ARTHUR F. COCA 1013 



some asthmatics is actually followed by a relief of the symptoms. Before the atopic 

 reagins were discovered, the protective effect of the injections of the excitant was as- 

 sumed to be due to a neutralization of the specific mechanism as in anaphylactic de- 

 sensitization. Some of the early authors reported a disappearance of the cutaneous 

 reaction after such treatment, and Mackenzie' reported local cutaneous desensitiza- 

 tion upon repeated injections of the excitant into the same site. However, Cooke^ 

 observed that in no case was the cutaneous reaction extinguished as a result of the 

 injections of pollen extracts, and that in many of them the reaction was quantita- 

 tively the same at the end of the course of injections as it had been at the beginning. 

 The reactivity of the conjunctiva also was not in Cooke's experience materially les- 

 sened by the course of injections. Upon repeating Mackenzie's experiments, he was 

 able to demonstrate that the local exhaustion which is obtainable by rapidly repeated 

 injection of the excitant was not specific, and was evidently due to a tiring of the 

 physiological functions that take part in the production of the local lesion, Cooke 

 concluded from his observations that the protective effect of specific treatment in hay 

 fever and asthma is not due to a desensitization, and proposed the term "hyposensi- 

 tization" to designate the establishment of the increased tolerance in atopy by specific 

 treatment. 



The discovery of the atopic reagins made it possible to examine this question 

 further, and it could be shown that, in hay fever subjects who had been successfully 

 treated by a course of injections, the atopic reagins were never diminished in the 

 blood, but were sometimes increased two to four times.^ This finding completed the 

 proof that the mechanism of hyposensitization in hay fever is different from that of 

 desensitization in anaphylaxis. 



Thus, we are left without any conception of the manner in which the injections of 

 the excitant bring about the increased tolerance to the injections, as well as a more or 

 less complete freedom from symptoms upon natural contact. In view of the absence 

 of precipitation in the "neutral" mixtures of atopen with its related reagin, it was 

 thought possible that such mixtures could be different from the mixtures of antigen 

 and its respective precipitating antibody from the rabbit in the development of a 

 "toxic" property. Such mktures have been tested by three observers in the human 

 skin and in the guinea pig (by intravenous injection), but without positive results. 

 The skin reactions obtained by such mixtures were not greater than those obtained 

 with the same atopic serum mixed with salt solution, instead of the solution of the 

 respective excitant. •* More recently, however, positive results have been reported by 

 Gay.5 This disagreement calls for further study. 



ATOPY IN LOWER ANIMALS 



Since atopic hypersensitiveness is seen to be subject to heredity and therefore not 

 induced in persons lacking the inherited predisposition, it should not be expected that 

 'Mackenzie, G. E.: J.A.AI.A., 77, 1563. 1921. 

 ^ Cooke, R. A.: /. Immunol., 7, 219. 1922. 

 3 Levine, Philip, and Coca, A. F.: op. cit., 11,435. 1926. 



^ Coca, A. F., and Grove, E. F.: loc. cit.; Levine, Philip, and Coca, A. F.: op. cit., 11, 411. 1926. 

 5 See Gay, L. N., and Chant, E.: Bull. Johns Hopkins Hasp., 40, 270. 1927. 



