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In 1919 Alexandre Mikhailovich Besredka showed that oral immunization of rabbits provided immunization against otherwise fatal Shiga bacillus infection regardless of the serum antibody level. Davis, in 1922, showed that fecal antibody was present in the stools of patients with bacillary dysentery before the antibody was found in serum. The discovery of the immunoglobulin classes in 1940, followed by the demonstration of a predominance of IgA at several local mucosal surfaces, renewed interest in mucosal immunity.

Burnett first proposed the concept of an antiseptic paint consisting in part of antibodies lining the GI tract. Cysteine residues have recently been shown to predominate in mucus and it has been proposed that through this mechanism, antibodies, particularly IgA, maybe bound to the luminal surfaces of the epithelial cells of the digestive tract. Lymphoid tissue underlies all mucosal epithelium, and is found in the stroma of all external glands, the heaviest concentrations being in the gut, evidently the site of the greatest and most dangerous antigenic load.

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