Immediate hypersensitivity. A brief, personal history.
The discovery of anaphylaxis by Portier and Richet that reinjection of a substance caused disease instead of immunity was sensational as it was against the prevailing DOGMA. Passive transmission of hypersensitivity with human antibody by Prausnitz (the P-K reaction, 1921) was an important step in the study of human hypersensitivity. Anaphylaxis was shown to be the consequence of liberation of vasoactive substances (histamine and SRS-A) from mast cells when the allergen crosslinks two IgE molecules fixed to mast cell Ig receptors (Ovary, 1961). The use of smooth muscle contraction (Dale, 1913) and vascular permeability increase (PCA, Ovary, 1948) became important for experimental studies. The clonal selection of antibody formation (Burnet, 1929) opened a new era in immunological concepts. The demonstration of the Fc receptor on mast cells (Ovary, 1961) called attention to the importance of cellular receptors. The carrier effect (Ovary & Benacerraf, 1963) was explained by recognition by T cell receptors of a processed carrier fragment complexed to Ia molecules (Unanue, Grey, 1981). Human IgE responsible for allergies was discovered in 1965 by K. & T. Ishizaka. Tonegawa in 1973 destroyed the "one gene-one protein" DOGMA, showing that the immunoglobulin, germline gene is discontinuous: i.e., composed of exons (which will form the Ig molecule) separated by introns. The CD4 cells were subdivided into Th1 and Th2 cells (Mosmann & Coffman, late 1980's). The Th2 secretes IL-4 necessary for IgE production (Paul, Vitetta, & others, early 1980's). B cells multiply before antibody production or become memory B cells, but what causes a B cell to become a memory cell is not known. The B cell does not change specificity but can switch the isotype using "switch recombinase" and the s segment of the Ig molecules (Honjo, early 1980's). IgE production was shown to be suppressed by lymphokines, such as IFN-gamma and IL-2. A great progress in understanding the mechanism of allergic reaction has been the result of intense investigations by many scientists. A more complete understanding, better prophylaxis and an improved treatment are the goals of the near future.
Ovary
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Department of Pathology, New York University Medical School.
D049673:History, 20th Century; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000266:history*