Serum IgA: modulation of complement activation and induction of susceptibility to bacterial dissemination.

Data are presented that support the conclusion that serum IgA functions as a regulatory Ig that modulates activation of complement by bacteria entering the circulation in showers of low inoculum from mucosal sites of colonization, and that preserves the antigenic mass by shunting such low inocula into macrophages and away from polymorphonuclear leukocytes, thus permitting immunologic processing. This regulation is an integral part of the physiologic immune response to environmental antigens and occurs during the peripheralization of the IgA response following stimulation of Peyer's patches and their analog in the lung. Down-regulation of complement mediated immune effector mechanisms by circulating IgA is balanced delicately. Pathologic states that increase the level of circulating IgA or decrease the phagocytic capacity of the monocyte/macrophage compartment may result in an oligospecific increase in susceptibility to bacterial dissemination. Fortuitous, co-temporal colonization of both gut and distal mucosal lymphoid tissue may result in augmentation of the serum IgA response to levels which induce monospecific susceptibility. This latter mechanism appears to account for the epidemic acquisition of susceptibility to disseminated meningococcal disease. A model of the relation of serum IgA to other components of mucosal immunity is presented.