The Regulation of Pleomorphic Trypanosoma brucei Infections in Immunocompetent Hosts

This thesis describes work conducted to elucidate mechanisms by which mammals control pleomorphism in bloodstream populations of Trypanosoma brucei. The hypothesis that division of T. brucei slender bloodstream forms is dependent upon the availability of a host-derived growth factor was tested by superimposing challenge doses of slender form trypanosomes onto preexisting infections at a time during the primary infection when stumpy forms predominated. The challenge populations grew in the doubly-infected mice indicating that depletion of a putative growth factor by the expanding population of the primary infection had not limited the trypanosomes' capacity for division. This effect was independent of the variable antigen type (VAT) of the trypanosomes and of their stock of origin. In assays of antibody-dependent complement-mediated lysis in vitro slender form parasites were lysed between 2.5 and 15 times more rapidly than stumpy forms. In assays of attachment of opsonised parasites to peritoneal macrophages in vitro the majority of both slender and stumpy form parasites attached to the macrophages in the presence of specific antibody, and this attachment occurred at the same rate for both morphological forms. When heat inactivated specific antiserum was used attachment did occur, indicating that Fc receptors on the macrophages mediated the attachment. VAT-specific antibody cannot be detected in the serum of rodents infected with monomorphic parasites. This has led to the supposition that slender form bloodstream trypanosome populations do not elicit antibody responses. Experiments were conducted to determine whether this effect is due to trypanosomes in the bloodstream of a mammalian host acting as a "sink" for specific antibody. High titres of specific antibody could be detected in serum within a few hours of drug-induced death of parasites. This antibody was newly-secreted from plasma cells that had been stimulated several days earlier; it became detectable as a free serum titre because the parasites which had been binding all secreted antibody had been removed from the circulation after drug-treatment. In non-cured mice serum antibody titres became detectable later in the infection and/or were present at lower titres. Monomorphic trypanosomes kill their hosts approximately 4 days after infection, before antibody titres are sufficiently high for free serum antibody to be detected. Therefore serum antibody titres are not reliable indicators of an anti-trypanosome immune response in vivo