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Hypersensitiveness to Diphtheria Bacterial Products

Comparison of Filtrates of Highly and of Weakly Toxicogenic Strains

From the Department of Bacteriology and Immunology, Vanderbilt University Medical School, Nashville, Tennessee

Abstract

The hypersensitive man (individual C) previously reported reactive with toxin-containing and non-reactive with non-toxin-containing test materials, was studied further by a comparison of the hypersensitive reactivity or non-reactivity of the filtrates of highly and of weakly toxicogenic strains of diphtheria bacilli. With a constant test dose (3.0 x 10^–4 cc.) of filtrate, each of the 18 highly toxicogenic strains produced a moderate to strong immediate skin reaction; in contrast, none of the 14 weakly toxicogenic strains gave any reaction at all. This sharp demarcation was acceptable proof that the agent of this man's hypersensitive reaction was consistently present in higher concentration in the filtrates of highly toxicogenic than in the filtrates of weakly toxicogenic strains.

When dealing with complex mixtures like bacterial filtrates, it is difficult to assign hypersensitive reactions to any one particular constituent. However, in the present instance, significance must be attached to the regular association between toxin and the agent of C's hypersensitiveness, particularly because of the biological assays of the filtrates for their contents of two other diphtheria constituents (the agent of the delayed "pseudo" reaction and the agent of the immediate reaction on individual A). The fact that some of the weakly toxicogenic strains non-reactive with C were just as potent as any of the highly toxicogenic strains in respect to other diphtheria bacterial substances was important because it showed that the consistent association between the toxin content and content of the agent of C's reaction was not due simply to a greater concentration of bacterial substance in the toxicogenic filtrates by virtue of more luxuriant growth or of consistently greater autolysis on the part of the toxicogenic strains.

While the evidence is of indirect nature, it strongly suggests that diphtheria toxin is the substance involved in the described hypersensitive immediate skin reaction.