1. The course of elimination of passive immunity in rabbits injected intravenously with diphtheria antitoxin obtained from a horse, consists of three phases:(a) an initial loss of 50 per cent, occurring within the first 24 hours;(6) a gradual constant percentage loss of approximately 25 per cent, from day to day, lasting 6–7 days;(c) a rapidly accelerated loss of 50 per cent, or more per day after the seventh or eighth day.2. In rabbits sensitised with small doses of horse serum the same three phases are seen, but(a) while the initial loss remains the same(b) the gradual constant percentage loss is of the same magnitude, but lasts only two or three days;(c) the rapidly accelerated loss occurs after the third or fourth day and over 90 per cent, of the antitoxin present is lost within 24 hours.3. Possible explanations of the three phases are:(a) initial loss due either to precipitin to horse serum normally present in rabbits or to saturation of or adsorption to the tissues;(b) a phase independent of precipitin action;(c) accelerated loss due to formation of precipitin commencing seven or eight days after injection of horse serum in normal rabbits and three or four days after injection in sensitised rabbits.

1. The course of disappearance of passive immunity in rabbits injected with diphtheria antitoxin obtained from goats, men, guinea-pigs and cows, consists of the same three phases that follow the injection of horse serum.2. The rabbits examined were more responsive to goat, human and guinea-pig serum than to horse and cow serum.3. The course of disappearance of passive immunity in rabbits, horses and guinea-pigs injected with homologous antitoxin, consists of Phases A and B only, and Phase B is far slower than when heterologous serum is injected into rabbits.4. Sheep and goats eliminate antitoxin obtained from a horse at a very slow rate, and Phase C is hardly detectable.5. Natural immunity of horses to diphtheria toxin is gradually acquired by a number of increasing responses to external stimuli.

1. There is some evidence that an injection of 0·00001 c.c. of horse serum causes an appreciable degree of active immunity to horse serum in rabbits.2. Rabbits actively immune to horse serum receiving a series of injections of antitoxic horse serum at intervals of three to ten weeks eliminated the antitoxin at rapidly increasing rates.3. An intravenous injection of antitoxic horse serum given six weeks after the second of a series of 0·5 c.c. in a rabbit already actively immune to horse serum was eliminated so rapidly owing to excess precipitin that less than 1/1000th remained 24 hours after injection.4. Another rabbit which, six days after a previous injection, was givenserum intravenously, lost over 99 per cent. of the antitoxin within 15 minutes of the injection.5. The maximum of circulating antitoxin detected after the second subcutaneous injection into a sensitised rabbit was only 1/15,000th of the amount injected.6. Antitoxic horse serum injected intravenously into rabbits at weekly intervals was rapidly eliminated and less than 2 per cent. could be detected 24 hours after each injection.7. After 12 daily intravenous injections of antitoxic horse serum into a rabbit, the antitoxic content was only one-half of that after the first injection; later injections were not eliminated so quickly and precipitin formation gradually ceased.8. The rate of elimination of antitoxic horse serum in a rabbit may be greatly delayed by daily injections of normal horse serum.

EARLIER work on the subject of passive immunity has shown that antitoxin given to a sensitive animal is rapidly lost from the circulating blood. The rate of disappearance has been traced in rabbits previously sensitised by small doses of serum such as are present in 1.0 C.C. of toxin-antitoxin mixtures used for human immunisation (Glenny and Hopkins, 1922). It became evident that this rate of loss might have an important bearing upon the effect of an injection, in a sensitised animal, of a toxin-antitoxin mixture, causing possibly the rapid elimination of either the antitoxin alone or the mixture as a whole. It was also considered that, apart from the question of direct loss of material injected, the cellular activity and the precipitin formation which follow the injection of serum into a sensitive animal might inhibit or interfere with the immunising power both of toxoid and toxin-antitoxin mixtures as primary and secondary stimuli. I n this paper, we shall deal with experimental work directed to investigate these two aspects of the subject.The possibility of a rapid elimination of the antitoxin from a toxinantitoxin mixture when injected into a serum sensitive animal was investigated on guinea-pigs. These animals were given toxin-an titoxin mixtures in doses sufficiently large that if the antitoxin alone were lost, there would remain in the circulation several lethal doses of toxin ; guinea-pigs not previously sensitised were used as controls. The serum-sensitive animals did not succumb to the injection, and produced no larger swellings than did the control pigs. It was therefore concluded that if any elimination had taken place, both the toxin and an titoxin had been eliminated from the circulation. Table I. and charts 1 and 2 show the results of an experiment upon the influence of precipitin formation upon the antigenic effect of a toxin-antitoxin mixture (T.A.M.) given as a secondary stimulus.Previous experiments had shown that in a normal rabbit precipitin production begins about the seventh day and is thus less rapid than in a sensitive animal in which rapid production begins four days after the injection of serum, so that the injection of a toxin-antitoxin mixture, preceded four days by serum, would probably be unable to produce any immunity response if rapid elimination 805

No abstract