Rapid expulsion (RE) is a major protective response in rats, accounting for the prompt elimination of 95-99% of infectious muscle T. spiralis larvae from the intestines of appropriately immunized rats. The phenomenon has an immune component; however, the mediator of RE, the mechanism that triggers the expulsion process, and the propagation of the response in the intestine are unknown. Our research seeks answers to these questions. We have two principal objectives. First, we wish to elucidate the phenomenon of RE by determining precisely where and when the first challenge larvae penetrate the intestine. We will follow the process of penetration for 90 minutes in rats expressing RE, in infected rats not expressing RE, and in non-immune controls. The response would be localized in the intestine in experiments using Thiry-Vella loops. Preliminary experiments have suggested a reduced incorporation of 3H-amino acids in worms undergoing RE. This indicates that the worms may be directly modified or impaired by RE rather than simply excluded from the intestine as previously thought. Therefore, we will analyze larval metabolism by quantitating the uptake of 3H-labelled amino acids in vitro by larvae removed from the intestine during rejection. The immunological basis for RE would be further analyzed by determining whether the intramuscular injection of secreted antigens of T. spiralis larvae can prolong RE and promote mucus-trapping of larvae in the intestinal lumen. We would also ascertain whether cells and/or serum can transfer a RE capability to appropriately primed recipients. Cells would be collected from naturally infected rats and from rats immunized by the intramuscular injection of T. spiralis antigens for transfer experiments. Recent evidence suggests that RE may exist in two forms, """"""""early RE"""""""", produced by intestinal stimulation and """"""""late RE"""""""" produced by a complete infection in which muscle larvae implant. We will analyze the effects of the known inhibitors of RE, cortisone and irradiation, on early and late RE with the object of determining whether these represent distinct processes or maturational stages of RE. The larval antigenic targets of RE have not yet been identified but are of major significance in defining the mechanism of response. We therefore propose an analysis of ML secreted antigens using rat immune spleen cells to form hybridomas producing monoclonal antibodies.
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