Date of Award


Degree Type


Degree Name

Doctor of Philosophy


Cell mediated immune responses (CMIR), mediated by T-lymphocytes, have been shown to play a role in tumour immunity and allograft rejection. Studies of specific cytotoxic responses indicate that the cells involved in the CMIR are capable of recognizing various cell surface markers. Although many investigations have been conducted the exact nature of the target antigens are not known.;Sensitization of human T cells in Marbrook tissue culture vessels and microtitre trays resulted in the production of effector cells capable of lysing certain target cells. The characterization of the reactivity of these cells was carried out in two systems, the first in which the target cell had been chemically modified with trinitrobenzene-sulphonic acid, and the second in which the target cells were not modified.;The effector cell capable of lysing chemically modified targets did not exhibit MHC restricted cytotoxicity. The cell was a large granular lymphocyte that resided in the non-T cell fraction of cells separated through sheep erythrocyte rosette formation. The cytotoxicity could also be developed, without specific sensitizing antigen, in the presence of factors derived during the generation of an allogeneic response. On the basis of the above observations it was concluded that the predominant effector cell within this system was a human NK-like cell.;Cytotoxic lymphocytes capable of lysing unmodified cells were directed at either major histocompatibility complex (MHC) coded targets or at stable, non-MHC coded targets. Three types of reactivity were delineated; (1) MHC explainable, (2) explainable on the basis of specific antigens on the cell surface that are not MHC antigens, and (3) reactivity that was not specific for a particular cell surface antigen.;Analysis of the distribution of reactivity within the two systems suggest that the primary CMIR is directed against modified self components of the target cell and that it is mediated by an NK-like cell. This form of reactivity is observed between MHC identical transplant pairs, certain randomly selected individuals from the normal population, and in response to hapten and tumour antigen altered self. Greater antigenic differences activate more specific T cells that mediate a selective, MHC specific response that is the major form of reactivity observed in anti-allogeneic responses or during allograft rejection.



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