258 IMMUNOLOGY 



Prophylactic Dose of Antitoxin. — When it is desired to pro- 

 tect a susceptible individual who has l)eeii exposed to diphtheria, 

 it is customary to administer 500 or 1,000 units of antitoxin sub- 

 cutaneously or intramuscularly. This will protect for two to 

 four weeks depending upon the rate of elimination from or de- 

 struction witliin the bodj\ Not infrequently Schick te.sts are 

 made to ascertain whether the contacts are susceptible or immune 

 and only the former given a prophylactic injection of antitoxin. 



Active Immunity. — As previously mentioned in this chapter, 

 active immunity to diphtheria toxin was produced first by Behr- 

 ing and Kitasato (1890). Interest in active immunization against 

 toxins resulted immediately in numerous publications. Ehrlich 

 (1892) reported the successful immunization of mice with ricin, 

 abrin and robin. He found that the otTspring of immunized fe- 

 male mice possess passive immunity to toxin. This he attributed 

 to antitoxin obtained largely through the mother's milk. Im- 

 munity was not transmitted from tlie father to tlie offspring. Two 

 years later Ehrlich and Iliibener (1894) immunized guinea pigs 

 with tetanus toxin and obtained similar results. Wernicke (1895) 

 treated guinea pigs with toxin and then antitoxin and finally with 

 several injections of toxin. He observed that immune females 

 transmit antitoxin to the offspring but he was apparently in some 

 doubt as to the mechanism involved. 



It remained for Anderson (1906) and Theobald Smith (1907) 

 to show definitely that the offspring of an immune female guinea 

 pig owes its passive immunity to antitoxin obtained through the 

 mother's milk. Such immunity persists for about three months. 



Active Immunization of Horses With T.A.T. — In 1897 Park 

 (1903) began immunizing horses with toxin-antitoxin mixtures. 

 It should be remembered that the injection of toxin-antitoxin 

 mixtures formed a part of Ehrlich 's method of determining a 

 unit of antitoxin and of standardizing toxins. The first careful 

 and extensive investigation of diphtheria toxin-antitoxin mixtures 

 as antigens was made by Theobald Smith (1909) and Smith and 

 Brown (1910). They found that partially neutralized or even 

 overneutralized mixtures of toxin could be used in producing 

 an active immunity to diphtheria. They suggest that the antitoxin 

 "smuggles" the toxin into the body where it is slowly liberated 

 with resulting antitoxin formation by the tissues of the body. 



