214 STUDIES IN IMMUNITY. 



sity, as we have already stated. To be sure, if a mixture is made in 

 vitro containing too little cholera serum in proportion to the vibrios 

 to give complete bacteriolysis, the injection of this mixture into the 

 peritoneal cavity of a normal animal will frequently result in a 

 granular transformation. It is evident, however, that by this pro- 

 cedure we increase the amount of alexin (peritoneal exudate), and 

 such an increase of one of the two substances required for bacteri- 

 olysis naturally produces a greater effect.* To estimate bactericidal 

 power correctly either in vitro or in vivo the vibrios used must 

 be mixed with comparable amounts of the two active substances; 

 if this precaution is observed it will be found that vibrios or cor- 

 puscles are altered as well in vitro as in vivo. 



The properties of the antitoxin studied in the preceding pages 

 suggests another objection to Pfeiffer's theory. 



Let us mix a certain amount (e.g., 0.4 of a cubic centimeter) of 

 hemolytic serum, 55 degrees (sensitizer), with a little fresh, normal 

 guinea-pig serum (0.2 of a cubic centimeter). Similar tubes are 

 prepared containing, in the place of guinea-pig alexm, rabbit and 

 rat alexin respectively. Any one of these mixtures is strongly 

 hemolytic for rabbit blood, although no one of the constituents 

 alone is so. What has happened according to Pfeiffer's theory? 

 The alexin employed has transformed the inactive thermostable 

 antibody into the active and specifically globulicidal antibody. 

 And consequently, in such a mixture, it is this active antibody and . 

 not the alexin that destroys the corpuscles. It may be added that 

 of the three alexins mentioned the one from the guinea-pig forms 

 the best hemolytic mixture with the sensitizer. 



Since each mixture contains the same hemolytic substance, we 

 should expect, according to Pfeiffer's theory, that an antitoxin 

 capable of neutralizing the destructive effect of one would also 



* We may recall the point demonstrated by us in 1895, that a fresh immune 

 serum does not contain appreciably more alexin than normal serum. The sen- 

 sitizing property of an immune serum, however, is so great that it can sensitize 

 many more vibrios than its alexin is able to destroy. Conversely, the amount of 

 alexin in a given dose of immune serum is too small to destroy all the vibrios that 

 the serum can sensitize. For this reason fresh immune serum is able to destroy 

 many more vibrios when fresh normal serum is added on account of the addi- 

 tional amount of the alexin. On summing up the facts on which our theory is 

 based we noted that a small dose of immune seorum suffices to endow a relatively 

 large dose of normal serum with intense bactericidal energy. 



