Award details

Influence of immune system modulation on TSE pathology

Reference	BBS/E/A/00001659
Principal Investigator / Supervisor	Professor Neil Mabbott
Co-Investigators / Co-Supervisors
Institution	The Roslin Institute
Department	The Roslin Institute Department
Funding type	Research
Value (£)	114,391
Status	Completed
Type	Institute Project
Start date	01/04/2007
End date	31/03/2010
Duration	36 months

Abstract

In most infectious diseases the immune system becomes activated resulting in the generation of an immune response to the infectious agent. Infection with TSE agents however does not provoke an immune response by the host and no immune dysfunction has been detected. In addition, most conventional infectious agents readily infect individuals with weakened immune systems; however TSE agents require the presence of an intact immune system, and mature follicular dendritic cells (FDCs), for efficient infection via peripheral routes. In these studies we propose to determine the influence that immune function, for example in ageing and modulation of the immune system has on TSE pathogenesis. Senescence in mammals results in impaired immune responses and a decline in the function of FDCs. In our studies, the reduced TSE susceptibility in aged mice appeared to coincide with a decline in FDC function. As FDCs appear to be involved in the pathogenesis of vCJD, but not sCJD, the decline in the function of these cells during middle age may contribute to the greater incidence of clinical vCJD in young adults. Although the reasons associated with the predominance of vCJD cases in young people may be complex, our data suggest that age-related immune dysfunction is likely to significantly influence disease susceptibility. Recent risk assessments of secondary transmission have suggested that contaminated surgical instruments, tissue transplantation and blood transfusion are plausible mechanisms for the occurrence of a secondary epidemic of vCJD. Therefore, it is essential to establish how factors such as age and the route of transmission affect host susceptibility. Our murine senescence model provides an excellent opportunity to study aged-related affects on TSE disease susceptibility. We also propose to determine if any effect on TSE pathogenesis by immunisation could be modulated by the use of immunosuppressant agents during the incubation period of disease.

Summary

unavailable

Committee	Closed Committee - Animal Sciences (AS)
Research Topics	Animal Health, Immunology, Neuroscience and Behaviour, TSEs (transmissible spongiform encephalopathies)
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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