Correlation of Parasitic Load and MHC – II Gene Regulation in relation to Malaria

Abstract

One of the difficulties hindering the design of a successful vaccine against Plasmodium is our incomplete understanding of how to induce protective immunity. Protective immunity against Plasmodium species requires efficient MHC class II antigen presentation to activate CD4+T cells, essential for providing help to B cells as well as to CD8+ T cells required to fight against different stages of Plasmodium infection. Although repeated exposures to parasite infection among endemic population is known to induce immunity, many under similar condition fail to resist the infection. Since, (HLA‐DRB1*1302‐DQB1*0501) MHC‐II haplotype expression is linked to resistant to malaria, it is possible that defective MHC‐II expression among individuals make them prone to infection or unable to clear infection efficiently. To address this issue, we estimated parasitic load estimation by using real‐time assay in clinical samples of malaria patients. Then MHCII expression was measured in relation to parasitic burden. MHCII expression in parasite positive samples were analysed at RNA label by q‐PCR. We found that MHCII expression was down regulated with increase in parasite numbers. This similar condition of lack of immune response has been encountered in a wide range of antigens, besides plasmodium, eg: Leishmaniasis, Tuberculosis, Tetanus, Meningococcal infection. This altered immune reactivity involves, both lower production of specific antibodies and reduced lymphocyte profileration and this significant immunosuppression is correlated with parasitemia. The impairment of MHC class II on the cell surface of APCs i.e. Macrophages, Monocytes and Dendritic cells is all because of hemozoin loading, which supresses the processing and phagocytic activity of MHC class II.