Clonal Selection Theory Research Articles

Termination of acquired immunological tolerance to protein antigens following immunization with altered protein antigens.

Acquired tolerance to BSA in rabbits was terminated following the injection of certain preparations of altered BSA. Injections of Freund's adjuvant containing BSA complexed to anti-BSA, heat-denatured BSA, acetyl-BSA, picryl-BSA, or arsanil-BSA failed to terminate the tolerant state. Except in an occasional tolerant rabbit, injections of these preparations failed to cause the production of precipitating antibody to the altered preparation. Similar results were obtained following injections of alum-precipitated preparations of pepsin-degraded BSA, acetyl-BSA, and picryl-BSA. Injections of Freund's adjuvant containing sulfanil-BSA terminated the tolerant state, but only small amounts of non-precipitating anti-BSA were produced. Injections of Freund's adjuvant containing picryl-acetyl-BSA terminated the tolerant state in two of six rabbits, but again, only small amounts of non-precipitating anti-BSA were produced. Injections of an alum-precipitated preparation of picryl-acetyl-BSA failed to terminate the tolerant state. On the other hand, injections of Freund's adjuvant containing arsanil-sulfanil-BSA terminated the tolerant state in eleven of eleven rabbits and caused the production of precipitating anti-BSA in all nine of the rabbits tested. The tolerant state was terminated also in six of six rabbits injected with an alum-precipitated preparation of arsanil-sulfanil-BSA. Only one of these rabbits produced precipitating anti-BSA. In addition, the injection of BGG-tolerant rabbits with arsanil-BGG, sulfanil-BGG, or arsanil-sulfanil-BGG terminated the tolerant state. These results were discussed in relation to both the clonal selection theory of antibody production and autoimmunity.

Quantitative aspects of the Simonsen phenomenon. III. The effect of immunization of the donor fowl.

SUMMARYImmunization of adult fowls with embryonic tissue does not increase the ability of their blood large lymphocytes to produce lesions on the chorio‐allantoic membrane. The results of Coombs' tests and of haemagglutination tests indicate that inoculation of spleens from 16–18 day embryos provides an antigenic stimulus in the adult fowl, but that 12‐day embryonic spleens evoke no detectable immune response. The bearing of these findings on the application of the clonal selection theory of acquired immunity to the Simonsen phenomenon is discussed.

The Clonal Selection Theory of Acquired Immunity

The Clonal Selection Theory of Acquired Immunity

Specific homograft tolerance in lymphoid cells of long-lived radiation chimeras.

(LxAF/sub 1/ hybrid mice were exposed to an LD/sub 100/ of x rays (870 n and then injected intravenously with bone marrow cells from genetically foreign (homologous) normal C/sub 3/H strain mice. It was found that the long-term survivors were still chimeras, as evidenced by the presence in the spleen of transplantation immunity isoantigens specific for the marrow donor strain (C/sub 3/H). Immunological reactivity of lymphoid tissue cells from these chimeras was assessed by their capacity, when transferred to lethaily x-irradiated (LxA)F/sub 1/ mice, to cause the rejection of homologous bone marrow. These chimera lymphoid cells brought about the rejection of marrow transplants derived from normal DBA/2 or BALB/c mice strains that are genetically foreign with respect to both the donor and host genotype of the chimeras. However, lymphoid cells from the chimeras were found to be nonreactive. i.e., tolerant. towards marrow transplants of (LxA)F/sub 1/ or of C/sub 3/H origin. Data are presented which indicate strongly the presence of immunologically reactive cells of donor (C/sub 3/H) genotype in the lymphoid tissues of these long-lived chimeras. It is suggested that a state of mutual homograft tolerance exists between the donor and host lymphoid cells in these long-lived radiation chimeras althoughmore » these cells reject grafts of cells which are homologous to both donor and host type. The implications of these findings as they relate to the phenomenon of actively acquired tolerance and to the clonal selection theory of immunity are discussed. (auth)« less

Analysis of major histocompatibility factors in a stock of closely inbred White Leghorn fowls using a graft-versus-host reaction on the chorioallantoic membrane.

SUMMARYA study of two sublines of a closely inbred White Leghorn stock has been made using the number of foci produced after transfer of adult leucocytes to chorioallantoic membranes as an indication of the degree of genetic difference between donor and embryonic host.If minor degrees of reactivity are neglected for the time being, the results are explicable in terms of three alleles, A, B, C, at a single locus, and following clonal selection theories of immunity, on the assumption that each fowl carries leucocyte cell clones capable of reacting with antigens not present in its body.

The Clonal Selection Theory of Acquired Immunity.

Abraham Flexner died last year. His name and memory are memorialized in an annual award for contributions to medical education given by the American Association of Medical Colleges and the Abraham Flexner Lectures given biennially at Vanderbilt University. Usually some distinguished foreign visitor is in residence for two months at Vanderbilt and joins intimately in the life of the students and faculty. Sir Macfarlane Burnet is the eighteenth holder of the Flexner Lectureship which was begun in 1928. His contributions add luster to the many distinguished medical scientists who have preceeded him. Sir Macfarlane is one of the most distinguished biologists of our time. His studies have illuminated many parts of virology, immunology, and epidemiology. Not only has he made classic contributions to our knowledge of influenza viruses and bacteriophages but he has been able to develop broad conceptual views of his work which have applications and implications far beyond

Immunity and Virus Infection

This volume is a collection of papers given at a symposium on immunity and virus infection held in May, 1958 by the Vanderbilt University School of Medicine on the occasion of a visit by Sin MacFarlane Burnet. The book opens with a thought-provoking discussion by Burnet of three theories of antibody production: the direct template theory of Haurowitz and Pauling; the indirect template theory of Burnet and Fenner; and the clonal selection theory of Jerne as modified by Burnet. The direct template theory states that antibody is formed by moulding against antigen; the continued production of antibody, therefore, depends on the persistence of the antigen.

A New Approach to Immunity

The Clonal Selection Theory of Acquired Immunity By Sir Macfarlane Burnet. (The Abraham Flexner Lectures of Vanderbilt University, 1958.) Pp. ix + 209. (Cambridge: At the University Press; Nashville, Tennessee: Vanderbilt University Press, 1959.) 22s. 6d. net.