Immunological Tolerance as the Result of Terminal Differentiation of Immunologically Competent Cells

Abstract

THE nature of immunological tolerance, the unresponsiveness evoked by the administration of large doses of an antigen to newborns^1,2, is usually explained on the basis of the views of individual authors on the mechanism of antibody formation^3–6. The solution of the problem has been transferred to the cellular level. Burnet⁷, on the basis of the clonal selection theory, explained acquired tolerance as allergic damage and elimination of the predetermined cell after contact with the corresponding antigen. Other authors⁸ assumed formation of the tolerant cell at various stages of its differentiation. Medawar⁹ and Lengerová¹⁰ suggested that the antigen might prevent normal maturation of reactive cells at the stage of the stem cell and that this induces the state of the immunological tolerance (heterogeneous model). On the other hand, somu authors¹¹, on the basis of experimental data, assume that the onset of tolerance is possible at all stages of cell differentiation when antigen is present in excess (homogeneous model).