Subject(s)
Antibodies, Anti-Idiotypic/pharmacology , Immunoglobulin E/immunology , Immunoglobulin G/pharmacology , Immunosuppression Therapy , Adjuvants, Immunologic/administration & dosage , Allergens/administration & dosage , Alum Compounds/administration & dosage , Animals , Animals, Newborn , Female , Mice, Inbred C57BL , Ovalbumin/administration & dosage , PregnancyABSTRACT
It has been a little more than 50 years since we discovered IgE, a key molecule for the allergic response and a target for treating allergies and severe asthma. Here, I trace my career, from the kindling of my interest in immunochemistry to groundbreaking discoveries in the biology and chemistry of immunoglobulins. I describe my service to the broader community of immunologists and my role in shaping departments and research institutes. My course starts in Japan and includes Southern California, Baltimore, and Denver.
Subject(s)
Allergy and Immunology , Famous Persons , Allergy and Immunology/history , Animals , History, 20th Century , History, 21st Century , Humans , Hypersensitivity/history , Japan , United StatesABSTRACT
Progress in protein chemistry in the 1950s revealed that the biologic activities of proteins, such as hemoglobin and enzymes, are based on partial structures in the protein molecules. This principle suggested to us the possibility that the human antibodies responsible for induction of reaginic hypersensitivity reactions might have unique structures that are lacking in the antibody molecules involved in immunity and that the differences in the structures of human antibody molecules can be recognized by the immune systems of experimental animals. Our studies were based on the hypothesis that reaginic antibody activity is associated with a unique immunoglobulin isotype, which is now called IgE. As expected, identification of IgE facilitated the analysis of immunologic mechanisms of reaginic hypersensitivity. Subsequent studies revealed that IgE specifically bound to basophilic granulocytes and mast cells through the Fc portion of the molecules and that cross-linking of the cell-bound IgE antibody molecules by allergen induced the release of bioactive mediators, such as histamine and leukotrienes, which initiate allergic reactions.
Subject(s)
Allergy and Immunology , Hypersensitivity/immunology , Immunoglobulin E/immunology , Allergy and Immunology/history , Animals , History, 20th Century , Humans , Hypersensitivity/metabolism , Immunoglobulin E/chemistry , Reagins/chemistry , Reagins/immunologySubject(s)
Antigen-Antibody Complex/immunology , Hypersensitivity/etiology , Animals , Antibodies/chemistry , Antibodies/immunology , Antigens/chemistry , Antigens/immunology , Humans , Hypersensitivity/metabolism , Hypersensitivity/therapy , Immunoglobulin G/chemistry , Immunoglobulin G/immunology , Immunoglobulins/isolation & purification , Immunoglobulins/therapeutic use , Japan , TokyoABSTRACT
Role of mast cells in allergy had remained undetermined until the discovery of IgE in 1966. Then, IgE purified from many Liters of plasma, which had been donated from a patient with fatal myeloma, was distributed to researchers all over the world, and thus accelerated exploring the mechanisms involved in allergic reactions, particularly about the role of mast cells and basophils in the IgE-mediated reactions. Identification of mast cells as a progeny of a bone marrow hematopoietic stem cell in 1977 led us to successful in vitro culture of human mast cells. Along with the development of molecular biological techniques, the structure of the high affinity IgE receptor (FcεRI) was determined in 1989. These findings and subsequent investigations brought deeper understanding of IgE-mediated allergic diseases in the past half century, especially where mast cells are involved. We have now even obtained the information about whole genome expression of FcεRI-dependently activated mast cells. In sharp contrast to our comprehension of allergic diseases where IgE and mast cells are involved, the mechanisms involved in non-IgE-mediated allergic diseases or non-IgE-mediated phase of IgE-mediated diseases are almost left unsolved and are waiting for devoted investigators to reveal it.
