Molecular mechanisms underlying the control of antigenic variation

If we were to count the number of parasites in your blood every day,” explained the doctor, “we would likely notice that the parasitemia level would steadily increase for a period of time, perhaps one week, then the parasitemia level would fall drastically over one or two days as large numbers of parasites were killed by your immune system, only to rise again the following week. This trend would continue until you were given medication to clear the parasites, and would look like this if graphed.” The doctor then pointed to a graph in a paper he was holding (Figure 2).

“I don’t understand,” said Robert. “If my immune system is capable of killing the parasites, why would the number of parasites in my blood repeatedly rebound in that way?”

The doctor explained that in order for African trypanosomes to become successful extracellular parasites and survive in the bloodstream of their human hosts, they had evolved a mechanism to evade the host’s immune response.

“African trypanosomes are covered by a protective coat containing proteins called variant surface glycoprotein (VSG). Although VSG helps protect the parasite, it’s also an antigen, which means it triggers the immune system to respond by making antibodies against it, which can lead to the destruction of the parasite. The genome of African trypanosomes contains many variations, or alleles, of the gene that encodes VSG. Only one allele is expressed at a time, but the parasite can vary which allele is expressed, allowing it to change its VSG coating as soon as the host’s immune system becomes effective at recognizing one particular variant of VSG.”

The doctor continued: “Every spike in parasitemia levels in the graph represents a switch in VSG expression. It takes time for the immune system to adapt to each new VSG. Once it does, parasites are rapidly killed and parasitemia levels drop sharply, only to increase again after another round of VSG switching.”


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Figure 2. Parasitemia level vs. time


Page 4“African Illness” by Kevin M. Bonney

Questions 1. Investigate the different parts of the human immune system and explain which cells/products of innate and

adaptive immunity are responsible for recognizing antigens on the surface of T. brucei and clearing the parasite.

2. What would happen if T. brucei suddenly loss the ability to undergo antigenic variation?

3. If researchers developed a drug that could prevent T. brucei from undergoing antigenic variation, do you think it could be successful in eradicating African Sleeping Sickness? Would the drug have to be administered at a certain point before or after infection in order to be helpful?

4. Based on the similarities and differences you identified earlier between T. brucei, P. falciparum, and T. cruzi, do you predict that P. falciparum and T. cruzi undergo similar antigenic variation? Why or why not?


Page 5“African Illness” by Kevin M. Bonney


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Part IV – Public Health Campaign In addition to the extensive toll on human life, African trypanosomes also cause a widespread and devastating disease in livestock cattle called Nagana. Nagana causes three million cattle deaths per year, which amount to a loss of $4 billion a year to struggling African economies. Because there is no effective vaccine against African trypanosomes, the most effective way to prevent the spread of the disease is through multi-faceted public health campaigns directed at eliminating parasite contact through other means.

Design a public health campaign to dramatically reduce or eradicate African trypanosomiasis in both humans and cattle from a community in Africa. In your plan, include strategies to stop the spread of African trypanosomes, as well as ways to educate the public and local governmental and health agencies so that this information can be disseminated and implemented.