378 INFECTION AND RESISTANCE 



development, acting then simply as though a larger dose had been 

 given in the first place. Thus if antigen is given by a method of 

 introduction and in a quantity which would justify us in expecting 

 hypersusceptibility to be developed at the end of 12 days, we can 

 render the animal "antianaphylactic" by a second administration 

 given, say, on the 8th, 9th, or 10th day. If we give it on the 2d, 3d, 

 or 4th day after the first injection, it is very likely that sensitization 

 will proceed nevertheless. Eosenau and Anderson have also investi- 

 gated the repeated injection of antigen during the incubation time, 

 and their results would also seem to emphasize the necessity of mak- 

 ing the preventive injection close to the time at which hypersuscepti- 

 bility may be expected. If quantities of 2 c. c. were injected 10 times 

 in the course of 17 days, and 15 to 17 days thereafter 6 c. c. of horse 

 serum were given, the animals showed symptoms proving that anti- 

 anaphylaxis was but partial. If amounts of 0.001 c. c. were given 

 5 times in a period of 8 days, and the animals were tested 23 days 

 later, death often ensued. It is also possible, as a number of investi- 

 gators have shown, to produce the antianaphy lactic state by the injec- 

 tion of sublethal doses, even after the time has set in at which the ani- 

 mals are hypersusceptible. ' This method can be carried out success- 

 fully according to Besredka by injecting very small amounts into the 

 brain (1/50 to 1/400 of a cubic centimeter). Within a few hours 

 after such an injection the animals may withstand an otherwise 

 fatal dose with slight or no symptoms; although it is generally 

 stated that intraperitoneal injections, carried out after hypersus- 

 ceptibility has set in, must be of considerable quantity (large enough 

 to cause symptoms) in order to induce antianaphylaxis. Besredka 62 

 states, in a recent resume, that 1/50 to 1/100 cubic centimeter in- 

 jected intraperitoneally and giving "practically no symptoms" in a 

 sensitized guinea pig, after the anaphylactic state has set in, may ren- 

 der the animal entirely refractory after 5 hours. 



On the other hand, Rosenau and Anderson, 63 working with sub- 

 cutaneous injection, obtained results which differ considerably from 

 those of Besredka. They sensitized a series of guinea pigs with 

 mixtures of toxin and antitoxin, and 48 days later, at a time when 

 the animals were hypersusceptible, gave 20 subcutaneous injections 

 of 0.001 c. c. daily. Two days after the last injection, 0.2 c. c. of 

 horse serum was given intracerebrally, and all of the animals showed 

 symptoms, and many of them died. They conclude, therefore, that 

 the repeated injection of small amounts of antigen into sensitized ani- 

 mals has no appreciable effect. The same worker has shown by ex- 

 periment that the introduction of large amounts of antigen into the 

 previously cleansed rectum of sensitive animals is entirely without 



62 Besredka in "Kraus u. Levaditi Handbuch," Erganzungsband I. 



63 Rosenau and Anderson. Loc. cit., U. S. Pub. Health and M. H. S. 

 Hyg. Lab. Bull. 45, 1908. 



