Malaria blood-stage infection and its control by the immune system

Malaria is caused by the protozoon Plasmodium, transmitted to humans by Ano pheles mosquitoes. The most dangerous of the plasmodia infecting humans is Plasmodium falciparum. The disease is caused by those parasite stages which multiply asexually in red blood cells, In non-immune individuals, P, falci parum may cause severe and life-threatening disease. Another risk group is constituted by pregnant women, particularly during their first pregnancies. Immunity to malaria usually requires repeated exposure to the parasite to b ecome long lasting. One reason for this is the capacity of the parasite to vary the antigens which are major targets for protective antibodies, Antibo dy-dependent protection is primarily mediated by cytophilic IgG antibodies activating cytotoxic and phagocytic effector functions of neutrophils and m onocytes, Malaria infection also involves elevated production of IgE antibo dies. However, IgE-containing immune complexes are pathogenic rather than p rotective by crosslinking IgE receptors (CD23) on monocytes, leading to loc al overproduction of TNF, a major pathogenic factor in this disease. T cells are essential for both acquisition and regulation of malaria immuni ty. The major T cells controlling blood stage infections are CD4(+) of both the Th1 and Th2 subsets. However, T cells carrying the gamma delta recepto r also contribute to this control. The balance between the cytokines produc ed by different cell types is critical for the course of infection, with IF N-gamma having a key role in anti-malaria defence. Blood-stage infections a re also under complex genetic control. Among the regulatory genes, those in volved in elevated production of TNF are associated with increased risk of severe disease and death due to P, falciparum infection.