Complexity of the first immune barrier against mucosal pathogens

Antibody-dependent mucosal immunity consists of different and complementary mechanisms which emerged during evolution. It is now established that S-Ig A is not the only isotype of Ig found in secretions, and that antigen-induc ed and naturally occurring antibodies play different roles. The antigen-ind uction of S-IgA antibodies by classical methods is inefficient, which may e xplain the persistent failures of mucosal vaccines. Polyreactive natural an tibodies, which precede any preliminary contact with antigens, appear to be the major agents in the first mucosal defence barrier against pathogens. T he presence of high affinity Fab fragments in the digestive tract, originat ing from liver release of serum IgG, as well as the evidence for a regional ization of mucosal IgG have led to reconsider the classical concepts in muc osal immunity. The major implications of this recent advances will be to op en new fields of investigations for trials of future mucosal vaccines.