PHENOMENA FOLLOWING IMMUNIZATION 95 



Antigens are all substances which, injected into the animal body, induce 

 specific antibody formation. They form a large group in nature and are 

 chemically proteins; indeed, we may say that all known proteins may act as 

 antigens. Whether or not this term may also include lipoid-protein com- 

 binations, lipoids or the higher protein derivatives is as yet uncertain and 

 need not in the present connection concern us, 



We may divide antigenic substances into two main classes. 1 One of these 

 comprises all of those substances of bacterial, animal or vegetable origin 

 which, injected into the animal body, give rise to specific neutralizing or 

 antitoxic properties in the blood of the injected animal. These are the bac- 

 terial exotoxins, the snake venoms, some powerful vegetable poisons and proteo- 

 lytic and other enzymes of animals and plants. They are all substances which 

 are powerfully active some of them strongly toxic to the living animal, 

 others true enzymes or ferments. Indeed all of them possess properties which 

 at least suggest our placing them into the class of enzymes in general. The 

 number of such substances known is limited. The reaction they call forth in 

 the animal body seems aimecl directly at the specific neutralization of their 

 respective activities, and is so unique and different from that induced by other 

 antigens that it would be convenient had we another term like "antitoxinogen" 

 to set them apart by themselves. 



The other class of antigens comprises all proteins which are inactive, 

 showing in themselves neither toxic nor enzyme-like properties. Introduced 

 into the animal body parenterally, they call forth a response of a nature 

 entirely unlike that of the antitoxins, and which as far as we can fathom 

 its purpose seems aimed merely at the assimilation or the removal of the 

 infected substance. For the cells of the animal cannot utilize the foreign 

 protein as such, and thus it is only foreign proteins injected into an animal 

 that act antigenically, and no antibodies are formed when homologous material 

 is injected. 



This large group, composed of all formed and unformed substances in 

 nature in which a protein structure is involved, does not induce the formation 

 of anything like the neutralizing antitoxins spoken of above. The antibodies 

 appearing in animals treated with such substances have been spoken of as 

 cytolysins or cytotoxins precipitins and in the case of formed antigens 

 like bacteria or blood cells agglutinins and opsonins. As we shall see in 

 another section, it is our opinion that all these various antibodies are iden- 

 tical in structure and significance. 



We must not forget, however, that the observation of antibodies in the 

 circulating blood is but one of the changes that have taken place in the 

 treated animal. Much has been made of this phase of the problem because 

 serum antibodies are readily studied in vitro; but their origin of course must 

 be sought in the body cell, in which the original and most profound changes 

 must necessarily have taken place during such treatment, changes the nature 

 of which are to a large extent still a mystery, but on which ultimately de- 

 pend the important physiological difference between treated and untreated 

 animals. For such changes whether we refer to those immediately under 

 discussion, namely, those of allergy or anaphylaxis, or whether we think of 

 the so-called immunity remaining after attacks of many diseases remain 

 present long after the circulating antibodies have disappeared and must there- 

 fore be regarded as associated with profound alterations in the ultimate tissue 

 unit, the body cell. 



1 See also Zinsser, "The More Recent Developments in the Study of Ana- 

 phylactic Phenomena." Arch, of Int. Med., Vol. XVI, 1915, pp. 223-256, 

 Harvey Lecture. 



