ANAPHYLAXIS 385 



Among the earliest definitely stated theories is that of Gay and Southard. 1 

 These workers were emphatic in denying that anaphylaxis has the nature of an 

 antigen-antibody reaction. Their views are summarized in the following para- 

 graphs given, as nearly as space permits, in their own words: 



Increased susceptibility in the sensitized animal is due to the continued 

 presence in the circulation of an unneutralized element of the antigen (in their 

 case horse serum), which they call ' * anaphylactin, " which acts as an irritant or 

 stimulant to the body cells, and, in some way, causes them to assimilate over 

 rapidly certain other elements of horse serum. These assimilated or toxic ele- 

 ments are the same as those eliminated without producing intoxication during the 

 incubation period following the first dose. This overassimilation after anaphy- 

 laxis is the cause of the intoxication. 



Gay and Southard find much support for their contentions in the results of 

 experiments done with the so-called "passive" transfer of hypersusceptibility. 

 As mentioned above, hypersusceptibility may be transferred to a normal animal 

 with the blood serum not only of a sensitive animal, but even more surely and 

 effectually with that of a refractory, or ' ' antianaphylactic, ' ' animal. They believe 

 that such transfer is not " passive" but "active" sensitization, being accom- 

 plished by the transfer of "anaphylactin" to the normal animal. The re- 

 fractory animal has received more horse serum than the merely sensitive one, 

 since antianaphylaxis is produced by massive injections. Therefore its blood 

 contains more anaphylactin and is consequently more active in transferring sen- 

 sitiveness. The fact that a considerable incubation time is necessary in active 

 sensitization they attribute to the gradual action of the anaphylactin. 



In passive sensitization, therefore, they assumed a similar gradual irrita- 

 tion of the vulnerable cells by the anaphylactin and, as we have seen, obtained 

 their reactions in animals so treated, usually 10 to 14 days after the sensi- 

 tive serum had been given. This conception of the mechanism of passive 

 anaphylaxis was, of course, rendered unlikely by the demonstrations by Friede- 

 mann, Otto, and others that shock could be elicited in passively sensitized animals 

 within 24 hours or less after transfer of the anaphylactic serum. 



To this, however, Gay and Southard 2 answer by implying that this greater 

 speed of development of sensitiveness in the experiments of Otto is due to the 

 larger doses used by him. They say "if the doses are sufficient it (transmitted 

 sensitiveness) may be shown in a single day (Otto)." However, it is very likely 

 that the sensitiveness noted by them in animals two weeks after the transference 

 of anaphylactic serum was actually positive sensitization with antigen rests, en- 

 tirely comparable to the usual "Theobald Smith" phenomenon. 



Gay & Southard's definite objections to the possibility of an antigen-antibody 

 reaction are found in the following arguments based on experimental observations: 



1. Sensibility persists for a long time, antibodies disappear rapidly. 



2. In the serum of animals sensitive to horse serum antibodies to this 

 serum are not demonstrable by complement fixation. 



3. Although sensitiveness can be transferred to a normal animal, neverthe- 

 less a definite period of incubation must elapse before the recipient becomes 

 sensitive. 



To the first of these arguments Besredka 3 objects by saying that, while it 

 is true that sensitiveness persists for a long time, the power to transmit anaphy- 

 laxis passively disappears rapidly, as Otto, Eichet, and others have shown. 



The second contention is "contradicted by the work of Nicolle and Abt. 4 

 But since these workers made their observations upon rabbits their experiments 

 do not necessarily contradict those of Gay and Southard. This point at best is 

 a difficult one to determine, especially as recent investigations have shown us 

 that under certain circumstances antigen and antibody may be found side by 

 side in the same serum without uniting and without therefore fixing alexin or 

 complement. 



*Gay and Southard. Jour. Med. Res.. Vol. 16, 1907; Vol. 18, 1908: 

 Vol. 19, 1908. 



2 Gay and Southard. Jour. Med. Res., p. 427, 1908. 



3 Besredka. Bull, de I'lnst. Past., 6, 1908, p. 826. 



* Nicolle and Abt. Ann. de I'lnst. Past., Vol. 22, p. 132, 1908. 



