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Evasion of the Immune Response
Plasmodium falciparum’s ability to cause persistent, recurrent infection is in part due to its vast repertoire of mechanisms to evade the host immune system
The parasite is most vulnerable when it is moving cell to cell within the body; however, Plasmodium is able to move very quickly. Sporozoites, for example, do not remain in the bloodstream before they enter the liver for enough time to be tracked by antibodies, and by the time T cells are ready to remove the sporozoites from the liver, they have transformed into merozoites and migrated to the red blood cells (Taubes, 2000).
As Plasmodium matures within an erythrocyte, the erythrocyte undergoes a number of changes: knob-like structures form on the cell membrane, the cell becomes more rigid, mechanisms of metabolite transport are altered, and parasite-derived proteins are inserted into the membrane. Although the reasons for these modifications are not understood, it is thought that immunity to malaria stems from responses to the malarial antigens expressed on the erythrocytes (Craig and Scherf, 2001).
P. falciparum erythrocyte membrane protein-1 (PfEMP1) is one protein the parasite puts on the surface of the infected red blood cell, and is the best-understood. PfEMP1 has been implicated in antigenic variation and adhesion during infection. PfEMP1 causes infected erythrocytes to bind to endothelium in the blood vessels, preventing splenic clearance of parasites from vascular circulation. This behavior is unique to falciparum malaria. Although it would seem that by avoiding the spleen, P. falciparum leaves itself vulnerable to destruction by the host immune system, scientists suggest that this allows the parasite to regulate itself and generate gametocytes before killing the host or being killed. Other evidence suggests that PfEMP1 can adhere to dendritic cells, causing immune dysregulation and reducing the efficiency of the host’s immune response (Craig and Scherf, 2001).
Like many other parasites, P. falciparum can evade the host immune response through antigenic variation, by expressing sequences of var genes that change the parasite’s characteristics. As immunity to the current var protein expressed during infection builds up and begins eliminating parasites, some switch on another var gene to escape. These new var proteins then expand and take over infection (Hastings, et al., 2004).
P. falciparum can also express as many as three “sticky” adhesin molecules on the surface of merozoites, which help the merozoite to invade an erythrocyte by engaging various receptors on the red blood cell’s surface (Barnwell, 1999).
Another strategy used by P. falciparum, which causes a severe malaria in humans, and by P. knowlesi, a monkey parasite, is to express up to three alternative ‘sticky’ adhesin molecules in merozoites. These adhesins all help the merozoite to invade its target host cell, but they each engage different receptors on the erythrocyte. The erythrocyte itself is weakened by not having any MHC class I receptors on its surface, as a parasite can invade the cell and remain undetected by cytotoxic T cells (Janeway et al., 2005).
Finally, gametocytes can only be attacked when they are inside the mosquito. They remain within human erythrocytes until they detect a decrease in temperature that indicates the parasite is safely in the mosquito’s gut, at which point it emerges, reproduces, and is able to infect humans again (Taubes, 2000).
Works Cited
Barnwell, John W. 1999. “A new escape and evasion tactic.” Nature 398: 562-63
Craig, A., and A. Scherf. 2001. “Molecules on the surface of the Plasmodium falciparum infected erythrocyte and their role in malaria pathogenesis and immune evasion.” Molecular & Biochemical Parasitology 115: 129–143.
Hastings, I. M., S. Paget-McNicol, A. Saul. 2004. “Can mutation and selection explain virulence in human P.falciparum infections?” Malaria Journal 3.2 <http://www.malariajournal.com/content/3/1/2>. Accessed 2007 Apr 11.
Janeway, C., P. Travers, M. Walport, M. J. Schlomnik, Eds. 2005. Immuno Biology: The Immune System in Health and Disease. 6th Ed. New York: Garland Science Publishing.
Taubes, Gary. 2000. “Searching for a parasite’s weak spot.” Science, New Series 290: 434-37
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