Prion diseases and the immune system

Transmissible spongiform encephalopathies are caused by unusual infectious agents that are purported to contain a single type of macromolecule, a modi fied host glycoprotein. The term prion has been applied to this group of ag ents. Surprisingly, the immune system appears to behave as a Trojan's horse rather than a protective fortification during prion infections. Because pr ions seem to be essentially composed of a protein, PrPSe, identical in sequ ence to a host encoded protein, PrPC, the specific immune system displays a natural tolerance. However, lymphoid organs are strongly implicated in the preclinical stages of the disease. Certain immunodeficient animals are res istant to prions after peripheral inoculation. In normal subjects, cells of the immune system support the replication of prions and/or allow neuro-inv asion. A better understanding of these aspects of prion diseases could lead to immunomanipulation strategies aimed at preventing the spread of infecti ous agents to the central nervous system. (C) 2000 Academic Press.