The role of the immune system in prion infection

Prion diseases are a unique group of chronic neurodegenerative diseases that affect humans and certain domestic and free-ranging animal species. Many natural prion diseases are acquired peripherally, such as by ingestion of contaminated food or pasture. Although the pathology during prion disease appears to be restricted to the central nervous system, where it causes extensive neurodegeneration, some prion diseases accumulate to high levels within the secondary lymphoid tissues of the host's immune system as they make their journey from the site of infection to the brain. The replication of prions within these tissues is essential for the efficient spread of disease to the brain. Moreover, the immune system has a profound influence on the development of disease within the central nervous system. This chapter describes the interactions between prions and the host's immune system. Particular emphasis is given to studies which have helped to identify the key tissues, cells, and molecules which the prions exploit to facilitate their propagation from peripheral sites of exposure (such as the intestine) to the brain. This chapter also describes how prion disease pathogenesis and susceptibility may be influenced by inflammation, co-infection with other pathogens, and aging. A thorough understanding of the factors which influence prion disease susceptibility is important as it may help to identify important targets for therapeutic intervention and to help determine the risk of susceptibility to novel peripherally acquired prion diseases.