Brief History of Important Immunologic Discoveries and Developments Year Event Author(s) 1798 Cowpox vaccination Edward Jenner 1866 Wound disinfection Joseph Lister 1876 Discovery of B. antracis, foundation of Robert Koch bacteriology 1880 Discovery of attenuated vaccine by Louis Pasteur invitro passages 1883 Phagocytosis, cellular immunity theory Elie I. I. Metchnikoff 1888 Discovery of bacterial toxins P. P. Emile Roux and Alexandre E. J. Y ersin 1890 Discovery of antitoxins, foundation of Emil A. von Behring and serotherapy Shibasaburo Kitasato 1894 Immunologic bacteriolysis Richard F. J. Pfeiffer and Vasily I. Isaeff 1894 Discovery of antibody and complement Jules J.B. V. Bordet activity as the active factors in bacteriolysis 1896 Discovery of specific agglutination Herbert E. Durham and Max von Gruber 1896 Agglutination test for the diagnosis of Georges F. I. Widal and typhoid (Widal test) Jean-Marie-Athanase Sicard 1900 Formulation of side-chain theory of anti- Paul Ehrlich body formation 1900 Discovery of A, B, 0 blood groups Karl Landsteiner 1900 Development of complement fixation Jules J.B. V. Bordet and reaction Octave Gengou 1902 Discovery of anaphylaxis Charles R. Richet and Paul Portier 1903 Local anaphylaxis due to antibody- Nicholas M. Arthus antigen complex: Arthus reaction 1903 Discovery of opsonization Almroth E. Wright and Steward R. Douglas 440 Brief History of Important Immunologic Discoveries and Developments Year Event Author(s) 1905 Description of serum sickness Clemens von Pirquet and Bela Schick 1910 Introduction of salvarsan, later neo- Paul Ehrlich and Sahachiro Hata salvarsan, foundation of chemotherapy of infections 1910 Development of anaphylaxis test William Schultz (Schultz-Dale) 1914 Formulation of genetic theory of tumor Clarence C. Little transplantation 1921 Experimental trial with BCG vaccine Albert L. C. Calmette and Camille Guerin 1921 Development of cutaneous anaphylactic Carl W. Prausnitz and Heinz reaction Kiistner 1923 Production of anatoxin (toxoid) by Ramon Gaston formaldehyde treatment 1928 Discovery of penicillin, the first anti­ Alexander Fleming biotic 1935 Discovery of sulfonamides for chemo­ Gerhard Domagk therapy of infections 1935 Discovery of local immunity; oral Alexandre Besredka vaccination 1935-36 Purification of antibodies, quantitative Michael Heidelberger and precipitation reaction Forrest E. Kendall 1937 Evidence for identity of the gene for Peter A. Gorer blood group antigen II with one gene for tumor resistance in the mouse (B-2) 1938 Evidence that antibodies are y-globulins Arne Tiselius and Elvin A. Kabat 1942 Discovery of cellular transfer of delayed Karl Landsteiner and Merrill type hypersensitivity in guinea pigs W.Chase 1942 Fluorescence labeling of antibodies and Albert H. Coons antigens 1942 Introduction of adjuvants Jules T. Freund 1943-44 Establishment of immunologic basis of Peter B. Medawar rejection of normal tissue transplants 1946--48 Theory of congenic mouse lines formu­ George D. Snell lated, first congenic lines initiated, and the term histocompatibility introduced 1945 Development of antiglobulin test for Robin R.A. Coombs, R.R.Race, incomplete Rh antibodies and A. E. Mourant Brief History of Important Immunologic Discoveries and Developments 441 Year Event Author(s) 1945 Description of tolerance (chimerism) in Ray D. Owen dizygotic cattle twins 1946 Development of precipitin test in gels Jaques Oudin 1947 Immunoglobulins as "transporteurs" Pierre Grabar 1948 Development of double immunodiffusion Orjan Ouchterlony and Stephen test in gels D. Elek 1948 Discovery of plasma cells as antibody Astrid E. Fagraeus producing cells 1949 Elucidation of the structure of A, B, 0 Elvin A. Kabat, W. T. J. Morgan, blood group antigens and W. M. Watkins 1952 Description of agammaglobulinemia in Ogdon Carr Bruton human 1952 Discovery of histamine in mast cells James F. Riley and Geoffrey B. West 1953 Development of immunoelectrophoresis Pierre Grabar 1953 Experimental evidence of acquired Milan Hasek immunologic tolerance 1956 Major histocompatibility (H-2) complex George D. Snell in the mouse defined 1956 Discovery of human leukocyte antigen, Jean Dausset later be shown to belong to the major histocompatibility complex of man (HLA) 1956 Experimental induction of autoimmunity Ernest Witebsky and Noel R. Rose 1956 Discovery of allotypes Rune Grubb and Jaques Oudin 1957 Discovery of interferon Jean Lindemann and Alick Isaacs 1957 Discovery of macroglobulins with anti- H. Hugh Fudenberg and Henry body activity G. Kunkel 1957 Discovery of Australia antigen, later Baruch Blumberg shown to be Hepatitis B antigen 1957 Discovery of human slow virus infection Carleton Gajdusek (Kuru) 1959 Introduction of the radioimmune assay Rosalyn Yalow and Solomon A. Berson 1960 Antibody structure Alfred Nisonoff, Gerald Edel- man, Rodney P. Porter, Henry G.Kunkel 1961 Discovery of the thymus as part of the Jaques F. A. P. Miller, Robert immune system A. Good 442 Brief History of Important Immunologic Discoveries and Developments Year Event Author(s) 1963 Development of the plaque formation Nils K. Jerne, Richard J. Henry, test Albert A. Nordin 1963 Ss Locus in the H-2 complex discovered Donald C. Shreffler coding for the C4-complement component 1963 (1953) Histamine release by mast cells in Ivan Mota anaphylaxis 1964 Development of rosette-test G. Biozzi 1965 Discovery of the variable region of anti­ Norbert Hilschmann body molecules 1965 Linkage of MLR reactivity to the HLA Fritz Bach, Kurt Hirschhorn complex discovered 1965 Immune response-l (Ir-1) locus in the Hugh O. McDevitt and Michael mouse discovered Sela 1966 Enzyme labeling of antibodies and S. Avremeas antigens 1966 Discovery of IgE as reaginic antibody Kimishige Ishizaka 1969 Thymus function defined, dichotomy of Jaques F. A. P. Miller and the immune system discovered Graham Mitchell 1969 H-2 antigen isolated Stanley G. Nathenson and Akira Shimada 1969 T helper function in antibody formation N. Avrion Mitchison described (T-B Collaboration) 1969 B lymphocytes as cells with surface­ Benvenuto Pernis bound Ig discovered 1969 Discovery of idiotypes Jaques Oudin 1971-72 Cytotoxic T cells described Jean-Charles Cerrotini, K. Theodor Brunner, Peter Perl­ mann, Hermann Wagner 1971 Discovery of MLR locus linked toHLA Edmond J. Yunis and Bernhard in man Amos 1971 Two-locus model of the mouse MHC George D. Snell, Jan Klein, (H-2) formulated Donald C. Shreffler, Jack Stimpfling 1971 T and B cell tolerance defined Jaques Chiller 1972 T suppressor cells described Richard K. Gershon 1972 Discovery of MHC-restriction of T cell Berenice Kindred and Donald dependent immune responses C. Shreffler 1973 Discovery of Ia antigens Chella S. David, Donald C. Shreffler, Jan Klein, Dietrich G6tze, David H. Sachs Brief History of Important Immunologic Discoveries and Developments 443 Year Event Author(s) 1973 T-B cell collaboration I region restricted David H. Katz and Baruch Benacerraf 1974 Idiotypic network theory formulated Nils K. Jerne 1974 K,D-restriction of cytotoxic T cells Peter Doherty and Rolf Zinker­ discovered nagel 1975 Fusion of myeloma cells with normal, George Kohler and Cesar specific antibody-producing plasma Milstein cells (hybridoma) 1978 Structure of MHC (H-2 and HLA) Stanley G. N athenson, Jack antigens defined Strominger 1978 Macrophage-T cell collaboration Jonathan Sprent I-region restricted 1978-80 Elucidation of immunoglobulin genes; Suzuma Tonegawa generation of diversity is (almost) solved 1980 Smallpox worldwide eradicated World Health Organization (WHO) 1982 CD antigens defined by monoclonal Leukocyte antigen workshop, antibodies Paris (Reinharz) 1983-85 T cell antigen receptor genes elucidated Marrack, Allison Glossary of Immunologic Terms Accessory cells. Lymphoid cells predominantly of cells by cytotropic antibodies following ex­ the monocyte and macrophage lineage which posure to antigen cooperate with T and B lymphocytes in im­ Anergy. The inability to react to an antigen (mi­ mune reactions croorganism) Acquired immunity. Immunity that develops as a Antibody. A protein that is produced as a result result of exposure to a foreigne substrate of the introduction of an antigen and which Activated lymphocytes. Lymphocytes that have has the ability to combine with the antigen that been stimulated by specific antigen or nonspe­ stimulated its production cific mitogen Antibody combining site. That configuration pre­ Adoptive transfer. Transfer of immunity by im­ sent on an antibody molecule which links with munocompetent cells from one animal to an­ a corresponding antigenic determinant other Antibody-dependent cell-mediated cytotoxicity Affinity. Binding strength between antibody and (ADCC). A form of lymphocyte-mediated cy­ antigen in an antibody-antigen reaction totoxicity in which an effector cell kills an anti­ Agglutination. An antibody-antigen reaction in body-coated target cell which a solid or particulate antigen forms a Anticomplementarity. Unspecific complement ac­ lattice with a soluble antibody tivation, i.e., not due to antibody-antigen reac­ Allelic exclusion. The phenotypic expression of a tion single allele in cells containing 2 different al­ Antigen. A substance which can induce a detect­ leles for that genetic locus able immune response when introduced into Allergens. Antigens which give rise to allergic sen­ an animal sitization by IgE antibodies Antigenic determinant (epitope). That area of an Allergy. An overshouting hypersensitivity reac­ antigen which determines the specificity of the