Transplantation

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.