Immunobiology of scrapie following transmission via the skin

• Main Author: Mohan, Joanne
• Published: University of Edinburgh 2005
• Subjects: 636.089
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.657905

Experiments in this thesis were designed to answer the following questions: firstly does scrapie accumulate within lymphoid tissues after transmission via the skin; secondly what cells are critical for the accumulation and replication of scrapie within lymphoid tissues; and finally how does scrapie reach the lymphoid tissues. To answer the first question lymphoid tissues were collected at serial time points after scrapie challenge and infectivity titres measured by incubation period assays in indicator mice. Experiments demonstrated that scrapie infectivity first accumulates in the draining lymph node after inoculation via the skin and subsequently spreads to other lymphoid tissues. To address the second aim of this thesis two separate approaches were taken; firstly a chimeric mouse model was used which had a mismatch in PrP status between FDCs and other bone marrow derived cells within the lymphatic tissues. This experiment demonstrated that PrP^C-expressing FDCs are required for scrapie accumulation within the spleen and that the PrP^C status of bone-marrow derived cells has not effect on scrapie pathogenesis. Secondly, mice were treated with a reagent to dedifferentiate FDCs either prior to or shortly after challenge to determine the role of FDCs in scrapie neuroinvasion. Data presented in this thesis shows that in the absence of FDCs prior to inoculation, disease susceptibility is reduced. Finally it is not known how scrapie is transported from the site of exposure (e.g. the skin) to the draining lymphoid tissue. To investigate the role of LCs in scrapie transport from the skin, mouse models were utilized in which the LCs migration was blocked. Experiments demonstrated that the early accumulation of scrapie within the draining lymph node and its subsequent neuroinvasion was not impaired in mice with blocked LCs migration. Thus, LCs are unlikely to be involved in scrapie transportation from the skin.