144 ANAPHYLAXIS 



after it lias 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 injections of 

 horse serum. If such animals are reinjected they show immediate 

 symptoms of a serious character; they become restless, dyspneic, 

 the heart action becomes feebler and feebler, the temperature drops 

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

 half hour (Theobald Smith phenomenon). Post mortem, a most 

 striking picture is seen which readily explains the majority of the 

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

 thorax the lungs do not collapse, but remain 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. 



