152 ANAPHYLAXIS 



been changed by corresponding antibodies, and that the period 

 of incubation represents the interval of time which is necessary for 

 antibody formation. Subsequently he showed in a joint publication 

 with Schick that his original observation merely illustrated the 

 general rule that a first injection of horse serum always sensitizes 

 the individual to subsequent injections, so that the latter are followed 

 by symptoms more rapidly and more uniformly and can be produced 

 by doses which are much smaller than the first ones. 



In contradistinction to Arthus who ascribed the hypersensitive- 

 ness of his animals to the repetition of the injections in a general 

 way, and who thought that it increased in intensity with each 

 injection, v. Pirquet and Schick emphasized that a single injection 

 suffices to bring about this result, and that a certain interval must 

 elapse before the animal responds in the changed manner to the 

 second 'injection. If, for example, the injection is repeated after 

 five days, no induration develops at the site of the puncture, while 

 at the expiration of ten days this is very marked. Subsequent 

 injections usually lead to still more marked reactions, but v. Pirquet 

 has shown that even then a diminution in susceptibility may occur, 

 and that hypersensibility and immunity can accordingly not be 

 separated in principle. 



Theobald Smith Phenomenon. Further experimental studies were 

 then called forth by the observation of Theobald Smith that guinea- 

 pigs which had once been used in the titration of diphtheria anti- 

 toxin and which had hence been injected with a toxin-antitoxin 

 mixture were thereafter hypersensitive to subsequent injection of 

 horse serum. If such animals were reinjected they showed immediate 

 symptoms of a serious character; they became restless, dyspneic, the 

 heart action became feebler and feebler, the temperature dropped 

 below the normal, and in fully 50 per cent, death occurred within 

 a half -hour (Theobald Smith phenomenon). Postmortem, a most 

 striking picture was seen which readily explained the majority of the 

 symptoms which preceded the fatal end, for on widely opening the 

 thorax the lungs did not collapse, but remained rigid in a state of 

 deepest inspiration. This phenomenon was first described by Auer 

 and Lewis, and is attributed by these investigators to spasm of 

 the smallest bronchioles, which virtually causes the suffocation of 

 the animal. 



At Ehrlich's suggestion, his pupil Otto took up the investigation 



