How the Immune System Recognizes Self and Nonself (eBook)

How the Immune System Recognizes Self and Nonself 2
Daisuke Kitamura 3
Immunoreceptors and Their Signaling 3
Preface 5
Contents 7
List of Authors 10
Color Plates 13
1 Recognition of Pathogens: Toll-Like Receptors 17
1.1 Introduction 17
1.2 Innate Immunity 17
1.2.1 Immune Responses in Drosophila 18
1.2.2 Discovery of TLR in Mammals 19
1.3 Pathogen Recognition by TLR 21
1.4 Toll-Like Receptor Signaling Pathways 25
1.4.1 Proinflammatory Cytokine Pathways 26
1.4.2 TRIF-Dependent Pathway 28
1.4.3 TLR7- and TLR9-Mediated Type I IFN Production 31
1.4.4 Other Molecules Involved in TLR Signaling 31
1.5 Negative Regulation of TLR Signaling 33
1.6 Conclusion and Future Prospects 38
References 39
2 Strategies of Natural Killer (NK) Cell Recognition and Their Roles in Tumor Immunosurveillance 53
2.1 Introduction: An Interesting Epistemological Case 53
2.2 Natural Killer Cells in Innate Immunity 54
2.3 Natural Killer Cell Recognition of “Missing-Self”: An Array of Inhibitory Cell Surface Receptors 56
2.4 Complexity of the “NK Cell Zipper” 60
2.4.1 Natural Cytotoxicity Receptors 61
2.4.2 NKG2D 62
2.4.3 CD16 63
2.4.4 Activating Homologues of Inhibitory MHC Class I Receptors 64
2.4.5 Natural Killer Cell Co-stimulatory and Adhesion Molecules 65
2.5 Coordination of NK Cell Activating and Inhibitory Signals in Cancer 69
2.6 Programming a “Natural” Killer: Steady-State and Situation- Speci . c Regulation of NK Effector Functions 78
2.6.1 Natural Killer Responsiveness to MHC Class I and Missing- Self 79
2.6.2 Natural Killer Responsiveness to Activating NK Ligands 82
2.7 Conclusions and Perspectives: NK Cells, “Self Versus Nonself,” and Cancer 83
References 83
3 Recent Progress on Paired Immunoglobulin- Like Receptors 98
3.1 Introduction 98
3.2 PIR Expression by Early Hematopoietic Cells 100
3.3 PIR Expression by Thymocyte Progenitors 101
3.4 Differentiation Potential of PIR+ and PIRLymphoid Progenitors 102
3.5 PIR Expression by Dendritic Cell Precursors 104
3.6 PIR Ligands 105
3.7 Paired Immunoglobulin-Like Receptor Function 107
3.8 Conclusion 109
References 110
4 Self–nonself Recognition through B-Cell Antigen Receptor 114
4.1 Introduction 114
4.2 Signal Transduction from BCR 116
4.3 BCR Signaling Pathways for Immune Response 127
4.4 BCR Signaling Pathways for Self Tolerance 4.4.1 Clonal Deletion 131
4.5 Concluding Remarks: To Respond or Not to Respond, That is the Question 135
References 137
5 How Do T Cells Discriminate Self from Nonself? 148
5.1 Introduction 148
5.2 Structure of the TCR Complex 150
5.3 How Does the 155
5.4 TCR Assembly During Intrathymic Development 162
5.5 How TCRs Bind pMHC 164
5.6 What Causes the Restriction in Orientation Imposed on TCR – pMHC Interactions? 171
5.7 Rationalizing the Purpose of TCR 174
5.8 Recessive and Dominant Tolerance 176
5.9 Evolutionary Perspectives 177
References 179
6 Fc Receptors 187
6.1 Introduction 187
6.2 Fc Receptors—Basic Facts 188
6.3 Fc Receptor Signaling 192
6.3.1 Signaling Pathways of Activating Fc Receptors 192
6.3.2 Inhibitory Signaling Pathways 194
6.4 Fc Receptor Biology In Vivo 195
6.4.1 The Role of the Inhibitory Receptor in the Afferent and Efferent Immune Response 196
6.4.2 FcgRIIB and Dendritic Cells 196
6.4.3 Loss of the Inhibitory Receptor on B Cells — Horror Autotoxicus 197
6.4.4 The Role of FcgRIIB in the Efferent Response: Controlling Innate Immune Effector Cell Activation 200
6.4.5 The Activating Fc Receptors in the Efferent Response 200
6.4.6 The Missing Piece in the IgG-Puzzle: Identi.cation of FcgRIV 202
6.4.7 Isotype Speci.c Fcg- Receptor Engagement and Differential Regulation by FcgRIIB 203
6.4.8 The Effect of Cytokines on FcR Expression 204
6.5 Summary 206
References 206
7 Self and Nonself Recognition by Coreceptors on B Lymphocytes: Regulation of B Lymphocytes by CD19, CD21, CD22, and CD72 213
7.1 Introduction 213
7.2 Regulation of B Cells by CD19/CD21 Complex 214
7.3 Regulation of B Cells by CD22 220
7.4 Regulation of B Cells by CD72 224
7.5 Self and Nonself Recognition by Coreceptors on B cells 226
References 227
8 Co-Receptors in the Positive and Negative Regulation of T- Cell Immunity 235
8.1 Introduction 235
8.2 Positive Co-stimulatory Molecules 238
8.3 Negative Co-stimulatory Molecules 243
8.4 Conclusion 250
References 251
Index 260