Elsevier S & T

Advances in Immunology

Alt, Frederick W.

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Table of contents
  • Contentsv
  • Contributorsix
  • Chapter 1: Fate Decisions Regulating Bone Marrow and Peripheral B Lymphocyte Development1
  • 1. Introduction2
  • 2. B Lymphocyte Development in the Bone Marrow3
  • 2.1. Stages of B lymphopoiesis4
  • 2.2. Specification versus commitment during B lymphopoiesis6
  • 2.3. Developmental checkpoints during B lymphopoiesis7
  • 2.4. Selection for functional BCR complexes10
  • 2.5. The hematopoietic microenvironment16
  • 2.6. Permissive versus deterministic models of B lymphopoiesis17
  • 2.7. Maintenance of early B lineage fate19
  • 2.8. Perturbations affecting primary B lymphopoiesis19
  • 3. Development of Immature B Cells in the Bone Marrow and Periphery21
  • 4. BCR-Dependent Signaling and Fate Decisions by Bone Marrow and Peripheral Immature B Lymphocytes23
  • 4.1. Biochemistry of BCR-induced fate decisions during negative selection23
  • 4.2. Alternative BCR-induced fate decisions27
  • 5. BCR Signaling During the Transitional to Mature B-lymphocyte Transition30
  • 5.1. Igalpha/beta and ITAMs31
  • 5.2. B-cell linker protein31
  • 5.3. Bruton's tyrosine kinase32
  • 5.4. Involvement of other BCR-signaling proteins32
  • 6. Peripheral B Lymphocyte Survival: Synergy Between BCR and BAFF-R Signaling33
  • 7. Development of FO and MZ Mature B Lymphocytes35
  • 8. Concluding Remarks36
  • Acknowledgments36
  • References37
  • Chapter 2: Tolerance and Autoimmunity: Lessons at the Bedside of Primary Immunodeficiencies51
  • 1. Introduction52
  • 2. PIDs Systematically Associated with Clinical AI56
  • 2.1. Immunodysregulation, polyendocrinopathy, enteropathy X-linked syndrome (IPEX)56
  • 2.2. Autoimmune polyendocrinopathy, candidiasis, and ectodermal dystrophy (APECED)62
  • 2.3. Omenn syndrome (OS)63
  • 2.4. Autoimmune lymphoproliferative syndrome (ALPS)65
  • 2.5. Complement deficiencies66
  • 3. PIDs Strongly Associated with Clinical AI67
  • 3.1. Selective IgA deficiency67
  • 3.2. Common variable immunodeficiency68
  • 3.3. Agammaglobulinemia69
  • 3.4. Hyper-IgM syndrome69
  • 3.5. Wiskott-Aldrich Syndrome70
  • 3.6. NF-kappaB essential modulator defects70
  • 4. PIDs that Are Mildly Associated with Clinical AI71
  • 5. PIDs that Are Not Associated with AID72
  • 6. Concluding Remarks73
  • Addendum in proof74
  • References74
  • Chapter 3: B-Cell Self-Tolerance in Humans83
  • 1. Antibody Diversity84
  • 2. Antibodies and Self-Tolerance85
  • 2.1. B-cell development and self-tolerance in the bone marrow86
  • 2.2. Transitional B cells and peripheral selection of naive cells89
  • 2.3. Defective early B-cell tolerance checkpoints and autoimmunity90
  • 2.4. Molecular defects associated with altered self-tolerance in autoimmunity93
  • 3. Marginal Zone B Cells94
  • 3.1. Mouse marginal zone B cells94
  • 3.2. The human MZ and circulating IgM+ CD27+ B cells94
  • 4. B-Cell Memory96
  • 4.1. Germinal centers97
  • 4.2. Activation and selection of autoreactive B cells98
  • 4.3. Autoreactivity and B-cell memory99
  • 5. Concluding Remarks100
  • References102
  • Chapter 4: Manipulation of Regulatory T-Cell Number and Function with CD28-Specific Monoclonal Antib111
  • 1. Aims of this Review113
  • 2. Positive and Negative Regulation of T-Cell Responses by the CD28/CTLA-4 System113
  • 3. The Importance of CD28 and CTLA-4 for the Generation and Homeostasis of Treg Cells115
  • 3.1. "Natural" regulatory cells115
  • 3.2. IL-2 dependence of Treg cells116
  • 3.3. Significance of CTLA-4 for Treg function117
  • 3.4. Role of CD28 in generation and homeostasis of Treg cells118
  • 3.5. Role of CD28 and IL-2 in antigen-driven expansion and activation of Treg cells119
  • 4. Manipulating the CD28 Pathway: General Considerations120
  • 5. Conventional and Superagonistic mAb to the Costimulatory Receptor CD28121
  • 5.1. Epitope-function relationship121
  • 5.2. Mode of mAb binding: A clue to superagonism?122
  • 5.3. Signaling pathways124
  • 6. In Vitro Expansion of Treg Cells with the Help of CD28-Specific mAb125
  • 6.1. Costimulation125
  • 6.2. CD28 superagonists125
  • 7. In Vivo Effects of Conventional CD28-Specific mAb126
  • 7.1. General126
  • 7.2. Experimental findings126
  • 8. In Vivo Effects of CD28 Superagonists: Predominance of Treg-Cell Activation128
  • 8.1. Studies in rats128
  • 8.2. Studies in mice129
  • 8.3. A model for preferential expansion of Treg cells in CD28-superagonist-stimulated rodents129
  • 9. Treatment of Autoimmune and Inflammatory Model Diseases with CD28 Superagonists132
  • 9.1. Overview132
  • 9.2. Prevention and treatment of EAE in the LEW rat134
  • 10. TGN1412„A Superagonistic mAb to Human CD28135
  • 10.1. Introductory remarks135
  • 10.2. Development of TGN1412136
  • 10.3. Biophysical properties of TGN1412136
  • 10.4. Cytokine release syndrome in humans but not in animal models137
  • 10.5. Follow-up in vitro studies139
  • 10.6. Lessons from the TGN1412 trial140
  • 11. Conclusions140
  • Acknowledgments141
  • References141
  • CH4Chapter 5: Osteoimmunology: A View from the Bone149
  • 1. Opening Remarks: The Old and the New150
  • 2. Osteoimmunology: A Developmental Encounter151
  • 2.1. Bone: Five cell types and two mechanisms of formation151
  • 2.2. The developmental encounter151
  • 2.3. Developmental consequences152
  • 3. The TNF Superfamily: A Developmental Link Between Bone and Immune System152
  • 3.1. Osteoclasts differentiation152
  • 3.2. Immune and bone developmental phenotypes in RANK axe mutated mice153
  • 3.3. TNF-alpha: A nonessential regulator of bone involved in autoimmune-induces bone pathology154
  • 3.4. RANKL, TNF-alpha: In search for differences154
  • 4. IFNs: Linking Bone Homeostasis to Immunity and T Cells155
  • 4.1. Type I IFNs establish an autoinhibitory loop in.osteoclasts155
  • 4.2. Type II IFN: A potent inhibitor of osteoclastogenesis secreted by T cells156
  • 5. B Cells and Bone157
  • 5.1. The hypothesis of myeloid lineage switch157
  • 5.2. Multiple myeloma: An osteolythic tumor158
  • 6. A Bone Quality Control of the Immune Response158
  • Acknowledgments160
  • References160
  • Chapter 6: Mast Cell Proteases167
  • Abbreviations169
  • 1. Introduction169
  • 2. Expression of MC Proteases171
  • 2.1. Human MC proteases171
  • 2.2. Murine MC proteases173
  • 2.3. Rat MC proteases174
  • 2.4. MC proteases from other species175
  • 2.5. MC protease expression profiles as MC markers175
  • 3. Genetic Organization and Regulation of Transcription176
  • 3.1. The chymase locus176
  • 3.2. The tryptase locus179
  • 3.3. The MC-CPA locus179
  • 3.4. Transcriptional regulation180
  • 4. Evolution of MC Proteases182
  • 4.1. MCs in evolution182
  • 4.2. MC proteases in early evolution183
  • 4.3. MC chymase in mammalian evolution183
  • 4.4. MC tryptase in mammalian evolution184
  • 5. Protein Organization and Processing184
  • 6. Three-Dimensional Structure187
  • 6.1. Chymase187
  • 6.2. Tryptase189
  • 6.3. MC-CPA190
  • 7. Cleavage Specificity190
  • 7.1. Chymase192
  • 7.2. Tryptase195
  • 7.3. MC-CPA195
  • 8. Interaction of MC Proteases with PGs: Implications for Storage, Activity, and Processing196
  • 8.1. Storage196
  • 8.2. Effect of PGs on MC protease activity/activation and processing201
  • 8.3. Structural basis for GAG: MC protease interaction202
  • 9. Substrates for MC Proteases203
  • 9.1. Chymase206
  • 9.2. Tryptase210
  • 9.3. MC-CPA213
  • 9.4. Concerted action of the MC proteases213
  • 10. In Vivo Function214
  • 10.1. Chymase214
  • 10.2. Tryptase222
  • 10.3. MC-CPA225
  • 11. MC Protease Inhibitors226
  • 11.1. Synthetic inhibitors226
  • 11.2. In vivo regulation227
  • 12. Summary and Future Perspectives228
  • Acknowledgments229
  • References229
  • Index257
  • Content of Recent Volumes269
  • Color Plate Section273
Book details
  • Vendor Elsevier S & T
  • SKU 9780123737083
  • ISBN-13 9780080553702
  • Author Alt, Frederick W.
  • Category Medical
  • Subject Immunology

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Advances in Immunology, a long established and highly respected publication, presents current developments as well as comprehensive reviews in immunology. Articles address the wide range of topics that comprise immunology, including molecular and cellular activation mechanisms, phylogeny and molecular evolution, and clinical modalities. Edited and authored by the foremost scientists in the field, each volume provides up-to-date information and directions for future research.