142 LOCAL ILSSUE REACTIVITY 



against 80 units ol liltralc and onh sonic i'al)l)its as^ainst 120 units, 

 llic jjioteciion titer oi this amount ol serum must l)e l)et^vcen 

 tliese two ligines or 100. Since the /// -oitro netitralizing titer ol 

 the sertnn was also determined, it was p;)ssil)le to derive the ratio 

 bet^veen /// x/iho and /// i>ivo neutralizations. 



It WAS found in this manner that, 1 c.c. of 1:4 dilution of the 

 innnune serum capable of neutral i/im> /// x'iho 125 reacting iniits 

 failed to give neutralization of as fe^v as 15 tuiits in vivo. The 

 lack of neutralization coidd ])e attributed to a loss of antibodies 

 in the general circulation. It was impossible to state whether the 

 loss ^vas jaartial or complete since ral)bits protected with this 

 amount of serum were not tested with a smaller nimiber of 

 reacting units. As the amount of serum injected was increased 

 it became possible to demonstrate /// vivo neutralization, de- 

 cidedly less, ho^vever, than Avotdd have been obtained in direct 

 ill vitro neutralization. Thus, a dose of 2 c.c. of serinn injected 

 per kilo of body w^eight, neutralized 100 reacting units, i.e., it ^vas 

 necessary to use ten times the number of neutralizing tniits as 

 compared to i)i vitro neutralization ^vith the same serimi. 



The experiments also clearly demonstrated /// vivo neutraliza- 

 tion of reacting factors in midtiple proportions. Thus, 250 units 

 of serimi protected against 25 reacting iniits; 4 x 250 serum units 

 protected against 4 x 25 reacting units; 8 x 250 serimi units pro- 

 tected against 7.2 x 25 reacting imits. However, 12 x 250 serimi 

 units protected against 24 x 25 reacting units and 18 x 250 serum 

 units protected against 40 x 25 reacting units. As is seen from 

 these figures, the protection took place in direct multiple pro- 

 portions until after a certain increase in the amount of serum 

 injected, ^vllen there occurred a two-fold and more than two-fold 

 gain in the protective value of the serum injected. In the inter- 

 pretation of these facts of which the mechanism may be quite 

 complex, there should be borne in mind a possible change in the 

 rate of retention (lower elimination) of antibodies in the general 

 circulation follo\ving the increase in the volume of serum injected. 

 This explanation suggests itself at the present moment as the 

 simplest, but it remains to be proven. 



The next point of interest ^vas to determine the specificity 

 of serimi protection /// vivo against B. tyjjhosus reacting factors. 

 In these experiments, immune anti-meningococcus horse serum 

 of high neutralizing potency for meningococcus reacting factors 

 and a normal horse serimi, Avere used. In \'iew of the fact that 



