Tiselius demonstrated that the immunologically active components of immune sera migrated electrophoretically in the gamma globulin region. His findings illuminated the classic observations of Jenner regarding development of resistance to infection, and those of von Pirquet, Pasteur, and Arthus regarding the transfer and specificity of resistance. Conceptual integration of these observations provided the impetus for the present modern era of immunology. Subsequent to Tiselius's work, multiple, rapid advances have occurred in the study of congenital and acquired immune deficiency states in mice, chickens, and humans. These studies have readily demonstrated that the immunologic ability of an organ­ ism to protect itself from environmental influences is a prerequisite for survival. Indeed, this necessity for protection from microenvironmental influences has promoted the evolu­ tionary development of immunologic diversification, namely, host dependence upon a sophisticated, multifaceted network of cells and effector mechanisms responsible for the clearance and neutralization of toxins and potentially harmful pathogens. The obligate dependence of animals upon the functional integrity of their immunologic systems is illus­ trated by the ready invasion of ubiquitous organisms when the host is in a state of immune defense derangement. Nevertheless, derangements in immune function can range from par­ tial to complete and can be compatible with survival. The consequences of such derange­ ments run the gamut from subclinical disease to inevitable mortality.

I. Defects of Immune Maturation.- 1 Immunologic Unresponsiveness in Fetal and Neonatal Mammals: A Paradigm for Immune Deficiency Diseases?.- 1. Introduction.- 2. The Thymus and Lymphatic System.- 3. Ontogeny of Immunocompetence.- 3.1. Humoral Responses.- 3.2. Cellular Responses.- 4. The Effect of Thymectomy on Immune Responsiveness.- 4.1. Growth and Development.- 4.2. Circulating Lymphocytes.- 4.3. Lymphoid Tissues.- 4.4. Antibody Responses.- 4.5. Transplantation Immunity.- 4.6. Delayed Hypersensitivity.- 4.7. Lymphocyte Transfer Reaction.- 4.8. Response to Polyclonal Mitogens.- 4.9. Life Span.- 5. The Immunologic Function of the Thymus.- 6. Conclusions.- References.- II. Incomplete Immune Function in Normal Animals.- 2 Genetic Regulation of High and Low Immunoresponsiveness.- 1. Introduction.- 2. Selection for Quantitative Antibody Response.- 2.1. Selective Breeding.- 2.2. Genetic Analysis.- 2.3. Characteristics of H- and L-Antibody-Responder Lines.- 2.4. Resistance to Aggression in H- and L-Antibody-Responder Lines.- 3. Selection for in Vitro Quantitative Proliferative Responses of T Lymphocytes to Phytohemagglutinin.- 3.1. Selective Breeding.- 3.2. Genetic Analysis.- 3.3. Characteristics of High- and Low-PHA-Responder Lines.- 3.4. Effects of the Selection on Immune Responses.- 4. Conclusions.- References.- III. Immunohematologic Abnormalities.- 3 Hematopoietic Stem Cell Differentiation and Its Role in Osteopetrosis: Immunologic Implications.- 1. Introduction.- 2. Cellular and Hormonal Basis of Bone Resorption and Related Processes.- 3. A Description of the Osteopetrotic Mutants.- 3.1. Mouse.- 3.2. Rat.- 4. Hematologic and Immunologic Characteristics of Mouse and Rat Osteopetroses.- 5. The Immunohematologic Origins of Osteopetrotic Disease.- 6. Human Osteopetrosis: Transplantation Immunology.- 7. Concluding Remarks.- References.- 4 The W/Wv Mouse: A Model of Bone Marrow Failure.- 1. Introduction.- 2. Regulation of Hematopoiesis.- 2.1. Discovery of the Regulatory Cell.- 2.2. The Role of TSRC in Self-Renewal of Stem Cells.- 2.3. TSRC Control of White Blood Cell Differentiation.- 2.4. Regulation by Products of the TSRC.- 2.5. Radiosensitivity of TSRC.- 2.6. The Ly Phenotype of TSRC.- 2.7. Genetic Requirement of Donor Cells for the Cure of Anemia in W/Wv Mice.- 3. Immunodeficiency of W/Wv Mice.- 4. TSRC Control of Erythropoiesis.- 4.1. TSRC Control of Erythroid Growth in Vitro.- 4.2. Separation of Helper TSRC from Suppressor TSRC.- 5. Summary.- References.- 5 The Murine Chediak-Higashi Mutation and Other Murine Pigmentation Mutations.- 1. Introduction.- 2. History and Genetics of the Beige Mutation.- 3. Altered Lysosomal Biogenesis and Properties.- 4. Lysosomal Enzyme Content.- 5. Lysosomal Secretion Defect.- 6. Other Lysosomal Functions.- 7. Effects on Other Subcellular Organelles.- 8. Possible Mechanism of Action of the Beige Mutation.- 9. Other Beigelike Mouse Pigment Mutants.- 10. Summary.- References.- 6 Cyclic Hematopoiesis in Gray Collie Dogs.- 1. Introduction.- 2. Clinical Presentation.- 3. Physiology.- 3.1. Neutrophil Studies.- 3.2. Erythrocyte Studies.- 3.3. Platelet Studies.- 3.4. Lymphocyte Studies.- 3.5. Additional Studies.- 4. Pathology.- 5. Treatment.- 6. Theoretical Models for Cyclic Hematopoiesis.- 7. Summary.- References.- IV. B-Cell Defects.- 7 Inherited Dysgammaglobulinemia of Chickens.- 1. Background.- 2. Immunologic Profiles.- 2.1. Ig Concentrations.- 2.2. UCD 140 PBL Have Normal Ig-Bearing Cells and Normal Proliferative Responses to Mitogens, but Impaired Pokeweed-Mitogen-Induced 7 S Ig Synthesis.- 2.3. Immune Responses.- 3. Suppressor Cells.- 3.1. Detection by Co-culturing.- 3.2. The Suppressor Cell Is a T Cell.- 3.3. UCD 140 B Cells Can Synthesize 7 S Ig When Supplied with Normal T Cells.- 4. Immunopathology of UCD 140 Birds.- 5. What Is the Relation between Suppressor Cells and Bursal Defects?.- 6. Autoimmune Manifestations.- 6.1. Hematology and Coombs' Reactivity.- 6.2. Cryoprecipitates.- 6.3. Anti-Gamma-Globulin Activity.- 6.4. Other Antibodies.- 7. Genetics.- 8. Summary.- References.- 8 B-Lymphocyte Development and Heterogeneity: Analysis with the Immune-Defective CBA/N Mouse Strain.- 1. Derivation and Genetics of the Immune-Defective CBA/N Mouse Strain.- 2. Studies of the Immune Function of Immune-Defective CN Mice.- 2.1. Proliferative Responses Induced by B- or T-Cell Mitogens and Antiimmunoglobulin Antibodies.- 2.2. Polyclonal Antibody Responses Induced by B-Cell Mitogens.- 2.3. Cytotoxic Function of Immune-Defective Mice.- 2.4. B-Cell Colony Formation.- 2.5. Immune Responses of CN Mice to Infectious Agents.- 2.6. Serum Antibody Levels.- 2.7. Responses to Thymic-Independent Antigens.- 2.8. Responses to Thymic-Dependent Antigens.- 2.9. Susceptibility to Tolerance Induction.- 3. Studies of the Surface Membrane Characteristics of CN B Lymphocytes.- 3.1. Surface Immunoglobulin.- 3.2. Surface I-Region-Associated Antigens.- 3.3. Minor Lymphocyte-Stimulating Determinants.- 3.4. Complement Receptors.- 3.5. Lyb Antigens.- 4. Studies of the Mechanism(s) Underlying the Immune Defect of GN Mice.- 4.1. T-Cell Function.- 4.2. Macrophage Function.- 4.3. B-Cell Function.- 5. The Lineage of B Cells in Normal and Immune-Defective CN Mice.- 6. The CN Strain as a Model to Study Natural Immunity.- 7. Summary.- References.- 9 The Significance of Hereditary Asplenia for Immunologic Competence.- 1. Introduction.- 1.1. Historical Background.- 1.2. Significance of Studies of Asplenia.- 2. Quantitation of Plasma Proteins.- 3. Antibody Synthesis.- 3.1. Changes in Immunoglobulin Class and Quantity.- 3.2. Alterations in Antigen Trapping.- 4. Alterations in Lymphocytic Interactions Attributable to the Spleen.- 4.1. Synergy for Antibody Synthesis.- 4.2. Responses to Mitogenic Stimulation and Altered Homing Patterns.- 5. Cell-Mediated Immunity.- 5.1. Unaltered Capabilities.- 5.2. Alterations in Graft Survival.- 5.3. Suppression in the Neonate.- 5.4. Tolerance.- 5.5. Suppressive Influence on Other Lymphoid Domains.- 6. Lymphocyte Surface Markers and the Splenic Environment.- 7. Splenic Regulation of Autoimmunity.- 8. Splenic Input on Tumor Immunity.- 8.1. Interferon Production.- 8.2. Response to Tumors.- 9. Summary.- References.- V. T-Cell Defects.- 10 Deficient and Sufficient Immune Systems in the Nude Mouse.- 1. Introduction.- 1.1. Morphology.- 1.2. T Lineage Cells.- 1.3…