Immunopathology of Insulin: Clinical and Experimental Studies

ISBN-13: 9783642806100 / Angielski / Miękka / 2011 / 188 str.

Konrad Federlin

Opis

Soon after the discovery of insulin in 1922, it became clear that the use of this hormone in the treatment of diabetics is often accom panied by allergy. In 1956 it became possible to determine quantita tively the insulin-binding antibodies which are responsible for the resistance to insulin. The methods developed since then make it possible to measure minute amounts of the pancreatic hormone in blood and extracellular fluids. There have been many attempts to relate insulin allergy and in sulin resistance to the primary, secondary or tertiary structure of the or B chains, or both, and more recently, to the proinsulin which is A present in all commercial preparations of insulin, i. e. to the species specific structure of the C peptide. In the great majority of papers dealing either with the immunogenic and antigenic properties of in sulin or with the relevant antibodies, the discussion has been restricted to the humoral antibodies. The existence of a brief period of delayed local allergy resulting from the cellular immune response has more or less escaped attention. It is specifically this period of delayed allergy that attracted the interest of Dr. FEDERLIN and his colleagues. Making use of immuno histological and other techniques which are rarely employed in clinical observation, and with the help of experiments on animals, Dr. FEDERLIN traces the course of insulin allergy from cellular immunity, through the production of humoral antibodies by the insulin-binding cells of the circulation, to the sessile immunological apparatus."

Spis treści

A. Introduction.- B. Brief Review of the Immunology of Insulin.- I. Antigenicity of Insulin.- II. Humoral Antibodies Against Insulin and Their Demonstration.- 1. Immunological Reactions and Serologic Methods.- 2. Neutralization of the Biological Effect of Insulin..- 3. Binding of 131lodine-labelled Insulin.- 4. The Types of Insulin Antibodies.- III. Cell Mediated Immunity Against Insulin.- 1. Some General Aspects of Cell Mediated Immunity.- 2. Previous Immunocytological Studies.- IV. The Clinical Symptoms of the Immune Response to Insulin.- 1. Insulin Allergy.- a) The Clinical Picture.- b) Frequency.- c) Etiology and Pathogenesis.- 2. Insulin Resistance.- a) Clinical Picture.- b) Frequency.- c) Methods for Measurement of Insulin-neutralizing Antibodies.- d) Relationships between Maximum Insulin-binding Capacity of the Serum and the Daily Requirement of Insulin.- V. Proinsulin and Newer Concepts in Insulin Immunology.- C. Investigations of Insulin Allergy in Diabetes.- I. Investigations of Delayed Insulin Allergy.- 1. Introductory Remarks.- 2. Cytological Investigations.- a) Immunofluorescence.- ?) The Different Techniques of Immunofluorescence.- ?) Principles of Labelling with Fluorochromes.- ?) The Biological Characteristics of FITC Insulin.- ?) The Immunological Characteristics of FITC Insulin.- ?) The Conjugation of Insulin with FITC.- ?)The Conjugation of Insulin Antibodies with FITC.- ?) The Isolation of Blood Leucocytes.- ?) Separation of Lymphocytes and Granulocytes.- ?) The Application of Immunofluorescence to Blood Cells.- ?) The Specificity Tests for Immunofluorescence.- ?) The Evaluation of the Cytologic Preparations.- b) Immune Adherence.- ?) Introductory Remarks.- ?) Technique.- ?) The Specificity Tests for Immune Adherence.- ?) The Evaluation of the Cytologic Preparations.- c) Lymphocyte Transformation.- ?) Introductory Remarks.- ?) Technique.- ?) Evaluation of the Cell Preparations.- d) The Cytology of the Peripheric Blood Cells.- 3. The Intracutaneous Skin Test.- 4. Histological and Immunofluorescent Studies in Skin Biopsies.- 5. Investigations of Humoral Insulin Antibodies.- a) Insulin-Neutralizing Antibodies.- ?) Measurement of the Maximal Insulin-binding Capacity.- ?) Passive Hemagglutination.- b) Skin-sensitizing Antibodies (Reagin).- ?) Remarks.- ?) The “Allergic Serum Transfer Test” (AST Test).- c) The Investigation of Cytophilic Antibodies.- 6. Results.- a) Case Reports.- b) Summary of the Findings.- ?) Clinical Picture.- ?) Antigen-binding by Sensitized White Blood Cells.- ?) Behaviour of Serum Antibodies.- ?) Cytophilic Antibodies.- ?) Histological Findings of Skin Biopsies..- ?) Findings with Lymphocyte Transformation.- 7. Discussion.- 8. Summary and Recommended Therapeutic Measures.- II. Investigations of Immediate Allergy to Insulin.- III. Coexistence of Insulin Allergy and Insulin Resistance.- D. Investigations of the Delayed Immune Reaction and Formation of Antibody to Insulin in Experimental Animals.- I. Investigations of the Delayed Immune Reaction to Insulin in Guinea Pigs.- 1. Material and Methods.- a) Animals, Mode of Sensitization, Skin Test.- b) Cytological Examination of Peripheral White Blood Cells.- c) Transfer Test.- d) Migration Inhibition Test.- e) Studies of Humoral Antibodies to Insulin.- 2. Results.- a) Cytological Investigations of the White Cells.- b) Transfer Experiments.- c) Migration Inhibition Test.- d) Humoral Antibodies.- 3. Discussion.- 4. Summary.- II. Investigations of the Production of Humoral Antibodies.- 1. Material and Methods.- a) Mode of Immunization.- b) Detection of Antibody-forming Cells in the Peripheral Blood.- ?) Isolation of Blood Cells.- ?) Plaque Technique (According to Cunningham).- c) Binding of 131Iodine-labelled Insulin.- d) Passive Hemagglutination.- e) Immunohistological Techniques.- f) Histological Techniques.- 2. Results.- a) Antibody-forming Cells in Blood.- b) Humoral Antibodies.- ?) Binding of 131lodine-labelled Insulin.- ?) Passive Hemagglutination.- ?) Binding of Insulin in Pancreatic Tissue..- ?) The Effect of Labelling with FITC on the Immunological Properties of Insulin and Insulin Antibodies.- c) Immunofluorescence Studies of Various Organs.- ?) Local Granulomatous Tissue.- ?) Regional Lymph Nodes.- ?) Spleen.- ?) Bone Marrow.- ?) Liver.- ?)Kidney.- ?) Pancreas.- d) Histological Studies.- 3. Discussion.- a) Blood Cells Producing Antibodies to Insulin.- b) Characteristics of the Humoral Insulin Antibodies in Guinea Pigs.- c) The Localization of Antigen and Antibody Formation.- d) The Kidney in Long-term Immunization with Insulin.- 4. Summary.- E. Appendix: Studies of Insulin-immunized Sheep.- I. Statement of Purpose.- II. Results.- III. Discussion.- IV. Summary.- F. General Summary.- References.