Quantitative Studies on the Neutralization of Pathogenic Agents in Tissues by Circulating Antibodies

Abstract

Summary and Conclusions The investigations reported in the present paper are part of the more general problem of studying immunity reactions with the aid of the methods of the direct and indirect test or, more specifically, by determining the Ai, Ad and Ai/Ad values. These terms have been defined and discussed in the first part of the paper. In particular, the present communication is concerned with the experimental analysis of previously reported observations. It had been found that the intracerebral or rather intraventricular Ai values were very different for individual tetanal toxins and thus revealed hitherto unknown qualitative differences between the toxins. In the present paper, it has been shown that similar differences exist between the intramuscular Ai values of tetanal toxins. On the basis of considerations which have been discussed in the first part of the paper and need not be repeated, the assumption was tentatively made that the differences in the Ai values might be due to differences in the rapidity with which toxins either enter the nerve endings or else are neutralized by antitoxin at the site of injection. In other words, the differences in the Ai values were explained by differences in the relative avidities of the toxins for nerve tissue and antitoxin. The validity of this explanation was tested by experiments in which the antitoxin was injected at various intervals after the toxin. It was found that an interval of 3 hours between the injection of toxin and the subsequent injection of antitoxin increased the antitoxin requirements 16 times for toxin 64 (Ai = 0.0031 ml) and 260 times for toxin 641B (Ai = 0.2 ml). This result shows that after a certain lapse of time the toxin with the high Ai value is more difficult to dislodge from the tissue than the toxin with the low Ai value. This observation can hardly be explained otherwise than by assumming that toxins with a high Ai value have either a greater affinity for nerve tissue or a lower avidity for antitoxin. After eliminating differences in the Lf values of the individual toxins, the avidities of the toxins for antitoxin were determined by measuring the velocity of flocculation in the Ramon test. These “reduced” flocculation rates were very similar for 5 tetanal toxins. Moreover, the small differences were in no way related to the Ai values. It follows that the differences in the Ai values of tetanal toxins cannot be explained by differences in their avidities for antitoxin. In connection with the above described experiments, this result leaves only the alternative that the differences in the Ai values of the toxins are due to differences in the avidities for nerve tissues.