Strategies of Immune Regulation

Contributors

Preface

Section I General Regulatory Features of the Immune System

Cybernetics and the Immune System

The Biological Significance of Cellular Regulation

Self-Tolerance, or Why the Immune System is so Highly Regulated

Immunoregulation: a Futuristic Review

Immunoregulation by T Lymphocytes

Cell-Cell Interactions in the Establishment and Maintenance of Lymphoid Tissue Architecture

The Role of the Major Histocompatibility Complex

The Significance of Genetic Control of Specific T Cell Immunity by the Major Histocompatibility Complex

Virus-Host Interactions: a Ideological Look at MHC Restriction

MHC Molecules as Guides for T Lymphocyte Parallel Sets

Role of MHC Gene Products in the Regulation of Cellular Interactions

Immune Responsiveness and Polymorphism of the Major Histocompatibility Complex: an Interpretation

Regulation Involving the Antibody Molecule

Regulation of Antibody Responses

Idiotypic Control: the Expression of Idiotypes and Its Regulation

The X-Y-Z Scheme of Immunocyte Maturation. I. Perturbations in the Ground State Induced by Antigen

Regulation by Antibody Feedback and Other Nonactive Site Control

Section II Organization of Ig Genes

Introduction I

Do Minigenes Code for All Framework Segments of Immunoglobulin Chains

One from Many: Immunoglobulin V Regions are the Products of Interactive Genes

Generation of Antibody Diversity: a Proposal from Current Data

V/C Rearrangement and the Molecular Basis of Allelic Exclusion

A View of the Current Status of Possible Somatic Variation of Immunoglobulin Genes

Origin of Antibody Diversity and the Number of V Genes

Antibody Diversity and the Development of the Immune Repertoire

Introduction 2

The Need for Rapid, Random Somatic Variation in God

Lymphocyte Differentiation: a Model of "Permissiveness" for V-C Gene Transposition and the Continuous Generation of New Ig Specificities

The Role of Germ Line Genes and Limited Somatic Mutation in the Development of the Immune Repertoire

Where Does Ig Diversity Arise?

At What B Cell Developmental Stage Does Clonal Commitment Occur

The Neonatal Antibody Specificity Repertoire and Its Diversification

Unanswered Questions about the B and T Cell Repertoires

Is a Unique T Cell Repertoire Generated in the Thymus?

MHC Restriction: Cytotoxic and Helper Cells

Introduction 3

Cytotoxic T Cells

What about MHC Restricted T Cells?

MHC and Other "Restrictions" May Be a Simple Result of Antigen Priming Experience

Are There Decisive Experiments Distinguishing Altered Self and Dual Recognition?

T Cell Recognition of Antigen in the Context of H-2 Allogeneic Determinants or Antigen H-2 Allospecific Recognition

Clonal Dominance as a Mechanism to Account for the Fact That Restrictions Appear to Be Imposed on Cytotoxic T Lymphocytes by the Thymus

T Cell Recognition: a Difficulty with the Two-Receptor Model

MHC Restriction: Mechanisms Involved in Ir Gene Action

Introduction 4

Ir Genes and I Region Restriction

Macrophage Interactions with T Cell Subsets in Antibody Responses

Hypothesis on MHC Control

Ia Antigen Structure and Its Relevance to I Region Functions

The MHC Influence on T Cell Receptor Expression

Regulation of B Cell Activation by Allogeneic Effect Factor (AEF)

MHC Restriction: the Macrophage-Mediated Perception of Antigen

Introduction 5

Early Events after Contact with Foreign Antigens

How Do Thymic H-2 Determinants Control T Cell Development and What is the Significance of Alloreactivity

Highly Selective Antigen Processing under the Influence of MHC Molecules Can Control Responsiveness to Protein Antigens

The Role of Soluble Mediators in T Helper Cell Induction

Lymphocyte Interactions and Regulatory Targets

Introduction 6

Integration of Signals in the Immune Response

A Minimal Model of T Cell-Mediated Regulation of the Antibody Response

The Concept of "Protected" Help in Ir Gene Control

Suppression of T Cell at Different Developmental Stages

Antigen-Specific Soluble Suppressor Factor(s)

Requirement for Macrophages in Suppressive Induction by T Suppressor Factors

Cell Interactions Early in Immune Induction

Direct Action of Suppressor Cells on a B Cell Hybridoma

Lymphocyte Interactions: Cell Contact and Soluble Mediators

Introduction 7

The Balance between Helper and Suppressor Factors

Soluble Effectors, Mediators, and Factors and Their Mechanisms of Action

Cell Contact is Necessary for Cooperation between T and B Memory Cells

Fc Receptors and Fc-Mediated Regulation

Specific and Nonspecific Small Molecular Weight Suppressive Factors

On the Nature of Antigen-Specific T Cell Factors

On the Relationship between T Cell Membrane Receptors for Antigen and Antigen-Specific T Cell Factors

Role of the Ig Receptor in Triggering

Introduction 8

On the "Intelligence" of Antigen-Specific Receptors from a Network Point of View

Are Idiotypic Interactions Symmetrical?

Triggering and Tolerance

B Cell-Antigen Interactions

The Secret Life of the Antigen-Binding Cell

Function of Igd

Introduction 9

Turning Cells on and off: Triggering and Tolerance

B Cell Triggering and Tolerance: Role of Surface Receptors

Heavy Chain Class Switching and a Role for Immunoglobulin D

An Alternative Role for Igd

A Role for Igd: Dissociation of Memory Induction from Affinity Maturation

Lymphocyte Maturation

Introduction 10

Receptor and Marker Expression during Differentiation and Maturation

Surface Immunoglobulins (Ig) and Physiological Characteristics of Virgin Memory B Cells

Differential Light Chain Expression

Clonal and Nonclonal Selection and Expansion of B Cells

Single Cells Responding to Two Unrelated Antigens

Class Switching in B Cells

Comments on Thymocyte and T Cell Differentiation Correlated with Function

On the Relationship between Lyt Phenotypes, MHC Subregions, and T Cell Function

Idiotype Regulation

Introduction 11

Idiotypic Networks, Restrictive Recognition, and Regulation in the Immune System

The Nature of Receptor Antibodies on T Lymphocytes

The Antigen Bridge and Idiotypic Interactions as Parallel Communication Systems

Analogous Dual Specificity of Helper T Cells Cooperating in the Generation of Clonally Restricted Antibody Responses

Clonal Dominance—a Product of Idiotype-Specific Interaction

Reliable Vaccines Using Hybridoma Products with Defined Idiotypes

Control of Antiself Reactions

Introduction 12

Control of Autoimmunity

Autoimmunity

Specificity of T Suppressors of Autoimmunity

How a Specific Antiself Deletion Mechanism Can Affect the Generation of the Specificity Repertoire

Self-Tolerance: an Alternative View

Varying Sensitivity to Tolerance Induction throughout Maturation

Central versus Peripheral Mechanisms in the Control of Antiself Reactions

The Broad Spectrum of Autoantigens and the Function of Self-Reactive T and B Cells

Autoimmunity as a Reflection of Immune Deficiency of T Cell Subpopulations

Index