Volker Oberle, PhD, is the EFI-Director of the Laboratory for Transplantation Immunology at Jena University Hospital. He studied chemistry and biochemistry at the Universities of Freiburg and Halle-Wittenberg, is a DGI-certified Fachimmungenetiker and holds an ESHI diploma.

Preface xxiii Part I Biological Basics 1 1 Innate Immune Defence 3Margot Lepage and Valérie Dubois 1.1 Introduction 3 1.2 Anatomical Barriers and Initial Chemical Defenses 3 1.3 The Complement System 6 1.4 Danger Recognition 8 1.5 Inflammatory Reaction and Effector Cells of the Innate Immune Response 16 1.6 Bridging Innate and Adaptive Immunity 27 1.7 Conclusion 29 1.8 Perspective: The Concept of Trained Immunity 31 Abbreviations 32 References 35 2 Specific Immune Defence 39Eric Spierings 2.1 Introduction 39 2.2 Components of the Adaptive Immune System 40 2.3 The Major Histocompatibility Complex and Adaptive Immune Responses 43 2.4 T Cell-Mediated Immune Response 47 2.5 B Cell-Mediated Immune Response 52 2.6 Receptors of the Specific Immune System 58 2.7 Immunological Memory 62 2.8 Conclusion/Summary/Future 64 References 65 3 The HLA/MHC System 69Neema Mayor and James Robinson 3.1 Introduction 69 3.2 IPD-IMGT/HLA Database 82 3.3 Limits to HLA Variation 83 3.4 Summary 84 References 84 4 The HNA System 89Anthony Poles 4.1 Neutrophils and Associated Functions 89 4.2 Human Neutrophil Antigens (HNA) 90 4.3 Clinical Conditions Associated with HNA Specific Antibodies 96 References 98 5 Natural Killer Cell Receptors 101Dianne De Santis and Lucy Sullivan 5.1 Introduction 101 5.2 NK Cells 101 5.3 "Missing Self" Hypothesis and Hybrid Resistance 102 5.4 NK Cell Receptors 103 5.5 Killer Immunoglobulin-Like Receptors (KIRs) 104 5.6 CD94-NKG2 Receptors 113 References 119 6 The HPA System 127Romy Pothof, Leendert Porcelijn, and Masja de Haas 6.1 Platelet Antigens 127 6.2 Human Platelet Antigens 127 References 131 7 Other Polymorphic Systems 133Hana Rohn and Vera Rebmann 7.1 Introduction 133 7.2 The Structure of HLA-like MICA and MICB Molecules 133 7.3 The Functions of HLA-like MICA and MICB Molecules 134 7.4 The Expression of HLA-like MICA and MICB Molecules 134 7.5 The Polymorphisms of HLA-like MICA and MICB Molecules and Functional Consequence 135 7.6 Nonclassical HLA Class I 136 7.7 Key Differences Between Nonclassical HLA Class I and Classical HLA Class I Molecules 136 7.8 The Expression of HLA-E Molecules 137 7.9 The HLA-E Peptide Presentation Controls the Functional Interaction with NK and T Cells 137 7.10 The Polymorphisms of HLA-E and Its Influence on Gene Expression 139 7.11 The Expression of HLA-G 139 7.12 The Unique Structural Features of HLA-G 140 7.13 The Functions of HLA-G are Directed by the Structural Features 141 7.14 The Polymorphisms of HLA-G and Its Impact on Gene Expression 142 7.15 The Expression of HLA-F 143 7.16 The Functions of HLA-F are Directed by Its Structural Features 144 7.17 The Polymorphisms of HLA-F and Its Impact on Gene Expression 144 7.18 Summary 145 References 147 Part II Clinical Applications 155 8 Basic Concepts of Organ Transplantation 157Ilias Doxiadis and Claudia Lehmann 8.1 Introduction 157 8.2 Overview of the Decision-Making Procedure 158 8.3 Registration and Waiting List 159 8.4 Procurement of the Organs 161 8.5 Postmortem Allocation 163 8.6 The Crossmatch 166 8.7 Prospective Outlooks 167 References 168 9 Basic Concepts of Organ Rejection 171Volker Oberle and Melanie Gerth 9.1 Introduction 171 9.2 The Immune System: Balancing Self and Foreign Recognition 171 9.3 Antigens: Self and Foreign? 172 9.4 Immune Tolerance: Maintaining the Balance 172 9.5 Autoimmunity 173 9.6 Foreign Recognition Leading to Rejection 173 9.7 GvHD 175 9.8 Conclusion 175 References 177 10 Treatment of Organ Rejection 179Marie Dirix, Britt Ceuleers, and Johan W. De Fijter 10.1 Introduction 179 10.2 Prevention of Rejection: Induction and Maintenance Immunosuppression 180 10.3 Treatment of Rejection 192 10.4 Conclusions 198 References 198 11 Stemcell Transplantation 209Effie W. Petersdorf 11.1 State-of-the-Art of Allogeneic Hematopoietic Cell Transplantation 209 11.2 Haploidentical HCT 212 11.3 Immunobiology of Haploidentical Related Donor Transplantation 215 11.4 Selection of Related Donors for Transplantation: Non-HLA Factors 229 11.5 Concluding Remarks 231 References 232 12 Stemcell Transplantation from Unrelated Donors 251Volker Oberle 12.1 Introduction 251 12.2 The Search for Unrelated Donors 251 12.3 Laboratory Work 254 12.4 Clinical Outcomes of Unrelated Stem Cell Transplantation 257 12.5 Challenges in Unrelated Stem Cell Transplantation 257 12.6 Future Directions and Emerging Technologies 258 12.7 Conclusion 258 References 258 13 Chimerism Testing in Stem Cell Transplantation 263Andreas Heinold 13.1 Introduction 263 13.2 Methods for Molecular Genetic Chimerism Testing 264 13.3 Sensitivity of Molecular Genetic Chimerism Testing 270 13.4 Choice of Markers for Quantification 271 13.5 Chimerism Testing for Nonmalignant Disorders 272 13.6 Reporting Chimerism 272 13.7 Time Course of Chimerism Analyses 273 13.8 Advantages and Disadvantages of Highly Sensitive Chimerism Testing 275 13.9 Cell Sources for Identifying Recipient- and Donor-Specific Markers 275 13.10 Cell Sources for Chimerism Monitoring 276 13.11 Intervals for Chimerism Testing 276 13.12 Chimerism-Related Diagnostics 277 References 279 14 Disease Associations with HLA Alleles 285Eduard Palou 14.1 HLA and Disease Association 285 14.2 Mechanisms of HLA and Disease Associations 286 14.3 Autoimmune Diseases Associated with HLA 289 14.4 Other Diseases Associated with HLA 295 14.5 Laboratory Diagnostics 298 14.6 Concluding Remarks 299 References 300 15 Drug Associations with HLA Alleles 303Melanie Gerth and Thomas M. C. Binder 15.1 Introduction 303 15.2 Classification of Drug Hypersensitivity Syndromes 304 15.3 Immunopathogenesis of Drug Hypersensitivity Syndromes 307 15.4 HLA and Hypersensitivity Reactions 310 15.5 Clinical Implications of HLA Testing 321 15.6 Future Directions 323 15.7 Conclusion 323 References 324 16 Diseases in the Field of Transfusion Medicine 333Andrea Bontadini, Roberto Crocchiolo, and Luca Mascaretti 16.1 Introduction 333 16.2 Platelet Transfusion Refractoriness 334 16.3 Transfusion-Related Adverse Events 340 16.4 Neonatal Alloimmune Neutropenia 345 16.5 Fetal and Neonatal Alloimmune Thrombocytopenia 347 16.6 Conclusions 349 References 349 Part III Methods in Immunogentics and Histocompatibility 359 17 Isolation and Purification of Test Material 361Ingrid Faé 17.1 DNA Extraction 361 17.2 RNA Extraction 365 17.3 cfDNA Extraction 366 17.4 Cell Preparation 368 Abbreviations 372 References 372 18 HLA-Antibody Determination 375Stefan Schaub, Caroline Wehmeier, and Gideon Hönger 18.1 Overview and Characteristics of Different HLA Antibody Detection Assays 375 18.2 The Multiplex Bead Array Platform (Luminex®) 379 18.3 Additional Methods/Tools 387 References 393 19 Low/Medium-Resolution HLA Typing 399Milena Ivanova and Velizar Shivarov 19.1 Introduction 399 19.2 Cellular and Serological Tests for HLA Typing 400 19.3 DNA-based Methods for HLA Low-Resolution Typing 401 References 408 20 High-Resolution HLA Typing 413EH Rozemuller and W. Mulder 20.1 Introduction 413 20.2 HLA Genes 414 20.3 PCR Amplification 414 20.4 Gene Capture Method 417 20.5 SBT by Sanger Sequencing 417 20.6 HLATypingbyNGSSBT 419 20.7 HLA Typing by Short-read Sequencing 421 20.7.1 Paired-end Sequencing 423 20.8 HLA Typing by Long-read Sequencing 424 20.9 Ambiguities 425 20.10 Phasing 427 20.11 Data Analysis 429 20.12 Special Cases 437 Abbreviations 439 References 440 21 Crossmatching in Transplantation 443Melanie Gerth and Volker Oberle 21.1 Introduction 443 21.2 The Mechanism of Crossmatching 444 21.3 Crossmatch Methods 444 21.4 Summary 452 References 453 22 Determination of Antibodies and Typing in the HPA System 455Volker Kiefel 22.1 Introduction to Platelet Antibody and Antigen Testing 455 22.2 Principles of Antibody Testing 455 22.3 Additional Techniques 457 22.4 Protocol: Platelet Suspension Immunofluorescence Test 458 22.5 Protocol: Isolation of Platelets for Serological Testing 459 22.6 Protocol: Monoclonal Antibody Immobilization of Platelet Antigens Assay (MAIPA) 460 22.7 New Developments for Platelet Antibody Detection 464 22.8 HPA-Antigen Testing 464 22.9 Concluding Remarks 465 References 466 23 KIR Genotyping 469Dianne De Santis, Katherine M. Kichula, and Paul J. Norman 23.1 Complexity of KIR Genomic Region 469 23.2 KIR Genotyping 471 References 479 24 Determination of Antibodies and Typing in the HNA System 485Anthony Poles 24.1 Introduction to Granulocyte Antibody and Antigen Testing 485 24.2 Principles of Antibody Testing 485 24.3 HNA Typing Techniques 490 References 491 25 Determination and Typing of Other Polymorphic Systems 495Falko M. Heinemann, Vera Rebmann, and Rafael Tomoya Michita 25.1 Introduction 495 25.2 MICA/B Allele Typing Methods 495 25.3 MICA/B Single Nucleotide Variant Genotyping Methods 508 25.4 HLA-G Allele Typing Methods 508 25.5 HLA-E Typing Methods 515 25.6 HLA-F Typing Methods 518 25.7 Technical Aspects for the Detection of Anti-MICA Antibodies in Transplantation Patients 521 References 523 Part IV Regulatory Aspects 535 26 Regulations in Histocompatibility and Immunogenetics: Accreditation, External Proficiency Testing, Quality Management 537Eduard K. Petershofen, Andrea Harmer, and Luca Mascaretti 26.1 Introduction 537 26.2 Legal Requirements 537 26.3 National Guidelines 538 26.4 Standards 538 26.5 Elements of Quality Management Systems 540 26.6 Practical Considerations for a QMS 540 26.7 Licensing, Accreditation, and Certification 544 26.8 EFI Accreditation Program 545 26.9 ISO Standards 546 26.10 Future Perspectives 547 Table of Acronyms and Abbreviations 548 References 549 Index 561