A history of modern immunology: the path toward understanding

Introductory Words About Science, Scientists, and Immunology

Part I. Pre-history with Far-reaching Consequences

1. The Immunological Revolution

1.1. The Clonal Selection Theory

1.2. The Birth of B and T Lymphocytes

1.3. T-B Cell Collaboration

1.4. The Structure of Immunoglobulins

1.5. Allergy: From Disease Symptoms to IgE

References

Part II. The History

2. A Very Special Location: The Basel Institute for Immunology

Reference

3. Immunological Specificity

References

4. Monoclonal Antibodies: The Final Proof for Clonal Selection

4.1. Discovery

4.2. Immunology Goes Business

4.3. The Technology Avalanche: Antibody Engineering

References

5. The First Victory of Molecular Biology: Mechanisms of the Generation of Antibody Diversity

5.1. Theoretical Treatment of the Problem

5.2. The Experimental Solution

5.3. What did we Learn from the Mechanisms of GOD?

5.4. A Baroque Embellishment of Antibody Diversity: The ldiotype Network

References

6. The Major Histocompatibility Complex

6.1. MHC Class I

6.1.1. Discovery

6.1.2. Class I MHC Molecules

6.1.3. Class I MHC-Associated Traits and Their Relationship

6.1.4. Participants of MHC Research in the Classic Era

6.2. MHC Class II

6.2.1. Immune Response Genes

6.2.2. Stimulation in the Mixed Lymphocyte Reaction

6.2.3. MHC Class II (la) Antigens

6.2.4. Biochemical Characterization of Class II MHC Molecules

6.2.5. What are Immune Response Genes in Reality?

6.2.6. Mechanisms of MHC-Controlled Unresponsiveness

6.3. Sorting Out the Genetics of MHC

6.3.1. The Era of Formal Genetics

6.3.2. A Simplified Interpretation of MHC Based on Biochemical and Functional Studies

6.3.3. Molecular Biology has the Last Word: The Organization of MHC at the DNA Level

References

7. Antigen Processing and Presentation

7.1. The Rules of Peptide Binding to MHC Molecules

7.1.1. T Cell Epitopes

7.1.2. Peptide-Binding Motifs for Class I MHC Molecules

7.1.3. Peptide-Binding Motifs for Class II MHC Molecules

7.2. The Most Revealing Crystallographic Study in the History of Immunology: The Three-Dimensional Structure of MHC Molecules

7.2.1. The Peptide-Binding Site of Class I Molecules

7.2.2. The Peptide-Binding Site of Class II Molecules

7.3. Antigen Processing and Loading Pathways

7.3.1. Initial Evidence for Antigen Processing

7.3.2. The Class I Pathway

7.3.3. The Class II Pathway

7.4. The Case for a Specialized Antigen-Presenting Cell

7.5. Antigen Processing and Presentation: Phenomena that Beg for a Concept

References

8. The Intricate Behavior of T Cells

8.1. Major Histocompatibility Complex Restriction of T-Cell Recognition

8.1.1. Discovery

8.1.2. MHC Restriction of Cytotoxic T-cell Responses

8.1.3. MHC Restriction of Helper T-Cell Responses

8.1.4. Theoretical Implications of MHC Restriction: One Receptor or Two Receptors?

8.1.5. Immunology and its Theoreticians

8.2. Chase for the Antigen Receptor of T Cells

8.2.1. Early Attempts at Identifying TCR: 'lg or not lg, this is the Question'

8.2.2. Serological Approaches to the Isolation of TCR

8.2.3. The Winner is Again Molecular Biology: The TCR Gene Complex

8.2.4. How T Cells Recognize Antigen: Crystallography of TCR-peptide-MHC Complexes

8.3. T-Cell Recognition: From Facts Toward Understanding

8.3.1. T-Cell Function in a Nutshell

8.3.2. Specificity Requirements for Docking of TCR on MHC

8.3.3. The Biology of Docking

8.3.4. Peptide Recognition by TCR

8.4. Thymus and the T-Cell Repertoire

8.4.1. Early Events of Thymocyte Development

8.4.2. The Germline Repertoire

8.4.3. Selection of the T-Cell Repertoire in the Thymus

8.4.4. The Mature T-Cell Repertoire

8.5. Alloreactivity: The Continuing Puzzle

8.5.1. Relationship Between Alloreactive and Self-MHC Restricted T Cells

8.5.2. Further Peculiarities of Alloresponses

8.5.3. Alloreactivity: A Pot-Pourri of Different Responses

8.6. Functional Subclasses of T Cells

8.6.1. Ly1 and Ly2,3: Markers to Distinguish Between Helper and Cytotoxic T Cells

8.6.2. How T-Cell Surface Markers Became Coreceptors

8.6.3. Th1 and Th2: Functionally Distinct Subsets of T Helper Cells

8.6.4. The Rise and Fall of Suppressor T Cells

8.6.5. Rebirth of the Phoenix: From Ts to Treg

8.7. Cell Adhesion, Costimulation, Co-Inhibition

8.7.1. Cell Adhesion Receptors of the Immune System

8.7.2. Costimulation, Co-Inhibition

References

9. Acquired Immunological Tolerance

9.1. Discovery

9.2. The Era of Theories

9.2.1. The Concept of Self-Non-Self Discrimination

9.2.2. What is Immunological Self?

9.2.3. Early Theories of Self-Non-Self Discrimination

9.2.4. The Two-Signal or Associative-Recognition-of-Antigen Model

9.2.5. Alternative Models

9.2.6. An Aside on the Regulation of Effector Response

9.2.7. The Bottom Line

9.3. The Era of Mechanistic Studies

9.3.1. Clonal Deletion of T Cells

9.3.2. Clonal Deletion of B Cells

9.3.3. Clonal Anergy

9.3.4. An Unexpected Turn: Display of Peripheral Self in the Thymus

9.4. Can Self Tolerance Be Understood?

9.4.1. Importance of the Perinatal Window

9.4.2. What Happens After the Perinatal Window Closed?

9.4.3. Adult Tolerance in the B-Cell Compartment

9.4.4. Adult Tolerance in the T-Cell Compartment

9.4.5. Final Plea

References

10. Autoimmunity

10.1. Genetic Factors Predisposing to Autoimmune Disease

10.1.1. Genetic Association with the Major Histocompatibility Complex

10.1.2. Selective Antigen Presentation: A Possible Mechanism for MHC-Disease Association

10.1.3. Other Possible Mechanisms for MHC-Disease Association

10.1.4. Non-MHC Genes Predisposing to Autoimmunity

10.2. How is Autoimmunity Initiated?

10.2.1. Escape from Central Tolerance

10.2.2. Escape from or Breaking of Peripheral Tolerance

10.2.3. Availability of Autoantigen

10.2.4. Environmental Triggers

10.3. Some Aspects of Pathogenesis

10.4. Approaches to Immunotherapy

10.4.1. Targeting Antigen Presentation by MHC Molecules

10.4.2. Targeting the Antigenic Ligand

10.4.3. Targeting the T-Cell Antigen Receptor

10.4.4. Targeting Co-Receptors, Co-Stimulation, and Cell Adhesion Molecules

10.4.5. Targeting the Effector Response

10.4.6. The Take-Home Lesson

10.5. What Is Needed for Better Understanding of Autoimmunity?

References

Concluding Remarks

Index