Immunoglobulin E and reaginic hypersensitivity

K. Ishizaka

Research output: Contribution to journalArticlepeer-review

Abstract

Human IgE represents a distinct immunoglobulin class and carrier of reaginic antibody activity. The protein is formed mainly in the lymphoid tissues in the respiratory and gastrointestinal tracts. IgE molecules have a characteristic structure in the Fc portion of the molecules, combine with basophil granulocytes and tissue mast cells through this structure, and sensitize these cells. Evidence has been obtained that reaction of basophil bound IgE with either allergen or anti IgE results in the release of histamine from the cells and causes degranulation. Similarly, the reaction of mast cell bound IgE with allergen initiates the release of histamine, SRS A and eosinotactic factor and thus induces allergic symptoms. The average number of IgE molecules per basophil is 10,000 to 40,000 in most of the cases. Studies on the anti IgE induced reactions and the number of cell bound IgE molecules strongly suggest that the number and affinity of cell bound IgE antibody molecules determine the sensitivity of the cells to allergen. The binding of IgE with receptors on basophils is reversible and does not involve covalent bond. At the physiological condition, IgE molecules avidly bind with the receptor with an association constant of 108 to 109 per mole. Such a high association constant is probably responsible for a long persistence of passive sensitization with IgE antibody. The initial step of the reaginic hypersensitivity reactions is probably bridging of cell bound IgE molecules by antigen which results in an interaction between the IgE molecules. It appears that such interaction may induce enzymatic sequences leading to the release of chemical mediators. Concerning the IgE antibody response, the authors set up a cell culture system by which IgE antibodies are formed in vitro. In this system, evidence was obtained that both T cells and B cells for IgE antibody response are different from the cells for IgG antibody response. Collaboration of the 2 cell lines is achieved through enhancing soluble factor released from T cells. This cell culture system was applied to analyze antigenic determinants in the major ragweed allergen. The results showed that urea denatured antigen as well as polypeptide chains isolated from the antigen do not induce allergic reactions in ragweed sensitive individuals but maintain the determinants to stimulate T cells. These modified antigens can prime T cells as well, and diminish on going reaginic antibody formation against native antigen. It is expected that basic experiments on IgE antibody response may elucidate the theoretical background of immunotherapy and the finding obtained in the basic experiment may be eventually applied to the clinical problem.

Original languageEnglish (US)
Pages (from-to)67-90
Number of pages24
JournalJohns Hopkins Medical Journal
Volume135
Issue number2
StatePublished - Jan 1 1974

ASJC Scopus subject areas

  • Medicine(all)

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