DEFENSIVE MECHANISM IN RELATION TO INFECTION 103 



capsulated organisms with increased virulence is produced, explaining 

 in a way the mechanism of animal passage in raising the virulence of a 

 given organism. This, however, is not invariable, and, indeed, may act 

 in a contrary manner, as the passage of smallpox virus through heifers 

 attenuates and modifies instead of increasing its virulence. 



Aggressins. The microorganism may actively secrete a material 

 that overwhelms the defensive forces of the host. This phase of the 

 subject has been studied exclusively by Bail, who sought to prove that 

 the question of pathogenicity of a microorganism is dependent upon its 

 ability to secrete substances that are able to paralyze the protective 

 forces of the host, especially the leukocytes. These substances are 

 called "aggressins, " and they were distinguished by the fact that they 

 were formed by living bacteria and only in the living body. In support 

 of this theory Bail was able to show that substances are present in the 

 exudates of fatal infections, which, when injected in small quantities 

 into another animal with sublethal doses of the microorganism, would 

 cause a rapidly fatal infection. Later Wassermann and Citron showed 

 that " artificial aggressins" could be prepared by autolyzing bacteria 

 in water or serum. While the subject of aggressins is still unsettled, 

 there is strong evidence to show that they are the endotoxins liberated 

 by the breaking-up of the microorganism. 



The well-known statement of Metchnikoff, that a particular virulent 

 microorganism is not so readily taken up by leukocytes as is an avirulent 

 strain, may be explained by the fact that the microorganism, in its 

 virulent parasitic state, secretes substances that repel the phagocytes, 

 neutralize the opsonins, or form actual leukocytic toxins. This action 

 may be due to liberated endotoxins, or, as Bail claims, to specific secre- 

 tory substances of the bacterium the aggressins specifically formed 

 and liberated by the microorganism for protection against the host. 



Hypothesis of Welch. Not entirely foreign to this subject is the 

 very interesting hypothesis of Welch. A bacterium may not only pro- 

 duce substances directly inimical to the defensive forces of the host, but 

 it may actually immunize itself against these defensive powers. " Looked 

 at from the point of view of the bacterium, as well as from that of the 

 animal host, according to the hypothesis advanced, the struggle between 

 the bacteria and the body-cells in infections may be concerned as an 

 immunizing contest in which each participant is stimulated by its op- 

 ponent to the production of cytotoxins hostile to each other, and thereby 

 endeavors to make itself immune against its antagonist." 



It is well known that, when freshly isolated from a patient having 



