Innate Alloimmunity - Part 2: Innate Immunity and Allograft Rejection (eBook)

Foreword 4
Preface 5
Acknowledgements 9
Contents 10
List of Abbreviations 24
Prologue 30
1 Early Appreciation in the 1990s: The Injured Allograft as an Acutely Inflamed Organ and the First Clues to the Existence of Innate Alloimmunity 35
1.1 Introduction 35
1.2 Historical Remarks 36
1.3 The Impact of Postischemic Reperfusion Injury on Acute Allograft Rejection– As Seen in the 1990s 51
1.4 Early Clinical Clues on the Existence of Innate Alloimmunity in the 1990s 94
1.5 Outlook 102
2 Oxidative Allograft Injury Revisited at the Beginning of the New Millennium 113
2.1 Introduction 113
2.2 The Modified and Extended Injury Hypothesis in 2002-2005 114
2.3 Sources and Mechanisms of Reactive Oxygen Species Production During Postischemic Reperfusion Injury and the Role of Antioxidative Defense Systems 118
2.4 Hypoxia- Induced Reactive Oxygen Species Production: An Evolutionary Approach to the Injury Hypothesis 169
2.5 Oxidative Injury to the Allograft During Reperfusion in the Recipient and Under the Condition of Donor Brain Death: The Dual Role of Reactive Oxygen Species 198
2.6 Oxidative Injury-Induced Complement Activation 236
2.7 Appendix: Acute Rejection-Mediated Allograft Injury and Innate Immune Response 238
2.8 Outlook 240
3 Oxidative Injury-Induced, Damage-Associated Molecular Pattern Molecules and Their Pattern Recognition Receptors 261
3.1 Introduction 261
3.2 Injury-Induced Damage-Associated Molecular Patterns Recognized by Toll- Like Receptor- Bearing Cells, for Example, Dendritic Cells: Class I Damage- Associated Molecular Patterns 263
3.3 Injury-Induced Damage-Associated Molecular Patterns Recognized by Special Receptors on Innate Lymphocytes: Class II Damage- Associated Molecular Patterns 321
3.4 Injury-Induced S100 Proteins, Sialic Acid, Uric Acid, Extracellular ATP, and Oxidized DNA: Class III Damage- Associated Molecular Patterns 333
3.5 Injury-Induced Damage-Associated Molecular Patterns Recognized by Natural IgM Antibodies: The Class IV Damage- Associated Molecular Patterns 346
3.6 Outlook 351
4 Role of Pattern Recognition Receptors in Mediating Oxidative Tissue Injury via Activation of Dendritic Cells, Innate Lymphocytes, and T Lymphocytes 371
4.1 Introduction 371
4.2 Pattern Recognition Receptor-Mediated Postischemic Reperfusion Injury: The Extrinsic/ Inflammatory Response of Postischemic Reperfusion Injury 372
4.3 Dendritic Cells That Translate Innate Immune Events to Alloimmunity or Allotolerance 393
4.4 Role of Innate Lymphocytes in Innate Alloimmunity 473
4.5 Role of T Cells in Postischemic Reperfusion Injury 482
5 Experimental and Clinical Findings in Direct and Indirect Support of the Existence of Innate Alloimmunity 507
5.1 Introduction 507
5.2 Experimental Findings in Direct Support for Innate Alloimmunity 507
5.3 Experimental Findings in Indirect Support of Innate Alloimmunity 514
5.4 First Clinical Data in Support of the Concept of Innate Alloimmunity 516
5.5 Outlook 519
6 Chronic Allograft Dysfunction: A Model Disease of Innate Immunity 527
6.1 Introduction 527
6.2 Historical Remarks 527
6.3 Interaction of Damage-Associated Molecular Patterns and Pathogen- Associated Molecular Patterns with Pattern Recognition Receptor- Bearing Vascular Cells and Myofibroblasts and Its Consequences for the Development of Chronic Allograft Dysfunction 550
6.4 Oxidative Allograft Injury and Other Acute and Chronic Risk Factors for the Development of Chronic Allograft Dysfunction – Revisited in Light of Innate Immunity 598
6.5 Outlook 617
6.6 References to Chapter 6 619
7 Immunosuppressive Strategies in Light of Innate Alloimmunity 635
7.1 Introduction 635
7.2 Some Principles 636
7.3 Prevention/Mitigation of Oxidative Injury to the Donor Organ: Potential Therapeutic Targets 661
7.4 Prevention of Development of Immunostimulatory Dendritic Cells: Potential Therapeutic Targets 684
7.5 Blockade/Inhibition of Effector Functions 701
7.6 Some Remarks on Ethics: Who Should Fund Innate Alloimmunity- Suppressing Drugs? 706
7.7 Outlook 713
8 Appendix: Innate Alloimmunity and Blood Coagulation 729
8.1. Introductory remarks 729
8.2 The Evolutionary Linkage Between Injury-Induced Inflammation and Coagulation 729
8.3 Inflammation and Blood Coagulation 732
8.4 Résumé 739
9 Epilogue 743
INDEX 747