252 PASSIVE IMMUNIZATION 



with the marked inhibitory effect which the serum exercises upon 

 the multiplication of the organisms, and to its manifest bacteriotropic 

 action, as evidenced by increased phagocytosis. 



Flexner thus records that in two children who had received sub- 

 dural injections of his serum, scarcely any extracellular diplococci 

 could be found after the first treatment, while the number of intra- 

 cellular cocci was much reduced, and that cultures could no longer 

 be secured, even though the free forms had not yet disappeared 

 altogether. 



. Flexner suggests that the phagocytic digestion not only prevents 

 further multiplication of the diplococcus, but also that it detoxicates 

 the endotoxin by reducing it to simpler and non-toxic or less toxic 

 compounds. 



That bacteriolysins per se, however, may also play a role is sug- 

 gested by the observation that in a few instances in which the 

 antiserum was injected into the spinal canal of monkeys infected 

 with the diplococcus the microorganisms disappeared without 

 marked phagocytosis, though more slowly than in the cases in which 

 outpouring of leukocytes was considerable. 



Preparation of the Antimeningococcus Serum (according to Flexner 

 and Jobling). Horses are first injected subcutaneously with cultures 

 of the diplococcus that have been heated for thirty minutes at 60 

 C., as many different strains being used collectively, as possible, so 

 as to give rise to a polyvalent serum. As first dose the equivalent 

 of a quarter surface test-tube growth on sheep-serum agar is recom- 

 mended. At each subsequent injection the dose is doubled until 

 an amount equal to four test-tube growths is given at intervals of 

 five to seven days. 



In the earlier work of Flexner and Jobling, intravenous inocula- 

 tions were then substituted for the subcutaneous, beginning with 

 one dose of living diplococci, the dose being progressively increased 

 to two, three, five, etc., oeses, then to one-half, three-quarters, one, 

 two, etc., agar slant cultures, and finally to one and a half bottles 

 (12 oz., Blake) of surface growth. As the larger injections caused 

 very severe reactions and alarming symptoms, they were discon- 

 tinued, and subcutaneous and intravenous injections of autolysates 1 

 substituted, the dose being gradually increased from 1 to 3 c.c., and 



1 Meningococci which have been allowed to undergo self-digestion. 



