342 BIOLOGY OF PNEUMOCOCCUS 



per cent contained agglutinins although 86 per cent were protec- 

 tive. In the case of animals receiving antigen by the subcutaneous 

 route, none produced agglutinins although protective substances 

 could be demonstrated in 71 per cent of the individual serums. 



With skin sensitivity and the presence of type-specific agglu- 

 tinins and protective substances in serum as criteria for the 

 strength and specificity of pneumococcal antigens, Harley 

 (1935) 592 obtained a higher degree of immunity and far greater 

 type-specificity when vaccines of smooth and rough organisms 

 were introduced intravenously than when injected intradermally. 



Killian (1924), 706 by continued subcutaneous and intraperi- 

 toneal injections — the so-called bigeminal method — obtained a 

 higher degree of protection in mice than by the subcutaneous route 

 alone, and he believed that the fact argued against the acceptance 

 of the hypothesis that a purely local immunity was necessary for 

 establishing a state of protection against pneumococcal infection. 

 By intravenous injection, extremely small quantities of antigen 

 sufficed to produce protection, the immune state being demonstra- 

 ble in an increasing degree from the third day after injection. 

 Killian reported that a short refractory period ensued after the 

 administration of antigen, and accordingly, delayed further anti- 

 genic stimulation for four days until the period had passed. 



It is reasonable to assume that the duration of the refractory 

 period — or the negative phase, as Wright termed it — depends on 

 the route employed in the injection of antigen, the ability of the 

 body cells to respond to subsequent stimulation being contingent 

 upon the rate of absorption of antigenic material from the site of 

 the injection. From foci under the skin, absorption would be less 

 rapid than that from the peritoneal cavity and, quite obviously, 

 the utilization of antigen would be most rapid when the injection is 

 made directly into the blood stream. Because of the slower seep- 

 age of antigenic materials from the subcutaneous tissues, that 

 route is preferred for the production of antitoxin, but for the 



