Progress in Immunology

List of Contributors

Preface

I The Structure and Genetics of Antibodies

Immunoglobulin Structure: Diversity, Gene Duplication, and Domains

Ammo Acid Sequence of the y Chain of He

Evolution by Gene Duplication

The Domain Hypothesis

The Nature of Immunoglobulin Diversity

Translocation and the Origin of Diversity

References

Three-Dimensional Structure of Immunoglobulins

Experimental

Results

References

Expansion and Contraction in the Evolution of Immunoglobulin Gene Pools

IgG Subclasses

Basic Sequences and Variable Genes

Nonrandom Mutation and Selection

References

Structural Localization, Allelic Exclusion, and Linkage Relationships of Rabbit Allotypes

Introduction

Regions of Rabbit Immunoglobulins and Location of Genetic Markers

Allelic Exclusion

Linkage Relationships

References

Genetic Control of the Biosynthesis of IgG and IgM

I. Introduction

II. Individual Antigenic Specificities in Til IgG and IgM

III. Amino Acid Sequences

IV. Cellular Localization of Til IgG and IgM

V. Discussion

References

II Lymphocyte Membranes

Receptors for C3 on B Lymphocytes : Possible Role in the Immune Response

I. What Are Complement-Receptor Lymphocytes (CRL)?

II. What Distinguishes CRL from Mononuclear Phagocytes?

III. Are CRL B or T Lymphocytes?

IV. Do All B Lymphocytes Have a Complement Receptor?

V. Which Is the Complement Component Involved?

VI. What May Be the Function of the C3 Receptor on Lymphocytes?

References

Subpopulations of Thymus Cells and Thymus-Derived Lymphocytes

I. Introduction

II. Thymus Cell Differentiation and Heterogeneity

III. Heterogeneity of T Lymphocytes

References

Classes and Subclasses of Surface-Bound Immunoglobulins on Peripheral Blood Lymphocytes in Man

Text

References

Immunoglobulin Determinants on the Surface of Antigen Binding T- and B-Lymphocytes in Mice

Introduction

Evidence That Both B and T Cells Form Rosettes

Methods

Results and Conclusions

References

Antiimmunoglobulin Antibody as Antigen. A Functional Approach to Receptor Immunoglobulin of Thymus Cells

Material and Methods

Experiments and Results

Discussion

Summary

References

III The Role of Antibodies and Complexes in Immune Tissue Damage

Initiating Events in Immune Complex Injury

An Active Process Responsible for the Deposition of Circulating Immune Complexes

Immunologic Release of Vasoactive Amines from Platelets

Basophils and IgE in the Release of Vasoactive Constituents of Platelets

A Soluble Factor (PAF) Released from the Basophils That Aggregates Platelets and Induces Release of Vasoactive Amines

Lack of Participation of Complement Components in the Release of Vasoactive Amines from Platelets in Acute Immune Complex Disease ( Serum Sickness ) in Rabbits

Correlation of the Basophil-Dependent Mechanism of Histamine Release from Platelets and the Deposition of Immune Complexes and Development of Injury

Summary

References

Release of Biologically Active Constituents from Blood Cells and Its Role in Antibody-Mediated Tissue Injury

I. Tissue Injury Induced by Antiglomerular Basement Membrane Antibody ( Nephrotoxic Nephritis )

II. Release of Constituents from Neutrophils Adhering to Immune Reactants on Nonphagocytosable Surfaces

III. The Release Mechanism in Nephrotoxic Nephritis

IV. Summary

References

The Immunological Release of Chemical Mediators of Immediate Type Hypersensitivity from Human Lung

I. Introduction

II. Chemical Mediators of Immediate Type Hypersensitivity

III. Immunologic Release of Chemical Mediators from Human Lung

IV. Pharmacologie Inhibition

V. Concluding Comments

References

Cytochalasin B Reversibly Inhibits Phagocytosis by Human Blood Leukocytes

Text

References

Actions and Interactions of Immunoglobulins in Immune Tissue Damage

I. Role of Antibodies of Known Immunoglobulin Classes

II. Interacting Roles of Antibodies of Different Classes

III. Target Accessibility to Immune Agents

IV. Conclusion

References

Cellular and Humoral Studies in Diseases with Heart-Reactive Antibodies

Heart-Reactive Antibodies in Rheumatic Fever

Heart-Reactive Antibodies in Transplantation

Heart-Reactive Antibodies in Other Disease States

Summary

References

IV Structure of Ig (Combining Sites and Chain Interactions)

Affinity Labeling of Rabbi Antibodies with ε-4-Azido-2-Nitrophenyl Lysine

Introduction

Isolation of Labeled Peptides from Anti-Nap Antibody Preparation A

Affinity Labeling of Anti-Nap Antibody Preparation B

Affinity Labeling of Antidinitrophenyl Antibodies with Nap-[3H]lysine

Discussion

References

Combining Sites of Anti-2,4-Dinitrophenyl Antibodies

Text

References

Modification of Immunoglobulin Combining Sites

Affinity-Labeling Studies

Studies with Tetranitromethane

Site-Directed Cross Linking

Discussion

References

Localization of Affinity Label within the Primary Structure of y2 Chain from Guinea Pig IgG(2)

Text

References

An Approach to the Mapping of Active Sites by Affinity Labeling

Text

References

Tentative Structure of Human IgM Immunoglobulin

Polypeptide Chain Structure and Carbohydrate Groups of IgM Immunoglobulins

Tentative Amino Acid Sequence of the μ Chain of IgM Ou

Evolutionary Origin of Heavy and Light Chains

Summary

References

V Cell Cooperation in the Immune Response

Immunological Unresponsiveness : Cellular Kinetics and Interactions

I. Cellular Events Involved in the Induction of Immunological Unresponsiveness

II. Termination of Immunological Unresponsiveness

III. Autoimmunity

References

Studies on the Influence of T Cells in Antibody Production

I. The Theta (θ) Alloantigen as a Marker for T Cells

II. Influence of Treatment with Anti-0 on the in Vitro Response of Spleen Cells from Neonatally Thymectomized Mice to SRBC

III. Influence of Thymectomy on IgM and IgG Antibody Production to SRBC and the Synthetic Polypeptide (T,G)-A-L

IV. Carriage of Long-Term Memory by Both T Cells and B Cells

V. Discussion

VI. Summary

References

Specificity of Helper Function

Introduction

Materials and Methods

Experimental Design

Results and Interpretations

Discussion

Summary

References

Is There Evidence for a Non-Antigen Specific Diifusable Chemical Mediator from the Thymus-Derived Cell in the Initiation of the Immune Response?

I. Introduction

II. Mechanisms of B-Cell-T-Cell Interaction: Hypotheses

III. Thymus-Derived Mediator: Statement, Predictions, and Experiments

References

Cell Interactions in the Graft-versus-Host Response

Introduction

Methods

Results

Conclusions

References

VI Effector Mechanisms of Cell-Mediated Immunity

Cytotoxic Lymphocytes as Eifector Cells of Cell-Mediated Immunity

I. Introduction

II. Formation of Specifically Sensitized Lymphocytes

III. Specificity of Target Cell Lysis by CL

IV. Cooperation of CL with Other Cells

V. Conclusions

References

Migration Inhibitory Factor and Mediators of Cellular Hypersensitivity in Vitro

Introduction

Migration Inhibitory Factor ( MIF)

Chemotactic Factor for Macrophages

Guinea Pig Lymphotoxin

Production of Mediators in Response to Mitogen Stimulation

Alterations of Macrophage Function by Lymphocyte Mediators

Summary and Conclusions

References

Delayed Hypersensitivity and the Mechanism of Cellular Resistance to Infection

Text

References

Lymphocyte Response as a Model of Cell-Mediated Immunity

Specificity of Antigen Recognition

Specificity of Cytotoxicity

Conditioned Medium Activities

Other Soluble Conditioned Medium Activities

References

Lymphocyte Effector Molecules: Mechanism of Human-Lymphotoxin Induced in Vitro Target Cell Destruction and Role in PHA-Induced Lymphocyte-Target Cell Cytolysis

Materials and Methods

Results

Discussion

References

Effect of Some Enzymes, Polysaccharides, and Lysosome-Active Drugs on Interaction of Immune Lymphocytes with Allogenic Target Cells

Materials and Methods

Results

Discussion

Summary

References

Recent Studies on Manifestations of Delayed Cellular Hypersensitivity in Vitro and in Vivo

I. Migration Inhibiting Factor (MIF)

II. Effect of Antilymphocyte ( ALS ) and Other Antisera on in Vitro and in Vivo Manifestations of Delayed Hypersensitivity

III. Some Similarities Between in Vitro and in Vivo Events

IV. Discussion

V. Summary

References

Human Lymphocyte-Dependent Cytotoxic Antibody and Mechanisms of Target Cell Destruction in Vitro

Introduction

Methods and Materials

Results

Discussion

Summary

References

VII Genetic Control of Immune Responsiveness

Specific Immune Response Genes of Guinea Pigs

I. Specific Immune Response Genes Controlling Responsiveness to Synthetic Polypeptide Antigens

II. Specific Immune Response Genes Controlling Responsiveness to Limiting Doses of Native Protein Antigens

III. Size of the Specific Immune Response Gene Pool

IV. Identity of the Cell Type where Specific Immune Response Genes Are Expressed

V. Linkage of Specific Immune Response Genes to the Major Histocompatibility Locus of Guinea Pigs

References

Genetic Control of the Immune Response to Branched Synthetic Polypeptide Antigens in Inbred Mice

I. Introduction

II. Characteristics of the Immune Response-1 Gene(s)

III. The Primary and Secondary Response to Immunization with Aqueous (T,G)-A- -L

IV. The Immune Response of Tetraparental Mice to (T,G)-A- -L

V. The Relationship between Ir-1 and the H-2 Chromosome Region

VI. Role of Immune Response Genes in Animal and Human Disease States

VII. Summary

References

Cellular Basis of the Genetic Control of Immune Responses

I. Introduction

II. Correlation between the Relative Numbers of Detectable Antigen-Sensitive Units and the Response Patterns in Inbred Mouse Strains to (Phe,G)-Pro-L

III. Transfer Studies of the Genetic Control of Immunological Responsiveness Using Thymocytes and Bone Marrow Cells

IV. Enhancement of Immune Responses in Low-Responder Mouse Strains

V. Concluding Remarks

References

Genetic Regulation of the Function of Antibody-Producing Cells

Genetic Selection of "High" and "Low" Responder Lines to Heterologous Erythrocytes

Responsiveness to Other Antigens

Immune Response to Histocompatibility Antigens

Production of Different Classes of Antibody and Serum Levels of Immunoglobulins

Transmission of Responsiveness by Transfer of Spleen Cells

Cytodynamics of Immune Response to Sheep Erythrocytes

Morphology of RFC

References

Genetic Control of Immune Responsiveness : Summary of Contributions by Discussants

Text

VIII Complement

Biochemistry of Complement

I. Introduction

II. Physical and Chemical Properties of Complement Proteins

III. The Molecular Concept of Complement Action

IV. The C3 Activator System

V. Conclusion

References

Enzymes of the Complement System

Activation of Cl

Nature of Cls

Formation of C4,2

Nature of C4,2

Formation of C4,2,3

Nature of C4,2,3 Action

The C3 Activator System

Similarities between the Complement Enzymes

References

Biologically Active Fragments of Complement

I. Introduction

II. Effects of Lysosomal Enzymes on Human Complement Components

III. Effects of Bacterial Proteinases on Human Complement Components

IV. The Properdin System

References

Ultrastructural Studies of C1q and of Complement-Membrane Interactions

I. Introduction

II. Ultrastructural Studies of C1q

III. Ultrastructural Studies of the Interaction between Complement Proteins and Membranes

References

Genetic Polymorphism of Complement Components as a Probe of Structure and Function

I. Introduction

II. Genetic Aspects of Complement

III. Genetic Variability, Function, and Structure

IV. Glycine-Rich ß-Glycoprotein Variability

References

IX Regulation of Immune Response

A Model for the Regulation of Antibody Synthesis by Serum Antibody

I. Methods

II. The Effect of Altering Antibody Levels on Antibody Formation to KLH and T2

III. The Combined Effect of Cyclophosphamide and Alteration of Anti-KLH Levels on Specific Antibody Formation

IV. Role of Antigen in "Feedback" Regulation

V. A Model for the Feedback Regulation of Antibody Synthesis

References

Antigen-Binding Receptors on Lymphoid Cells. Nature and Specificity of Receptors on Various Types of Immuno-Competent Cells

I. Nature and Specificity of Receptors of 125I-DNP-GPA-Binding Cells of Nonimmunized Guinea Pigs

II. Nature and Specificity of 125I-DNP-GPA ABC from Immunized Guinea Pigs

III. Receptors on Cells Mediating a Cellular Immune Response to DNP-GPA

IV. Discussion

References

Regulation of the Ig Class Distribution in Anti-Hapten Responses

I. Studies with Hapten-Protein Antigens

II. Studies with Hapten-Cell Conjugates

III. Discussion

IV. Summary

References

Recent Advances in Immunological Tolerance

I. Antigen-Binding Lymphocytes and Their Significance

II. Collaboration between T- and B-Lymphocytes and Its Relevance to Tolerance Induction

III. Tolerance Induction in Vitro

IV. T- and B-Lymphocyte Collaboration in Vitro

V. Tolerance Induction in T-Lymphocytes

VI. Two Further Key Areas in Tolerance Research

VII. Summary and Conclusions

References

X Immune Disorders in Man

Immunology of Glomerulonephritis

Text

References

Immunological Phenomena in Rheumatoid Arthritis

Antiglobulin Factors

The Role of Complexes

Triggering Mechanisms

References

Immunodeficiency Diseases of Man

Ontogenetic Development of the Lymphoid System and Its Function

Secondary Immunodeficiency Diseases

Primary Immunodeficiency Diseases of Man

Treatment of Immunodeficiency

Conclusion

References

Chemical Mediators of the Acute Inflammatory Response in Man

Humoral Effector Systems

Tissue-Derived Mediators

Control, Deviation, and Perpetuation of the Effector Pathways of the Acute Inflammatory Response

Inborn and Acquired Abnormalities of the Inflammatory Response in Man

References

Some Protein Disorders Associated with Neoplasms of Plasma Cells and Lymphocytes : Heavy Chain Diseases

Gamma-Chain Disease

Alpha-Chain Disease

Mu-Chain Disease

Biochemical Studies of Three Gamma-Chain Disease Proteins

Discussion

References

XI Viruses in Immunopathology

Virus-Antiviral Antibody Complexes

I. Introduction

II. Immune Complex Disease Associated with Viral Infection

III. Chronic Viral Infection Associated with Immune Complex Disease

IV. Acute Viral Infections Associated with Immune Complex Disease: LCM

V. Conclusions

References

Immunological Injury of Virus-Infected Cells by Antiviral Antibody and Complement

Text

References

Interaction of Viruses with Human Lymphocytes

Introduction

Morphologic Alterations

Lymphocytopenia

Reduction in the Cell-Mediated Immune Response

Response of Sensitized Lymphocytes

Inhibition of Blastogenesis

Virus Replication and Interferon Production in Human Lymphocytes

Studies with PHA and Vesicular Stomatitis ( VSV)

Studies with 17D Virus

Discussion

References

Expression of Antigenic Determinants and Virus Synthesis in Mammalian Cells

I. Spontaneous Variations of Antigenic and Viral Expressions in Mammalian Cells

II. Relationship between Viral Infection and Antigenic Expression of the Host Cell

III. Regulatory Mechanisms Involved in Viral and Antigenic Expression and Their Role in Oncogenesis

IV. Plasmocytoma Cells as a Model for Studies on Cell Differentiation

V. Concluding Remarks

References

Immunosuppression by Tumor Viruses: Effects of Leukemia Virus Infection on the Immune Response

Text

Summary

References

Immunopathologic Mechanisms in the Dengue Shock Syndrome

I. Introduction

II. Epidemiologie Factors

III. Pathophysiologic Changes

IV. Antibody Response

V. Role of Complement

VI. Discussion

References

XII Biological Functions of the Different Classes of Immunoglobulin

Immunoglobulin Classes and Complement-Fixing Activity

The Alternate Pathway of Complement Fixation

References

Biological Activities of IgG in Mammals

What Is an IgG?

Nomenclature

Biological Properties of the Immunoglobulins

Neutralization of Antigen

Complement Fixation and Related Phenomena

Anaphylaxis

Cytophilia

Transmission across Membranes

Evolutionary Aspects

References

Immunoglobulin E and Homocytotropic Properties

I. Reaginic Antibodies and Homocytotropic Antibodies

II. Immunologie Properties of IgE Antibodies

III. Structures in IgE Molecules Involved in Sensitization

IV. Target Cell Sensitized with IgE

V. Possible Role of IgG in Reaginic Hypersensitivity Reactions

VI. Summary

References

Biological Significance of IgA Antibodies in Serum and Secretions

I. Distribution and Structure of Immunoglobulin IgA

II. Biosynthesis and Metabolic Features of IgA

III. Significance of Secretory IgA

References

Metabolism of Immunoglobulins

I. Introduction

II. The Metabolism of the Different Classes of Immunoglobulins in Normal Man

III. Physiological Factors Controlling Immunoglobulin Metabolism

IV. Disorders of Immunoglobulin Metabolism

V. Summary

References

XIII Tumor Immunology

Tumor-Associated Antigens as Expressions of Chemically Induced Neoplasia and Their Involvement in Tumor-Host Interactions

I. Introduction

II. Results

III. Discussion

References

Antigens in Virally Induced Tumors

I. Introduction

II. General Characteristics of Tumor-Associated Antigens ( TAA ) of Viral Neoplasms

III. Implications of the Presence of TAA in Viral Neoplasms

References

Cell-Mediated Immunity to Human Tumor Antigens

I. Evidence for Cell-Mediated Immunity against Human Tumor Antigens

II. Differences in Antitumor Immunity between Patients Who Are Symptom-Free and Patients with Progressively Growing Tumors, as Detectable by Using the Microcytotoxicity Assay

III. Possible Implications of the in Vitro Data for Tumor Prophylaxis and Therapy

References

Immunologic Response to Human Sarcomas : Relation of Antitumor Antibody to the Clinical Course

Introduction

Materials and Methods

Results

Discussion

Summary

References

Experimental Basis and First Clinical Controlled Trials of Leukemia Active Immunotherapy

Text

References

XIV Transplantation in the Human

Old and New Facts and Speculations about Transplantation Antigens of Man

Introduction

The HL-A System

Lymphocyte Activation and HL-A

Fetomaternal Interactions

Tolerance and Pathology in a Tetragametic Human Chimera

Conclusions

References

The (Relative) Importance of HL-A Matching in Kidney Transplantation

I. Introduction

II. HL-A and Homograft Reactions

III. Variability of the Homograft Response

IV. Concluding Remarks and Synthesis

V. Summary

References

Mixed Lymphocyte Interaction: Disquisitions on a Popular Unknown

Introduction

Immunologic Basis of the MLI

Peculiarities of the MLI as an Immunological Model

Conclusions and Speculations

References

XV Manipulation of the Immune Response

Reconstitution: Grafting of Bone Marrow and Thymus

I. Introduction

II. Types of Immunodeficiency Considered Amenable to Reconstitution

III. Measures Employed in Attempts to Circumvent Graft-versus-Host Disease in Patients with Immunodeficiency

IV. Experience with Enhancement in Human Bone Marrow Grafting

V. Prospects

References

Immunoregulation by Antibody

I. The Mechanism of Immunosuppression by Antibody

II. The Biological Function of Immunosuppression by Antibody

References

Stimulation: Selective Activation of Subpopulations of Antibody-Forming Cells

Text

References

Cellular Immunosorbents

Text

References

Potentials for Immunologie Intervention in Cancer

I. Potential and Actual Immunologie Contributions to Diagnosis and Management

II. Augmentation of Existing Tumor Immunity

III. The Significance of the Antibody Response to Tumors and the Potential for Its Alteration

References

Workshop Summaries

Allotypes. I

Antibacterial Immunity

Lymphocyte Activation. I

Lymphocyte Activation. II

Cross Reactions between Microbial and Tissue Antigens

Lymphocyte Recirculation and Its Immunological Significance

The Fate of Antigens in Vivo

Blood Group Antigens

Structural Requirements for Immunogenicity

Ontogeny of the Immune Response

Catabolism of Immunoglobulins

Immunology of Gonorrhea and Syphilis

Antibodies to Enzymes

Radiation Effects on the Lymphoid Systems and Its Functions

Nucleic Acids as Antigens

Neutralization of Virus by Antibody

Granulocyte Functions in Immunological Reactions

Immunologic Aging and Lymphoid Involution

Immunology of Reproduction

Tumor Antigens, Carcinogen Induced

Immune Deficiency Diseases: Dysgammaglobulinemia

Immune Responses to Viral Antigens

Allotypes. II

Antibody Structure: Combining Site

Lymphocyte Activation. III

Cell Cooperation in the Immune Response. I

Cell Cooperation in the Immune Response. II

Immune Deficiency Disease: Thymic Aplasia

Macrophages: Role in Resistance to Microbial Parasitism

Adjuvants

Kinetics and Thermodynamics of Antibody-Antigen Interactions

Cellular Kinetics of the Immune Response

Immune Capabilities of Germ-Free Animals

Homocytotropic Antibodies

Phylogenetic Aspects of Immunity

Human Histocompatibility Antigens

Immunologic Assay of Biologically Active Materials

Autoimmune Diseases: Genetics, Mechanisms, and Diagnostic Approaches

Immunological Activation of the Kinin-Forming System

New Immunohistochemical Methods

Immunoglobulin Biosynthesis

Immunopathogenesis of Glomerulonephritis

Tumor Antigens: Relationship to Histocompatibility Antigens

Immunosuppression

Virus-Lymphocyte Interactions

Antibody Structure: Ig Diversity

Idiotypic Antibody

Membrane-Associated Antigens of Lymphoid Cells. I

Membrane-Associated Antigens of Lymphoid Cells. II

Histocompatibility Antigens : Characterization

Macrophages: Their Role in the Induction of Immunity

Immunosuppression: Antilymphocyte Serum

Genetic Control of Immune Responsiveness

Transfer of Immunity with Cell-Free Extracts

Theories of Antibody Formation

Immunological Disorders of Inbred Strains of Mice

Chemotaxis of Leukocytes: Immunologie and Nonimmunologic Factors

Thymic Hormones

Immunity to Parasitic Infections

Biochemistry of Complement

Separation of Different Functional Classes of Small Lymphocytes

Bacterial Endotoxins

Cytotoxic Activities of Lymphocytes

Tumor Antigens: Virus Induced

Antibody Structure and Evolution

In Vitro Models of Delayed Hypersensitivity

Relationships among Major Histoeompatibility Systems

Immunological Tolerance

The Origin of Antigen-Sensitive Lymphocytes. I

The Origin of Antigen-Sensitive Lymphocytes. II

Secretory Immunoglobulins

Immunologic Derangements Caused by Chronic Viral Infections

Homogeneous Antibody and Myeloma Proteins with Antibody Activity

Ultrastructure of Immunoglobulin and Ag-Ab Complexes

Antibody Synthesis in Vitro

Antigenic Competition

Purification and Characterization of Allergens

Complement and Disease States

Histology of the Immune Response

Soluble Mediators of Delayed Hypersensitivity

Pathogenesis of Runting Syndrome

Allergic Release of Amines from Cells

Established Lymphoblastoid Cell Lines

Immunological Enhancement

Subject Index