Our presentation will be about the role of IgM in CSA binding pregnancy malaria proteins.
I will start by defining what malaria is.
Malaria is an infectious disease common in tropical countries caused by the Plasmodium falciparum parasite and it is transmitted by a vector the female anopheles mosquito. The parasite has between 50 and 60 var genes in its genome. Many researches have been done on malaria mainly because it’s very hard to find a vaccine for the disease. There is a lot of antigenic variation that makes it hard to make an appropriate vaccine. This is the life cycle of the parasite: First the Mosquito injects blood containing the parasite from a sick person, then the parasite goes into the liver where it incubates for about 10days and after that the parasite infects the red blood cells. The parasite multiplies into the cells and when there is no more room for it, the cell lysis releasing more parasites. There are two pathways: One that will lead to the gametocyte and another one that will lead to the merozoite which is another infected red blood cell. One characteristic of malaria is antigenic variation which is caused by a switch in the domain that is being expressed. Each time the parasite expresses one domain, there is a protein that is synthesized and the protein is exported at the surface of the cell. Antigenic variation happens when the parasite alters it surface protein in order to evade the immune systems. It can do that by recombination, alteration or switching. In the case of malaria it’s by switching the gene being expressed thus the surface proteins will change. PfEMP1s have two regions a variable extracellular region and a conserved intracellular region. They cause cytoadherance which we will talk about and the reason why it is hard to find a vaccine for malaria is that everytime the antibodies bind to the PfEMP and give immunity to the patient the parasite switch and start expressing new gene to evade the immune system. Another characteristic of malaria is cytoadherance. Cytoadherance is when the PfEMPS on the infected red blood cells stick to different parts of the body in order to avoid clearance by the spleen. They stick to organs like the brains, muscles, the placenta or the spleen. In our study we are particularly interested in pregnancy associated malaria and I will let my partner Tenaya talk about it.
PfEMPs evolve under the influence of the two factors: need to evade the host immune system and the need to preserve cytoadherance functions.
Only one var gene is expressed at a time.
The parasite switches it to stop the immune system from keeping up.
By identifying domain patterns responsible for binding we can begin to define the PfEMP1s important in cytoadherence
By studying expression patterns we will learn what var genes are turned on in response to particular receptors and cell types
CSA sulfated glycosaminoglycan