470 PROTEIN POISONS 



However, under their influence certain body cells are stimu- 

 lated to produce a ferment which will split up the foreign 

 substances into simpler non-specific bodies. The fact that 

 animals injected with serum do not become hypersensitive 

 to a second injection until after the lapse of from seven to 

 ten days indicates clearly the length of time necessary for 

 the new ferment to be formed in appreciable amount. 

 Symptoms developing after an incubation period are, 

 therefore, to be explained by the fact that the foreign 

 proteins still existing in the tissue are acted upon by the 

 enzyme called forth by their presence. Under these con- 

 ditions, however, no large amount of ferment will be active 

 at any given time, and consequently the amount of poison 

 liberated through protein cleavage at any one period will 

 be small in amount, although the cleavage itself will con- 

 tinue over a comparatively long interval and the resulting 

 poisoning will be more chronic in type. This affords a 

 plausible explanation of the fact that late manifestations 

 of serum sickness are milder in character, being confined 

 for the most part to those of peripheral irritation, and also 

 of longer duration. 



Provided the theory advanced above is correct, one would 

 expect to find a difference in the time interval elapsing 

 between the injection of the foreign serum and the subse- 

 quent appearance of symptoms of poisoning, depending on 

 whether the individual had previously been treated with 

 serum or not. While it is true that, in many instances in 

 which alarming symptoms develop immediately, a history 

 of previous treatment is unobtainable, the results quoted 

 by Pirquet are interesting as bearing on this point. Thus 

 it has been found that of 214 individuals who developed 

 symptoms after the first injection of serum for therapeutic 

 purposes, 111, or 51.8 per cent., manifested symptoms of 

 poisoning on from the seventh to the tenth day inclusive; 

 while in 172 patients who received a second injection, 89, 

 or 51.7 per cent., showed signs of poisoning within the first 

 forty-eight hours. 



As has been previously mentioned, alarming symptoms 





