The cellular basis of the immunity to and immunopathogenesis of tropical theileriosis

The intracellular protozoan parasite Theileria annulata causes a severe and often fatal disease of pure and crossbred cattle in tropical and subtropic al countries. Animals that recover from the infection are immune against ch allenge with homologous parasite strains. In the present review we refer to the role of immunocompetent cells and their products in containing the inf ection or in facilitating the progress of the disease. Parasite-infected ho st cells produce cytokines, which, depending on their concentration and tim ing of production, may enhance the establishment of the infection. Thus, ce ll lines producing high levels of proinflammatory cytokines cause severe po stvaccinal reactions when inoculated into cattle. This may be supported by an aberrant non-specific activation of naive T-cells, leading to the produc tion of high levels of gamma-interferon (IFN-gamma). Under these circumstan ces development of the specific immune response may be inhibited. At this s tage, innate immune reactions are operating to contain the infection. Natur al killer cells and macrophages may represent the most important part of th is immunity. Antibodies and specific T-lymphocytes, CD4(+) T-cells and cyto toxic T-lymphocytes (CTLs), play the most important role in a challenge inf ection. In this context, CD4(+) T-cells produce cytokines required for the clonal expansion of CTLs that kill their target cells in a major histocompa tibility complex (MHC) class I-restricted manner. In addition, CD4(+) T-cel ls produce macrophage-activating cytokines such as IFN-gamma. Such activate d macrophages produce mediators such as NO, which destroy the intracellular schizonts. Attempts have been directed toward the identification of parasite antigens involved in the induction of immunity. To date, only a limited number of sp orozoite and merozoite antigens have been identified and examined for their immunogenicity, and the protection achieved is partial. An effective vacci ne must include schizont proteins, notably, those proteins that are secrete d into the host cell cytoplasm because these may have access to the MHC cla ss I and II compartments to be presented to CTLs and CD4(+) T-cells, respec tively. Several schizont proteins have been identified and these are now un der investigation.