Transplantation

ISBN-13: 9783642663949 / Angielski / Miękka / 2011 / 1070 str.

Johann W. Masshoff

Opis

Organ transplantation has almost disappeared from headlines in the daily press, possibly because it failed to fulfill exaggerated expectations. Transplanta tion pathology has become more and more important, not only with relation to therapeutic transplantations but even more in its fundamental theories. There is some analogy here to the development in space science where spectacular achievements were followed by sobering frustrations and where, for the time being, the effect on technology is more fruitful than the outcome of the original far-reaching projects. That transplant rejection was defined, in most of its stages, as an immunologic process, has given many new impulses to immunology in general. Transplantation assays have become a pet experiment in immunobiology and an abundant source of general information and knowledge. The implications of such a development could not be predicted when the present volume was outlined and planned. In accordance with the concept of WILLI MASSHOFF, general transplantion pathology was given a central position as a fundamental science, while the chapters on the transplantation of various tissues are of a more paradigmatic character. It was MASSHOFF who invited competent authors and who managed to balance their articles, despite some overlapping, so as to draw a comprehensive picture of contemporary transplanta tion pathology. WILLI MASSHOFF died while he was editing the first manuscripts. As co-editors we have undertaken to complete the publication that we began together."

Spis treści

The Main Histocompatibility System in Man.- A. Introduction.- B. Historical Background.- C. Methodology and Serological Considerations.- I. Leukoagglutination.- II. Lymphocyte Cytotoxicity.- III. Platelet Complement Fixation.- IV. Serum Sources.- 1. Polytransfused Patients.- 2. Pregnancy.- 3. Immunization of Human Volunteers.- 4. After Organ Transplantation.- 5. “Natural” Lymphocytotoxins.- 6. Immunization of Animals.- D. Genetics of the HL-A System.- E. Heterogeneity and Cross-Reactivity of HL-A Antigens.- F. HL-A, Mixed Lymphocyte Culture (MLC), Cell-Mediated Lympholysis (CML), and Cellular Immunity.- G. HL-A System and Clinical Transplantation.- I. Skin Graft Survival.- II. Kidney Transplantation.- III. Variability in the Host Immune Response.- IV. Donor Selection for Kidney Transplantation.- V. Bone Marrow Transplantation.- H. HL-A System and Human Diseases.- I. HL-A and Hematologic Malignant Diseases.- II. HL-A and Cancer (other than Lymphomas).- III. HL-A and Immunopathic Diseases.- IV. HL-A and Infectious Diseases.- V. HL-A and Rheumatoid Diseases.- VI. HL-A System and Various other Diseases.- I. HL-A System and Blood Transfusion.- J. HL-A System and Disputed Paternity Cases.- K. Conclusions.- References.- Gene Products of the Major Histocompatibility Complex: Biology and Chemistry.- 1. Introduction.- 2. The MHC in Man and Animals.- 2.1 Similarities.- 2.2 Differences.- 3. Biology of Human MHC Products.- 3.1 HL A Antigens.- 3.2 ß2-Microglobulin (ß2m).- 3.3 Ir-Region in Man.- 3.4 Association of HL A with Disease.- 4. Additional Information from Animal Studies.- 4.1 Genetics of the H-2 Complex.- 4.2 I-Region Traits and Functions.- 4.3 Donor Specific Prolongation of Transplant Survival.- 5. Chemistry of Human and Mouse MHC Gene Products.- 5.1 Homology.- 5.2 Membranes and Models.- 5.3 Methods.- 5.4 Biochemistry of HL A/H-2 Antigens.- 5.5 ß-Microglobulin.- 5.6 Immune Response Region Associated Antigens (Ia).- 6. Concluding Remarks.- References.- Lymphocyte—Defined Components of the Major Histocompatibility Complex.- A. Introduction. General Principles of MLC.- B. Technical and Statistical Aspects of Human MLC.- I. Macro- and Micro-Methods.- II. Determination of Non-Stimulation.- 1. Controls.- 2. Statistical Analysis.- 3. Quantitation of MLC Results.- C. Mouse MLC Techniques.- D. Genetics of MLC in Humans.- I. Basic Principles.- II. Correlation of MLC Non-Stimulation in Siblings with Inheritance of the Same HL-A Haplotype.- III. Exceptional Cases of Stimulation and Non-Stimulation.- IV. Association of Stimulation with Four-Locus Region.- V. Minor loci.- VI. MLC and HL-A Typing in Unrelateds.- E. Genetics of MLC in the Mouse.- F. MLC Typing.- I. Principle of Typing—Use of Homozygous Cells.- II. Problems in Defining a “Typing” Response.- G. Cell-Mediated Lympholysis (CML) Reaction.- I. CML in the Human.- II. CML in the Mouse.- III. Relation of CML and MLC.- H. Correlations of MLC with Grafting.- I. Conclusion.- Appendix I. Statistical Definitions.- Appendix II. Definition of Genetic Terms.- Addendum.- References.- Phylogenetic Aspects of Transplantation.- A. Introduction.- B. Transplantation Reactions in Invertebrates Other than Annelids and Echinoderms.- 1. Organelle Transplantation in Protozoans (Sarcodina, Ciliata).- 2. Metazoans—Specificity of Reaggregation in Porifera.- 3. Incompatibility in Cnidaria (Hydrozoa, Anthozoa).- 4. Platyhelminthes and Sipunculida.- 5. Equivocal Incompatibilities in Mollusca (Pelecypoda, Gastropoda, Cephalopoda).- 6. Arthropoda.- 7. Genetic Control in Urochordata.- 8. Summary of Quasi Immunorecognition.- C. Transplantation Reactions in Invertebrates that Reveal Primordial Cell-Mediated Immunity.- I. Short-term Immunologic Memory.- II. Cell and Tissue Responses that Indicate Self Recognition in Echinoderms.- III. Transplantation in Asteroidea.- IV. Short-term Memory.- V. The Earthworm Model.- 1. First- and Second-Set Allograft Rejection in Lumbricus terrestris and Eisenia foetida.- 2. Rejection of First- and Second-Set Xenografts Exchanged between Lumbricus and Eisenia.- 3. Specificity and Anamnesis.- 4. The Cellular Response.- 5. The Role of Temperature in Earthworm Tissue Graft Rejection.- 6. Summary.- D. Transplantation Immunity in Fishes.- I. Introduction.- II. The Hagfish.- III. The Lamprey.- IV. Cartilaginous Fishes.- V. Bony Fishes (Holosteans; Teleosts).- E. Transplantation Immunity in Amphibians.- I. Adult Apodans.- 1. Introduction.- 2. General Description of Autografts and Allografts.- 3. Histopathology.- II. Adult Urodeles.- 1. The Latent Phase.- 2. The Rejection Phase.- 3. The Chronic Rejection Response to Xenografts.- 4. Role of the Thymus in Graft Rejection.- 5. Histologic Differences in Skin.- 6. Suppression of Transplantation Immunity.- III. Anurans.- 1. Larvae.- 2. Bone Marrow Restoration of Transplantation Immunity in Adult Leopard Frogs.- F. Transplantation Immunity in Reptiles.- I. Introduction.- II. The Chronic Response in Turtles.- III. The Importance of Temperature in Turtles.- IV. The Mexican Iguana.- V. The Garter Snake.- References.- Ontogenetic Aspects.- A. Introduction.- B. Ontogeny of Lymphoid Structures.- C. Ontogeny of Transplantation Immunity.- D. Ontogeny of Thymus-Dependent Functions.- E. Concluding Remarks.- References.- Humoral and Cell-Mediated Mechanisms of Allograft Rejection.- A. Introduction.- B. Assay Methods of Cell-Mediated Cytotoxicity (CMC).- C. Cytotoxicity Mediated by Specifically Sensitized T-Cells.- D. In Vivo Formation of Cytotoxic T Lymphocytes.- E. In Vitro Formation of Cytotoxic T Lymphocytes.- F. Mechanism of T-Cell Cytotoxicity.- G. Specificity of Target Cell Destruction by Cytotoxic T Lymphocytes.- H. Antibody-Dependent Cytotoxicity Mediated by Normal Lymphoid Cells.- I. Cytotoxicity Mediated by Macrophages.- K. Relevance of CMC to Allograft Rejection.- L. The Role of Antibody in Allograft Rejection.- References.- Cell Systems Participating in Graft Rejections.- A. Introduction.- B. Lymphocytes.- I. Development of the Immune System and Lymphocyte Subclasses.- 1. Early Ontogenesis of Lymphoid Organs and Cells.- 2. Postnatal Development of the Lymphocytic Systems.- 3. The Central Role of the Thymus.- II. Peripheral Lymphocytes.- 1. Lymphocyte Subclasses.- a) T Cells.- b) B-cells.- c) Null Cells.- 2. The Functions of Peripheral Lymphocytes.- a) Helper and Suppressor Activity.- b) Cell-Mediated Cytotoxicity.- c) Mixed Lymphocyte Cultures.- d) Graft-Versus-Host Reaction (GVHR).- C. Macrophages.- D. Neutrophilic Granulocytes.- E. Other Cells and Structures.- References.- General Tolerance Phenomena.- A. Introduction.- B. Tolerance Phenomena and Other Specific Inhibitions of Immune Reactions.- I. Inhibition States Classified as Immunologic Tolerance.- 1. The Sulzberger-Chase Phenomenon.- 2. Immunologic Paralysis.- 3. Tolerance to Heterologous Serum Proteins.- 4. Tolerance to Other Antigens.- II. Other Antigen-Induced States of Specific Inhibition of the Immune Response.- 1. Immunologic Enhancement.- 2. Immune Deviation.- C. Mechanisms of Immunologic Tolerance.- I. The Relation of Antibody-induced Suppression to Immunologic Tolerance.- II. Cellular Processes in Immunologic Tolerance.- III. Suppressor Cells.- IV. Transplantation Tolerance.- V. Mechanism of Unresponsiveness to Self Components.- D. Conclusions.- References.- Transplantation of Cells: Experimental and Clinical Observations.- A. Introduction.- B. Historical Notes.- C. Cell Types Used for Transplantation and Indications for the Respective Procedure.- I. Experimental Transplantation.- II. Human Transplantation.- 1. Indications for Transplantation of Blood and its Components.- 2. Indications for Transplantation of Bone Marrow.- D. Techniques of Cell Transplantation.- I. Details of Patient Selection.- 1. Selection of the Host.- 2. Selection of the Donor.- II. Preevaluation and Pretreatment of Host and Donor.- 1. Pretreatment of the Donor.- 2. Pretreatment of the Recipient.- III. Procurement of Bone Marrow Cells.- IV. Cell Grafting.- V. Cells other than Bone Marrow Cells used for Transplantation in Man.- VI. Posttransplant Clinical Investigation of Bone Marrow Recipient.- E. Demonstration and Localization of Engrafted Cells.- F. Graft-Host Interactions.- I. Microenvironmental Influences.- II. Graft Rejection.- III. Graft-Versus-Host Reaction (GVHR).- IV. Therapeutic Intervention of Postengraftment Disease.- G. Conclusions.- References.- Skin Grafts in Animals and Man.- A. Introduction.- B. Operational Definition of Transplant Antigens.- C. Morphologic Changes Occurring in Skin Allografts.- I. Sequential Changes in Gross and Microscopic Appearance.- II. Characterization and Quantitation of the Infiltrating Cells.- III. Comparison of Morphologic Events in the Homograft Reaction and in other Hypersensitivity Reactions.- D. The Immune Responses Induced by Skin Grafting.- I. Afferent Phase—Antigen Recognition.- II. Central Phase—Clonal Proliferation, Yielding both Memory and Differentiated Effector Cells.- III. Effector Phase—the Expression of Immunity.- 1. Specific Immune Cytotoxic Mechanisms.- 2. Recruitment of Nonsensitized Effector Cells by Lymphokines Secreted by Sensitized T-Cells.- 3. Local Activation of the Host’s General Inflammatory Response.- 4. Correlation of Immunologic and Pathophysiologic Events with Clinical Skin Graft Rejection Syndromes.- IV. Autoregulatory Phase.- 1. Complete or Partial Tolerance.- a) Conditions Affecting Induction, Maintenance, and Reversal of Immunologic Tolerance.- b) The Absence of Reactive Cells or the Presence of Nonreactive Cells.- c) The Presence of Immunologically Active Lymphocytes Blocked by Serum Factors.- d) Other Alternatives: Suppressive or Regulatory Events Mediated by Lymphocytes on Immune Reactions.- 2. Immunologic Enhancement.- a) General Features of Graft Survival.- b) Relationship Between Organ Vascularity and Immunologic Enhancement.- References.- Transplantation of Connective Tissue.- A. Introduction.- B. General Section.- I. Anatomic Structure of Connective-Tissue Types as it Affects Suitability for Transplantation.- II. Viability and Nonviability: Denaturation of the Graft as it Affects Primary Healing and Restructuring.- III. Biological and Mechanical Merits of Auto-, Homo-, and Heterologous Transplants.- IV. Changes with Age in Connective Tissue as they Affect Transplantation.- V. Immune Reactions in the Transplantation of Living and Preserved Connective Tissue.- VI. Preservation.- VII. Healing.- C. Specific Section.- I. Tendon.- II. Cutis.- III. Fascia.- IV. Dura.- D. Future Prospects.- References.- Transplantation of the Cornea in Man and Animal.- I. Introduction and Historical Background.- II. Basic Principles of Keratoplasty.- A. Terminology.- B. Indications for Keratoplasty.- C. Criteria for Donor Material and Storage.- 1. General.- 2. Donor-Cornea Evaluation (Laboratory and Clinical).- 3. Storage.- D. Surgical Techniques in Keratoplasty.- E. Factors Determining Prognosis of Keratoplasty.- 1. Quality of the Donor-Cornea.- 2. State of the Recipient Cornea.- 3. Other Ocular Disease.- 4. Quality of Surgery.- F. Healing of the Corneal Wound in Keratoplasty.- G. Fate of Donor Cells in Keratoplasty.- III. Unsuccessful Keratoplasty.- A. Nonimmunologic Factors for Graft Failure.- B. Immunologic Reasons for Graft Failure.- IV. Experimental Keratoplasty and Heterografting.- References.- General Pathology of the Transplantation Reaction in Experimental and Clinical Organ Grafts.- A. The Many Facets of the Transplantation Reaction.- I. Introduction.- II. Terminology.- 1. Donor-Recipient Relationship.- 2. Chronologies of Rejection.- III. Elements of the Transplantation Reaction.- 1. Dichotomy of the Immune Response.- 2. T-Helper Cell Mechanisms.- 3. Effector Mechanisms of Cell-Mediated Cytotoxicity.- a) Autonomy of T-Lymphocyte Cytotoxicity.- b) Mediators of the Cellular Immune Reaction.- c) Cell-Mediated Cytotoxicity Independent of Thymus.- IV. Humoral Factors Involved in Graft Rejection.- B. Effector Cells and the Target Cell Injury.- I. Morphology of Infiltrating “Lymphoid Cells”.- 1. Small Lymphocytes.- 2. Medium-Sized Lymphocytes.- 3. Atypical Lymphocytes.- 4. Large Lymphocytes.- 5. Transformed Lymphocytes.- 6. Lymphoid Killer Cells.- 7. Monocytes.- 8. Macrophages.- II. Morphology of the Cell-Mediated Target Cell Destruction in vitro.- 1. Membrane Contact.- 2. Morphology of Cell-Mediated Target Cell Lysis.- 3. Morphology of Antibody-Dependent Cell-Mediated Cytotoxicity.- 4. Other Mechanisms of Cell-Mediated Target Cell Destruction.- III. Features of Antibody-Mediated Injury.- 1. Morphology of the Complement-Dependent Immune Cytolysis.- 2. Relationship Between Immune Complexes and Clotting.- 3. Pathogenesis of Tissue Injury Mediated by Immune Complexes.- C. Pathways of Host Sensitization.- I. Cellular Mechanisms.- 1. Central Reactions.- 2. Recirculation of Immunocompetent Cells.- II. Pathways of Sensitization to Solid Organ Grafts.- 1. Soluble Antigens.- 2. Macrophage-Processed Antigen.- 3. Peripheral Sensitization.- 4. Passenger Leukocytes.- D. Hyperacute Rejection.- I. Pathogenesis.- II. Pathology of the Hyperacute Rejection.- 1. Kidney.- a) Course of Events.- b) Cellular Mechanisms and Mediators Involved in Hyperacute Rejection.- 2. Heart.- 3. Liver.- 4. Lungs.- 5. Pancreas.- III. Nonimmunologically Caused Primary Graft Failure and Damage.- 1. Pretransplantation Anoxemic Lesion.- 2. Mechanical Traumatization.- 3. Morphology of the Pretransplantation Ischemic and Mechanical Damage.- a) Kidney.- b) Heart.- c) Liver.- d) Lung.- e) Pancreas.- E. Accelerated (Delayed Hyperacute) Rejection.- F. Acute (Intermediate) Rejection.- I. Pathogenesis.- 1. Cellular Infiltration and Vascular Lesions.- 2. Mechanisms of Acute Cell-Mediated Graft Rejection.- II. Particular Patterns of Acute Rejection.- 1. Kidney.- 2. Heart.- 3. Liver.- 4. Lung.- 5. Pancreas.- 6. Small Bowel.- G. Chronic or Late Rejection.- I. Arterial Obliterative Lesion.- II. Interstitial Fibrosis, Parenchymal Atrophy and Chronic Cellular Infiltration.- III. Chronic Glomerulopathy.- H. Future Prospects of Organ Transplantation.- I. Current Experience in Organ Transplantation.- II. Histocompatibility Typing.- III. Organ Preservation and Storage.- 1. Simple Hypothermic Storage.- 2. Short-Term Preservation.- 3. Intermediate-Term Storage and Long-Term Preservation.- IV. Artificial Organs.- V. Modification of the Immune Response.- 1. Immunosuppression.- 2. Immunologic Enhancement.- 3. Immunosuppressive Antibodies.- 4. Immunologic Tolerance.- 5. Specific Immunologic Unresponsiveness.- 6. Attempts to Render the Graft Nonantigenic.- VI. Xenotransplantation.- VII. Abbreviations and Definitions.- References.- Bone Transplantation in Animals and in Man.- A. Introduction and Historical Review.- B. Anatomy and Physiology of Intact Bone.- 1. Structural Elements of Bone.- 1.1. Osteoblasts.- 1.2. Osteoclasts.- 1.3. Osteocytes.- 1.4. Collagen.- 1.5. Amorphous Intercellular Substance.- 1.6. Hydroxyapatite.- 2. Transformation of Bone Tissue.- 2.1. Physiologic Transformation.- 2.2. Adaptation of Bone to Mechanical Forces.- 2.3. Pathologic Bone Transformation.- C. Bone Transplantation.- 1. Blood Supply to Transplanted Bone Tissue.- 2. Osteogenesis in Autografts.- 2.1. Osteogenesis in Transplanted Periosteum.- 2.2. Osteogenesis in Transplanted Compact Bone.- 2.3. Osteogenesis in Transplanted Cancellous Bone.- 2.4. Osteogenesis by Induction.- 3. Immunology of Homologous and Heterologous Bone Transplantation.- 3.1. Bone Homografts.- 3.2. Bone Heterografts.- 4. Transplantation of Pretreated Bone Ground Substance.- 5. Conclusions Drawn From the Results of Experimental Bone Transplantation.- D. Clinical Aspects of Bone Transplantation.- 1. Cancellous Bone Autografts.- 2. Clinical Scale of Merit of Autografts.- 3. Graft Bed.- 3.1. Stable, Well-Vascularized Bed.- 3.2. Secondarily Stable Bed With Impaired Vascularization (Pseudarthroses and Fresh Fractures).- 3.3. Continuity Defects of the Long Bones.- 3.4. Grafting into a Septic Milieu.- E. Conclusion.- References.- Radiation-Induced Tolerance.- A. Introduction and History.- B. Humoral Immunity.- I. Primary and Secondary Immune Response.- II. Time of Irradiation and Antigen Injection.- III. Radiation Type and Amount.- IV. Type of Antigen.- C. Cellular Immunity.- I. Bone Marrow Grafting.- 1. Irradiation Dose.- a) Injury.- ?) Hematopoietic.- ß) Gastrointestinal.- ?) Central Nervous System (CNS).- b) Conditioning of Recipients for Hematopoietic Grafting.- ?) The Midlethal Dose (MLD) Effect.- ß) Rejection of the Marrow Graft and “Reversal”.- ?) Exposure Rate Effects.- ?) Conditioning by Irradiation Other Than Total Body (TBI).- ?) Time of Marrow Infusion in Relation to Irradiation.- 2. Histocompatibility Differences Between the Host and Donor.- 3. The Presensitized Recipient.- 4. Successful Hematopoietic Engraftment.- a) Evidence of Chimerism.- b) GVHD.- ?) Pathology.- ß) The Prevention and Treatment of GVHD.- c) Immunologic Reconstitution of Chimeras.- d) Long-Term Survivors as Examples of Irradiation Induced Immunologic Unresponsiveness: “True Tolerance” or “Enhancement Phenomenon”?.- e) Clinical Marrow Grafting Studies.- ?) Marrow Grafting in Hematologic Malignancy.- ß) Marrow Grafting in Aplastic Anemia.- ?) Conclusions and Summary of Outstanding Problems in the Field of Irradiation and Clinical Marrow Grafting.- II. Other Organ Grafts.- References.- Immunosuppression by Antibodies.- A. Introduction.- B. Concepts of Immunosuppression by Antibodies.- C. Xenogeneic Antilymphocyte Sera.- I. General Aspects.- II. Types of Xenogeneic Antilymphocyte Sera.- III. Effects on Lymphoid Cells in vitro.- IV. Effects on the Lymphatic System.- V. Immunosuppressive Activity of ALS.- 1. Humoral Immunity.- 2. Delayed Hypersensitivity.- 3. Transplantation Immunity.- 4. Autoimmune Phenomena.- 5. Graft-Versus-Host Immunity.- VI. Cooperative Effects With Other Immunosuppressive Regimens.- VII. Assays for Immunosuppressive Potency.- VIII. Mode of Action.- IX. Side-Effects and Complications.- 1. Toxic Effects.- 2. Hyperergic Reactions.- 3. Infections.- 4. Neoplasms.- X. Immunosuppression with ALS in Humans.- D. Passive Enhancement.- I. General Aspects.- II. Types of Antibodies Initiating Enhancement.- III. Prolongation of Allograft Survival by Passive Enhancement.- IV. Immune Status of Passively Immunized Allograft Recipients.- V. Mechanisms of Enhancement.- VI. Side-Effects and Complications.- VII. Immunologic Enhancement in Humans.- References.- Medications and Their Toxicity.- A. Introduction.- B. Pharmacology and Immunopathology.- I. Adrenocorticosteroids.- II. Alkylating Agents.- III. Antimetabolites.- IV. Vinca Alkaloids.- V. L-Asparaginase.- VI. Miscellaneous Agents.- VII. Antilymphocyte Sera (ALS).- C. Toxicology and Adverse Effects.- I. Adrenocorticosteroids.- II. Alkylating Agents.- III. Antimetabolites.- IV. Vinca Alkaloids.- V. L-Asparaginase.- VI. Miscellaneous Agents.- VII. Antilymphocyte Sera (ALS).- D. Special Topics.- I. Infection.- II. Carcinogenesis.- E. Summary.- References.- Graft-Versus-Host-Reactions.- 1. Introduction.- 2. Experimental Models.- 2.1. Systemic GVHR.- 2.1.1. Juvenile Forms.- 2.1.1.1. Chorioallantoic Membrane Test.- 2.1.1.2. A ? A + B Type.- 2.1.1.3. DA ? Fischer + DA-Type.- 2.1.2. Adult Forms.- 2.1.3. Reaction Parameter.- 2.1.3.1. Weight of the Spleen.- 2.1.3.2. Number of Lymphocytes.- 2.1.3.3. Body Weight.- 2.1.3.4. Survival Time.- 2.1.3.5. Phagocytosis Index.- 2.1.3.6. Other Reaction Parameters.- 2.2. Local GVHR.- 2.2.1. The Intrarenal Form.- 2.2.2. The Intracutaneous Form.- 2.2.3. Popliteal Lymph Node Test.- 2.2.4. The Intra-Ocular Form.- 2.3. In-Vitro Analogies.- 2.3.1. The Mixed Lymphocyte Culture.- 2.3.2. The Spleen Expiant Test.- 3. Clinical Observations.- 3.1. “Spontaneous” GVHD in Humans.- 3.2. GVHD After Bone Marrow Transplantation.- 3.2.1. In Case of Primary Immuninsufficiency or Aplastic Anemia.- 3.2.2. In Leukemias.- 3.2.3. After Blood Transfusions.- 4. Histopathology.- 4.1. Mice.- 4.1.1. Spleen.- 4.1.2. Lymph Nodes.- 4.1.3. Liver.- 4.1.4. Skin.- 4.1.5. Bone Marrow.- 4.1.6. Other Tissues.- 4.2. Rats.- 4.2.1. Spleen.- 4.2.2. Lymph Nodes.- 4.2.3. Liver.- 4.2.4. Skin.- 4.2.5. Bone Marrow.- 4.2.6. Other Tissue.- 4.3. Chickens.- 4.4. Other Animals.- 4.5. Humans.- 4.5.1. Spleen.- 4.5.2. Lymph Nodes.- 4.5.3. Liver.- 4.5.4. Skin.- 4.5.5. Gastrointestinal Tract.- 4.5.6. Bone Marrow.- 4.5.7. Remaining Tissue.- 5. Hematology.- 5.1. Mice.- 5.2. Rats.- 5.3. Other Species of Animals.- 5.4. Humans.- 6. Causal Pathogenesis.- 6.1. Immunologic Factors.- 6.2. Unspecific Factors.- 7. Formal Pathogenesis.- 7.1. Trigger Antigens.- 7.2. Immunocompetent Lymphocytes.- 7.3. Behaviour of Donor Lymphocytes.- 7.3.1. Nidation.- 7.3.2. Proliferation.- 7.3.3. Cellular Interactions.- 7.4. Behaviour of Host Cells.- 7.4.1. Damages.- 7.4.2. Reactive Hyperplasia and Allogenetic Effect.- 7.4.3. Immune Suppression.- 7.5. Mechanisms of Immune Regulations.- 8. Therapeutic Influence.- 8.1. Results of Experiments with Animals.- 8.1.1. Treatment of Donor Animals.- 8.1.2. Treatment of Donor Cells.- 8.1.3. Treatment of Host Animals.- 8.2. Clinical Results.- 9. Late Complications.- 9.1. Glomerulonephritis.- 9.2. Other Forms of Allogeneic Diseases.- 9.3 Malignant Tumors.- 10. Prospects.- References.- Author Index.