Malaria is one of the infectious diseases caused by protozoan Plasmodium species. It is a vector-born disease and transmits by infected Anopheles mosquitoes to human. Studies shows that children are more affected compare to adults. The common symptoms include fevers and chills. The experiment on living organisms and new intravital imaging technology allow scientists to study host interactions at molecular and genetic level. Scientists conducted experiments to study how the Plasmodium parasiteâ€™s distinct life cycle phases between mosquitos to mammalian host, sporozoites to merozoites, skin to red blood cells and cell recognition proteins play important role in developing malaria.
In the experiment, a mouse was infected with Plasmodium berghei. The mouse helps to discover the activity of four stages; from skin to liver, development of merozites in liver, entry into red blood cell, and development inside red blood cells (silvie et al. 4). In the first stage, sporozoites forms of Plasmodium that present in mosquitoes enter in to skin when they bite to mammalian host. Studies indicated that only few of sporozoites migrate to liver cell. Some sporozoites that stay in dermis layer of skin can destroy by phagocytosis or activation of CD8 and T cells if they enter into lymphatic system. The three proteins SPECT-1, SPECT-2 and a phospholipase are responsible in migration of sporozoites from skin to liver cells. The surface circum-sporozoites protein (CSP) on the sporozoites and heparan sulfate proteoglycans (HSPGs) on liver cells initiate the cell recognition. At this point, sporozoites form PV (parasitophorous vacuole) complex and invade liver cells without destroying plasma membrane. However, study suggests that mechanism of binding to host receptors or activation by cellsingnal has not been clear yet.
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The second stage is the development of merozoites in liver. These stage also known as a silent stage because host immune system does not recognize the rapid growing merozoites before they enter into red blood cells. According to the experiment in vitro, the upregulated in infective sporozoites gene3 (UIS3) and liver-fatty acid binding protein (L-FABP) are necessary to form merozoites. Even though, relationship between UIS3 and L-FABP is not known, it reduces the parasite growth without regulation of fatty acids. The mature merozoites are bounded with merosomes released from liver cell to blood stream by egress process. The study based on intravital microscopy point out that merosomes protect merozoites from kupffer cells, thus prevent phagocytosis. Kupffer cells are macrophages that are present in liver cells and activate during infection. Based on gene and protein survey, around 2000 active genes and 800 proteins are involved in parasite development at the liver stage (Silvie et al 4).
The third stage is entry of merozoites into red blood cell. A series of receptor-ligand interactions is necessary in attachment process between merozoites and erythrocytes even though process occur quickly. Experiment based on antibodies inhibiter from individual exposed to malaria, show that it prevents particular invasion pathway of parasite. Transmembrane protein apical membrane antigen1 (AMA1), can target by antibodies to prevent invasion of parasite to red blood cell. EBA175 and EBA 181 are erythrocyte binding antigens are present in parasite and binds to glycoprotein of erythrocytes of host.
The forth stage is development of merozoites inside red blood cells. Once merozoites enter into red blood cell, they form ring stage. At this stage, they replicate by budding process. Exonemes play important role in egress of merozoites. These infected merozoites can attach with new red blood cell rapidly and start new cycle. The recent proteins studies discover that 592 and 644 are soluble membrane proteins in human red blood cell and ETRAMPs (early transcribed membrane proteins) that located on PVM in parasites play important role in parasite development.
Scientists use mouse that was infected by Plasmodium berghei as a model to study cerebral malaria (CM). The study showed that histamine mediated signaling, chemokine receptors, dendritic cell and T cell responsible for developing CM. However, enzyme that catalyzed heme oxygenese 1(HO1) in host prevent CM, neuroinflammation and brain microvasculature congestion. Recent study point out that HO1 regulation is important in liver stage development and erythrocyte of parasite in malaria (Silvie et al. 4).
In conclusion, scientist found other factors played important role in malaria development beside just the genetic basis. Since Plasmodium parasite can survive in both liver and blood cell, interactions of parasite in host are regulated by different proteins or ligand at specific level. Among these experiments of different stages, the third stage experiment is the most important. From this experiment, scientists can conduct research to develop a malaria vaccine. To destroy malaria parasite before they can enter into red blood cells, AMA1 antigens can be targeted by antibodies. However, the further detail study needs to focus on the silent stage of malaria parasite that does not recognized by host immune system.
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