ANTIANAPHYLAXIS 153 



of this problem and almost simultaneously with his report there 

 appeared a detailed study of the same subject by Rosenau and 

 Anderson. From the experiments of these observers it appears that 

 the toxin in itself has nothing to do with the sensitization of the 

 animals, and that the horse serum produces this effect only if used 

 in small doses, but that the toxin in some manner which is not yet 

 understood facilitates the sensitizing influence of the serum. The 

 small size of the dose of serum which in itself is sufficient to cause 

 sensitization is indeed remarkable. In one instance Rosenau and 

 Anderson produced this result with -nnnrmnr f a c - c -> while 

 amounts ranging from y^y to yoVfr c - c - were sufficient in every 

 instance; and while a first injection of 10 c.c., which is equivalent 

 to 40 c.c. pro kilo of animal, caused no symptoms of any kind in 

 the guinea-pig, 0.1 c.c. a second injection, was sufficient to bring 

 about death. 



Like Arthus, they found the reaction to be specific insofar as it 

 was impossible to produce symptoms in animals that had been 

 sensitized with horse serum, by subsequently injecting them with the 

 serum from animals of a different species. Like v. Pirquet, they 

 could also show that a certain time interval must elapse between 

 the two injections before anaphy lactic symptoms develop, and that 

 this depends to a certain extent upon the point at which the first 

 injection is given; if this is made into the brain the animal becomes 

 sensitive after the eighth day, while following a subcutaneous injec- 

 tion this occurs at least two days later. 



Antianaphylaxis. Especially interesting also was the discovery 

 that if an animal is reinjected shortly before the twelfth day the 

 reaction is only slight or may not occur at all, and that subsequent 

 injections, for a certain time at least, produce no deleterious conse- 

 quences; in other words, the animal has become resistant instead 

 of hypersensitive (antianaphylaxis} . This condition, however, is 

 not permanent and after a number of weeks the animals gradually 

 become hypersensitive again. If, however, the injections are 

 repeated in increasing doses and properly spaced, a state of resist- 

 ance can be produced which lasts for many months. 



The same condition may, however, also be brought about at a 

 time when the animal is already hypersensitive, by injecting it with 

 a sublethal dose of the antigen. The animal may then become 

 violently ill, it is true, but it will recover, and is then markedly 



