Intestinal mucosa of sheep infected with M. paratuberculosis (Johne's bacillus) contains two substances that seem to be specific for this disease. One of these substances—the antigen—has been previously described (1, 2, 3, 4). It fixes complement in suitable mixtures with a specific antiserum. The second substance in the infected mucosa—the inhibitor—impedes the fixation of complement by the antigen.

The inhibitor is soluble at all hydrogen-ion concentrations between pH 3 and pH 9. This fact may be used to separate it from the antigen which is insoluble between pH 3 and pH 5. The inhibitor is not precipitated by 3 per cent trichloroacetic acid, and it is insoluble in ether. It will withstand boiling, but does not dialyze through a cellophane membrane.

The inhibiting substance was found to be present in all of the 13 infected intestines which were tested, while 13 normal intestines which were also tested as controls were not found to contain any of the inhibiting principle.

The inhibitor is thus a product of the specific morbid process. It seems reasonable to assume that its function in the tissue is somehow directed against the antigen as it is in vitro, where it inhibits one of the functions of the antigen.

To our knowledge no soluble, specific “antiinfectious” substances have previously been known to arise in the organism as a result of infection except the “antibodies” which are globulins or inseparably associated with globulins. The results reported in this paper, however, do seem to indicate that the organism may also form antiinfectious substances of other kinds, and these may also play a role in the pathogenesis of infectious diseases.

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