H. M. POWELL 827 



the other hand, that many antigen-antibody reactions occur rapidly, indicating high 

 affinities, and little probability of coexisting uncombined antigen and antibody. 



In a great part of the work with the precipitin reaction, highly complex antigens 

 have commonly been used. These include a wide range of substances such as normal 

 serum and egg albumen. There is little doubt that these materials are in reality mix- 

 tures of many individual, simple precipitinogens. When these mixtures are injected 

 into various animals the resulting precipitins are also mixtures, made up of different 

 antibodies. If one animal is used, certain components in the complex precipitinogen 

 may be more antigenic than others and a mixture of unequal amounts of the various 

 simple precipitins may result in the immune serum. If another test animal is treated 

 with the same precipitinogen, certain other individuals in it may be highly antigenic 

 while those most antigenic in the former case may be of little potency or perhaps 

 entirely innocuous. The precipitin incited in the latter animal may differ very much 

 from the former. 



Great variability in the constitution of ordinary precipitin in the hands of dif- 

 ferent experimenters may be expected according to the duration of the course of arti- 

 ficial immunization. Ordinary precipitin serum, which is very often an extensive mix- 

 ture, drawn early from the animal would contain those individual precipitins in excess 

 which are most easily and quickly incited, while that drawn later would contain the 

 slower-appearing individual antibodies. These conditions, together with different de- 

 grees of affinity between the different sets or pairs of antigens and antibodies, would 

 easily permit an apparent coexistence of antigen and antibody with no resulting ac- 

 tion. Also instances would occur where supposedly similar immune sera would pre- 

 cipitate on being pooled. 



Opie' has shown that in normal animals an injection of a foreign protein as a pre- 

 cipitinogen brings about a state of affairs in which the introduced antigen may soon 

 be detected in the animal's blood stream. Detection of the antigen in this way may be 

 successful for a considerable time both in experimental animals and in persons who, 

 for example, have received antipneumococcus serum. As soon as precipitin begins to 

 appear in the blood, precipitinogen starts to disappear rapidly. This holds good for 

 both innocuous complex precipitinogens like native serum and also for more purified 

 antigens. The latter, however, tend to disappear more quickly. It appears, then, that 

 as immunization proceeds foreign proteins introduced into the animal body have con- 

 tinually less chance of gaining access to the general circulation, while in the normal 

 animal they may soon easily pass into the circulation in amounts sufficient to be de- 

 tected. 



If the same procedures are applied to a highly immune animal, i.e., one with a 

 high precipitin titre, entirely different results are obtained. The injected dose of anti- 

 gen, given subcutaneously, may rarely gain access to the blood stream of the treated 

 animal. The animal's precipitin titre may be little affected or again it may fall con- 

 siderably but it does not disappear completely, provided the antigen is a complex one 

 such as a native serum. The decline in titre would depend largely on the quantity of 

 each individual, simple antigen in the dose injected, and the various amounts of 

 really homologous precipitins existing at this time within the animal. In the case in 



' Opie, E.: op. cit., p. 55. 1923. 



