Analysis of B cell dysfunctions that occur during experimental trypanosome infections in mice.

Student thesis: Master's Thesis

Abstract

Trypanosome infections are parasitic infections that affect large areas of the less developed world. African trypanosomiasis encompasses both human and livestock infections in Sub-Saharan Africa. The disease affecting humans is known as sleeping sickness or Human African Trypanosomiasis (HAT) while the cattle disease is known as Nagana. Besides the repression of social development in the affected countries, Trypanosomiasis also represents a drastic threat to the countries economic development. Trypanosomiasis is 100% lethal if left untreated and till now no eradication procedure has been shown effective against this parasite. This is mainly due to high drug toxicity, increasing drug resistance and the vast distribution of the parasite throughout the wild life reservoir.
So far, ongoing research dealing with the development of an effective vaccine for trypanosomiasis does not show any promising results, meaning that no specific long term adaptive immunity can be achieved. The main reason for this failure must certainly involve the high complexity of the parasite's life cycle as well as its tremendous capacity of continuously evading the immune system of the host by antigenic variation. By modeling and studying experimental trypanosome infections in mice, it might be possible to unravel the key interactions between the parasite and the host immune system and hence determine the mecheanisms causing the trypanosomiasis-associated pathology. Better understanding the parasite-host interactions could, in turn, lead to the development of new anti-parasite treatments or preventive strategies.
The immune system om mammals can be divided into two arms, the innate and the adaptive immune system. Both are crucial int the interaction with the parasite all along the different stages of infection. The way in which the host immune system responds to a trypanosome infection determines the degree of pathology to which the host will be exposed. Indeed, in trypanosome infections, the major cause of pathology seems to be due to the inflammatory response of the host himself towards the parasite (so called immunopathology), rather than resulting from a direct effect of the infecting parasite on the host. This indicates again the need for identification of occurring host-parasite interactions during infection as well as the impact these interactions induce on the host.
To get a better insight in these trypanosome-host interactions and their impact at the level of adaptive immune system of the host, this work was dedicated to the study of modulations of specific adaptive immune cell populations in the host that occur during trypanosome infection.
Date of Award8 Sep 2008
Original languageEnglish
SupervisorStefan Magez (Promotor)

Keywords

  • Trypanosome infections
  • B cell dysfunctions

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