40 THE PRINCIPLES OF IMMUNOLOGY 



Classification of Bacterial Toxins. The bacterial toxins are 

 classified as exotoxins and endotoxins, the former appearing in the 

 culture medium as soluble substances and the latter appearing within 

 the bacterial bodies. These intracellular toxins can be liberated by 

 digestion, autolysis, freezing and fine grinding, and by expression 

 with a Buchner press. They cause the symptoms of their special 

 diseases, and in the natural course of the disease are probably liber- 

 ated either by autolysis or by the action of the enzymes of the cells 

 or fluids of the host. The tendency to-day, however, is to accept 

 the view that the so-called endotoxins are not produced as such, but 

 are produced from the bacteria during the process of hydrolytic 

 cleavage of the bacterial proteins by ferments provided by the host. 

 Certain bacteria, such as diphtheria and tetanus, produce only exo- 

 toxins, whereas the typhoid group and certain other organisms were 

 supposed formerly to produce only endotoxins. However, Bull has 

 shown that certain strains of the gas bacillus of Welch produce an 

 active exotoxin, and Ecker has shown that certain strains of bacillus 

 paratyphosus B produce exotoxins, and this has been confirmed by 

 Aronowitch. Kraus has shown a similar relationship in bacillus 

 dysenteriae. Studies of Admont Clark and Felton indicate that the 

 streptococcus hemolyticus produces a filterable toxic product 

 answering all the requirements of a true toxin. The production of 

 exotoxins is important for practical purposes because the endo- 

 toxins do not lead to antitoxin formation with the same degree of 

 facility as do exotoxins. Recent studies by Olitsky and Kligler have 

 shown that the dysentery bacillus (Shiga) produces a thermolabile 

 exotoxin and a thermostable endotoxin, the latter not being neutral- 

 ized by anti-exotoxic serum. A potent antiserum for both toxins 

 can be developed in the horse. The exotoxin appears to have spe- 

 cial affinity for the nervous system of the rabbit and the endotoxin 

 operates particularly upon the intestine. 



Organisms which produce exotoxins show a considerable variation of 

 this property, but, on the whole, such toxins are more virulent and more 

 highly antigenic than the exotoxins of those organisms which are essen- 

 tially endotoxin producers. Being more highly antigenic the antitoxins 

 produced by exotoxins are the more powerful, as is well known in the 

 case of diphtheria and tetanus antitoxins. Nicolle, Cesari, and Jouan 

 maintain, on the basis of certain work with the bacillus of Nocard, that 

 exotoxins and endotoxins are identical in the case of a given organ- 

 ism, but the more recent studies of Olitsky and Kligler quoted above 

 would indicate that this is not true of dysentery bacillus (Shiga), 

 and therefore not a general law. 



The exotoxins include diphtheria toxin, tetanus toxin, botulinus 

 toxin, dysentery toxin, paratyphoid toxin, and bacillus aerogenes 

 capsulatus (perfringens) toxin. Toxins are produced also by 

 bacillus edematiens (Weinberg), vibrion septique, bacillus of symp- 

 tomatic anthrax, bacillus pyocyaneus, streptococcus, and bacillus in- 

 fluenzse. In addition it is claimed by Kolmer and his co-workers 



