758 PASSIVE IMMUNIZATION SERUM THERAPY 



its antitoxin is somewhat unstable, so, in like manner, it is probable that 

 the union of toxin and body-cells is not so firm but that it may, during 

 an early stage, -be dissociated to some extent by the more attractive 

 antitoxin. This factor is to be borne in mind in the treatment of diph- 

 theria, and is an additional argument for the administration of large 

 doses of the serum. 



2. Antitoxin pure and simple does not, however, constitute the 

 only factor of value in antidiphtheric serum. While the pure antitoxin 

 neutralizes the toxin, it has no injurious action on the bacilli themselves, 

 and, indeed, it is said that the bacilli may live and multiply in the pres- 

 ence of large amounts of antitoxin. How, then, are we to explain the 

 gradual disappearance of the membranous exudate and the bacilli at the 

 local site of infection? It has been shown experimentally that virulent 

 diphtheria bacilli resist phagocytosis. This condition is probably due 

 to an actual leukotoxic action of the diphtheria toxin, aided by an ag- 

 gressin-like action of the toxin which neutralizes opsonin, and in this 

 manner prevents phagocytic activity. I in common with other ob- 

 servers, have shown that the antiserum as ordinarily produced neutral- 

 izes the antiphagocytic action of diphtheria bacilli, and enables the 

 polynuclear leukocytes to ingest them readily. 1 Whether this is brought 

 about through neutralization of the toxin by antitoxin, or is due to the 

 presence of an immune opsonin (bacteriotropin) that lowers the re- 

 sistance of the bacilli, or to the presence of an anti-aggressin that neu- 

 tralizes the intrinsic defensive mechanism of the bacilli and thus favors 

 phagocytosis, I am unable to state, but probably all three factors are 

 operative. 



3. As ordinarily prepared, diphtheria antitoxin possesses little or no 

 bacteriolytic activity. I have found, however, that antitoxin will fix 

 complement with an antigen of diphtheria bacilli, 2 indicating, therefore, 

 the presence of bacteriolytic amboceptors. Serums produced by im- 

 munizing horses with unfiltered cultures of diphtheria bacilli instead of 

 with the filtered toxin alone have been advocated for the general and 

 the local treatment, in the hope of securing lysis of the infecting bacilli. 

 Certainly it would appear wise to raise the bacteriotropic and bacterio- 

 lytic content of an immune serum by injecting the horses occasionally 

 with unfiltered cultures, for it is highly probable that the action of the 

 antiserum depends not only upon an antitoxin, but also, to some extent 

 at least, upon a bacteriotropin and possibly a bacteriolysin. 



Administration of Diphtheria Antitoxin. Antitoxin is usually ad- 

 1 Jour. Med. Research, 1912, xxvi, 373. 2 Jour. Infect. Dis., 1912, xi, 44. 



