ANAPHYLAXIS 363 



about by the use of extracts of various bacteria. In such cases also 

 the reaction is specific. The first determinations with bacterial ex- 

 tracts carried out by Rosenau and Anderson were made with colon, 

 anthrax, typhoid, and tubercle bacilli. 



By these observations, then, the possibility of a direct relation 

 between the phenomena of anaphylaxis and infectious diseases in 

 animals was indicated. 



This, in essence, is the harvest of the two earliest purposeful re- 

 searches into this problem. A large number of investigators now 

 took up the question, and its further elucidation, as we shall see, has 

 proved, not only the most directly fruitful of the phases of recent 

 immunological studies, but has thrown much indirect light upon 

 antigen-antibody reactions apart from the anaphylactic phenomena 

 themselves. 



Before entering into the further discussion of the experimental 

 data, however, it will be necessary to describe briefly the clinical 

 manifestations which follow upon the second injection of an anaphy- 

 lactic antigen into a sensitized animal, manifestations which we have 

 heretofore summarized in the phrase "anaphylactic shock." For 

 there has been much controversy regarding the physiological mech- 

 anism which lies at the bottom of these symptoms, and the matter 

 has been complicated by the unquestionably different reactions oc- 

 curring in various species of animals in response to the anaphylactic 

 experiment. 



Since anaphylactic studies were begun largely as the result of 

 Theobald Smith's observations upon guinea pigs, and subsequent 

 study has revealed these animals as peculiarly susceptible to the 

 anaphylactic poison, the large bulk of the experimental data at our 

 disposal was worked out upon these animals. In consequence our 

 understanding of the mechanism of the reaction is based largely 

 upon guinea pig studies. 



If a properly sensitized guinea pig receives a second injection of 

 an antigen after a suitable incubation time a very characteristic 

 train of symptoms ensues. There is usually a short preliminary 

 period lasting either a fraction of a minute or several minutes ac- 

 cording to the violence of the reaction and the mode of administra- 

 tion during which the pig appears normal. At the end of this time 

 the animal will grow restless and uneasy, and will usually rub its 

 nose with its forepaws. It may sneeze and occasionally emit short 

 coughing sounds. At the same time an increased rapidity of res- 

 piration is noticeable and the fur will appear ruffled. In light cases 

 the animals may remain in this condition, with further irregularity 

 and difficulty of respiration, possible discharges of urine and feces; 

 then gradual slow recovery may set in, with complete return to 

 normal in from 30 minutes to several hours. In more severe cases 

 these preliminary stages are rapidly followed by great apparent 



