8 THE PRINCIPLES OF IMMUNOLOGY 



be obtained from other proteins, such as those of cheese and milk. 

 The poisonous effect is in some way connected with the foreign 

 character of proteins. In some respects these substances resemble 

 ptomains, but they are certainly not of the same constitution. They 

 are obtained from bacteria regardless of whether these produce 

 toxins, endotoxins, or ptomains, and are fatal for animals in very 

 short periods of time. The methods for the production of endo- 

 toxins are such as may lead to splitting of bacterial proteins, and at 

 the present time no satisfactory differentiation can be made. The 

 chapter on anaphylaxis and hypersusceptibility will present a dis- 

 cussion of the poisonous substance called anaphylatoxin, which may 

 also be related to the general group of poisonous split products. 

 The influence of toxin on invasion by certain bacteria is illustrated 

 by the recent work of Bullock and Cramer. They found that 

 bacillus aerogenes capsulatus, vibrion septique, bacillus edematiens, 

 and often bacillus tetani, when completely freed of toxin by washing 

 or by heating to 80 C. for one-half hour do not produce the special 

 disease upon injection into the rat or guinea-pig. The usual de- 

 fenses of the animal, such as bacteriolysis and phagocytosis, are 

 sufficient to rid it of the bacteria in the absence of toxins. A point 

 of further interest in this work is the discovery that if a small dose 

 of a soluble ionizable calcium salt be injected before or at the same 

 time as the spores or toxin-free bacteria, the defenses are broken 

 down and the special disease results. The experiments showed that 

 this is not the result of action upon the bacteria, but is due rather 

 to some influence upon the host. Bullock and Cramer suggest the 

 name " cataphylaxis " for the rupture of defense. Other salts have 

 no such effect, and it is possible to demonstrate the antagonistic 

 action of magnesium upon calcium in similar experiments. It is 

 difficult to find a series of experiments showing more clearly the 

 delicacy of balance between resistance and infection. 



Alterations of Virulence Increase of Virulence. As has been 

 indicated above, virulence may be increased by the passage of organ- 

 isms through animals, and this method is commonly employed in 

 laboratory work. The increase of virulence of the pneumococcus by 

 passage through mice is an excellent example of the process. The 

 organisms are injected intraperitoneally, recovered upon the death 

 of the animal, cultivated for twenty-four hours, reinoculated, and the 

 process repeated until a satisfactory degree of virulence is obtained. 

 The degree of virulence is usually measured in terms of the bulk of 

 broth culture which will kill an animal in a given period of time. 

 In the case of some bacteria an increase of virulence by animal 

 passage is only effective for the animal concerned; and the fact 

 that an organism exhibits increased virulence for a guinea-pig does 

 not necessarily presuppose that the same increase will apply to other 

 animals. Not only is this true of direct animal passage but, as has 

 been shown by Danysz, cultivation of an organism upon media con- 

 taining rat tissue may increase the virulence for the rat but not for 



