Prion diseases and the immune system

Unlike other infectious diseases, transmissible spongiform encephalopathies elicit no specific immune response, Indeed, because the infectious agent, the prion, seems to be essentially composed of a protein with a primary str ucture identical to a host encoded protein, the lymphoid system is naturall y tolerant. However, lymphoid organs are strongly implicated in the early p eripheral steps of the disease. Paradoxically, immunodeficient animals, whi ch are more susceptible to infections by usual pathogens, appear to be part ially or completely resistant to experimental infection by prions by periph eral route. Several studies suggest that in normal subjects, cells of the i mmune system support the replication of prions and might allow their spread ing from the periphery to the central nervous system, Thus, the lymphoid sy stem appears to behave as a Trojan horse rather than a protective fortifica tion in the process of prion infection. A greater understanding of the path ophysiology of these aspects of prion diseases could lead to immunomanipula tion strategies aimed at preventing prion spread into the central nervous s ystem, once peripheral exposure has occured.