326 BIOLOGY OF PNEUMOCOCCUS 



trates, while Foa and Carbone 463 obtained a certain degree of 

 immunity with alcohol and ammonium sulfate precipitates from 

 culture filtrates. The antigenic action of these agents was feeble, 

 but Foa and Carbone demonstrated that both the intact cell, living 

 or dead, and substances elaborated by the cell during cultivation 

 evoke an immune response. The work of Denys 312 and of Wash- 

 bourn 1486 established the fact that in order to produce immunity of 

 high grade it was essential that pneumococci, whether used in the 

 living or dead state or in the form of heated or filtered cultures, 

 should be virulent. 



These were the beginnings of immunizing procedures which have 

 become routine, but there are many features of the subject that 

 deserve more detailed discussion. The use of pneumococci taken 

 from growths on solid media or in broth for the production of im- 

 mune serum for experimental purposes has long been the common 

 custom. For some time it was believed that for the production of a 

 potent serum it was necessary to inject living organisms, but ex- 

 perience has shown that response to antigenic stimulus, that is the 

 production of a serum with a high content of strictly type-specific 

 antibodies, is conditioned less by the viable state of the organism 

 than by the biological state of the culture at the time it is em- 

 ployed as antigen. 



Influence of Virulence on Immunological Response 



It is now generally accepted that for the production of a high 

 degree of type-specific immunity the antigen, whether in a living or 

 devitalized condition, must come from a robust, virulent culture. 

 This conviction arises from the results of experiments on animals 

 with strains possessing varying degrees of invasiveness, from the 

 fully virulent, smooth forms to the degraded, rough forms, and 

 from the experience of those workers who are engaged in the manu- 

 facture of therapeutic serum. The reason supporting the convic- 

 tion is the chemical demonstration that complete antigenicity is 



