Immune Regulation and Immunotherapy in Autoimmune Disease (eBook)
XVI, 570 Seiten
Springer US (Verlag)
978-0-387-36003-4 (ISBN)
This volume reviews the most recent advances in the understanding of cellular and molecular mechanisms for immune responses and immune regulation. The books editor, Dr. Zhang, is well-known internationally, particularly in the field of multiple sclerosis and T-cell vaccination as a potential treatment of multiple sclerosis. He has much experience and expertise in both basic and clinical aspects of autoimmune disease.
This book critically reviews both clinical and immunological aspects of auto- mune disease with a strong emphasis on multiple sclerosis (MS). Research in MS is one of the fastest-developing areas in modern medicine. It employs some of the newest concepts in autoimmune mechanisms and an array of new treatments that would have been considered science fiction only two decades ago. It is an area in which research findings are being actively translated into treatment strategies. Advances in this area have both clinical and scientific implications for other autoimmune conditions that share many similarities with MS. The book, which comprises 24 chapters contributed by experts and thought leaders in the field, is designed to provide new insights into two arenas: our current understanding of autoimmune mechanisms and immune regulation and the latest developments in immunotherapy. This book is intended for both researchers and clinicians. Its purpose is not only to provide a comprehensive review on the recent advances in the two arenas m- tioned above but also to reflect the current opinions or concepts that influence our thinking about the disease mechanisms and our way of treating MS patients. Many of these issues have emerged from recent studies and are somewhat contradictory to traditional thinking. For example, recent studies have indicated that MS is more heterogeneous in many aspects than traditionally thought. Pathologically, in ad- tion to demyelination and inflammation, there is axonal loss or damage detectable in the central nervous system (CNS) lesions.
Preface 5
Contents 8
Contributors 11
Immune Regulation and Autoimmune Disease 15
Autoimmune Response and Immune Tolerance 16
1 Introduction 16
2 Thymic Selection of the Self-Reactive Repertoire 16
3 Peripheral Mechanisms of Tolerance 21
4 Conclusion 27
References 27
Priming Regulatory T Cells and Antigen- Specific Suppression of Autoimmune Disease 33
1 Summary 33
2 Introduction 33
3 Identification of T Cells With Suppressor Function 34
4 Immunotherapeutic Strategies to Treat Autoimmune Disease 37
5 Antigen-Presenting Cells and Priming of Treg 41
6 Conclusion 43
References 44
Peripheral T Cell Regulation and Autoimmunity 49
1 Introduction 49
2 Biological and Clinical Impact of Immunoregulation 50
3 Suppressor Cell Subsets 54
4 Affinity/Avidity Model of Peripheral T Cell Regulation 60
References 62
Anti-Ergotypic Regulation of the Immune Response 69
1 Introduction 69
2 Anti-Ergotypic Response 70
3 Overlap and Interactions With Other Regulatory Populations 74
4 Conclusions 75
References 77
How B Cells Contribute to Multiple Sclerosis Pathology 79
1 Introduction 79
2 B Cell Development and Activation 80
3 B Cells in Autoimmunity 81
4 B Cells in Multiple Sclerosis 82
5 B Cell Antigen Target Discovery 86
6 B Cells at the Site of Myelin Destruction: CSF and the CNS Tissue 87
7 B Cell-Directed Therapy for MS 92
8 Conclusion 93
References 93
Molecular Basis for Induction of Tolerance in Type 1 Diabetes 100
1 Introduction 100
2 Maintenance and Loss of Tolerance to ß Cell Autoantigens 101
3 Approaches to Restore Self-Tolerance to ß Cell Antigens 109
4 Conclusion 119
References 119
Co-stimulation Regulation of Immune Tolerance and Autoimmunity 134
1 Introduction 134
2 Regulation of T Cell Tolerance and Autoimmunity by ICOS and B7h 136
3 Regulation of T Cell Tolerance by PD-1 and Its Ligands 139
4 B7-H3, B7S1, and BTLA 144
5 Conclusion 145
References 147
Invariant NKT Cells and Immune Regulation in Multiple Sclerosis 152
1 Introduction 152
2 Invariant NKT Cells 153
3 Invariant NKT Cells and Autoimmune/Inflammatory Disease Models 155
4 iNKT Glycolipid Ligands and Autoimmune Disease Models 156
5 Human iNKT Cells 157
6 Analyzing iNKT Cells in Human Diseases 157
7 iNKT Cells Are Reduced in MS 159
8 CD4+ iNKT Cells Are Th2 Biased in Remission of MS 159
9 Implications and Future Research 160
References 161
CD4+CD25+ Regulatory T Cells in Autoimmune Disease 165
1 A Need for Regulation 165
2 Discovery and Rediscovery of Regulatory/Suppressor T Cells 166
3 Identifying a Regulatory T Cell 167
4 Origin and Specificity of CD4+CD25+ Treg Cells 170
5 Mechanisms of Regulation 171
6 Target Populations of Treg Cells 174
7 Clinical Relevance 175
8 Conclusion 179
References 179
Immunopathogenesis of Multiple Sclerosis: Overview 184
1 Introduction 184
2 Genetic Factors Influencing MS Susceptibility 185
3 Environmental Factors Contributing to MS Risk 185
4 Autoimmunity as the Pathogenic Effector 186
5 Interaction of Genes, Environment, and Autoimmunity 186
6 Immune Surveillance of the CNS 187
7 Immunology of MS 188
8 Immunopathogenetic Concept 193
References 194
Viral Infection and Multiple Sclerosis 201
1 Introduction 201
2 Multiple Sclerosis 202
3 Making a Viral Association 208
4 Viruses Implicated in Multiple Sclerosis 208
5 Human Herpesvirus-6 and Multiple Sclerosis 212
6 Conclusion and Future Directions 218
References 219
Multiple Sclerosis Pathology During Early and Late Disease Phases: Pathogenic and Clinical Relevance 227
1 Introduction 227
2 MS Lesions in Relation to Lesion Activity and Disease Duration 228
3 Complex Role of Inflammation in MS 234
4 Oligodendrocyte Pathology and Remyelination in Relation to Lesion Activity and Disease Phase 252
5 Axonal Pathology and Mechanisms of Injury During Early and Late Disease 256
6 Gray and Nonlesional White Matter Pathology in MS 260
7 Inflammation/Neurodegeneration Paradox: Why Does It Exist in MS? 263
8 Conclusions 265
References 266
CD8+ T Cells in Multiple Sclerosis 278
1 Genetic Basis for an Association of MS With Different T Cell Subsets 278
2 Evidence from Animal Models of MS for Contributions by Different T Cell Subsets 279
3 Clinical Trials Emphasizing a Possible Role of CD8+ T Cells in MS Patients 281
4 CD8+ T Cell Infiltration in MS Lesions 282
5 Preferential Clonal Expansion of CD8+ T Cells in MS 282
6 MHC Class I Expression in the CNS 284
7 Cytotoxic Response of CD8+ T Cells on CNS Resident Cells 286
8 Peripheral Activation of Autoreactive CD8+ T Cells 286
9 Mechanisms of CD8+ T Cell Infiltration of the CNS 288
10 Reactivation of Autoreactive CD8+ T Cells in the CNS 289
11 Proteins and Epitopes Recognized by Autoreactive CD8+ T Cells in the CNS 289
12 Conclusions and Perspective 290
References 291
Novel Immunotherapeutic Strategies and Emerging Treatments 299
Review of Novel Immunotherapeutic Strategies for MS 300
1 Introduction 300
2 Immunopathogenetic Rationale for Strategies in MS 302
3 Novel Immunotherapeutic Strategies 304
4 Neuroprotection and ÏNeurorepairÓ 333
5 Conclusions 333
References 335
T Cell Vaccination in Autoimmune Disease 350
1 Introduction 350
2 Early TCV in Autoimmune Animal Models 352
3 Human Studies in TCV 354
4 Application of TCV to Other Autoimmune Diseases 363
5 Regulatory Mechanisms Induced by TCV 366
6 Technical Improvements 369
7 Future Directions 374
References 375
Trivalent T Cell Receptor Peptide Vaccine for Treatment of Multiple Sclerosis Targets Predominant V Genes Widely Implicated in Autoimmune Diseases and Allergy 380
1 Introduction 381
2 Development of the Peripheral T Cell Repertoire 382
3 V Gene Expression Patterns in Autoimmune Diseases and Allergy 389
4 Regulation of Autoimmunity With T Cell Receptor Peptides 403
References 411
Nonmyeloablative Stem Cell Transplantation for Multiple Sclerosis 420
1 Stem Cell Replacement Therapy 420
2 Hematopoietic Stem Cell Transplantation in Multiple Sclerosis 422
3 Conclusion 432
References 432
T Cell-Targeted Therapy for Rheumatoid Arthritis 436
1 Introduction 436
2 T Cell-Targeted Therapy by Depletion 437
3 T Cell-Targeted Therapy With Disease-Modifying Antirheumatic Drugs 438
4 T Cell-Directed Therapies With Biologicals 440
5 Clinical Experience With CTLA4Ig (Abatacept) 442
6 Experience With Alefacept 443
7 Other Approaches to Inhibiting T Cell Activation 444
8 Conclusion 444
References 445
Estrogens in the Treatment of Multiple Sclerosis 449
1 Introduction 449
2 Estrogen Treatment: Attempting to Recapitulate Pregnancy 450
3 Estrogen Treatment in Experimental Autoimmune Encephalomyelitis 453
4 Estrogen Treatment in Multiple Sclerosis 457
5 Risk/Benefit Ratio of Estrogen Treatment 460
6 Estrogen Treatment: Early Versus Late in Disease 462
7 Conclusion 464
References 464
Immune Regeneration Through Hematopoietic Stem Cell Transplantation to Restore Tolerance in Autoimmune Disease 472
1 Introduction 472
2 Treating Autoimmune Diseases With HSCT: The Underlying Hypotheses 474
3 Immunological Results from Studies on HSCT for Autoimmune Disease 478
4 Conclusions 486
References 486
Cell Transplantation of Peripherally Derived Adult Cells for Promoting Recovery from CNS Injury 491
1 Introduction 491
2 Bone Marrow-Derived Cells for Cell Therapy in CNS Disorders 491
3 Peripheral Myelin-Forming Cells 496
4 Challenges in Cell Therapy Approaches for Demyelinating Disorders 500
5 Prospects of Cell-Based Clinical Approaches 501
References 504
Multiple Sclerosis: Future Directions and Prospects 508
1 Is Multiple Sclerosis an Important Disease? 508
2 Is MS One Disease? 509
3 Is MS an Autoimmune Disease? 510
4 What is the Role of CD8 T Cells in MS? 512
5 A Role for B Cells in MS? 513
6 Which are the Target Autoantigens? 514
7 Which Factors Precipitate Onset and Relapses? 516
8 What is the Interplay of Immune Response and Neuronal Degeneration? 517
9 Immune (Dys)regulation? 518
References 521
Author Index 525
Subject Index 569
Erscheint lt. Verlag | 25.1.2007 |
---|---|
Zusatzinfo | XVI, 570 p. 68 illus., 11 illus. in color. |
Verlagsort | New York |
Sprache | englisch |
Themenwelt | Medizin / Pharmazie ► Allgemeines / Lexika |
Medizin / Pharmazie ► Medizinische Fachgebiete | |
Studium ► Querschnittsbereiche ► Infektiologie / Immunologie | |
Naturwissenschaften ► Biologie | |
Technik | |
Schlagworte | Antigen • autoimmune disease • autoimmunity • Infection • Infectious Diseases • Transplantation • Vaccine • Viral Infection |
ISBN-10 | 0-387-36003-4 / 0387360034 |
ISBN-13 | 978-0-387-36003-4 / 9780387360034 |
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