Idiotypy in Biology and Medicine (eBook)

Front Cover 1
Idiotypy in Biology and Medicine 4
Copyright page 5
Table of Contents 6
Contributors 16
Preface 20
SECTION I. Idiotype Concepts 24
Chapter 1. The Immune Network Revisited 26
I. Introduction 26
II. The B-Cell Idiotype Network 26
III. T-Cell Idiotypes 28
IV. The Immune Network as an Evolutionary Factor 31
V. Idiotopes on Non-lg Molecules 32
VI. The Need for a Network 34
References 35
Chapter 2. Idiotypy and Internal Images 38
I. Introduction 38
II. A Recurrent Idiotype (6, 26) 43
III. Classical Idiotypes 44
IV. Internal Images 46
References 49
Chapter 3. Regulatory Idiotopes 52
I. Introduction 52
II. Immunochemical Properties of Syngeneic Ab1, Ab2, Ab3, and Ab4 Antibodies 53
III. Functional Properties of Syngeneic Ab1, Ab2, Ab3, and Ab4 Antibodies 56
IV. Regulatory Idiotype Network 59
References 64
Chapter 4. The Uniqueness and Boundaries of the Idiotypic Self 66
I. A Change of Paradigm in the Immunological Theory 67
II. Are We Concerned with the Most Complex System in Biology? 68
III. An Organism-Centered Perspective of the Immune System 71
IV. The Immune System Is More Than an Antiinfectious Machine 77
V. Conclusions 80
References 81
SECTION II. Idiotypes in the Immune System 84
Chapter 5. Structural Properties and Genetic Control of an Idiotype Associated with Antibodies to the p-Azophenylarsonate Hapten1, 2 86
I. Introduction 87
II. Linkage of CRIA Expression to Genes Controlling CH Regions and Kappa Chains 87
III. Preparation of Monoclonal Antibodies with Anti-Ar Activity 90
IV. A Minor Intrastrain Cross-Reactive Idiotype (CRIm) in A/J Anti-Ar Antibodies 90
V. Relationship of the Idiotypes of Anti-Ar Antibodies of A/J and BALB/c Mice 96
VI. Strain Distribution of CRIC and Concentrations of CRIC in Individual BALB/c Mice 97
VII. Hapten-Binding Specificities of CRI+A Anti-Ar Antibodies 100
VIII. An Unrelated Major Idiotype Associated with Antibodies to the Phenylarsonate Hapten in A/J Mice 101
IX. Serological Properties of Monoclonal CRI+A HP 102
X. Amino Acid Sequencing of CRI+A Antibodies from Serum and Hybridomas 105
XI. Investigations of Genes Controlling the Synthesis of H Chains of CRI+A Molecules 107
XII. Random Somatic Mutation versus Programmed Expression of Idiotypes 109
References 110
Chapter 6. Idiotype-Specific T Helper Cells 112
I. The Role of T Cells in Idiotype Networks 112
II. Induction of Idiotype-Specific T Helper Cells 114
III. Cells Involved in the Induction Circuit of Idiotype-Specific T Helper Cells 117
IV. Specificity of Idiotype-Recognizing T Helper Cells 117
V. Conclusions 120
References 122
Chapter 7. Manipulating an Idiotypic System with Asymmetric Circuitry: Antiidiotypic Antibodies versus Idiotype-Recognizing T Cells1 124
I. The B Cell Predominant Idiotype and the T Helper Cell Idiotypes: Occupants of Separate Universes2 124
II. Driving B-Cell Maturation with T Cells and Other Agents 125
III. Modulation of IdXL-Bearing B Cells in Responder Strain Mice 126
IV. Effect of Anti-IdXL on Ts in Nonresponder H-2b Mice 129
V. Conclusions: The Relative Roles of Antiidiotype Antibodies and Idiotype-Recognizing T Cells 131
VI Summary 133
References 133
Chapter 8. Biochemical, Functional, and Genetic Aspects of T-Cell Idiotypes 136
I. Introduction1 136
II. The Concept of Antigen–Antibody Interactions and the Use of Anti-Id Antibodies 138
III. Model Systems for the Study of T-Cell Idiotypes 139
IV. Idiotypes on Normal and in Vivo/in Vitro Immunized T Cells 141
V. Interaction of Anti-Id Antibodies and T Cells 144
VI. Induction of Specific T Cells by Anti-Id Antibodies 146
VII. Detection of Idiotypes on T-Cell Products Isolated by Antigen-Specific Immunoadsorbents 147
VIII. Studies on the Genes Responsible for the Synthesis of T-Cell Idiotypes 148
IX. Function of T-Cell Idiotypes 152
X. Biochemical Analysis of 5936-ld-Bearing T-Cell Proteins 156
XI. Molecular Biology of T-Cell Receptor Genes 160
XII. Conclusions 161
Acknowledgments 161
References 161
Chapter 9. Ontogeny of the HA-Responsive B-Cell Repertoire: Interaction of Heritable and Inducible Mechanisms in the Establishment of Phenotype 166
I. Introduction 167
II. Early Studies of Antibody Repertoire Ontogeny 167
III. Genetics of Antibody Repertoire Formation 168
IV. Dynamics of the Emerging Primary B-Cell Pool 175
V. Longevity and the Basis of Ligand-lnduced Effects 181
VI. The "Moving Window" Model of Primary Repertoire Phenotype Expression 189
Acknowledgments 192
References 193
Chapter 10. Ontogeny of Antilevan and Inulin Antibody Responses1 196
I. Introduction 196
II. Characteristics of the Antibacterial Levan Immune Response 197
III. Ontogeny of the ß2-6 Fructosan Response 198
IV. Ontogeny of the ß2-1 Fructosan Response 202
V. Conclusions 206
References 207
Chapter 11. Selective Alteration of the Humoral Response to al-3 Dextran and Phosphorylcholine by Early Administration of Monoclonal Antiidiotype Antibody 210
I. Introduction 210
II. Description of Methodology 211
III. Id-Specific B-Cell Unresponsiveness after MAID Exposure 214
IV. Mechanism of MAID-lnduced Id-Specific B-Cell Unresponsiveness 220
V. Summary 224
References 224
Chapter 12. Isogeneic Antiidiotype Repertoire and Modulation of Idiotype Expression in the Antidextran System1 226
I. Introduction 226
II. The Isogeneic Antiidiotypic Repertoire 227
III. Idiotype Expression Manipulated by Passive Antiidiotype 232
IV. Igh-Dependent Congeneic Rejection of the Antidextran Response 237
V. Conclusions 239
References 240
Chapter 13. Idiotypic Manipulation of the Rabbit Immune Response against Micrococcus luteus 242
I. Introduction1 242
II. Antigenic and Idiotypic Properties of Antibodies Induced by Micrococcus luteus 243
III. Manipulations of the Immune Response with Antiidiotypic Reagents 247
IV. Immunochemical Studies on Cross-Reactive Idiotypes 256
V. Conclusions 260
Acknowledgments 262
References 262
Chapter 14. Idiotypes of Anti-MHC Monoclonal Antibodies 266
I. Introduction1 266
II. Production, Purification, and Specificity of Anti-MHC Antiidiotypes 268
III. Prevalence of MHC Idiotypes in Conventional Alloantisera 270
IV. In Vivo Effects of Antiidiotypes 276
V. Modification of the Expressed Anti-MHC Repertoire by in Vivo Treatment with Anti-Id 285
VI. Conclusions and Future Approaches 288
References 289
SECTION III. Idiotypes in Other Biological Systems 294
Chapter 15. Production of Monoclonal Antibodies to Integral Membrane Transport and Receptor Proteins and Their Use in Structural Elucidation 296
I. Introduction 297
II. Production of Monoclonal Antibodies to Membranes 300
III. Antibody Assays for Functional Proteins (Receptors and Transport) 306
IV. Indirect Immunoprecipitation Assays 307
V. Immunoaffinity Chromatography of ß-Adrenergic Receptors Using Monoclonal Antibodies 313
VI. Elucidation of Receptor Structure and Function 316
VII. Antiidiotypic Antibodies and Receptors 321
VIII. Conclusions 322
References 323
Chapter 16. Studies on Idiotypes Shared by Neuronal and Lymphoid Cells 326
I. Introduction 326
II. Role of the Reovirus Sigma 1 Protein 327
III. Identification of the Id3 Determinant 329
IV. Expression of HA-Specific Idiotype on Tc Cells 342
V. Summary 347
Acknowledgments 349
References 349
Chapter 17. Idiotypy in Autoimmune Central Nervous System Demyelinating Disease: Experimental Allergic Encephalomyelitis and Multiple Sclerosis 352
I. Introduction 352
II. Experimental Studies 354
III. Discussion 363
IV. Relevance of These Studies to Human CNS Demyelinating Disease 365
Ackowledgments 367
References 367
Chapter 18. Idiotypes in Myasthenia Gravis 370
I. Introduction 370
II. Autoantibodies Against the Acetylcholine Receptor (AChR) 371
III. Experimental M G: Production of Monoclonal Antibodies (mAbs) and T-Cell Lines Specific for AChR 373
IV. Idiotypic Analysis in M G 374
V. Summary 385
Acknowledgments 386
References 386
Chapter 19. Antiidiotypic Antibodies as Immunological Internal Images of Hormones 388
I. Introduction 389
II. Similarities in Binding Properties of Receptors and Antibodies 390
III. Interaction of Antiidiotypic Antibodies with Receptors 391
IV. Antiidiotypic Antireceptor Antibodies and Autoimmune Diseases 399
V. The Nature of the Interaction between the Antiidiotypic Antibody and the Receptor 401
VI. Potential Applications of Antiidiotypic Antibodies in Basic Research 402
VII. Medical Applications of Antiidiotypic Antibodies 403
VIII. Prospects 404
Acknowledgments 405
References 406
Chapter 20. Immunization to Insulin Generates Antiidiotypes That Behave as Antibodies to the Insulin Hormone Receptor and Cause Diabetes Mellitus 408
I. Hormone Receptor Antibody: The Immune SystemImage of a Hormone 408
II. The Insulin Molecule: Structure–Function Relationships 409
III. Four Questions 411
IV. Experimental Approach 411
V. Insulin Receptor Antibodies Generated as Specific Antiidiotypes 412
VI. Selectivity of the Immunological Network 414
VII. Effect of Antiidiotypic (Receptor) Antibodies on Glucose Homeostasis 416
VIII. Down-Regulation and Desensitization of Insulin Receptors 418
IX. Receptor Antibodies in Human Patients 420
X. Summary: Four Answers 421
References 422
Chapter 21. Induction of Protective Immunity Using Antiidiotypic Antibodies: Immunization against Experimental African Trypanosomiasis 424
I. Introduction 424
II. Immunization with Anti-Id Antibodies 425
III. Idiotype Expression in Anti-Id-Treated Mice 427
IV. Genetic Control of Idiotype Induction 429
V. Specificity of Induced Idiotypes 433
VI. Summary 437
Acknowledgments 437
References 438
Chapter 22. The Idiotype Network: Theoretical and Practical Implications for Autoimmune Disease 440
I. Introduction 440
II. Systemic Lupus Erythematosus (SLE) 441
III. Cryoglobulins 444
IV. Rheumatoid Factor 444
V. Antitetanus Toxoid Antibodies 445
VI. Leukemia and Lymphoma 447
VII. Conclusions 448
References 450
Chapter 23. Human Antiidiotypic Antibodies 452
I. Introduction 452
II. Auto-Antiidiotypic Antibodies 453
III. Antiidiotypic Antibodies against Stimulated T Cells 455
IV. Antiidiotypic Antibodies against Maternal Antibodies 456
V. Summary 458
References 459
Index 460