242 IMMUNOLOGY 



Etiological Agents of Diphtheria and Tetanus Discovered. — In 



1883, Klebs recognized what we now know to be C. diphtheriae, 

 in sections of a diphtheritic membrane. The following year (1884) 

 Loeffler confirmed Klebs' observation and obtained the organism 

 in pure culture. In studying its virulence for mice, rats, rabbits, 

 guinea pigs, chickens, etc., he found that mice and rats are quite 

 refractory to infection while rabbits and guinea pigs are exceed- 

 ingly susceptible. He was very much impressed with the fact 

 that when an animal dies following the local injection of the 

 organism the organisms are not, as a rule, generally disseminated 

 throughout the body but remain localized at the point of inocu- 

 lation. Loeffler concluded that the disease and death of these 

 animals was probably due to some toxic substance produced by 

 the bacteria. In 1888, 1889, Roux and Yersin discovered that 

 sterile filtrates of broth cultures of C. diphtheriae are exceedingly 

 poisonous and can produce the classical symptoms, pathological 

 changes and death in susceptible animals. 



Within the next two years Kitasato (1889-1891) isolated the 

 tetanus bacillus in pure culture and discovered tetanus toxin. 

 Behring and Kitasato (1890) immunized animals with diphtheria 

 and tetanus toxin respectively and demonstrated specific neutral- 

 izing substances (antitoxins) in their blood. In other words, they 

 showed that these toxins are antigenic. They were the first in- 

 dividuals to produce active immunity against a soluble toxin. Ac- 

 cording to Dean (1913) Behring did the pioneer work in diphtheria 

 antitoxin and collaborated with Kitasato in producing tetanus 

 antitoxin. 



Invasive Power of C. Diphtheriae. — It is now known that C. 

 diphtheriae possesses relatively little invasive power. In a pre- 

 vious chapter attention has been called to recent work on the 

 variation in invasive power of different strains of C. diphtheriae 

 (Wells, 1932, Feierabend and Schubert, 1929, Ivanic, Dimitrijevic- 

 Speth and Javanovic, 1923), Apparently some strains that are 

 relatively poor toxin producers possess more invasive power than 

 the majority of strains of C. diphtheriae. It is thought that this 

 may account for the failure of antitoxin treatment in a few cases 

 treated early where satisfactory results might have been expected. 



Effect of Toxin on Lower Animals. — It is interesting to note that 

 the relative immunity to diphtheria toxin which Loeffler observed 



