A mechanism for the induction of immunological tolerance by antigen feeding: antigen-antibody complexes.

Abstract

We have previously reported on the induction, in mice, of a systemic (splenic) immune response with IgA as the dominant antibody, as a result of a short (4 day) intragastric immunization course with foreign erythrocytes. This response was followed by a prolonged period of hyporesponsiveness to similarly administered antigen. Here it is shown that this hyporesponsiveness is also manifested towards antigen given intraperitoneally, and that one is therefore dealing with tolerance, not with failure to absorb antigen from the gut. In contrast, mice primed parenterally and then challenged intragastrically behaved as if never having any previous contact with the antigen, i.e., with a primary-type splenic response of predominant IgA character. This agrees with our former conclusion that splenic responses to enterically absorbed antigen reflect colonization of the spleen by cells sensitized locally in the gut wall, a site not readily primed by the parenteral route. Serum from intragastrically immunized mice contained a very active tolerogen. In vivo, it was capable of conferring tolerance to nonimmune recipient mice. In vitro, it paralyzed the activity of antibody-producing cells. Inhibitory sera has weak antibody activity, restricted to the IgA class, and contained immune complexes reacting with rheumatoid factor but not with C1q. Elimination of these complexes by means by insolubilized rheumatoid factor abolished the tolerogenic effect. In conclusion, the enterically induced tolerogen seems to consist of immune complexes with IgA as the antibody.

Selective induction of an immune response in human external secretions by ingestion of bacterial antigen.

“…The reason for the absence of a pronounced serum response after oral immunization is not clear; however, the induction of a selective systemic hyporesponsiveness could be considered (43).…”

Oral Immunization with Bacterial Lysate against Infection with Streptococcus pneumoniae in Mice

“…The scientific acceptance of oral immunization is limited because results often seem to be contradic tory. Several studies reported the induction of ge nuine forms of systemic tolerance after oral feeding of antigens like ovalbumin, P-lactoglobulin or erythro cytes [13][14][15]. Systemic tolerance and mucosal immun ity may appear concomitantly after oral immuniza tion, and antigen feeding is associated with the devel opment of regulatory antigen-specific suppressor and helper T cells [16,17], The type of antigen may also play an important role because a difference in muco sal immunogenicity between bacterial and food anti gens has been reported [ 15].…”

The Microflora of the Gut: Recent Findings and Implications

“…However, circulating antibody -predomi nantly IgM isotype -and antigen-antibody complexes suppressed the immune response to particulate antigens such as bacteria or erythrocytes in erythrocyte-fed mice [36,[38][39][40],…”