Main description:

The initial impetus to create a work combining aspects of cel- lular immunology with their clinical applications grew from the ed- itors' discussions of the area's needs with many of the leaders in the field over a period of time. From the nucleus of ideas that emerged, we have here attempted to create a unified and inte- grated coverage of the rapidly growing field of cellular immunology research and to trace out-from what seems at times a genuine plethora of important new findings-the many and often impor- tant clinical implications. Because of this approach, the chapters of Clinical Cellular Im- munology attempt to be more than critical reviews of research and clinical data, going beyond analysis to synthesize working hypotheses about the functional meaning of cellular immunological phenomena and their likely clinical significance. To accomplish this undertaking, the text begins first with a consid- eration of the molecular aspects of antigen recognition (Luderer and Harvey) and of the ensuing regulatory program initiation (Fathman).
Then, the functional subsets oflymphocytes as they in- teract to produce and control the developing immune response are explored in detail (Sigel et a1.), followed by a unique analytical dis- section of the action of immunosuppressive agents on the sundry inductive and regulatory immunologic pathways (Sigel et al.). A majority of the data and conclusions drawn by the authors in the previous chapters arise from work on murine systems, al- though wherever appropriate, human data has been introduced.

Contents:

1 The T Cell Antigen Receptor: Structural and Functional Considerations.- 1. Overview.- 2. Functional and Physical Analysis of T Cell Antigen-Specific Receptors.- 2.1. Functional Studies.- 2.2. Direct Physical Measurements.- 2.3 Conclusions.- 3. Serological and Biochemical Analysis of T Cell Antigen-Specific Receptors.- 3.1. Serological Approaches.- 3.2. Ability of Anti-Idiotypic Reagents to Induce Functional T Cell Populations.- 3.3. Additional Molecular Analysis of the T Cell Receptor Structure.- 3.4. T Cell Hybridomas as an Approach to Studying the T Cell Receptor Structure.- 3.5. Conclusions.- 4. Physiologic Constraints in the Recognition Function of the T Cell Antigen Receptor.- 4.1. General Antigen Processing Cell (APC) Requirements.- 4.2. APC Antigen Processing.- 4.3. APC-T Cell Interaction Structures.- 4.4. Conclusions.- 5. Cytotoxic T Cell Ligand-Binding Sites are Critically Affected by Recognition Structures on Other Cells.- 5.1. Introduction.- 5.2. Ligand-Histocompatibility-Antigen Display.- 5.3. Molecular Relationships and Models of Interaction Structures.- 5.4. Conclusions.- 6. Summary.- References.- 2 Regulation of the Immune Response.- 1. Introduction.- 2. Ir Genes in Guinea Pigs.- 2.1. The PLL Gene.- 2.2. PLL Gene Control of T Cell Responses.- 2.3. The Role of MHC Products in the PLL Response.- 3. The Ir-1 Gene.- 3.1. Introduction.- 3.2. (T,G)-A -L and Ir Gene Control.- 3.3. Ir-1 Control of T Cell Responses.- 3.4. Mechanisms of Ir-1 Gene Control.- 3.5. Characteristics of the Ir-1 Gene.- 4. Genetic Control of Immune Responsiveness to Staphylococcal Nuclease.- 4.1. Introduction.- 4.2. Staphylococcal Nuclease Molecule.- 4.3. Ir-Nase.- 4.4. T Cell Responses to Nuclease Controlled by Ir-Nase.- 4.5. Anti-Idiotype Antibodies and Ir-Nase.- 4.6. At Least Three Genes Control Immune Response to Nuclease.- 5. Ia Antigens.- 5.1. Introduction.- 5.2. Anti-Ia Antisera and Ir-Gene-Controlled Responses.- 6. Complementing Ir Genes.- 6.1. GL-Phenyl Ir Genes (? and ?).- 6.2. Anti-Ia Antisera and GL-Phenyl ? and ? Genes.- 6.3. Cells Involved in Ir-Gene-Controlled Response.- 7. Immunosuppressor Genes.- 7.1. GAT Is Genes.- 7.2. Complementing Is Genes.- 8. Genetic Control of Cellular Immune Responses.- 8.1. Mixed Lymphocyte Reactions.- 8.2. Cytotoxic T Cell Responses.- 9. Human Immune-Response Genes.- 9.1. Antigen-Specific Helper Factors in Humans.- 9.2. Cytotoxic T Cell Responses in Humans.- 10. An Hypothesis to Explain the Interrelationship Among Ir Genes, Ia Antigens, and MLR-Stimulating Determinants.- 11. Conclusions.- References.- 3 Immunosuppressive Agents: A Conceptual Overview of Their Action on Inductive and Regulatory Pathways.- 1. Introduction.- 2. Inductive and Regulatory Aspects of Immune Responses: Current Concepts.- 3. Classes and Subclasses of Lymphocytes and Their Functions.- 4. Antibody Responses to Thymus-Independent and Thymus-Dependent Antigens.- 4.1. T-Independent Responses.- 4.2. The Heterogeneity of B Cells.- 4.3. T-Dependent Responses.- 4.4. Modes of Help and the Heterogeneity of TH Cells.- 5. Inductive and Regulatory Functions: Antigens, Cells, Cognitive and Regulating Molecules, and Networks.- 5.1. Recapitulation and Projections.- 5.2. LAF and TCGF Promote T Cell Proliferation and Function.- 5.3. The Role of Antigens.- 5.4. Genes Regulating Immune Responses, Macrophages, and Antigen Presentation.- 5.5. Inductive and Regulatory Networks and Circuits.- 6. A Closer Look at Induction and Regulation of Cell-Mediated Immunity.- 6.1. General Considerations.- 6.2. CMI, Though Sovereign, Is Not Entirely Free of Antibody Influence. The Inverse Relationship of DTH and Antibody.- 6.3. DTH-Induction and Regulation As An Example of CMI/Antibody Interplay Under Control of Dose and Route of Antigen.- 6.4. Contact Sensitivity (CS) Provides New Clues to Immune Induction and Regulation.- Acknowledgments.- References.- 4 Immunosuppressive Agents-Their Action on Inductive and Regulatory Pathways: The Differential Effects of Agents Used Clinically or Experimentally in the Treatment of Cancer.- 1. Variables that Determine the Effect of Cancer Therapeutic Agents on Antibody Production.- 1.1. Suppression of Antibody Production in the Primary Response: Some Agents Preferentially Affect Stimulated (Proliferating) Cells, Others Are More Effective Against Resting Systems. TD and TI Responses are Affected Differently.- 1.2. Some Drugs Seem to Discriminate Among B Cell Subsets.- 1.3. Differential Effects on Memory Cell Precursors and Effectors.- 2. Diversity of Effects of Immunosuppressive Drugs on CMI.- 2.1. Dissociation of Antiproliferative, Anticytotoxic, and Anti-PFC Effects.- 2.2. Selective Action Against Macrophage Cytotoxicity.- 2.3. DTH Reactions Can Be Enhanced or Inhibited by Alkylating Agents.- 3. Alkylating Agents Exert Selective Action Against Cells in the Suppressor Pathway.- 4. A Closer Look at Agents That Are More Suppressive Before Immunization.- 4.1. General Considerations.- 4.2. The Multifaceted Effects of Ecteinascidia turbinata.- 4.3. C. parvum Potentiates and Suppresses Immune Responses.- 4.4. Other Natural Products.- 4.5. Radiation Paradox.- 4.6. Ultraviolet Radiation and Immunosuppression.- 5. The Many Faces and Interfaces of Cyclophosphamide Action.- 5.1. General Considerations of Cyclophosphamide Action.- 5.2. A Brief Review of Reports on the Variable Action of Cyclophosphamide on the Immune Response.- 5.3. The Effects of Cyclophosphamide on Cell Membranes.- Acknowledgments.- References.- 5 The Immunobiology of Human Non-Hodgkin's Lymphomas.- 1. Introduction.- 2. Classification Schema.- 3. Functional Studies.- 4. The Ontogeny of Lymphocytes.- 4.1. B Cells.- 4.2. T Cells.- 5. Overview of Immunoregulation.- 6. Lymphocyte Identification.- 6.1. B Cell.- 6.2. T Cell.- 6.3. Enzyme Studies.- 7. New Directions.- Acknowledgments.- References.- 6 Cell-Mediated Immunity in Autoimmune Disease.- 1. Introduction.- 2. Self-Recognition and Tolerance.- 3. Induction of Autoimmunity.- 4. Pathogenic Mechanisms in Autoimmune Disease.- 5. Cell-Mediated Immunity in Autoimmune Diseases of Animals.- 5.1. Experimental Allergic Encephalomyelitis.- 5.2. Experimental Allergic Orchitis.- 5.3. Spontaneous and Experimental Autoimmune Thyroiditis.- 6. Cell-Mediated Immunity in Autoimmune Disease of Humans.- 6.1. Connective Tissue Disorders.- 6.2. Endocrine-Associated Organ-Specific Diseases.- 6.3. Non-Endocrine Organ Diseases.- 7. Summary.- References.- 7 Cell-Mediated Immunity in Tumor Rejection.- 1. Immune Surveillance-A Theory Under Scrutiny.- 2. Tumor Antigens.- 3. Effector Mechanisms in Cell-Mediated Immunity.- 4. Effector Molecules.- 5. Depression of Immunity by Tumors: Suppressor Cells and Factors.- 5.1. Suppressor T Cells.- 5.2. Suppressor B Lymphocytes.- 5.3. Suppressor Macrophages.- 5.4. Tumor-Induced Suppression without Suppressor Cells.- 6. Immunotherapy.- 7. Conclusions.- References.- 8 Transfer Factor and Other Factors in Leukocyte Dialyzates That Affect Cell-Mediated Immunity.- 1. Introduction.- 2. The Transfer Phenomenon.- 3. Clinical Use of Leukocyte Dialyzates or Transfer-Factor Preparations.- 4. Biochemical Characterization.- 4.1. Dermal Transfer Activity.- 4.2. Other In Vivo Activities of Fractionated Dialyzed Leukocyte Extract.- 4.3. In Vitro Activities.- 5. Experimental Considerations.- 5.1. Donor.- 5.2. Recipient.- 5.3. Preparation of Leukocyte Material.- 6. Implications for Immunotherapy.- References.- 9 Hybridization of Lymphocytes: Techniques and Applications.- 1. Introduction.- 2. B Cell Hybrids.- 2.1. Cell Lines.- 2.2. General Hybridization Protocol.- 2.3. Optimizing Fusion Parameters.- 2.4. Screening.- 2.5. Selection and Maintenance of Positive Clones.- 2.6. Loss of Antibody Production.- 3. T Cell Hybrids.- 4. Applications and Future Perspectives.- Notes Added in Proof.- Acknowledgment.- References.- 10 Immunologic Tests for Diagnosis and Monitoring of Defects in Cell-Mediated Immunity.- 1. Introduction.- 2. Anatomy of the Immune System.- 3. In Vivo Manifestations of Cell-Mediated Immunity.- 3.1. Granuloma Formation.- 3.2. Delayed-Type Hypersensitivity.- 3.3. Cutaneous Basophil Hypersensitivity.- 3.4. General Conclusions.- 4. In Vitro Tests of Cell-Mediated Immunity.- 4.1. Membrane Receptors on T Cells.- 4.2. Antigenic Surface Markers on T Cells.- 4.3. Functional Assays.- 5. Clinical Immunodeficiencies.- 5.1. Prethymic Failure of T Cell Differentiation.- 5.2. Failure of Intrathymic Maturation or of Thymic Development.- 5.3. Defects of Regulation.- 6. Conclusion.- Acknowledgments.- References.