[Immunology and immunopathology of African trypanosomiasis]

Human African trypanosomiasis (HAT) is characterized by a major deregulation of the immune system. Hypergammaglobulinemia, auto-antibodies, and immunodepression are cardinal features. Parasitemia occurs in waves due to the successive appearance of parasites with different variable glycoprotein surface antigens (VGSA). Antigenic variation enables parasites to elude the host's immune defenses. Although high levels of immune complexes have been detected during HAT, it seems unlikely that they play a significant pathophysiological role. Numerous auto-antibodies have been detected. B lymphocyte activation is uncommon. In vitro T lymphocytes do not proliferate normally, but synthesize cytokines, such as interferon-g which enhance parasite development. Macrophages bind and destroy parasites in the presence of antibodies. They also synthesize large quantities of TNF-alpha which promote parasite destruction but also increase the severity of clinical symptoms. Nitric acid synthesized by activated macrophages has an antiparasitic effect but induces immunosuppression. In the meningoencephalitic stage of HAT, a severe inflammatory reaction is observed. This event is preceded by astroglia which could be induced by astrocytes secreting TNF-a and IL-1. Auto-antibodies against the central nervous system (e.g. anti-galactocerebrosides, anti-tryptophan-like auto-antibodies) may also be involved in the development of encephalitis. VGSA play a key role in the immunopathology of HAT (antigenic variation, induction of cytokine and autoantibody production). Successive relapses occur with the appearance of new antigenic variants and production of antibodies. The resulting continuous stimulation of the immune system leads to deregulation of immunoglobulin production and cytokine network.