Malaria Pathophysiology: Antigenic Variation

While circulating in human blood Plasmodium falciparum exhibits antigenic variation. On the surface of the infected red blood cell a certain protein is expressed: the P. falciparum-infected erythrocyte membrane protein 1 (PfEMP-1). The parasite is able to make many variants of this protein. By interchanging which variant of PfEMP-1 is present, the parasite can evade the immune response to these immunodominant antigens. PfEMP-1 also inhibits antigen presentation by dendritic cells. The proteins can bind to endothelial receptors [such as ICAM-1 (intercellular adhesion molecule type 1), VCAM-1 (vascular cell adhesion molecule-1), ELAM-1 (E-selectin), CD36 and thrombospondin]. The PfEMP1 proteins are the gene products of what are called var-genes, of which there are 50 to 150 present in the genome of the parasite. There are also some other variant multigenic families, the products of which can be expressed on the surface of infected red blood cells. Antigenic variation has important implications for the development of vaccines. The repertoire of proteins which are expressed in the Anopheles mosquito is far less pronounced, probably because the vector has no adaptive immune system.

Category: Medicine Notes