740 CHEMISTRY OF TOXIN AND ANTITOXIN 



would be difficult and, at best, would shed no light on the real nature of toxin and 

 antitoxin. 



THE ADSORPTION THEORY OF BORDET 



The failure of the law of chemical combination in definite proportions in im- 

 munological reactions was shown by Danysz' with ricin and anti-ricin, by Bordet^ 

 with alexin and anti-alexin, and by von Dungern^ with diphtheria toxin and anti- 

 toxin. In these reactions the neutralizing dose was found to vary, depending upon 

 whether the toxin was added in a single or in several doses. Bordet-' first character- 

 ized these reactions as "combinations in varying proportions" and likened them to the 

 adsorption of varying amounts of dye by cloth. Landsteiner and Jagic^ then pointed 

 out the analogy between immunological reactions and the adsorption phenomena 

 of inorganic colloids. The colloidal adsorption theory which was developed from 

 these observations has successfully explained many characteristic phenomena of toxin 

 and antitoxin reactions and is only limited in its application by our meager knowledge 

 of the chemistry of colloidal reactions. 



Toxins and antitoxins exhibit the colloidal reactions of large molecular complexes. 

 They can be dialyzed in collodion membranes, and are adsorbed by charcoal and 

 kaolin.* Their sensitive reactions to all of the reagents which are known to alter 

 natural proteins suggest that they might be of protein nature or firmly adherent to, 

 and dependent upon, proteins. Like the proteins, toxins and antitoxins are at- 

 tacked by enzymes, and they are precipitated by ammonium sulphate and the salts 

 of the heavy metals. They are inactivated on shaking in air.^ That the toxin molecule 

 is smaller than the antitoxin molecule is indicated by the fact that it diffuses into 

 gelatin more rapidly than antitoxin.^ 



Antitoxin is always associated with the pseudoglobulin fraction of serum — that 

 fraction which behaves like a true globulin in being precipitated by half-saturation 

 with ammonium sulphate, but which, unlike a true globulin, is soluble in water. 

 Adolf' found that when immune diphtheria serum was electrodialyzed until the 

 supernatant fluid had practically the same conductivity as distilled water the anti- 

 toxin was in the globulin precipitate. However, when the electrodialysis was inter- 

 rupted at intervals before the removal of all electrolytes, the antitoxin was located in 

 the last fractions to be precipitated, corresponding to the pseudoglobulin fraction. 

 This close association of antitoxin with a definite fraction of the immune serum which 

 is commonly'" but not necessarily" increased upon immunization of the animal might 



' Danysz, J.: Ann. de VInsl. Pasteur, i6, 331. 1902. 

 ' Bordet, J.: ibid., 12, 692. 1898. 



3 V. Dungern: Deutsche med. Wchnschr., 30, 275, 310. 1904. 

 < Bordet, J.: op. cit., 13, 225. 1899; 14, 267. 1900; 17, 161. 1903. 

 s Landsteiner, K., and Jagic, N.: Miinchcn. med. Wchnschr., 50, 764. 1903. 

 ••Zunz, E.: Arch, internal, de physioL, 8, 227. 1909; Eisler, M.: Biochein. Ztschr., 135,416. 1923. 

 7Biltz, W., Much, H., and Siebert, C: Behring's Beitrdge, lo, 30. 1905. 

 ^Arrhenius, S.: op. cit., p. 25. 'Adolf, M.: Klin. Wchnschr., 3, 1214. 1924. 



"Doerr, R., and Berger, W.: Ztschr. f. Hyg. u. Infcktionskrankh., 93, 147. 1921. 

 " Glaesner, K.: Ztschr. f. exper. Path. 11. Therap., 2, 154. 1906. 



