A Historical Perspective on Evidence-Based Immunology focuses on the results of hypothesis-driven, controlled scientific experiments that have led to the current understanding of immunological principles. The text helps beginning students in biomedical disciplines understand the basis of immunologic knowledge, while also helping more advanced students gain further insights.

The book serves as a crucial reference for researchers studying the evolution of ideas and scientific methods, including fundamental insights on immunologic tolerance, interactions of lymphocytes with antigen TCR and BCR, the generation of diversity and mechanism of tolerance of T cells and B cells, the first cytokines, the concept of autoimmunity, the identification of NK cells as a unique cell type, the structure of antibody molecules and identification of Fab and Fc regions, and dendritic cells.
•Provides a complete review of the hypothesis-driven, controlled scientific experiments that have led to our current understanding of immunological principles
•Explains the types of experiments that were performed and how the interpretation of the experiments altered the understanding of immunology
•Presents concepts such as the division of lymphocytes into functionally different populations in their historical context
•Includes fundamental insights on immunologic tolerance, interactions of lymphocytes with antigen TCR and BCR, and the generation of diversity and mechanism of tolerance of T and B cells

Cover image
Title page
Table of Contents
Dedication
Copyright
Foreword
Glossary of Historical Terms
Chapter 1. Innate Host Defense Mechanisms and Adaptive Immune Responses Introduction
Innate Defense Mechanisms
Adaptive Immune Responses
Conclusion

Chapter 2. Hallmarks of the Adaptive Immune Responses Introduction
Immunologic Specificity
Self–Non-Self-Discrimination
Immunologic Memory
Conclusion

Chapter 3. Two Effector Mechanisms of the Adaptive Immune Response Introduction
Antibody
Cell-Mediated Immunity
Conclusion

Chapter 4. The Small Lymphocyte Is the Antigen Reactive Cell Introduction
The Small Lymphocyte
Passive Transfer Experiments
Migratory Pathways of Small Lymphocytes
Depletion Experiments
Immunocompetence of Thoracic Duct Lymphocytes
Morphological Changes of Activated Small Lymphocytes
Conclusion

Chapter 5. Lymphocytes Transform into Plasma Cells and Produce Antibodies Introduction
Cells and Antibodies
Antigens and Antibodies in Lymphoid Organs
Lymphocyte–Plasma Cell Debate
Passive Transfer Studies
Visualization of Antibody-Forming Cells
Transformation of Small Lymphocytes into Plasma Cells
Conclusion

Chapter 6. The Clonal Selection Theory of Antibody Formation Introduction
Early Models of Antibody Formation
Challenges to Instruction Models
Paradigm Shift: From Instruction to Selection
The Clonal Selection Theory
Conclusion

Chapter 7. Plasma Cells Produce Antibody of a Single Specificity Introduction
Single Cell Experiments: Development of the Microdrop Technique
Immunofluorescent Studies
Antigen Receptors on B Lymphocytes
Multiple Myeloma and the One Cell: One Antibody Concept
Development of Monoclonal Antibodies
Conclusion

Chapter 8. Self–Non-self Discrimination: How the Immune System Avoids Self-Destruction Introduction
Horror Autotoxicus
Production of Autoantibodies
An Experiment of Nature
Acquisition of Self–Non-self Discrimination
Conclusion

Chapter 9. The Thymus in Lymphocyte Maturation Introduction
Early History of the Thymus
Serendipity and Neonatal Thymectomy
Naturally Occurring Examples of Euthymic States
Conclusion

Chapter 10. The Bursa of Fabricius in Lymphocyte Maturation Introduction
Early History of the Bursa of Fabricius
Serendipity and Bursectomy
Rediscovery of the Role of the Bursa of Fabricius
Search for the Bursa Equivalent in Mammals
Division of Lymphocytes into Two Functionally Distinct Populations
Markers to Differentiate T and B Lymphocytes
Conclusion

Chapter 11. Revealing the Structure of the Immunoglobulin Molecule Introduction
The Unitarian Hypothesis of Antibodies
The Composition and Structure of Antibodies
Development of the Four Chain Model of Antibody
Location of the Antigen Binding Site
Immunoglobulin Isotypes (Classes)
Conclusion

Chapter 12. Complement Introduction
Early Evidence for Complement
The Classical Pathway
The Alternate (Properdin) Pathway
The Lectin Pathway
Biological Activity of Complement and Its Fragments
Conclusion

Chapter 13. Antibody Production Requires Thymus-Derived and Bone Marrow (Bursa)-Derived Lymphocyte Interactions Introduction
The Hemolytic Plaque Assay
T-B Lymphocyte Collaboration in Antibody Formation
T-Independent Antigens
Conclusion

Chapter 14. Cell Collaboration in the Antibody Response: Role of Adherent Cells Introduction
Morphological Changes
Information Exchange
Collaboration Between Adherent and Nonadherent Cells
Genetic Control of Macrophage–Lymphocyte Interactions
Conclusion

Chapter 15. Recognition Structures on Cells of the Innate Host Defense Mechanisms Introduction
Early Investigations on Recognition by Phagocytic Cells
Discovery of Pattern Recognition Receptors
Conclusion

Chapter 16. The Adaptive Immune Response and Histocompatibility Genes Introduction
Discovery of Histocompatibility Antigens and Genes
Regulation of the Adaptive Immune Response by MHC Genes
Correlation of MHC Gene Expression with Pathology
Molecular Structure of MHC-Coded Proteins
Conclusion

Chapter 17. Interaction of Lymphocytes with Antigen: Identification of Antigen-Specific Receptors Introduction
Discovery of the B Cell Receptor
Discovery of the T Cell Receptor
Conclusion

Chapter 18. Generation of Diversity in the Adaptive Immune Response Introduction
Generation of Diversity in B Lymphocytes
Generation of Diversity in T Lymphocytes
Conclusion

Chapter 19. B Lymphocyte Activation Introduction
Two-Signal Model of B Lymphocyte Activation
Signal 1: The B Cell Receptor
Signal 2: Soluble Factors and Cell-to-Cell Interactions
Isotype Switching
Conclusion

Chapter 20. Activation of T Lymphocytes and MHC Restriction Introduction
Experimental Approaches to Measure T Lymphocyte Activation
The Two-Signal Hypothesis of T Lymphocyte Activation
Signal 1: TCR Recognition
MHC Restriction
Role of CD3 Molecules in T Lymphocyte Activation
Signal 2: Role of Costimulatory Molecules
Conclusion

Chapter 21. Development of Tolerance to Self in B Lymphocytes Introduction
Development of Central Tolerance to Self
Peripheral B Lymphocyte Unresponsiveness
Conclusion

Chapter 22. Development of Tolerance to Self in T Lymphocytes Introduction
Differentiation of T Lymphocytes in the Thymus
Positive Selection of T Lymphocytes
Negative Selection of T Lymphocytes
Conclusion

Chapter 23. T Lymphocyte Subpopulations Introduction
Antibody Studies to Identify T Lymphocyte Subsets
Cytokines Secreted by T Lymphocyte Subpopulations
Conclusion

Chapter 24. T Lymphocyte Control of the Immune Response: From TS to TREG Introduction
Suppressor T Lymphocytes
Rise of T Regulatory Lymphocytes
Conclusion

Chapter 25. Intercellular Communication in the Immune System Introduction
Early Studies of Soluble Factors in the Immune Response
Identification of Other Select Cytokines
Chemokines
Nomenclature
Conclusion

Chapter 26. Antibody-Mediated Effector Mechanisms Introduction
Neutralization
Activation of Complement
Opsonization
Antibody-Dependent Cell-Mediated Cytotoxicity
Release of Vasoactive Mediators
Conclusion

Chapter 27. T-Lymphocyte-Mediated Effector Mechanisms Introduction
Cell-Mediated Immune Responses
Conclusion

Chapter 28. Lymphocytes that Kill: Natural Killer (NK) and Natural Killer T (NKT) Lymphocytes Introduction
Discovery of NK Lymphocytes
NK Lymphocytes
Self–Non-self Recognition by NK Lymphocytes
NKT Lymphocytes
Conclusion

Chapter 29. Role of Dendritic Cells in the Adaptive Immune Response Introduction
Dendritic Cells in the Adaptive Immune System
Characterization of Dendritic Cells
Functional Characterization of Dendritic Cells
Relationship Between Langerhans Cells and Dendritic Cells
Dendritic Cell Vaccines
Conclusion

Chapter 30. The Mucosal Immune System and Secretory IgA Introduction
Identification of Mucosal-Associated Lymphoid Tissue (MALT)
Evidence for a Separate Mucosal Immune System
Discovery of Secretory IgA
Migratory Path of Lymphocytes in the Mucosal Immune System
Discovery of Microfold (M) Cells and Their Function
Conclusion

Chapter 31. Disorders of the Innate Host Defenses Introduction
Deficiencies of the Cells of Innate Host Defense Mechanisms
Deficiencies of the Complement System
Autoinflammatory Diseases
Conclusion

Chapter 32. Defects in the Adaptive Immune Response Leading to Recurrent Infections Introduction
Primary (Congenital) Immunodeficiencies
Acquired Immunodeficiency Syndrome (AIDS)
Conclusion

Chapter 33. Pathologies Resulting from Aberrant Immune Responses Introduction
Type I Hypersensitivities
Type II Hypersensitivity
Type III Hypersensitivity
Type IV Hypersensitivity
Immune-Mediated Pathologies Secondary to Infections
Conclusion

Chapter 34. Immune Responses Directed Against Self Introduction
Early Studies on Autoimmune Reactivity and Disease
Autoimmune Diseases—New Pathologic Mechanisms for Old Diseases
Conclusion

Chapter 35. Lymphoproliferative Diseases Introduction
Lymphoma
Leukemia
Monoclonal Gammopathy (Paraproteinemia)
Conclusion

Chapter 36. Transplantation Immunology Introduction
Clinical Experience with Transplantation
Immunology of Transplant Rejection
Antigenic Stimulus for Graft Rejection
Mechanism of Graft Rejection
Control of Graft Rejection
Conclusion

Chapter 37. Tumor Immunology Introduction
Tumor Antigens
Adaptive Immune Responses to Tumors
Immunotherapeutic Approaches
Conclusion

Chapter 38. Therapies That Manipulate Host Defense Mechanisms Introduction
Active Immunization
Passive Transfer of Immunity
Immunosuppression
Reconstitution of Immunodeficiencies
T Regulatory (TREG) Lymphocytes as Therapeutic Agents
Conclusion

Chapter 39. Techniques to Detect and Quantify Host Defenses Introduction
The Cells of Host Defense Mechanisms
Functional Studies of Lymphocytes
Skin Tests
Measurement of Antibodies
Quantitative Techniques Using Immunologic Principles
Conclusion

Chapter 40. The Future of Immunology Introduction
Basic Science
Clinical Applications
Conclusion

Index