CHAPTER LIII 

 HETEROPHILE ANTIGENS AND ANTIBODIES 



C. G. BULL 

 School of Hygiene and Public Health, Johns Hopkins University 



In 191 1 Forssman' observed that emulsions of the tissues (other than the blood 

 cells) of the guinea pig, cat, and horse stimulate the production of lysins for sheep 

 blood corpuscles, just as sheep corpuscles themselves do when injected into rabbits. 

 He found the tissues of the ox and rat to be devoid of this property. 



It is unnecessary to say that these observations attracted widespread attention 

 and aroused the interest of immunologists in general. The original observations have 

 been abundantly confirmed and greatly extended, thereby revealing one of the most 

 peculiar phenomena of immunity reactions or of general biology. 



It has been found that the red blood corpuscles of the sheep possess two distinct 

 antigenic substances, both of which are capable of stimulating the production of lysins 

 for these corpuscles when injected into rabbits. One of these antigens is not destroyed 

 by treatment with alcohol and withstands boiling and higher temperatures. The other 

 is easily destroyed by heat. 



Antigenic substances similar to the heat-resistant one of sheep corpuscles occur in 

 various tissues of the guinea pig, horse, cat, and other animals. Because of distinctly 

 peculiar properties common to the group and because the antibodies which they en- 

 gender do not conform to the laws of species specificity, these substances have come 

 to be designated as "heterophile" antigens. Accordingly, the antibodies produced by 

 them are known as "heterophile" antibodies. The second antigenic substance of 

 sheep corpuscles, which is thermolabile and species specific, as well as the antibodies 

 engendered by it, are distinguished by the term "isophile." 



THE OCCURRENCE OF HETEROPHILE ANTIGEN IN NATURE 



Substances having chemical and immunological properties indistinguishable from 

 those of the thermostable — "heterophile" — antigen of sheep red blood corpuscles have 

 been found to occur also in the tissues of the goat (erythrocytes only), guinea pig (not 

 in the erythrocytes), horse, chicken, cat, dog, camel, ostrich, mouse, a number of other 

 mammals and birds, and in certain fish and bacteria. On the other hand, heterophil 

 antigen has not been found in the tissues of man, rabbit, rat, ox, swine, pigeon, goose, 

 etc. 



The distribution of the antigen in the various tissues and organs of the animals 

 in which it does occur is of interest. It occurs, for example, in the erythrocytes and 

 spermatozoa of sheep and in the erythrocytes of goats but not in any other tissue, 

 while it has been found in practically all of the tissues of the guinea pig, horse, and 

 dog, with the exception of the blood corpuscles. If heterophile antigen occurs in the 



■ Forssman, J.: Biochem. Ztschr., 37, y8. 1911. 



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