762 PASSIVE IMMUNIZATION SERUM THERAPY 



then numerous investigators have supported Bordet's findings, so that 

 it may be accepted as true that one of the chief antibodies in antistrep- 

 tococcic serum is of the nature of a bacteriotropin or immune opsonin. 

 A potent serum also contains an antitoxin, as may be shown experi- 

 mentally by neutralization of the hemotoxic poison of streptococci, 

 and also clinically, when the rapid subsidence of fever and general im- 

 provement of the patient are probably due, in part, to neutralization of 

 streptococcal toxins. Thus far the presence of bacteriolysins has not 

 been definitely proved, although they may be present and operative 

 in vivo. I have found that antistreptococcus serum contains an anti- 

 body capable of fixing complement with streptococcus antigens. 1 It 

 may be stated, therefore, that the action of antistreptococcus serum is 

 dependent primarily upon bacteriotropins, and secondarily upon anti- 

 toxins and, possibly, bacteriolysins. 



Preparation of Antistreptococcus Serum. Some differences of opinion have 

 been expressed regarding the advisability of passing cultures that are being used 

 for purposes of immunization through a lower animal in order to increase their viru- 

 lence. For example, the unsatisfactory results that have followed the use of Mar- 

 morek's serum have been ascribed not only to the fact that it is monovalent, but also 

 to possible alteration of the strain in its biologic characteristics by animal passage, so 

 that its virulence for the human being was diminished or lost, and, accordingly, 

 while the antiserum is protective for the animals through which the passage has been 

 conducted, it is inactive for the human being. Tavel, Krumbein, and Paltauf have 

 prepared polyvalent serums with different strains from human infections without 

 animal passage. Menzer has prepared a serum with strains of cocci derived from acute 

 rheumatic fever, and Moser with strains obtained from scarlet fever, which have also 

 not been passed through animals. Aronson has attempted a combined procedure, 

 making use of passed and unpassed cultures conjointly, and this appears to be the 

 method of choice. In other words, those who prepare antistreptococcus serums should 

 use as many fresh strains as possible, and in several of the older cultures the virulence 

 should be increased from time to time by passage through animals. 



In preparing the serum young and healthy horses should be used. The injections 

 should first commence of dead cultures given subcutaneously, then of autolysates, 

 and finally of living cultures administered intravenously. Occasionally severe local 

 and general reactions are observed, and the whole procedure should be conducted 

 under careful supervision. 



First Method. Cultures are grown on a solid medium, and an emulsion and 

 autolysate prepared as described for immunizing with meningococci. Begin by 

 injecting subcutaneously 5 c.c. of emulsion heated to 60 C. for an hour, and in- 

 creasing the dose each week by 5 c.c. until 100 c.c. are given at one time. If the 

 reactions are mild (general and local), the doses may be increased more rapidly. Then 

 begin with 2 c.c. of living culture and increase the dose each week. When a dose of 

 10 c.c. is reached, inject with autolysate and living cultures alternately, gradually 

 increasing the dose until a dose of 50 c.c. is reached. Living cultures are then given 

 intravenously and the dose rapidly increased until 100 c.c. and more are given at 



1 Arch, of Int. Med., 1912, ix, 220. 



