PROTEIN SENSITIZATION OR ANAPHYLAXIS 219 



The Sensitizer. The sensitizing agent most thoroughly 

 studied is blood serum. When a small dose of blood serum 

 is injected into a guinea-pig intravenously, subcutaneously, 

 intracranially, or intra-abdominally, and, after a period 

 of twelve days or longer has elapsed, a second injection is 

 made, the animal develops the symptoms of anaphylactic 

 shock, which, in the majority of instances, terminate 

 fatally. This reaction is specific. The animal is sensitized 

 to the blood serum of the species of' animal from which the 

 blood was taken and not to the sera of other species. The 

 amount of serum necessary to sensitize a guinea-pig is 

 surprisingly small. Rosenau and Anderson found 0.000001 

 c.c. of horse serum sufficient. Besredka places the minimum 

 amount necessary to secure uniform results at 0.001 c.c. 

 while one-tenth of this proved sufficient in a considerable 

 percentage of the animals. The sensitizing dose of horse 

 serum ordinarily employed in experiments upon guinea-pigs 

 is 0.01 c.c. Large doses sensitize, but a longer time is 

 required. When 5 c.c. is given the time which elapses 

 before complete sensitization results may be as long as 

 three months. The larger the dose the longer the time 

 essential to sensitization. Besredka is inclined to the 

 opinion that when large doses are given there is no sensitiza- 

 tion until the greater part of the injected protein is elimin- 

 ated. If he means that it is eliminated unchanged, he is 

 certainly wrong. The protein of the first injection is slowly 

 digested, and the larger the amount the longer the time 

 required for the digestion, and complete sensitization does 

 not occur until all the protein of the first injection has been 

 disposed of and the cells have had time to accumulate a 

 reserve of the preferment. At least this is our explanation 

 of this point. The second dose, in order to produce a fatal 

 result, must be considerably larger than the minimum 

 sensitizing dose. The proportion between the minimum 

 sensitizing and minimum fatal dose has been placed by 

 Doerr and Russ at 1 to 1000. The second dose, in order 

 to kill the animal promptly, must contain at least a fatal 

 dose of the protein poison, but it may contain many times 



