56 THE PRINCIPLES OF IMMUNOLOGY 



theria bacilli themselves may also be practised at the same time by adding 

 1000 millions killed organisms. The value of this latter procedure has not 

 been demonstrated as yet and it is not widely practised. 



The advantage of the use of toxin-antitoxin mixtures is that a last- 

 ing active immunity is established. It has been suggested, however, 

 that the use of the antitoxin in the mixture may lead to the de- 

 velopment of anaphylaxis. It has been maintained, on the other 

 hand, that the mixture of the toxin probably avoids the sensitizing 

 effect of the horse serum, but this is not borne out experimentally 

 or in human medicine. Nevertheless, the amount of horse serum 

 given is relatively small and the development of hypersusceptibility 

 in man following these small amounts is not very common. Park 

 has found that even with the therapeutic dose of diphtheria antitoxin 

 the danger of anaphylaxis is extremely small, and states that 

 among 330,000 cases on record there were only five deaths. As we, 

 will point out subsequently (see page 230), the reports of deaths 

 following antitoxin administration would indicate that, in a certain 

 percentage at least, factors other than anaphylaxis are operative. 

 If sensitiveness to horse serum is known it is suggested that anti- 

 toxin prepared in some other animal, such as the goat, may be em- 

 ployed, but sera of this sort are not easily obtainable in the market. 



Tetanus Toxin and Antitoxin. In the foregoing consideration 

 much stress has been laid on diphtheria toxin and antitoxin, with 

 the idea that the problem might thus be presented as simply as pos- 

 sible. Tetanus toxin and antitoxin have been studied almost if not 

 quite as intensively as diphtheria and deserve, both practically and 

 theoretically, more than passing mention. The important facts may 

 be given briefly. The toxic broth produced by growth of bacillus 

 tetani contains a body which is actively hemolytic, tetanolysin, and 

 more important, a body which produces the symptoms of tetanus, 

 tetanospasmin. These are capable of specific absorption, so that 

 one or the other remains free. In other words, the tetanolysin may 

 be removed from the mixture by saturation with red blood-cor- 

 puscles, leaving in the broth the tetanospasmin which may be in- 

 jected with the production of symptoms and death. An antitoxin 

 may be produced specifically for the tetanospasmin, but in practice 

 the antitoxin is made without separation of the two toxins. 



The toxin is produced in anaerobic broth cultures. It is readily 

 injured by heat and light, and is best preserved in the dried state. 

 The white mouse is extremely susceptible, the guinea-pig less so 

 and the horse somewhat less, whilst pigeons and fowl are highly 

 resistant. The antitoxin is produced for commercial purposes in the 

 horse, the earlier doses being with an attenuated toxin following a 

 previous injection of antitoxin. The serum is standardized by the 

 use of white mice or by guinea-pigs, the procedure being practically 

 the same as for standardization of diphtheria antitoxin. In the 

 United States the toxin is used as a standard. It is precipitated by 

 ammonium sulphate and dried. The minimum lethal dose is that 



