Advances in Immunology (eBook)

Cover 1
Copyright Page 5
Contents 6
Contributors 10
Chapter 1: Posttranscriptional Mechanisms Regulating the Inflammatory Response 12
1. Coordinate Regulation of Pro-Inflammatory Proteins 12
2. Control of mRNA Stability 16
3. Translational Inhibition 27
4. Animal Models 30
5. Clinical Significance 34
6. Conclusions 36
Acknowledgments 36
References 37
Chapter 2: Negative Signaling in Fc Receptor Complexes 50
1. Fc Receptors 51
2. Positive Signaling by Activating FcRs 55
3. Negative Signaling by Activating FcRs 61
4. Negative Signaling by Inhibitory FcRs 71
5. Conclusion 81
Acknowledgments 85
References 85
Chapter 3: The Surprising Diversity of Lipid Antigens for CD1-Restricted T Cells 98
1. Introduction: From Molecules to Functions 98
2. CD1 Protein Expression on Antigen-Presenting Cells 101
3. Subcellular Lipid Antigen Processing Pathways 105
4. 3-Dimensional Structures of CD1-beta2-Microglobulin-Lipid Complexes 113
5. Microbial Antigens and Infectious Disease 122
6. Self Antigens, Autoreactivity, and Autoimmune Disease 130
7. Synthetic Lipid Antigens and Prospects for Immunotherapy 136
8. Conclusion: Prospects for Immunotherapy 137
Acknowledgments 139
References 139
Chapter 4: Lysophospholipids as Mediators of Immunity 152
1. Introduction 152
2. LPL Synthesis 154
3. Cell Surface Receptors for LPLs and Their Signaling Pathways 156
4. Expression of LPA and S1P Receptors by Immune Cells and Their Functions in In Vitro Studies 159
5. In Vivo Functions of LPLS in Immune Responses and Inflammation 167
6. Clinical Applications of S1P Receptor Agonists 170
7. Summary 171
References 171
Chapter 5: Systemic Mastocytosis 180
1. Introduction 180
2. Mast Cell Biology 181
3. Biology of Kit 195
4. Mastocytosis 204
5. Prognosis and Predictive Factors 220
6. Treatment 220
7. Supportive Care and Long-Term Management 227
8. Future Therapy 229
9. Conclusions 231
Acknowledgment 231
References 231
Chapter 6: Regulation of Fibrosis by the Immune System 256
1. Introduction 256
2. Fibrotic Disease Pathogenesis 257
3. Cellular Mediators of Fibrosis 260
4. Inflammatory Chemokines that Regulate Fibrosis 272
5. The Role of Integrins in Regulating the Fibrotic Response 275
6. Other Potential Targets for Anti-Fibrotic Therapy 279
7. Conclusions 281
References 284
Chapter 7: Immunity and Acquired Alterations in Cognition and Emotion: Lessons from SLE 300
1. Introduction 301
2. Lupus 304
3. Neuropsychiatric Lupus 306
4. Mechanisms of NPSLE 307
5. Mouse Models of NPSLE 309
6. Peptide Reactivity of DNA-Reactive Antibodies 309
7. Presence of DWEYS-Reactive Antibodies in Murine and Human SLE 311
8. Proteins Harboring the D/E W D/E Y S/G Concensus Sequence: Glutamate Receptors 311
9. Antibody-Mediated Neurotoxicity 313
10. A Murine Model for Antibody-Mediated Neuronal Death 315
11. Antibody-Mediated Neurotoxicity in the Amygdala 318
12. Evidence that Antibodies Are Involved in NPSLE in Patients 319
13. Anti-Peptide Antibody Activates Prolactin Secretion 320
14. Anti-Peptide Antibodies and Manifestations of NP-SLE 321
15. Implications for SLE 321
16. Implications for Human Pathobiology 322
References 322
Chapter 8: Immunodeficiencies with Autoimmune Consequences 332
1. Autoimmune Manifestations in Primary Immune Deficiencies: Relevance and Mechanisms 333
1.1. Introduction 333
1.2. Primary Immunodeficiencies Associated with Autoimmunity 333
2. AIRE, Central Tolerance, and the Pathophysiology of Autoimmune Polyendocrinopathy 335
2.1. Clinical and Immunological Features of APECED 335
2.2. Molecular Genetics of APECED 340
2.3. Cellular Expression of the AIRE Protein 341
2.4. Immunobiology of AIRE 344
3. Defective AIRE Expression Explains the Pathophysiology of Autoimmunity in Omenn Syndrome 348
3.1. Omenn Syndrome: Clinical and Laboratory Features 348
3.2. Molecular Pathophysiology of Omenn Syndrome 350
3.3. Unraveling the Molecular Basis of Immune-Mediated Damage in Omenn Syndrome: Implications for Other Forms of T Cell Immunodeficiency with Autoimmunity 352
4. CD4+ CD25+ Regulatory T Cells and the Pathophysiology of IPEX (Immunodysregulation - Polyendocrinopathy - Enteropathy - X-linked) 357
4.1. IPEX Syndrome: Clinical and Laboratory Features 357
4.2. The Mouse Model for IPEX 363
4.3. Molecular and Cellular Pathophysiology of IPEX 364
5. Concluding Remarks 368
Acknowledgments 370
References 370
Index 382
Contents of Recent Volumes 396