Exploiting immune surveillance mechanisms in mucosal vaccine development

Historically, immune responsiveness was regarded by many as an ability to discriminate self from non-self, but this definition has recently been revised to be a distinction between threatening infectious organisms versus innocuous molecules from autologous tissues. Such distinctions can be made in the context of adjuvant effects from triggering of 'pattern recognition receptors' by pathogen-associated molecules. Mucosal sites such as airway and intestinal passages present a particularly interesting challenge to this system, as distinctions must be effectively made between innocuous non-self molecules associated with food and commensal bacteria versus pathogenic viruses and bacteria. Given the simultaneous presence of all these molecular types at mucosal lymphoid sites, immunological discrimination mechanisms must be especially precise, as immune responses must be directed only at pathogen-associated targets. Ongoing research is identifying genes that may be critical to triggering mucosal immunity, an understanding of their role in discrimination may lead to the development of new vaccines.