Molecular Mechanisms of Immunological Self-Recognition
- 1st Edition - February 11, 1993
- Imprint: Academic Press
- Editors: Frederick Alt, Henry J. Vogel
- Language: English
- Paperback ISBN:9 7 8 - 1 - 4 8 3 2 - 0 2 5 0 - 1
- eBook ISBN:9 7 8 - 1 - 4 8 3 2 - 1 5 9 3 - 8
Molecular Mechanisms of Immunological Self-Recognition covers the understanding of immunological self-recognition. The introductory chapter of the book summarizes the dawn of the… Read more
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Request a sales quoteMolecular Mechanisms of Immunological Self-Recognition covers the understanding of immunological self-recognition. The introductory chapter of the book summarizes the dawn of the insight into immunological tolerance, and provides an overview of research on the underlying mechanisms. The book addresses the developments in the molecular mechanisms of B and T cell tolerance and describes the failure of tolerance in autoimmunity. The text concludes by furnishing orienting perspectives and highlighting new information presented. The novel findings characterized as impressive advances pertain to the areas of B cell development and the generation of molecular diversity; V gene usage, especially from transgenes, in positive and negative thymic selection; the handling of positive and negative signals by T and B cells; anergy in postthymic T cells; the design of peptide-based therapy for autoimmune diseases; and the design of therapy with the aid of monoclonal antibodies. Immunologists will find the text useful.
Preface
Part I Introduction
1 Immunological Tolerance Revisited in the Molecular Era
The Dawn of Immunologic Tolerance
One Cell-One Antibody, and Implications
In Vitro Lymphocyte Cloning Techniques Validate Repertoire Purging as a Tolerance Mechanism; Clonal Abortion versus Clonal Anergy
Clonal Abortion and Clonal Anergy Come of Age in the Molecular Era
The Genesis of High-Affinity Antibodies
Soluble Antigen Can Cause Adult Tolerance, Including a Failure of Appearance of High-Affinity B Cells
Summary and Conclusions
References
Part II B Cell Tolerance
2 Mechanisms and Meaning of B Lymphocyte Tolerance
Introduction
The Deletion-Anergy Decision
Consequences of Deletion versus Anergy
References
3 Tolerant Autoreactive B Lymphocytes in the Follicular Mantle Zone Compartment: Substrates for Receptor Editing and Reform
Introduction
Localization of Transgene-Expressing B Cells within Peripheral Lymphoid Organs
Timing of Tolerance Induction during Bone Marrow B Cell Differentiation
Recovery from Receptor Modulation and Tolerance
Deletion or Anergy?
Does the Follicular Mantle Zone Serve as a "Reform School" for Wayward B Cells?
References
Part III Lymphocyte Signaling
4 T Cell Anergy
Introduction
Cellular Characteristics
Biochemical Events Resulting from TCR Occupancy
Reversal of Anergy
Conclusion
References
5 The T Cell Antigen Receptor: Biochemical Aspects of Signal Transduction
Introduction
Substrate Analysis in Murine and Human T Cells; Possible Tyrosine Kinase Regulation of Phospholipase C
Analysis of Tyrosine Phosphatases
The Serine Kinase Pathway
FYN Is a T Cell Receptor-Associated Tyrosine Kinase
References
6 Structure and Signaling Function of B Cell Antigen Receptors of Different Classes
Introduction
Results
References
Part IV T Cell Tolerance
7 Self-Nonself Discrimination by T Lymphocytes
Introduction
Negative and Positive Selection of a Transgenic Receptor Specific for the Male-Specific Peptide Presented by Class I H-2Db MHC Molecules
Lack of Allelic Exclusion of the a TCR Chain in αß TCR Transgenic Mice
Mutations in the Peptide-Binding Groove of MHC Molecules Affect Antigenicity and Negative as Well as Positive Selection
Positive Selection: Expansion of Mature Thymocytes or Maturation of Immature Thymocytes?
Postthymic Expansion of Mature T Cells
Postthymic Tolerance
Discussion
References
8 Transgenic Mouse Model of Lymphocyte Development
Introduction
T Cell Receptor Transgenic Mouse as a Model System to Study T Lymphocyte Development
Clonal Deletion of Self-Reactive T Cells
Positive Selection Model of the Origin of MHC-Restricted T Cells
Molecular Requirements for Positive Selection
Future Issues in T Cell Development Using TCR Transgenic Mice
References
9 Recognition Requirements for the Positive Selection of the T Cell Repertoire: A Role of Self-Peptides and Major Histocompatibility Complex Pockets
Introduction
Results and Discussion
Summary
References
10 Mechanisms of Peripheral Tolerance
Introduction
Results
Distinct Mechanisms of Peripheral Tolerance
Conclusions
References
11 An Analysis of T Cell Receptor-Ligand Interaction Using a Transgenic Antigen Model for T Cell Tolerance and T Cell Receptor Mutagenesis
Introduction
T Cell Receptor Mutagenesis
A Paired Antigen/TCR Transgenic System
References
12 T Cell Repertoire and Tolerance
Introduction
Superantigens
Tolerance to Self-Superantigens Shapes the T Cell Repertoire
Vβ Interaction with the Self-Superantigen Mls-la
Vβ Interaction with the Foreign Superantigens
References
13 Sequential Occurrence of Positive and Negative Selection during T Lymphocyte Maturation
Introduction
Results and Discussion
References
14 Tolerance Induction in the Peripheral Immune System
Introduction
Materials and Methods
Results
Discussion
References
Part V Autoimmunity
15 Activation-Induced Cell Death of Effector T Cells: A Third Mechanism of Immune Tolerance
Introduction
Experimental Results
Interpretations
References
16 T Cells Involved in Inductive Events in the Pathogenesis of Autoimmune Diabetes Mellitus
Text
References
17 Genetic Control of Diabetes and Insulitis in the Nonobese Diabetic Mouse: Analysis of the NOD.H-2b and B10.H-2nod^ Strains
Introduction
Materials and Methods
Results and Discussion
Concluding Remarks
References
18 Islet Tolerance in Humans and Transgenic Mice
Text
References
19 Fluorescence-Activated Cell Sorter Analysis of Peptide-Major Histocompatibility Complex
Introduction
FACS Binding Assay
Results
Discussion
References
20 Tolerance to Self: A Delicate Balance
Introduction
Monoidiotypy
TCR-Specific Antibody Modulation of Disease
TCR Peptide Modulation
Discussion
References
21 Prevention, Suppression, and Treatment of Experimental Autoimmune Encephalomyelitis with a Synthetic T Cell Receptor V Region Peptide
Introduction
Animal Studies
Human Studies
Summary
References
Part VI Perspectives
22 Tolerance of Self: Present and Future
The 1975 Baseline
F Liver Antigen
Negative Signaling
Anergy, and the Need for a Defined Anergic Phenotype
Thymus Lobe Cultures
Autoimmunity and Epitope Linkage
Toward Gene Therapy in Autoimmunity
References
Index
- Edition: 1
- Published: February 11, 1993
- No. of pages (eBook): 274
- Imprint: Academic Press
- Language: English
- Paperback ISBN: 9781483202501
- eBook ISBN: 9781483215938
FA
Frederick Alt
Frederick W. Alt is a Howard Hughes Medical Institute (HHMI) Investigator and Director of the Program in Cellular and Molecular Medicine (PCMM) at Boston Children's Hospital (BCH). He is the Charles A. Janeway Professor of Pediatrics and Professor of Genetics at Harvard Medical School. He works on elucidating mechanisms that generate antigen receptor diversity and, more generally, on mechanisms that generate and suppress genomic instability in mammalian cells, with a focus on the immune and nervous systems. Recently, his group has developed senstive genome-wide approaches to identify mechanisms of DNA breaks and rearrangements in normal and cancer cells. He has been elected to the U.S. National Academy of Sciences, the U.S. National Academy of Medicine, and the European Molecular Biology Organization. His awards include the Albert Szent-Gyorgyi Prize for Progress in Cancer Research, the Novartis Prize for Basic Immunology, the Lewis S. Rosensteil Prize for Distinugished work in Biomedical Sciences, the Paul Berg and Arthur Kornberg Lifetime Achievement Award in Biomedical Sciences, and the William Silan Lifetime Achievement Award in Mentoring from Harvard Medical School.
Affiliations and expertise
Professor of Pediatrics and Professor of Genetics, Harvard Medical School, Boston, MA, USARead Molecular Mechanisms of Immunological Self-Recognition on ScienceDirect