Immunology

The Perverse and Often Baffling Immune Response to Prions

 

The holy grail of an effective vaccine is sterilizing immunity mediated by powerful neutralizing antibodies. Proof-of-principle has been shown in studies promoting mucosal immunity against prions [22]. The Complement system opsonizes most of the resulting antibody-antigen complexes, marking them for disposal mainly by Kupfer cells, the macrophages of the liver. However, compelling evidence shows that Complement facilitates prion transport to germinal centers within FDCs, where efficient prion replication occurs [9,23,24]. Generating prion-specific antibodies could therefore facilitate Complement trapping and transport of prions to draining lymph nodes—the very place they replicate most efficiently.

 

So maybe a cell-mediated response is better. Perhaps a more effective prion vaccine stimulates prion-specific T cells in the periphery to produce inflammatory cytokines like IFNγ, that can activate macrophages to phagocytose prions and degrade or at least sequester them, as has been shown to occur [6,7]. Such an atypical, cell-induced innate immune vaccine may be just what a host needs to respond to such an atypical pathogen. Or not, says Anne.

Via Krishan Maggon