30 THEORIES OF IMMUNITY 



dred doses, lethal for a guinea-pig, while in the case of typhoid 

 or plague 2 or 3 c.c. of a broth culture are necessary to kill, 

 but we do not know to what quantity of active substance a 

 fatal dose corresponds nor whether typhoid or plague bacilli 

 produce quantities of toxins greater in the organism than in 

 artificial cultures. We cannot then know whether typhoid 

 or plague toxin produces on the organism effects analogous 

 to those of diphtheria toxin even if it were possible to obtain 

 typhoid and plague toxin in very much greater concentration 

 than other more or less poisonous substances in our culture 

 media. 



At all events, however much we can judge by the apparent 

 results of present experiments, we may admit that the prod- 

 ucts of the secretions of certain bacteria as well as certain 

 other antigens may exercise a direct action on the organism, 

 while in the case of other bacteria the pathogenic reaction 

 manifests itself only after a special preparation an indirect 

 action. 



Thus, for example, we know that the toxins of diphtheria 

 and tetanus act quite quickly on normal tissues while tuber- 

 culin, malein, and very probably also the secretion of the 

 treponema of syphilis do not act under the same conditions, 

 but only on infected tissues and only in a longer or shorter 

 time after the infection. In the first case the tissue is sus- 

 ceptible without preparation of any sort; in the other it 

 becomes susceptible only after a specific preparation. The 

 action of antigens on tissues may then be direct or indirect 

 and this difference can be determined only by the physico- 

 chemical properties of these substances, or by the nature 

 of the compounds which they form with their " normal anti- 

 bodies," or finally, by the biologic properties of the compounds 

 thus formed which may be neutral or more or less pathogenic 

 to the organism. 



In order to fully understand the first stages in the evolution 

 of a disease as well as the mechanism of the defense of the 

 organism, the question of the infecting dose is of capital 

 importance. We may assume that no antigen is exclusively 

 pathogenic as none is exclusively harmless. We can always 

 find for the most active toxin a dose, which will provoke no 



