Advances in Immunology (eBook)

Front Cover 1
Advances in Immunology 4
Copyright 5
Contents 6
Contributors 10
Chapter One: Group 2 Innate Lymphoid Cells in the Lung 12
1. Introduction 12
2. General Features of ILC2s 13
3. Lung ILC2s at Resting Condition 14
4. Regulation and Function of Lung ILC2s 17
5. Potential Crosstalk Between ILC2s and Other Immune Cells 18
6. Roles of ILC2s in Asthma and Allergic Airway Responses 19
7. Roles of ILC2s in Allergic Airway Diseases in Humans 22
8. Concluding Remarks 23
References 24
Chapter Two: The Ubiquitin System in Immune Regulation 28
1. Introduction 29
1.1. The ubiquitin system 29
1.2. Deubiquitination 30
1.3. Protein ubiquitination in the immune responses 31
2. E3 Ligases in T-Cell Activation and Anergy 32
2.1. Cbl-b 34
2.2. Itch 35
2.3. GRAIL 36
2.4. TRAF6 37
2.5. Peli1 38
2.6. Roquin 39
3. E3 Ligases in T-Cell Differentiation 39
3.1. Tregs 40
3.2. Th1 cells 43
3.3. Th2 cells 43
3.4. Th17 cells 44
4. Ubiquitination in NF-.B Signaling 45
4.1. TNFR1 signaling 45
4.2. IL-1R/TLR4 signaling 51
4.3. T-cell receptor signaling 53
4.4. Noncanonical NF-.B signaling: CD40 56
5. Ubiquitination in Hematopoiesis 57
5.1. E2 enzyme 58
5.2. RING finger E3s 58
5.3. HECT-type E3 61
5.4. Deubiquitinating enzymes 62
6. Concluding Remarks 62
Acknowledgments 64
References 64
Chapter Three: How Immunoglobulin G Antibodies Kill Target Cells: Revisiting an Old Paradigm 78
1. Introduction 79
1.1. The beginnings of antibody-dependent cytotoxicity 80
1.2. Fc.-receptors as effector molecules in ADCC reactions 82
2. How an ADCC Works In Vivo: Insights from Mouse In Vivo Model Systems 85
2.1. IgG-mediated depletion of B cells 85
2.2. IgG-dependent therapy of solid tumors 90
3. Relevance of the Mouse Studies for the Human System 95
4. Outlook 97
Acknowledgments 98
References 98
Chapter Four: A Transendocytosis Perspective on the CD28/CTLA-4 Pathway 106
1. Introduction 107
1.1. The problem of immune self-tolerance 107
2. The CD28 Pathway 108
2.1. CD28 in the thymus 109
2.2. CD28 and Treg homeostasis 110
2.3. CD28 signals and T cell activation 112
2.4. CD28 and T cell differentiation 113
2.5. CD28 and memory responses 114
2.6. CD28 and anergy 115
2.7. CD28 and metabolism 116
3. CD80 and CD86: The Ligands for CD28 and CTLA-4 117
4. CTLA-4 121
4.1. Cell biology of CTLA-4 122
4.2. CTLA-4 function 124
4.2.1. A cell-extrinsic function for CTLA-4 in vivo 125
4.2.2. CTLA-4 and Treg 126
5. Transendocytosis as a Model of CTLA-4 Function 127
5.1. CTLA-4-expressing cells can reduce the levels of ligand on APC 129
5.2. Transendocytosis exploits the biophysical ligand-binding characteristics of CTLA-4 130
5.3. Transendocytosis explains the requirement for ligand sharing by CD28 and CTLA-4 130
5.4. Transendocytosis is a cell-extrinsic, ligand-dependent, CD28-dependent mechanism 131
5.5. Transendocytosis exploits the complex trafficking behavior in CTLA-4 132
5.6. Suppression by transendocytosis is easily overridden 132
6. An Integrated Perspective on CD28 and CTLA-4 133
References 134
Chapter Five: How to Trigger a Killer: Modulation of Natural Killer Cell Reactivity on Many Levels 148
1. Introduction 149
2. Early Notions About the Regulation of NK Cells 150
2.1. Inhibitory receptors 150
3. Activating NK Cell Receptors 152
3.1. Immunoreceptor tyrosine-based activation motif-based activating receptors 152
3.2. NKG2D 153
3.3. Immunoreceptor tyrosine-based switch motif-based receptors 154
3.4. DNAM-1, NKp80, and NKp65 154
3.5. Common activating signaling pathways 155
4. Regulation of Responsiveness During NK Cell Development 156
4.1. NK cell education 157
5. Activating Resting Mature NK Cells 161
5.1. NK cell activation via CD16 161
5.2. Synergistic signals for the activation of NK cells 162
6. Activation of Cytokine-Stimulated NK Cells 164
7. Same Receptor: Different Signals 165
8. The Reactivity of Memory NK Cells 167
8.1. Cytokine-induced memory-like cells 168
8.2. MCMV-induced memory cells 170
8.3. Liver-restricted memory NK cells 171
9. Outlook 172
Acknowledgments 172
References 173
Chapter Six: Roles for Helper T Cell Lineage-Specifying Transcription Factors in Cellular Specialization 182
1. Introduction 183
2. Specialized CD4+ Helper T Cells 184
3. Expanding View of Specialized Helper T Cell Subtypes 185
4. Hybrid Helper T Cell Phenotypes 187
5. Mechanisms: How Are the Complex Phenotypes Established? 188
6. Helper T Cell Lineage-Specifying Transcription Factors 189
7. Epigenetic States During Cellular Differentiation 190
8. Role for T-Bet in Regulating Epigenetic States 191
9. T-bet and Its Interacting Partners 193
10. T-bet and Bcl-6: Complex Functional Implications 194
11. Assessing Stability Versus Flexibility of Helper T Cell Subtypes 195
12. Epigenetic States 196
13. Expression of Cell Surface Receptors 198
14. Additional Regulatory Proteins 198
15. Signaling Cascades 200
16. Complexity of Factors Involved in Predicting Stability/Flexibility of Specialized Helper T Cells 200
17. Summary of Concepts Related to Stability and Flexibility in Helper T Cells 203
18. Role for ``CD4+ Helper T Cell´´ Lineage-Specifying Transcription Factors in Other Cell Types 204
19. Innate Lymphoid Cells 204
20. The Expression of the Th2-Cytokine Locus in ILC Versus Th2 Cells 205
21. Mechanisms That Contribute to the Development of ILC Versus Specialized Helper T Cells 206
22. Lineage-Specifying Transcription Factor Activity in Unique Cellular Settings 207
23. Summary and Future Challenges 209
Acknowledgments 210
References 211
Chapter Seven: MHC Class I Recognition by Monocyte-/Macrophage-Specific Receptors 218
1. Introduction 219
1.1. Major histocompatibility complex as a recognized molecule of allografted tumor cells undergoing rejection 219
1.2. Allograft rejection by cytotoxic T lymphocyte 220
1.3. Three fundamental issues in T-cell-mediated allorecognition 221
2. Three Types of Cytotoxic Cells Infiltrating into the Rejection Site of Allografts 223
2.1. Allograft-induced macrophages cytotoxic against allografts 223
2.1.1. In vivo distribution of cells cytotoxic against allografts 223
2.1.2. In situ effector cells cytotoxic against allografts 224
2.1.3. Allograft rejection by simultaneous inoculation of AIM 225
2.1.4. Failure to reject allografts after elimination of macrophages 225
2.1.5. Morphology of AIM 226
2.2. AIM-2 cytotoxic against tumor cells 228
2.3. CTLs cytotoxic against donor-type lymphoid cells or lymphoid allografts 229
3. Mechanisms of Allograft Rejection 232
3.1. Role of T cells in AIM-mediated allograft rejection 232
3.2. Allo-MHC-recognition by AIM 234
3.2.1. H-2 haplotype-dependent cold target inhibition 234
3.2.2. Antibody-independent allo-MHC-recognition 234
3.3. Cyototoxic mechanisms of AIM against allografts 235
3.3.1. Cell-to-cell contact-dependent and NO- and TNF-a-independent cytotoxicity 235
3.3.2. Ca2+- and ``bite-off´´-dependent and perforin- and Fas-independent apoptotic cell death 236
4. Tolerance to Skin Allografted onto CD4, But Not onto CD8, Knockout Mice 238
5. Three Types of Cytotoxic Cells Infiltrating into Rejection Site of Allografted Skin 238
6. Establishment of mAbs Against AIM 239
6.1. Four kinds of mAbs specific for activated macrophages including AIM 239
6.2. R12 and R15 mAbs specific for AIM 240
7. Monocyte/Macrophage MHC Receptors on AIM 241
7.1. Mouse MMR1 recognizes H-2Dd molecules 241
7.2. Mouse MMR2 recognizes H-2Kd molecules 243
7.3. Human homolog of mouse MMR1 and its ligand 245
7.4. Human homolog of mouse MMR2 and its ligands 247
8. Establishment of H-2Dd- and/or H-2Kd-Transgenic C57BL/6 Mice 249
9. Establishment of C57BL/6 Mice-Lacking MMR1 and/or MMR2 250
10. Graft-Versus-Host Disease and Graft-Versus-Leukemia Effect 252
11. Conclusions 252
Acknowledgments 253
References 253
Chapter Eight: Regulation of Regulatory T Cells: Epigenetics and Plasticity 260
1. Introduction 261
2. Generation of nTregs in the Thymus 262
3. Factors Involved in Foxp3 Expression 264
3.1. NFAT 265
3.2. c-Rel 265
3.3. AP-1 266
3.4. Nr4a 266
3.5. STAT5 268
4. Generation of Tregs by TGF-ß 269
5. Differences Between nTregs and iTregs 270
6. Epigenetic Changes in Tregs and Their Role in Treg Stability 271
7. Treg Stability and Its Implication in Immunological Diseases 272
8. Factors that Control Treg Stability 274
9. Conclusion 277
References 277
Index 286
Contents of Recent Volumes 296
Color Plates 310