736 HETEROPHILE ANTIGENS AND ANTIBODIES 



THE TOXICITY OF HETEROPHILE IMMUNE SERUM 



In 1909 Friedberger and Hartoch' observed that the serum of rabbits which had 

 been injected with sheep corpuscles was toxic for guinea pigs, even small quantities of 

 the serum producing death on intravenous injection. It was believed that this toxicity 

 was due to the coexistence of antigen and antibody in the rabbit serum, and there arose 

 a great deal of confusion concerning the toxicity of various immune and normal sera 

 for certain animal species. The discovery of heterophile antigen by Forssman led to 

 observations which made it possible to explain many instances of primary serum 

 toxicity. It has been found, for example, that rabbit serum can be rendered toxic for 

 guinea pigs by injecting the rabbits with sheep corpuscles, emulsions of horse kidneys, 

 guinea pig kidneys, or any tissue containing heterophile antigen. These sera are toxic 

 for any animal whose tissues contain heterophile antigen but they are not necessarily 

 toxic for those animals whose tissues do not contain heterophile antigen. 



Intoxication with heterophile-immune serum gives rise to symptoms very similar 

 to those of anaphylactic shock. It is possible that the mechanism underlying the two 

 phenomena is the same. There is, however, one important difference, viz., in ana- 

 phylaxis the antibody concerned is in the tissues of the animal and the antigen is sup- 

 plied by injection, while the reverse is the case in heterophile-serum intoxication, i.e., 

 the tissues of the animal under test contain the antigen and the antibody is supplied 

 from without by injection. 



As already pointed out, heterophile-immune serum hemolyzes sheep and goat 

 corpuscles, fixes complement in the presence of the antigen, causes specific precipita- 

 tion, and finally is toxic for animals whose tissues contain heterophile antigen, partic- 

 ularly the guinea pig. There has been a great deal of discussion as to whether the 

 toxic body is the same as the hemolytic body and whether or not intoxication with 

 heterophile-immune serum is the same as that occurring in anaphylactic shock. 



Forssman and Hintze^ claim that the toxic substance does not develop during 

 immunization parallel to the other antibodies but that the toxic property of the serum 

 is a product of the process of immunization and is removed from the serum by treat- 

 ment with heterophile antigen along with the hemolytic and other antibodies. Fried- 

 berger and Goretti'' also claim that the toxicity of heterophile-immune serum is not 

 directly related to the hemolytic power of the serum. They found further that the 

 hemolysin is more sensitive to heat than the toxic body and that the hemolysin and 

 toxin can be separated by dialysis and treatment with CO., the hemolysin separating 

 out with the globulin fraction while the albumin fraction holds the toxin. 



More recently, Redfern-' made a comparative study of the pathological effects of 

 heterophile sera and of anaphylactic shock. This author found some distinctive dif- 

 ferences: first, intoxication with heterophile serum causes more extensive edema and 

 hemorrhage in the lungs than anaphylactic shock; second, guinea pigs cannot be de- 



' Friedberger, E., and Hartoch, O.: ihiJ., 3, 581. 1909. 

 ^ Forssman, J., and Hintze, A.: Biochem. Zlsclir., 44, 336. 191 2. 



3 Friedberger, E., and Goretti, G.: Ztschr.f. Iminnnitiilsforsch. u. exper. Therap., 21, 91. 1914. 

 t Redfern, W. W.: Am. J. Hyg., 6, 276. 1926. 

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