ANTI-ENZYME IMMUNITY 209 



to produce unstable derivatives. As referred to above, Boor and Miller 

 (1939) found that ketenized gonococci after standing a week in the 

 cold fully regained their toxicity to mice. 



In the light of v\'hat we know about the above discussed reversible 

 inactivations, one is inclined to justify the assumption that this process 

 occurs provided the protein under consideration has not been subjected 

 to greater changes. 



The many observed inhibitions of enzymes and toxins by their 

 specific antibodies may lend themselves to two types of interpretations. 

 These inhibitions may be due to direct combination between the spe- 

 cific groupings in the enzyme and anti-enzyme antibody molecules. If 

 such is the case it is immaterial whether or not the substrate molecule 

 can penetrate the immune complex to reach the site of the active 

 enzyme groups. The substrate could not be activated under these con- 

 ditions. Or, the antibody molecule may not contain groups specific for 

 the enzyme, but the antibody molecules occupying positions on the 

 surface of the enzyme may be so closely packed that the substrate 

 molecules are incapable of reaching the site of the active enzyme or 

 toxin groups. 



There are no experimental data to show that antibody molecules 

 on the surface of antigen constitute a mechanical barrier to the sub- 

 strate molecules. Before such an argument can be deemed worthy of 

 consideration it would be desirable that experimental results be pro- 

 vided. One may perhaps be able to work out conditions for the treat- 

 ment of the enzyme-antienzyme complexes with acetylating and other 

 agents containing tagged isotopic atoms. On separating the antigen 

 from the antibody, the relative amounts of the tagged agents in each 

 component could be estimated. Using the size of the reagents as a 

 measure for the space available between the antibody molecules on the 

 surface of antigen one may be able to gain some information concern- 

 ing this question. 



On the basis of various experimental data it would seem difficult 

 to conceive that antibodies combining with an enzyme molecule con- 

 stitute a wall impermeable to the specific substrates. In the reaction of 

 diphtheria toxin with antitoxin, in the presence of extreme excess of 

 the latter, at least eight molecules have been shown to combine with 

 one molecule of toxin. The composition of toxin-antitoxin soluble com- 

 plex in the zone of toxin excess has been reported to consist of only one 



