nucleotides in the Early Events of Mitogenic Action.- 5. Calcium in the Early Events of Mitogenic Action.- 6. Other Components of Mitogenic Action.- 7. Lymphocyte Nuclear Activation and Cyclic Nucleotides.- 8. Cyclic GMP and Calcium as the Intracellular Mitogen Signal.- 9. Hormone Induction of Thymocyte Differentiation.- 10. Cyclic Nucleotides in Thymocyte Differentiation.- References.- 2 Involvement of Cyclic Nucleotides as Intracellular Mediators in the Induction of Antibody Synthesis.- 1. Introduction.- 2. Induction and Paralysis.- 3. Effect of Cyclic Nucleotides on the Induction of Antibody Synthesis.- 4. Mitogen-Induced B-Lymphocyte Proliferation: Immunologic Effects.- 5. Cyclic Nucleotides and B-Lymphocyte Proliferation and Differentiation.- References.- 3 Regulation of Alloimmunity by Cyclic Nucleotides.- 1. Introduction.- 2. Cyclic Nucleotides.- 3. Pharmacological Abrogation of Target-Cell Lysis Mediated by Cytotoxic T Lymphocytes.- 4. Pharmacological Augmentation of Target-Cell Lysis Mediated by Cytotoxic T Lymphocytes.- 5. Pharmacological Abrogation of K-Cell-Mediated Lysis of Antibody-Coated Target Cells (Antibody-Dependent Lymphocyte-Mediated Cytotoxicity.- 6. Pharmacological Augmentation of K-Cell-Mediated Lysis by Cyclic GMP.- 7. Modulation of Graft-vs.-Host Proliferation by Cyclic Nucleotides.- 8. Modulation of Mixed Lymphocyte Culture Proliferation by Cyclic Nucleotides.- 9. Discussion.- References.- 4 Regulation of Polymorphonuclear Leukocyte, Macrophage, and Platelet Function.- 1. Introduction.- 2. Polymorphonuclear Leukocytes (Neutrophils).- 3. Mononuclear Phagocytes (Macrophages).- 4. Platelets.- 5. Summary and Conclusions.- References.- 5 Molecular Aspects of Macrophage Activation and Proliferation.- 1. Introduction.- 2. Macrophage Activation in Vivo.- 3. Macrophage Activation in Vitro.- 4. Mechanism of Action of Macrophage Mitogenic Factor.- 5. Lysosomal Enzyme Induction in the Mediation of Macrophage Activation.- 6. Other Mechanisms of Macrophage Activation.- 7. Summary.- References.- 6 Pharmacological Control of Mediator Release from Leukocytes.- 1. Introduction.- 2. General Properties of Histamine Release.- 3. Mechanism of Action of Antigen.- 4. The Phenomenon of Desensitization.- 5. Release of Mediators Other Than Histamine.- 6. Summary.- References.- 7 Generation, Function, and Disposition of Chemical Mediators of the Mast Cell in Immediate Hypersensitivity.- 1. Introduction.- 2. Generation and Release of Chemical Mediators.- 3. Characteristics of the Chemical Mediators.- 4. Modulation of Mediators of Immediate Hypersensitivity.- 5. Summary.- References.- 8 Plasma Factors: The Hageman-Factor-Dependent Pathways and the Complement Sequence.- 1. Introduction.- 2. Hageman-Factor-Dependent Pathways.- 3. Complement.- 4. Interactions with Other Mediator Systems.- 5. Pharmacological Modulation.- References.- 9 Prostaglandins in the Regulation of Immune and Inflammatory Responses.- 1. Introduction.- 2. Biological Function of the Prostaglandins.- 3. Inflammatory and Immunologic Diseases.- 4. Summary and Speculation.- References.- 10 Lymphokines: Physiologic Control and Pharmacological Modulation of Their Production and Action.- 1. Introduction: What Are Lymphokines?.- 2. Macrophage Migration-Inhibitory Factor (MIF).- 3. Macrophage Activation.- 4. Evidence for a Role of MIF in Vivo.- 5. Physiologic Control of MIF.- 6. Pharmacological Modulation of MIF.- 7. Physiologic Control and Pharmacological Modulation of Other Lymphokines.- 8. In Vivo Realities-Role of Lymphokines in Immunity and Nonimmunologic Processes.- References.- 11 Mechanism of Action of Antiallergic Drugs and Relationship of Cyclic Nucleotides to Allergy.- 1. Introduction.- 2. Cyclic Nucleotide Metabolism and Actions.- 3. Pathophysiology of Asthma.- 4. Drugs Used in Treatment of Asthma.- 5. Summary and Speculation.- References.- 12 Modulation of the Expression of the Immune Response by Antiinflammatory Drugs.- 1. Introduction.- 2. Effect of Antiinflammatory Agents on Lymphocytes and the Immune Response.- 3. Neutrophils.- 4. Macrophages.- 5. Conclusions.- References.- 13 Immunosuppressive Agents.- 1. Introduction and General Remarks.- 2. Steroids.- 3. Azathioprine and 6-Mercaptopurine.- 4. Cyclophosphamide.- 5. Other Chemical Immunodepressants and the Problem of Selective Immunosuppression.- 6. Nonspecific Biological Immunodepressants.- 7. Perspective for Immunologic Control.- References.- 14 Mechanisms of Immunopotentiation.- 1. Introduction.- 2. Biological Substances.- 3. Chemical Immunopotentiators.- 4. Products of the Immune System.- 5. Conclusions.- References.- 15 Immunoassay of Drugs and the Biological Use of Antidrug Antibodies.- 1. Introduction.- 2. Production of Antidrug Antibodies.- 3. Characterization of Antidrug Antibodies.- 4. Use of Antibodies in Immunoassays.- 5. Biological Properties of Antibodies to Drugs and to Other Compounds of Pharmacological Importance.- References.- 16 Receptors for Low-Molecular-Weight Hormones on Lymphocytes.- 1. Introduction.- 2. Determination of the 'Physiologic' Importance of Leukocyte Receptors.- 3. Somatic Genetic Analysis of Cyclic AMP Action as a Means of Assessing Receptor Function.- 4. Separation of Cells on the Basis of a Physiologic Function.- 5. Conclusions.- References.- 17 Polypeptide Hormone Receptors on Lymphoid Cells: Application to the Study of Receptor Alterations and Radioreceptor Assay of Polypeptide Hormones.- 1. Introduction.- 2. Existence of Insulin Receptors on Circulating Cells.- 3. Characteristics of the Insulin Receptor on Lymphoid Cells.- 4. Effects of Insulin on Lymphoid Cells.- 5. Existence of Human Growth Hormone (hGH) Receptors on Lymphoid Cells.- 6. Existence of Calcitonin Receptors on Human Lymphoid Cells.- 7. Radioreceptor Assay of Polypeptide Hormones Using Lymphoid Cell Receptors.- 8. Further Applications of Polypeptide Hormone Receptors on Lymphoid Cells.- 9. Conclusions.- References.- 18 Assays for Cyclic Nucleotides Including Clinical Applications.- 1. Introduction.- 2. Extraction, Purification, and Measurement of Cyclic Nucleotides.- 3. Clinical Applications.- References.