Review: 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 subtropical countries. Animals that recover from the infection are immune against challenge with homologous parasite strains. In the present review we refer to the role of immunocompetent cells and their products in containing the infection or in facilitating the progress of the disease. Parasite-infected host cells produce cytokines, which, depending on their concentration and timing of production, may enhance the establishment of the infection. Thus, cell lines producing high levels of proinflammatory cytokines cause severe postvaccinal reactions when inoculated into cattle. This may be supported by an aberrant non-specific activation of naive T-cells, leading to the production of high levels of gamma-interferon (IFN-y). Under these circumstances development of the specific immune response may be inhibited. At this stage, innate immune reactions are operating to contain the infection. Natural killer cells and macrophages may represent the most important part of this immunity. Antibodies and specific T-lymphocytes, CD4+ T-cells and cytotoxic T-lymphocytes (CTLs), play the most important role in a challenge infection. In this context, CD4+ T-cells produce cytokines required for the clonal expansion of CTLs that kill their target cells in a major histocompatibility complex (MHC) class I-restricted manner. In addition, CD4+ T-cells produce macrophage-activating cytokines such as IFN-gamma. Such activated 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 sporozoite and merozoite antigens have been identified and examined for their immunogenicity, and the protection achieved is partial. An effective vaccine must include schizont proteins, notably, those proteins that are secreted into the host cell cytoplasm because these may have access to the MHC class I and II compartments to be presented to CTLs and CD4+ T-cells, respectively. Several schizont proteins have been identified and these are now under investigation.