Malaria is the largest parasitic disease in the world and is caused by the protozoon Plasmodium. The most severe form in humans is caused by Plasmodium falciparum. Immunity to malaria involves both cell-mediated and humoral responses and develops slowly over a period of ten to fifteen years, requiring repeated infections.
This thesis describes work aimed at investigating some of the immunological mechanisms occurring during human and experimental murine infections. The results show that polyclonal and specific Immunoglobulin (Ig) E elevations occur during blood-stage P.falciparum and P.chabaudi infections and that it is the malaria parasite itself that is responsible for this IgE induction. Elevated levels of IgE in humans are correlated with severity of disease. Studies in mice showed that the genetic background and the number of infections influence the development of IgE antibodies.
Interleukin (IL)-4 plays a major role in the switching of IgM/IgG to IgE antibody production and functions as a B cell stimulatory factor. Activated T cells are a major source for IL-4 in the immune response but recently other non-lymphocyte cell types, potent producers of IL-4, have been described. One such cell type is the FceRI+ non-B non-T (NBNT) cell, probably a cell of the basophilic lineage. The data presented in this thesis show that a population of IL-3-responsive IL-4-producing NBNT cells expand in the spleens of P.chabaudi infected mice during and shortly after peak parasitemia. During this time period the mice are anemic and display elevated levels of IL-3 in their serum. The expansion of IL-4 producing NBNT cells correlates with the switch from Th1 to Th2 that takes place in the spleen during this time period. Thus, NBNT cells may represent a source of IL-4 involved in directing the Th-response towards a Th2 phenotype.
The changes in cellular dynamics that take place in the spleen and peripheral blood during a malaria infection are complex, and the kinetics apparently differ between spleen and peripheral blood. The changes in the spleen involve apoptosis during the peak parasitemia. Thus, apoptosis may be of importance in the control and development of the splenic immune response.
Concomitant infections with the trematode worm Schistosoma mansoni and P.chabaudi malaria resulted in higher malaria parasitemia and increased mortality. The malaria specific Th1 response was not affected by the concomitant S.mansoni infection but a significant suppression of macrophage activity was seen. The malaria infection suppressed S.mansoni-specific antibody production and Th2 cytokine responses showing that both pathogens affected the immune response to the other infection. These data emphasize the importance for similar studies in humans since multiple infections are common in malaria endemic areas.
Stockholm: Stockholm University , 1998. , 83 p.