26 THE PRINCIPLES OF IMMUNOLOGY 



the use of these sera has not always been so clear cut as in the case 

 of antitoxic sera. Nevertheless the use of anti-meningococcus sera 

 has reduced the mortality of epidemic cerebrospinal meningitis from 

 75 or 80 per cent, down to 35 or 40 per cent, or lower. The results 

 with anti-streptococcus sera have been variable. Although the 

 early reports of the use of anti-pneumococcus sera were highly en- 

 couraging, later study has thrown some doubt upon the value of 

 this method of treatment. Much further study of the subject is re- 

 quired before a definite conclusion can be reached. 



Theories of the Nature of Immunity. In the early study of im- 

 munity numerous hypotheses were advanced as to the action and 

 development of immune bodies. It was known, for example, that 

 when bacteria are grown for a long time upon a culture medium 

 certain substances are produced which have a deleterious influence 

 upon the further growth of the organisms and may actually lead to 

 their death. It was easy to assume, therefore, that recovery from 

 an infectious disease might be due to the development of similar 

 antagonistic substances within the infected host. Another theory 

 was to the effect that bacteria growing in the body utilize and 

 exhaust the specific nutritive substances necessary for their growth 

 and then die. It was also thought that the death of bacteria in the 

 body was due to changes in reaction of the blood, and further that 

 altered osmotic conditions changed the permeability of cell mem- 

 branes so as to permit ready entrance of poisonous substances. 

 These theories, however, could not withstand the demonstration of 

 passive transfer of immunity, the production of immunity by the 

 use of killed organisms, or perhaps more important, the clear demonstra- 

 tion of immune reactions in vitro. 



The Ehrlich Side-chain Theory. As more and more facts were 

 added to the knowledge of the subject, Ehrlich propounded his side- 

 chain theory. This was based upon the law of Weigert, which 

 states that when animal cells are required to repair an injury 

 they not infrequently exceed the absolute necessity for repair and 

 produce tissue in excess. Ehrlich, therefore, hypothesized that the 

 injurious substances of infection demand of the cells the forma- 

 tion of protective bodies, and that the cells respond to this demand 

 in such excess that the protective bodies are formed in amounts not 

 only sufficient to meet the requirements, but in such excess as to free 

 circulating immune substances in the blood. This hypothesis in- 

 troduced an entirely new terminology into the subject. It was 

 supposed that cells normally possess certain specific receptors or 

 combining groups for the injurious substances much as a struc- 

 tural chemical formula exhibits free valencies on the part of certain 

 elements or groups. When all these combining groups of the cell 

 are utilized and uncombined poisonous material exists in the circula- 

 tion, the cell produces and liberates additional receptors even in 

 excess of demand. These free receptors constitute the circulating 

 immune substances. The study of immune substance demon- 



