LECTURE #10 - MALARIA

After studying lecture #10, you should be familiar with the following concepts.
1. Malaria. Malaria is a global health challenge that threatens 40% of the world
population and causes 20% of childhood deaths in Africa. Malaria is caused by
Plasmodium parasites, of which the species falciparum is the most lethal. Plasmodium
parasites are transmitted from one mammalian host to another by female mosquitoes.
2. Mosquito Stage of Life Cycle. The female mosquito draws Plasmodium gametes in a
blood meal from an infected host. Gamete fertilization in the mosquito gut results in the
formation of zygotes, which migrate to the gut epithelium and develop into oocysts.
Sporozoites rupture from oocysts, migrate to salivary glands and are transmitted to a
mammalian host as the female draws another blood meal. Salivary antigens can result
in IgE-based hypersensitive reactions in the host.
3. Liver stage of infection. Sporozoites rapidly shed their coats and migrate to the liver
of their mammalian host. Infected liver cells express sporozoite antigens on MHC I
molecules and are targets for CD8 cytolytic T cells. At this stage of the infection cycle,
comparatively few hepatocytes are destroyed. Sporozoites mature into merozoites
during the liver stage of infection, which exit hepatocytes and enter the blood.
4. Blood stage of infection. Merozoites enter host red blood cells (RBCs) and consume
RBC material as resources for merozoite replication. The RBC stage of infection is
responsible for the main symptoms of malaria (fever, chills, nausea, etc). During the
RBC stage of infection, parasites are essentially inaccessible to several key features of
the host defense.
a) Infected RBCs express Var surface antigens. The Var antigens are expressed on the
surface of the RBC and cause the infected RBC to adhere to the lining of small blood
vessels. As a result, infected RBC are not processed in the spleen and parasite
antigens are not presented to naive B cell activation.
b) RBCs do not express MHC I molecules and are not targets for CD8 T cells.
c) RBCs do no express activating ligands are are not targets for NK cells.
d) Plasmodium parasites frequently alter expression of their surface Var antigens and
thereby continuously evade Ig-mediated responses.
Eventually some merozoites differentiate into gametes, exit RBCs and are drawn up by
female mosquitoes in a subsequent blood meal.