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

Abstract

Summary The neutralization of diphtheric toxin in the skin by intravenously injected antitoxin follows the law of multiple proportions provided that the antitoxin is given before the toxin. If the antitoxin is injected only two minutes after the toxin, neutralization no longer follows the law of multiple proportions, larger amounts of toxin requiring more antitoxin than calculated. From the above experimental observations it follows that when the injection of antitoxin precedes that of the toxin the latter is neutralized before combining with the tissue. The endpoint of titration is the same whether the antitoxin is injected immediately, 1, 2, and sometimes even 4 or 6 hours before the toxin is injected intracutaneously. The distribution of antitoxin between blood and skin, therefore, must reach equilibrium immediately after its intravenous injection. This rapid exchange of antibodies between blood and tissue is explained by the assumption that the cutaneous reaction will be negative when the toxin is neutralized in a molecular zone of fluid bordering on the tissue structures and that within this area the exchange takes place in no measurable time. The result of the cutaneous test under these experimental conditions, therefore, is independent of the velocity of the toxin-tissue reaction. The application of these conclusions to experiments with viruses is discussed.