478 IMMUNITY. 



increased after it was treated in the usual way for the production 

 of antitoxin. Such a supposed difference in the sizes of the 

 molecules might explain the fact, observed by Fraser and also 

 by C. J. Martin, that antitoxin is much more slowly absorbed 

 when introduced subcutaneously than is the case with toxin. 



Antitoxin, when present in the serum, leaves the body by 

 the various secretions, and in these it has been found, though 

 in much less concentration than in the blood. It is present in 

 the milk, and a certain degree of immunity can be conferred on 

 animals by feeding them with such milk, as has been shown by 

 Ehrlich, Klemperer, and others. Klemperer also found traces 

 of antitoxin in the yolk of eggs of hens whose serum contained 

 antitoxin. Bulloch also found in the case of hsemolytic sera 

 {vide infra) that the anti-substance ("immune-body") is trans- 

 mitted from the mother to the, offspring. 



The Evidence for Ehrlich's Theory of the Constitution of Toxins. — This 

 was found in the course of investigations on diphtheria toxin, and so far 

 applies only to the extracellular toxins. Ehrlich found that, taking an anti- 

 toxin standardised against one toxin, it did not follow that it would neutralise 

 exactly the same number of M.L.D. of other toxins. Thus an amount which 

 would neutralise loo M.L.D. of one, might neutralise only 20 pf another and 

 perhaps 130 of a third. The second fundamental observation was as follows : 

 If a mixture of toxin and antitoxin behaved like a mixture of say hydrochloric 

 acid and sodium hydrate, then the addition to a neutral mixture of i M.L.D. 

 would, if the mixture were injected into a guinea-pig, cause death. In none 

 of the toxins investigated was this the case ; sometimes as many as 28 M.L.D. 

 had to be thus added before death occurred. A third fact observed was that 

 in the case of one toxin when freshly filtered the M.L.D. was found to be 

 .003 c.c. ; nine months later it was .009 c.c, but it was found that after the 

 lapse of this period one antitoxin unit neutralised exactly the same amount of 

 toxin as at first. In other words, one antitoxin unit when the toxin was fresh 

 neutralised 100.2 M.L.D., and nine months later only 33.4 M.L.D., and care 

 had been taken that the antitoxin itself had not changed. The theory to 

 account for these facts is that the ultimate toxin molecule contains two un- 

 satisfied affinities, one of which can combine with antitoxin, the other having 

 a toxic action ; the former Ehrlich calls the " haptophorous " group, the latter 

 the " toxophorous " (w(& p. 179). Further, each of these groups can, under 

 the action of light, oxidation, etc., lose a certain amount of combining power, 

 the toxophorous being more easily weakened than the haptophorous (these 

 weakened toxins Ehrlich calls "toxoids" or "toxones"). Now, the above 

 facts can be explained if crude diphtheria toxin contains both of these sub- 

 stances, i.e. true toxin with powerful haptophorous and toxophorous affinities, 

 and toxoid with- slightly weakened haptophorous group and greafly weakened 

 toxophorous group. Take the second fundamental observation alluded to. 



