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Immune Evasion Strategies: Antigenic Variation and Trypanosomiasis
| The African trypanosome is a protozoan that, once it enters the
blood of human beings and cattle, causes a fatal neurologic disease called
trypanosomiasis, or "sleeping sickness" in humans. The key to the
trypanosome’s success lies in its ability to evade the host’s immune system via
antigenic variation. A mammalian host defends itself against the foreign protozoa by
manufacturing specific IgM and IgG antibodies against their variable surface glycoprotein
coat (VSG). The host’s antibodies facilitate the neutralization and killing of approximately 99% of the original protozoan population. However, during this time a few of the trypanosomes have shed their coat, switched VSGs, and covered themselves with a new antigenically distinct VSG coat. These distinct protozoa give rise to a new population expressing the new VSG coats. The immune system again responds to this proliferated population by producing a new set of antibodies that succesfully kill 99% of the trypanosome population. But once again, VSG switching among a small portion of trypanosomes renders them undetectable, and they succesfully evade the host immune response. This cycle continues indefinitely, eventually causing the demise of the host.
Hundreds of genes encode VSGs in each trypanosome’s genome. These genes lie either in the interior of the chromosome or near the telomeres. The transcribed VSG gene always lies near the telomere. VSG switching occurs by two mechanisms. In the first, transcription within a single chromosome takes place. An interior VSG copy is duplicated onto a cassette, translocated to the expression site at the telomere and becomes activated. Alternatively, some VSG genes are expressed without being duplicated and translocated. In these cases, the active telomeric site on one chromosome is silenced and a telomeric site on another chromosome is activated. This silencing of expression sites appears to be developmentally regulated.
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Links to other sites on trypanosomiasis
Sources
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Damian RT: Parasite immune evasion and exploitation: Reflections and projections. Parasitology 115: 169-175, 1997. |
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Deitsch KW, Moxon RE, Wellems TE: Shared themes of antigenic variation and virulence in bacterial, protozoal and fungal infections. Microbiology and Molecular Biology Reviews 61: 281-293, 1997. |
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Donelson JE, Turner MJ: How the trypanosome changes its coat. Parasitology Today 8: 44-54, 1992. |
