194 THE ANTIGEN-ANTIBODY REACTIONS 



involved. In 1903 Wright and Douglas, in an extensive series of experiments, 

 demonstrated that this action of normal serum was due to a thermolabile substance 

 which acted directly upon the bacteria and not upon the leucocytes. To this 

 substance they gave the name of opsonin. Neufeld and Rimpau (1904, 1905) 

 demonstrated the presence of thermostable substances in the blood serum of 

 animals immunized against streptococci and pneumococci, which acted specifically 

 on these bacteria in such a way as to increase the degree to which they were 

 ingested by phagocytic cells. To these substances they gave the name of bacterio- 

 tropins. 



Thus, in the earliest years of the present century, we had at our disposal a con- 

 siderable body of facts with regard to the action of the sera of normal and of im- 

 munized animals on bacteria, foreign cells and foreign proteins. Little indeed has 

 been added, during the intervening years, to our knowledge of what may happen 

 when a normal or immune serum is mixed in vitro with the material against which 

 it is active. Investigators during this period have been mainly engaged in trying 

 to discover how these reactions are brought about. On this aspect of the problem 

 a mass of information has been collected ; and, although the correlation of the 

 ascertained facts has been a difficult matter, and our understanding of the under- 

 lying mechanism of the serum reactions is still far from complete, we seem during 

 the last two decades to have made appreciable progress towards an orderly arrange- 

 ment of evidence and a generalization of theory, which has resulted in a clearer 

 conception of the processes involved. 



Terminology. — With the gradual development of our knowledge of the serum 

 reactions new names have been invented to describe the phenomena observed 

 and to designate the substances which are assumed to be the essential reagents. 

 As in other terminologies which have grown naturally and have never yet been 

 systematized, the terms employed are often ill-defined, and there is much over- 

 lapping. There has indeed been a riotous creation of hypothetical entities in the 

 discussion of the available data, and this redundant growth is responsible for many 

 of the obstacles encountered by the student in mastering the facts of a subject, 

 which in its main outlines is not intrinsically difficult. It is, however, quite impos- 

 sible to dispense with the use of some kind of scientific shorthand, and it is therefore 

 necessary to gain an adequate acquaintance with the terms in common use, and 

 especially to realize their limitations. 



It is usual to refer to the substances which make their appearance in the blood 

 serum, in response to the inoculation of foreign substances of various kinds, and 

 which react with these substances, in vitro or in vivo, in some observable way, as 

 antibodies. The foreign substances which, on inoculation into the tissues, stimulate 

 the formation of these antibodies, are referred to as antigens. These two terms 

 may be defined as follows. 



An ANTIGEN is any substance which, when introduced parenterally into the animal 

 tissues, stimulates the production of an antibody, and which, when mixed tvith that 

 antibody, reacts .specifically tvith it in some observable way. 



An ANTIBODY is any substance which makes its appearance in the blood serum 

 or body fluids of an animal, in response to the stimulus provided by the introduction 

 of an antigen into the tissues, and reacts specifically with that antigen in some 

 observable way. 



The introduction of the antigen into the tissues is usually made by the parenteral 

 route, since the antigen must reach the tissues in an unaltered state. Antigens 



