NR AOWO
AU McGovern,G.; Brown,K.L.; Bruce,M.E.; Jeffrey,M.J.
TI Structural changes of germinal centres suggest immunological alterations are a consequence of scrapie infection in mice
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - PG-02
PT Konferenz-Poster
AB In the lymphoreticular system (LRS), follicular dendritic cells (FDCs) are necessary for peripheral replication of some transmissible spongiform encephalopathies (TSEs) including murine scrapie models. We have previously shown that disease specific PrP (PrPd) accumulation occurs in association with the plasmalemma and extracellular space around FDC dendrites but no specific immunological response has yet been reported in the TSEs. In the present study, light microscopic and ultrastructural morphology of the secondary follicles of the spleen were examined in mice infected with the ME7 scrapie strain and uninfected mice, with and without an additional immunological challenge with sheep red blood cells (SRBC) at 10 weeks post inoculation or at clinical stages of disease. Comparison of the four groups (ME7, ME7+SRBC, control +SRBC and control) showed that scrapie infection was associated with hypertrophy of FDC dendrites, increased retention of electron dense material at FDC plasma membrane, and increased maturation and numbers of B lymphocytes within secondary follicles. FDC hypertrophy was most conspicuous in immune stimulated ME7 infected mice. The electron dense material was associated with PrPd accumulation when examined in immunogold labelled sections by electron microscopy. We hypothesise that immune system changes are associated with increased immune complex trapping by scrapie hypertrophic FDCs expressing PrPd molecules at the plasmalemma of dendrites and that this process is exaggerated by immune system stimulation. Contrary to previous dogma, these results show that a pathological response within the immune system follows scrapie infection.
AD Gillian McGovern, Martin J. Jeffrey (m.jeffrey@vla.maff.gov.uk), VLA Lasswade Veterinary Laboratory, Pentlands Science Park, Bush Loan, Penicuik, Edinburgh EH26 OPZ, Scotland, UK; Karen L. Brown (karen.brown@bbsrc.ac.uk), Moira E. Bruce (moira.bruce@bbsrc.ac.uk), Institute for Animal Health, BBSRC and MRC, Neuropathogenesis Unit, Ogston Building, West Mains Road, Edinburgh EH9 3JF, Scotland, UK
SP englisch
PO Deutschland