Schematic representation of possible immunopathologic pathways leading to brain dysfunction in late-stage human African trypanosomiasis. Concepts are based on a combination of human and animal model data and ideas, particularly from refs. 43, 48, 51, 53, and 56. Cytokines shown in red probably have important roles in neuropathogenesis. The schematic emphasizes the central importance of early astrocyte activation, cytokine responses, and macrophage activation. One should note that there are likely to be multiple factors acting together to produce brain damage and also multiple potential sources of different cytokines. Tltf, trypanosome-derived lymphocyte triggering factor.