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 structure identical to a host encoded protein, the lymphoid system is naturally tolerant. However, lymphoid organs are strongly implicated in the early peripheral steps of the disease. Paradoxically, immunodeficient animals, which are more susceptible to infections by usual pathogens, appear to be partially or completely resistant to experimental infection by prions by peripheral route. Several studies suggest that in normal subjects, cells of the immune system support the replication of prions and might allow their spreading from the periphery to the central nervous system. Thus, the lymphoid system appears to behave as a Trojan horse rather than a protective fortification in the process of prion infection. A greater understanding of the pathophysiology of these aspects of prion diseases could lead to immunomanipulation strategies aimed at preventing prion spread into the central nervous system, once peripheral exposure has occurred.