Immune Mechanisms in Renal Disease by Nancy CummingsImmune Mechanisms in Renal Disease by Nancy Cummings

Immune Mechanisms in Renal Disease

byNancy Cummings

Paperback | December 12, 2012

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Anti-native DNA antibodies and DNA are present in cryopreClpItates from patients with systemic lupus erythematosus and some other cryoglob­ ulinemic states. The data suggest that these antibodies may be bound in immune complexes. The demonstration of native DNA in these precipitates raises the likelihood that they represent specific antigen in these complexes. Whether or not these complexes play a pathogenetic role in nonlupus inflammatory diseases remains to be demonstrated. References Aarden, L. A., de Groot, E. R., and Feltkamp, T. E. W., 1975, Immunology of DNA. III. Crithidia luciliae, a simple substrate for the determination of anti-dsDNA with the immu­ nofluorescence technique, Ann. N.Y. A cad. Sci. 254:505. Agnello, V., Winchester, R. J. and Kunkel, H. G., 1970, Precipitin reactions of the Clq component of complement with aggregated 'Y-globulin and immune complexes in gel diffusion, Immunology 19:909. Anker, P., Stroun, M., and Maurice, P. A., 1975, Spontaneous release of DNA by human blood lymphocytes as shown in an in vitro system, Cancer Res. 35:2375. Bankhurst, A. D., and Williams, R. C., 1975, Identification of DNA-binding lymphocytes in patients with systemic lupus erythematosus,]. Clin. Invest. 56:1378. Bluestone, R., Goldberg, L. S., Cracchiolo, A., and Barrett, E. V., 1970, Detection and characterization of DNA in mixed (IgG-IgM) cryoglobulins, Int. Arch. Allergy Appl. Immunol. 39:16.
Title:Immune Mechanisms in Renal DiseaseFormat:PaperbackDimensions:564 pagesPublished:December 12, 2012Publisher:Springer-Verlag/Sci-Tech/TradeLanguage:English

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ISBN - 10:1461346274

ISBN - 13:9781461346272

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Table of Contents

1 Functional Organization of the Glomerulus: Presence of Glycosaminoglycans (Proteoglycans) in the Glomerular Basement Membrane.- 1. Introduction.- 2. Glomerular Capillary Organization Is Highly Specialized.- 3. Epithelial Polyanion Functions to Maintain Normal Foot Processes and Filtration Slits.- 4. Epithelial Slits Effectively Ruled Out as the Main Filtration Barrier.- 5. The GBM Is Both the Size-Selective and the Charge-Selective Barrier in the Glomerulus.- 6. Distinction between Anionic Sites in the GBM and Those on Cell Surfaces.- 7. Anionic Sites Are Lost from the GBM as Well as the Epithelium in Aminonucleoside Nephrosis.- 8. Evidence That the Anionic Sites in the Laminae Rarae of the GBM Consist of Proteoglycans Rich in Heparan Sulfate.- 9. Concluding Comments.- References.- 2 Mechanisms of Glomerular Permselectivity.- 1. Introduction.- 2. The Glomerular Capillary Wall as a Size-Selective Filter.- 3. The Glomerular Capillary Wall as a Charge-Selective Filter.- 4. Effects of Glomerular Injury on the Size-Selective and Charge-Selective Properties of the Glomerular Capillary Wall.- References.- 3 The Molecular Structure of Basement Membranes as It Relates to Function.- 1. Introduction.- 2. Morphologic Considerations.- 3. Physicochemical Properties.- 4. Biosynthesis of Basement Membrane Procollagen.- 5. Immunochemical Properties of Basement Membrane.- 6. Supramolecular Organization.- 7. Molecular Properties of Basement Membranes and Structure-Function Relationships.- 7.1. The Ultrastructural Appearance of Basement Membranes.- 7.2. Permeability Properties of Basement Membranes.- 8. Summary.- References.- 4 Glomerular Basement Membrane Antigens.- 1. Introduction.- 2. Reactivity of Rabbit Anti-GBM with Normal Kidney.- 3. Staining of Kidney with GP Renal Eluates.- 4. Preparations of Isolated GBM.- 5. Measurements of Linear Widths by Immunofluorescent Staining and Phase Microscopy.- 6. Distribution of RAHGBM and GP Antibody Staining in GBM of Diseased Kidneys.- 7. Discussion.- References.- 5 Physiologic Approaches to the Mechanisms of Glomerular Immune Injury.- 1. Introduction.- 2. An Evaluation of Glomerular Capillary Injury by the Use of Micropuncture Techniques.- References.- 6 Physical Interactions between Macromolecules and the Glomerular Filter.- 1. The Nature of the Filter.- 1.1. Physical Chemistry of the Cell Coats and GBM.- 1.2. The Filtration Slit Diaphragms.- 2. Filtration of Macromolecules.- 3. The Physical Basis for Glomerular Restriction.- 3.1. Role Played by the Cell Coats and GBM.- 3.2. Role Played by Slit Diaphragms and Epithelial Pinocytosis.- 4. Summary.- References.- 7 Pathologic and Functional Correlations in the Glomerulopathies.- 1. Introduction.- 2. Methods.- 3. Results.- 3.1. Normal Subjects.- 3.2. Minimal Change Nephrotic Syndrome.- 3.3. Glomerulonephritis.- 3.4. Modification of Permselectivity by Treatment.- 3.5. Prognostic Value of Measurements of Permselectivity.- 4. Discussion.- 5. Summary.- References.- 8 Glomerular Mesangium: Introductory Remarks.- 1. Introduction.- 2. Morphologic and Antigenic Relationships.- 3. Morphologic Tracer Studies.- 4. Kinetic Studies of Mesangial Function.- 5. Modulating Factors Affecting Afferent and Efferent Limb.- 5.1. Afferent Limb.- 5.2. Efferent Limb.- 6. Modulation of Mesangial Afferent and Efferent Limb.- 7. Conclusion.- References.- 9 The Influence of Hemodynamic Factors upon Mesangial Kinetics of Macromolecules.- 1. Introduction.- 2. Methods.- 3. Results.- 3.1. Influence of Reduced Renal Blood Flow and Perfusion Pressure on Mesangial Uptake and Release of Macromolecules.- 3.2. Effects of Ureteral Obstruction upon Mesangial Kinetics of Macromolecules.- 3.3. Mesangial Kinetics of Macromolecules in Mercury Chloride Acute Renal Failure.- 4. Conclusions.- References.- 10 Deposition and Removal of Glomerular Immune Complexes: Relationships to the Mononuclear Phagocyte System.- 1. Introduction.- 2. Removal of Circulating Complexes by the MPS.- 3. Glomerular Deposition of Circulating Immune Complexes.- 4. Removal of Immune Complexes from Glomeruli by Bone Marrow-Derived Macrophages.- 5. Removal of Immune Complexes from Glomeruli by Antigen Excess.- 6. Summary.- References.- 11 LCM Virus Infection and Nephritis.- 1. Description of Chronic LCM Virus Infection in Mice.- 2. Adoptive Immunization of LCM Mice.- 3. Mesangial and Reticuloendothelial Function in LCM Virus Carrier Mice.- References.- 12 Diabetic Nephropathy: Relevance of Animal Models to the Understanding of Pathological Processes in Immune Renal Disease.- 1. The Pathology of Diabetic Nephropathy.- 2. The Glomerular Mesangium in Diabetic Nephropathy.- 3. Reversibility of Mesangial Lesions of Diabetes in Animals.- 4. Glomerular Capillary Permeability and GBM Thickening in Diabetic Rats.- 5. Glomerular Hemodynamics and the Development of Diabetic Nephropathy.- References.- 13 Characterization of Rat Glomerular Cells in Vitro.- 1. Introduction.- 2. Materials and Methods.- 2.1. Culture of Whole Glomeruli and Dissociated Glomerular Cells.- 2.2. Morphologic Studies.- 2.3. Immunological Studies.- 2.4. Phagocytosis in Vitro.- 2.5. Renin Determinations.- 2.6. Studies with Aminonucleoside of Puromycin.- 2.7. Studies with Nephrotoxic Serum.- 3. Results.- 3.1. Isolation of Glomeruli.- 3.2. Culture of Cells from Whole Glomeruli and Dissociated Glomerular Cells.- 3.3. Characteristics of Isolated Cells.- 4. Discussion.- 5. Summary.- References.- 14 Culture of Human Glomerular Cells.- 1. Introduction.- 2. Materials and Methods.- 2.1. Tissue Procurement.- 2.2. Isolation and Culture of Glomeruli.- 2.3. Isolation of Tubular Cells and Fibroblasts.- 2.4. Cytochemical Techniques for Light Microscopy.- 2.5. d-Amino Acid Oxidase Histochemistry.- 2.6. Transmission Electron Microscopy.- 3. Results.- 3.1. Culture of Adult Human Glomeruli.- 3.2. Culture of Infant Human Glomeruli.- 3.3. Ultrastructural Characterization of Cellular Outgrowths.- 3.4. Cytochemical Characterization of Human Glomerular Cells.- 3.5. Biochemical Characterization of Extracellular Matrix Produced by Human Glomerular Cells in Culture.- 4. Discussion.- References.- 15 Immunochemical and Biochemical Studies of Human Glomerular Cells in Culture.- 1. Introduction.- 2. The Immunochemical Approach to Glomerular Cell Specialization: Limitations.- 3. Human Glomerular Cells Types in Vitro.- 4. Early Events in Glomerular Explant Culture.- 5. Glomerular Explant Conditions: Comparative Studies from Bovine Glomeruli.- 6. Summary of Published Reports of Human Glomerular Cells in Vitro.- 7. Specific Markers and the Future of Glomerular Cell Culture.- References.- 16 Results of Immune Complex Detection in Glomerular Diseases.- 1. Introduction.- 2. Detection of IC in Patients with Glomerulonephritis.- 3. Ubiquitous Occurrence of IC in Man.- 4. The Future Use of IC Methods.- References.- 17 Nephritogenic Immune Responses Involving Basement Membrane and Other Antigens in or of the Glomerulus.- 1. Anti-Basement Membrane Antibody Mechanisms.- 2. Anti-Basement Membrane Antibodies and the Diseases They Produce in Man.- 3. Nephritogenic Immune Responses Involving Non-Basement Membrane Antigens in or of the Glomerulus.- 3.1. Non-GBM Glomerular Capillary Wall Antigen in Glomerulonephritis.- 3.2. Foreign Antigens Which Become Trapped or "Planted" within the Glomerulus.- 4. Conclusions.- References.- 18 Autoimmune Disease Induced in Rabbits by Administration of Mercuric Chloride: Evidence Suggesting a Role for Antigens of the Connective Tissue Matrix.- 1. Introduction.- 2. Mercuric Chloride-Induced Autoimmune Disease.- 2.1. Induction and Course of the Disease.- 2.2. Antibodies and Immune Complexes.- 2.3. Search for the Antigen(s) Responsible for the Autoimmune Disease.- 2.4. Systemic Localization of Immune Deposits.- 2.5. Transformation of Anti-GBM Disease into Immune Complex Disease.- 3. Relevance for Human Diseases.- 4. Summary.- References.- 19 Experimental Autoimmune Renal Tubulointerstitial Disease.- 1. Introduction.- 2. Induction of RTD in Guinea Pigs.- 2.1. TBM Antigens.- 2.2. Adjuvants.- 2.3. Strain Differences.- 2.4. Lack of an Effect of Antigen Competition on RTD.- 3. Passive Transfer of RTD.- 3.1. Transfer of RTD with Serum Antibodies.- 3.2. Differences in the Time Course of Passively Induced RTD in Strain 2 and A Strain Guinea Pigs.- 4. Characteristics of Lesions in RTD.- 5. The Role of Complement.- 5.1. Immunofluorescent Observations.- 5.2. Depletion of C with Cobra Venom Factor.- 5.3. RTD in C4-Deficient Guinea Pigs.- 5.4. Differences in Reactivity of in Vivo and in Vitro Bound Anti-TBM Antibodies with Protein A.- 6. The Nature and Origin of the Cellular Infiltrates.- 6.1. Inhibition of Passive Transfer of RTD in Leukocyte-Depleted Recipients.- 6.2. Passive Transfer of Renal Lesions by Anti-TBM Antibody and Nonimmune Bone Marrow Cells to Leukocyte-Depleted Recipients.- 7. Conclusions and Speculation.- References.- 20 Experimental and Human Anti-Tubular Basement Membrane Nephritis.- 1. Introduction.- 2. Experimental Anti-TBM Nephritis.- 2.1. Guinea Pigs.- 2.2. Anti-TBM Nephritis in Rats.- 2.3. Possible Role of Sensitized Cells in Experimental Anti-TBM Nephritis.- 3. Human Anti-TBM Disease.- 4. Summary.- References.- 21 Autoimmunity to Tamm-Horsfall Protein.- 1. Immune Complex-Mediated Tubulointerstitial Nephritis.- 2. TH Protein.- 2.1. Morphologic Localization.- 2.2. TH in Human Disease.- 3. Experimental Anti-TH Antibody-Mediated Tubulointerstitial Nephritis in Rats.- 4. Pathogenesis of in Situ Immune Complex Formation.- References.- 22 Renal Antigens in Experimental Immune Complex Glomerulonephritis.- 1. Introduction.- 2. Materials and Methods.- 2.1. Animals.- 2.2. Induction of Glomerulonephritis.- 2.3. Immunological Procedures.- 3. Results.- 3.1. Immunofluorescence.- 3.2. Immunoelectron Microscopy.- 4. Discussion.- References.- 23 Mechanisms of Proteinuria Induced by Antikidney Antibodies in Noninflammatory Experimental Glomerulonephropathy.- 1. Introduction.- 2. Complement-Independent Nephrotoxic Nephritis in the Guinea Pig.- 3. Experimental Membranous Nephropathy Induced by Antibodies to Renal Tubular Epithelial Cell Antigens.- 3.1. General.- 3.2. Mechanisms of Subepithelial Complex Formation in PHN.- 3.3. Effect of Properties of the Glomerulus on Subepithelial Deposit Formation in AICN and PHN.- 3.4. Kinetics of Glomerular Antibody Binding in Relation to Proteinuria in PHN.- 3.5. Role of Complement in Proteinuria in PHN.- 3.6. Role of Neutrophils (PMNs) in Proteinuria in PHN.- 3.7. Mechanisms of Proteinuria in AICN.- 4. Summary.- 5. Brief Overview-Immunologic Mechanisms of Proteinuria.- References.- 24 The Pathogenesis of Autologous Immune Complex Glomerulonephritis in Rats.- 1. Introduction.- 2. Materials and Methods.- 3. Experimental Groups.- 3.1. Immunizations.- 3.2. Experimental Procedure.- 3.3. Circulating Antibody to RTE.- 3.4. Analysis of CIC.- 3.5. Histology and Immunofluorescence.- 3.6. Size Characteristics of CIC.- 3.7. Detection of RTE Antigens in CIC.- 3.8. Statistical Analysis.- 4. Results.- 4.1. Documentation of Nephritis.- 4.2. Circulating Antibody Studies.- 4.3. CIC.- 4.4. Characteristics of the Clq-Reactive Material.- 4.5. Demonstration of RTE Antigens in CIC.- 5. Discussion.- 6. Summary.- References.- 25 Immunopathogenesis of Murine SLE.- 1. Introduction.- 2. Comparison of SLE in NZB × W, MRL/1, and BXSB Mice.- 2.1. Genetic Background.- 2.2. Immunologic Features of SLE Syndrome in Mice.- 3. Summary.- References.- 26 Studies on Detection of Nephritogenic Immune Complexes.- 1. "Hot" Immunoelectrophoresis.- 2. Dissolving Immune Complexes in Excess of Antigen.- 3. Neutralization and Absorption of Anti-antibody.- References.- 27 The Significance of Cryoimmunoglobulinemia in Immunologically Mediated Kidney Diseases.- 1. Introduction.- 2. Materials and Methods.- 3. Results.- 4. Discussion.- References.- 28 Relationship of Serum Cryoglobulins and Their Composition to Glomerulonephritis in Systemic Lupus Erythematosus.- 1. Introduction.- 2. Evidence Implicating DNA/Anti-DNA Complexes in SLE Glomerulonephritis.- 2.1. Immunofluorescent and Glomerular Elution Studies.- 2.2. Serologic Studies.- 3. Relationship between Cryoglobulinemia and Glomerulonephritis.- 4. Immunochemical Analysis of Cryoprecipitates.- 4.1. Methodology.- 4.2. Anti-immunoglobulins.- 4.3. Antipolynucleotide Antibodies.- 4.4. DNA.- 5. Comment.- References.- 29 Cryoprecipitable Immunoglobulins with Native DNA Reactivity in the Glomerulopathies.- 1. Introduction.- 2. Methods.- 2.1. Patients.- 2.2. Cryoprecipitation of Serum.- 2.3. Antinuclear and Anti-native DNA Assays.- 2.4. Control Studies.- 2.5. Native DNA Content of Cryoprecipitates.- 3. Results.- 3.1. Cryoglobulin Protein Content.- 3.2. Control Studies.- 3.3. Antinuclear and Antikinetoplast (Native DNA) Antibody Content of Cryoglobulins.- 3.4. IgG Anti-native DNA in Cryoglobulins and in Supernatant Serum.- 3.5. Native DNA Content of Cryoglobulins.- 4. Discussion.- 5. Summary.- References.- 30 The Role of Streptococcal and Glomerular Basement Membrane Antigens in Glomerulonephritis.- 1. General Introduction.- 2. A Streptococcal Extracellular Protein Unique to Nephritogenic Strains.- 2.1. Introduction.- 2.2. Methods of Isolation.- 2.3. Polyacrylamide Gel Electrophoresis Pattern.- 2.4. Purification of the Protein.- 2.5. Presence of the Protein in Human Kidney Biopsies.- 2.6. Discussion.- 3. The Role of Altered GBM and Cross-Reactive Streptococcal Antigens in Progressive Glomerulonephritis.- 3.1. Introduction.- 3.2. Background.- 3.3. Methods of Isolation of GBM and Enzymatic Alteration.- 3.4. Cellular Immune Studies in Patients with Progressive Glomerulonephritis.- 3.5. Biochemical Studies of Altered GBM.- 3.6. Discussion.- References.- 31 The Contact (Hageman Factor) System in Inflammation.- 1. Introduction.- 2. Molecules Involved in the Activation of the Contact System in Plasma.- 3. The Association of Activation of Molecules with Limited Proteolytic Cleavage.- 4. A Role of Prekallikrein in the Activation of HF.- 5. A Role of HMW Kininogen in the Activation of HF and Prekallikrein.- 6. Dissemination of Activity into the Fluid Phase.- 7. Cleavage and Activation of HF by Cellular Enzymes.- References.- 32 The Function of the Reticuloendothelial System in Autoimmune Disease.- 1. Introduction.- 2. Hepatic Clearance of Erythrocytes Coated with IgM and Complement via C3b Receptors.- 3. Splenic Clearance of Erythrocytes Coated with IgG via Fc Receptors.- 4. Studies in Human Disease.- References.- 33 A Role of Mononuclear Phagocytes in Immunologically Induced Glomerulonephritis.- 1. Introduction.- 2. An Accelerated Model of NTN with a Mononuclear Cell Component.- 2.1. Experimental Design.- 2.2. Effect of X-Irradiation.- 2.3. Pathogenesis of the Mononuclear Infiltrate.- 3. Conclusions.- References.- 34 Genetic Structure of the HLA Region and Implication for Function.- 1. The Major Histocompatibility Complex.- 1.1. HLA-A,B,C,.- 1.2. Mixed Lymphocyte Response: HLA-D.- 1.3. HLA-DR, The Human "I" Region.- 1.4. CML Typing.- 1.5. Population Studies.- 1.6. Chromosomal Order of Genes (Short Arm of Chromosome 6:6p).- 2. HLA and Disease.- 2.1. Statistical Considerations.- 2.2. Ankylosing Spondylitis.- 2.3. Other Arthritides.- 2.4. The HLA-B8 Group.- 2.5. Multiple Sclerosis.- 2.6. Malignancy.- 2.7. Idiopathic Hemachromatosis.- 2.8. Congenital Adrenal Hyperplasia (21-OH Deficiency).- 2.9. Rheumatic Diseases and C2 Deficiency.- 2.10. Renal Disease.- 2.11. Recombination.- 2.12 Reflections on the Current Disease Association Data.- 3. Mechanisms.- References.- 35 Genetic Defects of the Complement Pathways: Relationship to HLA and Disease.- 1. Introduction.- 2. Association between Complement Deficiences and Disease.- 3. Role of Inherited Complement Deficiencies in Disease.- 4. Summary.- References.- 36 Complement Abnormalities in Allergy and the Nephrotic Syndrome.- 1. Introduction.- 2. Atopy, Complement, and Glomerular Disease.- 3. Conclusion.- References.- 37 Immunogenetic Aspects of Glomerulonephritis.- 1. Development of Immune Complex Glomerulonephritis.- 2. Immune Responsiveness in the Mouse.- 3. Genetics of Nephritis in Experimental Models.- 4. Hypothesis.- 5. Immunogenetic Aspects of Human Nephritis.- 6. Summary.- References.- 38 Autoantibodies in Systemic Lupus Erythematosus.- 1. Introduction.- 2. Autoantibodies to Nucleic Acids.- 3. Antibodies to Histones and DNA-Histone Complexes.- 4. Antibodies to Nonhistone Components.- 5. Discussion.- 6. Summary.- References.- 39 Serological Studies of Antibodies Reactive with RNA and RNA-Protein Antigens.- 1. Introduction.- 2. Antiribosomal Antibodies.- 3. Anti-RNA Antibodies.- 4. Anti-Poly A Antibodies.- 5. Anti-dsRNA Antibodies.- 6. Anti-Nuclear RNP Antibodies.- 7. Anti-La Antibodies.- 8. Antinucleolar Antibodies.- References.- 40 Modulation of Autoimmunity by Sex Hormones.- 1. Sexual Influence in Autoimmune Disease.- 2. Summary.- References.- 41 Thymic and T-Cell Function in Murine and Human Lupus.- 1. Thymic and T-Cell Function in Lupus.- 1.1. NZB and B/W Mice.- 1.2. Human Lupus.- 2. Mechanisms of T-Cell Abnormalities.- 3. Relationships between T-Cell Dysfunction and Pathogenesis of Autoimmunity.- 4. Thymic Substitution or Stimulation in Lupus Syndromes.- References.- 42 Immune Regulatory Abnormalities in Systemic Lupus Erythematosus.- 1. Introduction.- 2. Materials and Methods.- 3. Results.- 3.1. B-Cell Studies.- 3.2. T-Cell Studies.- 4. Discussion.- References.