402 LOCAL TLSSUE REACTIVITY 



same leiimli ol liiiu' possessed only slightly move neutral i/.in<^ 

 power tlian seiuiii ol a nonnal horse in the control test. Sickles 

 stated that the results su^t^est the possibility of using the method 

 to test the neiurali/ing j^oteiu y of sera against the toxic products 

 of meningococcus, and important information which is not suj> 

 plied by in vilro tests may be gained concerning the different 

 sera. The technique ^vith the use of agar for the intravenous in- 

 jection is recommended by this aiuhor. 



Pabst and Branham (193,'^) studied the neutralizing potency 

 of 90 polyvalent anti-meningococcus sera and 25 heterologous 

 innnune sera and also a fe^v sera of patients convalescent from 

 meningococcus infection. About 38 of 90 sera tested gave com- 

 plete netUralization (42 per cent) ; 47 sera produced irregular 

 neutralization (52 })er cent) ; and 5 sera gave no neutralization. 

 T^vo lieterologous sera sho^ved complete neutralization and 12 

 heterologous sera gave irregular neutralizations. These authors 

 employed mixtures of various dilutions of the sera with 6 reacting 

 units. None of the sera tested ^vere prepared by immunization of 

 horses with the actixe principles of the phenomenon. These au- 

 thors concluded from their experiments that non-specific neu- 

 tralization is so marked and so frequent that it seems to limit the 

 usefulness of the phenomenon in the evaluation of anti-menin- 

 gococcus serum. Inasmuch as there is a \videspread normal occur- 

 rence of all sorts of antibodies, testing of sera against as small a 

 ntmiber of reacting units as employed by these authors gives no 

 indication as to the specificity of the antibodies neutralizing the 

 active principles of the phenomenon. It shoidd be emphasized 

 here, ho^vever, that persistent immunization of animals ^vith ap- 

 propriate materials may give rise to sera exceeding 20 to 30 times 

 the neutralizing potency of the bleedings obtained from the same 

 animal before beginning the immunization. 



Pabst and Branham also encountered difficulties because of 

 fluctuations in the reacting potency of the filtrates. In the methods 

 developed in my laboratories in recent years, the indirect titra- 

 tion of the filtrates against a standard serum preserved by freezing 

 in vacuo overcomes the difficidties arising from fluctuations in 

 the potency of the filtrates and also from the spontaneous forma- 

 tion of toxoid (p. 111). The indirect method of titration of filtrates 

 against the standard immune serum is similar to the one univer- 

 sally adopted for neutralization titrations of diphtheria toxin. 



Studies on the toxic substances derived from meningococcus 



