Innate Alloimmunity - Part 2: Innate Immunity and Allograft Rejection

Foreword

Preface

Acknowledgements

Contents

List of Abbreviations

Prologue

1 Early Appreciation in the 1990s: The Injured Allograft as an Acutely Inflamed Organ and the First Clues to the Existence of Innate Alloimmunity

1.1 Introduction

1.2 Historical Remarks

1.3 The Impact of Postischemic Reperfusion Injury on Acute Allograft Rejection– As Seen in the 1990s

1.4 Early Clinical Clues on the Existence of Innate Alloimmunity in the 1990s

1.5 Outlook

2 Oxidative Allograft Injury Revisited at the Beginning of the New Millennium

2.1 Introduction

2.2 The Modified and Extended Injury Hypothesis in 2002-2005

2.3 Sources and Mechanisms of Reactive Oxygen Species Production During Postischemic Reperfusion Injury and the Role of Antioxidative Defense Systems

2.4 Hypoxia- Induced Reactive Oxygen Species Production: An Evolutionary Approach to the Injury Hypothesis

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

2.6 Oxidative Injury-Induced Complement Activation

2.7 Appendix: Acute Rejection-Mediated Allograft Injury and Innate Immune Response

2.8 Outlook

3 Oxidative Injury-Induced, Damage-Associated Molecular Pattern Molecules and Their Pattern Recognition Receptors

3.1 Introduction

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

3.3 Injury-Induced Damage-Associated Molecular Patterns Recognized by Special Receptors on Innate Lymphocytes: Class II Damage- Associated Molecular Patterns

3.4 Injury-Induced S100 Proteins, Sialic Acid, Uric Acid, Extracellular ATP, and Oxidized DNA: Class III Damage- Associated Molecular Patterns

3.5 Injury-Induced Damage-Associated Molecular Patterns Recognized by Natural IgM Antibodies: The Class IV Damage- Associated Molecular Patterns

3.6 Outlook

4 Role of Pattern Recognition Receptors in Mediating Oxidative Tissue Injury via Activation of Dendritic Cells, Innate Lymphocytes, and T Lymphocytes

4.1 Introduction

4.2 Pattern Recognition Receptor-Mediated Postischemic Reperfusion Injury: The Extrinsic/ Inflammatory Response of Postischemic Reperfusion Injury

4.3 Dendritic Cells That Translate Innate Immune Events to Alloimmunity or Allotolerance

4.4 Role of Innate Lymphocytes in Innate Alloimmunity

4.5 Role of T Cells in Postischemic Reperfusion Injury

5 Experimental and Clinical Findings in Direct and Indirect Support of the Existence of Innate Alloimmunity

5.1 Introduction

5.2 Experimental Findings in Direct Support for Innate Alloimmunity

5.3 Experimental Findings in Indirect Support of Innate Alloimmunity

5.4 First Clinical Data in Support of the Concept of Innate Alloimmunity

5.5 Outlook

6 Chronic Allograft Dysfunction: A Model Disease of Innate Immunity

6.1 Introduction

6.2 Historical Remarks

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

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

6.5 Outlook

6.6 References to Chapter 6

7 Immunosuppressive Strategies in Light of Innate Alloimmunity

7.1 Introduction

7.2 Some Principles

7.3 Prevention/Mitigation of Oxidative Injury to the Donor Organ: Potential Therapeutic Targets

7.4 Prevention of Development of Immunostimulatory Dendritic Cells: Potential Therapeutic Targets

7.5 Blockade/Inhibition of Effector Functions

7.6 Some Remarks on Ethics: Who Should Fund Innate Alloimmunity- Suppressing Drugs?

7.7 Outlook

8 Appendix: Innate Alloimmunity and Blood Coagulation

8.1. Introductory remarks

8.2 The Evolutionary Linkage Between Injury-Induced Inflammation and Coagulation

8.3 Inflammation and Blood Coagulation

8.4 Résumé

9 Epilogue

INDEX