Abstract
A total of 9 differing experimental models of scrapie were surveyed initially. This thesis has shown that there is at least one model, 87V in Sinc p7 mice, in which changes in the host's humoral immune responsiveness have been consistently demonstrated. These changes were identified initially as a significant increase in the serum IgG concentrations, which is probably not produced as a specific response to scrapie agent as antigen nor to brain antigens. It is not the cause of disease, as judged by its late appearance during the incubation period, and its occurrence is independent of the route of infection. It appears to be directly linked to the persistence of agent in the spleen, which causes selective (i.e. IgGl subclass) but non-specific (i. e. polyclonal) changes. This polyclonal expansion of immunoglobulin-secreting lymphocytes has been confirmed by isoelectricfocusing studies of the increased IgG fraction, and also from its accelerated catabolism in serum. As a further consequence of the longterm presence of 87V strain of scrapie in the spleen, a significant decrease of some T cell subsets, possibly T suppressor cells, was also noted. It was also possible to identify an early immunological consequence of infection with the 87V strain of scrapie, which is independent of T cell involvement. There is an early and sustained increase in the activity of IgGl-secreting B cells, as demonstrated in studies with other IgGl-stimulating antigens (i.e. ovalbumin and KLH), and which parallels the concentration of agent in the spleen. This also suggests that T cells are not involved in the initial extraneural phase of scrapie (87V) pathogenesis.