600 ANAPHYLAXIS 



days in succession) the incubation period is shorter (about ten days 

 after the last injection); the minimal anaphylactic lethal dose is larger 

 (0.4 c.c.), and the minimal desensitizing dose is at least more than 0.2 

 c.c. of serum given intravenously. 



Besredka and Steinhardt observed that the refractory state could 

 easily be developed in sensitized guinea-pigs by one of the following 

 methods: (1) The intracerebral injection of 0.25 c.c. of horse serum 

 before the expiration of the period of incubation (twelve days). (2) The 

 intracerebral injection of less than the fatal dose (from 0.002 to 0.025 c.c.) 

 after the period of incubation. (3) Rectal injections of from 5 to 10 

 c.c. of serum. (4) By slowly reinjecting small amounts while the 

 animal is deeply narcotized with ether or alcohol. As shown later by 

 Rosenau and Anderson, a narcotic may mask but does not prevent the 

 occurrence of severe or fatal symptoms. Of these methods, Besredka 

 prefers the rectal injection, or, better still, the subcutaneous injection 

 of less than a fatal dose. 



The subject of anti-anaphylaxis is of great importance from its rela- 

 tion to serum therapy. No satisfactory method for producing this 

 state in a sensitized person has as yet been devised, owing, probably, to 

 the important quantitative factors shown, by the studies of Weil, to exist. 

 This subject will be discussed again in the following chapter, under the 

 head of Serum Sickness. 



The Mechanism of Anti-anaphylaxis. A true explanation of this 

 phenomenon cannot as yet be given. In the first place, the term anti- 

 anaphylaxis cannot be considered a proper one, as the animal is not 

 entirely and permanently anti-anaphylactic, but subsequently becomes 

 sensitive. The blood-serum of a refractory or anti-anaphylactic animal 

 does not confer a similar condition on a second sensitized animal. 



As previously stated, Friedberger believes that the refractory state 

 is due to neutralization or absorption of the anaphylactic antibody by 

 the antigen, but this explanation does not fit in with the facts, first, 

 because the serum of an anti-anaphylactic animal will still passively 

 sensitize a normal animal, and, secondly, as shown by Weil, passive 

 anaphylaxis of a guinea-pig, such as that induced by the injection of a 

 rabbit antihorse serum, may be prevented for at least eight days by a 

 previous injection of normal rabbit or sheep serum. In other words, 

 it would appear that normal rabbit and sheep serum may protect the 

 body-cells of the guinea-pig against the anaphylatoxin produced by 

 horse protein and horse anaphylactin or antibody. In explanation of 

 this paradoxic and non-specific reaction Weil, 1 who believes in the cel- 

 1 Jour. Med. Research, 1914, 30, No. 3, 299. 



