STUDIES ON BACILLUS TYPHOSUS TOXIC SUBSTANCES : II. THE EFFECT OF SERA UPON THE FACTORS DETERMINING LOCAL SKIN REACTIVITY TO FILTRATES OF BACILLUS TYPHOSUS CULTURES.
It is shown in this paper that homologous immune sera are able to neutralize the B. typhosus skin-preparatory factors. The neutralization experiments were performed on a large number of rabbits, at least ten rabbits which showed positive control reactions being used for the titration of each serum. The rabbits into which the mixtures of B. typhosus culture filtrates with immune sera were injected can be divided into the following categories: those showing complete neutralization in highest dilutions (HN), those showing complete neutralization only in lower dilutions (LN) and those showing no neutralization (NN). The results indicate that the potency of a given serum as measured by the method outlined above has a direct relation to the reactions obtained in these groups of rabbits. For practical purposes the highest dilution of the serum which gives complete neutralization of the B. typhosus skin-preparatory factors (HN titer) may be taken as the actual titer of the serum as expressed in terms of their neutralization. The occurrence of a phenomenon suggestive of the prozone reaction is demonstrated. It also appears that the filtrates possess an antigenicity equal to that of dead and live bacteria. The studies on normal sera bring out the fact that normal sera fail to neutralize the B. typhosus skin-preparatory factors unless agglutinins can be demonstrated for B. typhosus. No normal sera have thus far been obtained which neutralized the skin-preparatory factors yet contained no B. typhosus agglutinins, but there were sera which contained these agglutinins but failed to neutralize the skin-preparatory factors. Some of the normal animals whose sera failed to neutralize the skin-preparatory factors were subsequently injected with B. typhosus culture filtrate and responded with neutralizing sera of high titer. Several heterologous sera were also investigated namely, scarlet fever, erysipelas, Shiga bacillus, Flexner bacillus, Mt. Desert bacillus, P. coli and B. avicida. These did not neutralize the B. typhosus skin-preparatory factors. Paratyphosus A and B sera on the other hand produced neutralization in various proportions. And the rabbits into which the serum-filtrate mixtures were injected could also be divided according to the results obtained into the same three groups as those with B. typhosus sera. It is not known yet whether this neutralization is a group reaction or whether the skin-preparatory factors are identical with those of B. typhosus. It would appear from these studies that a method is available for the quantitative titration of substances in the serum which neutralize the skin-preparatory factors of local skin reactivity to B. typhosus culture filtrates. It should be emphasized that it is possible to control the individual susceptibility of rabbits to this phenomenon. The method should permit of considerable accuracy in the quantitative titration of the neutralizing properties of a serum when a standardized procedure is developed. Experiments are under way to determine whether the method can be applied to the preparation of therapeutic sera. Work is also in progress to determine the effect of specific antisera upon B. typhosus skin-reacting factors introduced by the intravenous route.
Laboratories of the Mount Sinai Hospital, New York.
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Shwartzman