This thesis reports the results of a large number of experiments which were designed to elucidate the mechanisms whereby Gambian children, suffering from acute Plasmodium falciparum malaria may eventually control their infections. These experiments were carried out in vitro and success or failure of the various test systems was judged by their effect on parasite multiplication. Early in the course of these investiqations it was demonstrated that mononuclear cells from these children could cooperate with antibodies present in their serum to bring about a marked reduction in parasite growth. The efficiency of this antibody-dependent cellular cytotoxicity (ADCC) mechanism was related to levels of parasitaemia in the children, being greater in convalescent children than in those with acute malaria. Attempts were now made to identify the effector cells in this ADCC. Purified T and B cells were ineffective and although purified adherent cells (A) had an effect, it was much less than that mediated by the undepleted mononuclear cell population. Adherent cells were, however, fully effective in ADCC if they were exposed to the supernatant from T cells non-specifically activated by PHA. Thus cell cooperation leading to activation appears to play an important role in this system. Finally, experiments were set up to determine whether activated mononuclear cells could exert an inhibitory effect on parasite multiplication which was independent of anti-malarial antibody. It was shown that depression of parasite growth could be achieved by mononuclear cells, either from the children or from Europeans, if these cells were exposed to supernatants of previously stimulated mononuclear cells. These findings can be assembled to provide a tentative model of the development of protective responses in vivo. Perhaps following phagocytosis of parasite antigens and their presentation on the cell surface, T cells become activated: they may cooperate with B cells to produce parasite specific antibodies; they may also activate other mononuclear cells (non T, non B) to become effector cells. These cells, either alone, or perhaps more efficiently in cooperation with antibody, are able to kill parasites by the release of toxic factors, and the infection is brought under control. Finally, large amounts of specific antibodies of appropriate isotypes are synthesized. Acting as opsonins or by activating complement, they may serve to destroy remaining parasites. Their continued presence, by preventing merozoite penetration, may provide at least a temporary defense against reinfection. It is assumed that Gambian adults who have suffered repeated malaria infections and are now immune are defended by their possession of circulating IgG antibodies and B memory cells of all appropriate specificities.

The effect of temperature on the sensitivity of poikilothennic cells to toxicant exposure was investigated, with particular attention to the relationship between temperature induced changes in cellular activity, and cell sensitivity to toxicants. Temperature was shown to have a significant influence on the metabolic activity and sensitivity to toxicants ofthree types ofpoikilothenns: E. coli, a consortium of cells isolated from activated sludge (ASBC), and a genetically modified bioluminescent fish cell line (BF-2Ilucl). The influence of temperature on the ASBC and BF-21/ucl cell sensitivity to toxicants appeared to be related to its effects on toxicant uptake and reactivity. However temperature induced changes in E. coli metabolic activity were shown to have a pronounced influence on its sensitivity to toxicants. The increased metabolic rate supported by higher temperatures was associated with decreases in E. coli sensitivity to narcotic toxicants as were the increases in E. coli metabolic activity that resulted from changes in respiratory substrate solution composition. Subsequent biosensor and growth assays demonstrated that E. coli responded to low concentrations of phenolic toxicants by increasing it respiration rate at the expense of growth. This suggests that the protective effect ofincreased metabolic activity at higher temperatures was related to the energetic costs of toxicant exposure. Additionally an impedance spectroscopy assay was developed and showed that 3,5-DCP caused only limited disruption ofE. coli membrane integrity. This study demonstrated for the first time that temperature effects on E. coli metabolic activity and on E. coli sensitivity to toxicants are directly linked. Further work is needed to develop a fuller understanding ofhow E. coli metabolic activity influences its sensitivity to toxicants.

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 4 uppsatser.

Thesis (Ph. D.)--University of Nevada, Reno, 2008. / "May, 2008." Includes bibliographical references (leaves 101-117). Online version available on the World Wide Web.

Dissertation (Ph.D.).--University of Texas Graduate School of Biomedical Sciences at San Antonio, 2007. / Vita. Includes bibliographical references.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2010.

Thesis (M. Phil.)--University of Hong Kong, 1992.

Thesis (Ph. D.)--University of Canterbury, 2009. / Typescript (photocopy). Includes bibliographical references (leaves 191-230). Also available via the World Wide Web.

Thesis (Ph.D.) - University of Queensland, 2005. / Includes bibliography.

Thesis (Ph.D.)--University of California, San Francisco, 2004. / Includes bibliographical references. Also available online.