SOME ASPECTS OF ANAPHYLAXIS 435 



normal guinea-pig will easily tolerate five, a rabbit twenty and a dog 

 one hundred cubic centimeters intravenously, without showing any 

 obvious effect on blood-pressure or respiration. Harmlessness on first 

 injection is, however, not an absolute essential, and animals may easily 

 be sensitized by primarily toxic sera or poisonous animal extracts, for 

 the amount needed to sensitize is very slight, and is only a small frac- 

 tion of the lethal dose. 



The amount necessary to sensitize is almost unbelievably minute; 

 according to Eosenau and Anderson, 0.000,001 cubic centimeters of 

 horse serum may suffice for a guinea-pig, and Wells has succeeded in 

 sensitizing the same animal species with a still smaller quantity of pure 

 egg albumen, 0.000,000,05 gram. These quantities are beyond the 

 capacity of any balance or test tube to detect, and the biological reaction, 

 as usual, is shown to be the most delicate. 



The substance used for sensitization may be incorporated in a 

 variety of ways: by subcutaneous, peritoneal or intravenous injection. 

 Even by feeding the proteid, sensitization may be produced in the 

 guinea-pig according to Eosenau and Anderson. The usual method 

 employed, however, is either subcutaneous or intraperitoneal injection; 

 both these procedures are swiftly and easily carried out, and give but 

 slight or no discomfort to the animal. 



Although not every species of animal has been tested, it seems prob- 

 able that all may be sensitized. The only difference noted is that some 

 species are more difficult to sensitize than others; the guinea-pig is 

 most easily sensitized of all animals tested so far, and for this reason 

 has been the classical animal for investigation. The dog and the rabbit 

 are also rendered hypersusceptible with comparative ease. Fowl are 

 more refractory ; man also can be sensitized. 



The length of time that sensitization lasts varies in the different 

 animal species. In the guinea-pig that state persists for life, which is 

 about three years (Eosenau and Anderson). In the rabbit the degree 

 of sensitization diminishes after three or four weeks, but persists to a 

 greater or less extent for many months, and in man symptoms have been 

 noted seven years after the first injection. 



The degree of sensitization varies also in the different animals and 

 will be considered more fully later. 



Incubation. — After the animal has received an unaltered foreign 

 proteid into its circulating juices, this foreign material causes a pro- 

 found change in the reactions of the host to this proteid. This change 

 occurs gradually and reaches its maximum only after some weeks. If 

 the animal is tested after a few days no reaction will be obtained. In 

 guinea-pigs, for example, ten to fourteen days must elapse before an 

 anaphylactic response can be expected with some certainty, and even 

 with these animals it is best to allow three weeks to pass before testing. 



