HYPERSENSITIVENESS, PROTEIN INTOXICATION 225 



are comparable to the immediate reactions described by von Pirquet. Oc- 

 casionally delayed reactions are observed in which the urticarial wheal and 

 erythema make their appearance, only after an interval or. latent period of 

 from 24 to 12-24 hours after the test is performed. 



Not only are there variations in the degree of hypersensitiveness to 

 the same proteins in different individuals, but in a single individual 

 the different tissues may vary so absolutely in their sensitiveness 

 to the same protein that the impression is obtained that the sensi- 

 tiveness is highly developed in some tissues and entirely absent in 

 others (local hypersensitiveness). Occasionally, instances are recorded 

 in which an extract of pollen or of some protein calls forth no reaction 

 when the dermal or intradermal test is employed, but produces a very 

 marked reaction when applied to the mucous membrane of the nose or con- 

 junctiva. In other individuals, the application of the protein or an ex- 

 tract to the skin may result in a violent reaction, whereas ingestion of 

 the protein and contact with the mucous membrane of the mouth and gastro- 

 intestinal tract produce no observable effect. 



Some observations have recently been made by Mackenzie and Bald- 

 win to show that these local reactions are in all probability true cellular 

 reactions and represent a union of the antigen with the cells with which 

 it comes in contact. They have found that the repeated application 

 of a protein such as egg white or an extract of ragweed to a single 

 area of the skin of an individual hypersensitive to either one of these 

 substances results in a gradual diminution of the local reaction until 

 finally, after several applications, there comes a complete exhaust in the 

 localized area of the skin, so that it no longer shows any reaction to the 

 application of these substances. This exhaustion of reactivity of the tis- 

 sues may persist for 3-5 days, and then gradually return. The exhaust 

 appears to be specific. The exhaustion of the reactivity of the tissues to 

 the specific protein is not interfered with by the application of histamin, 

 a non-specific toxic amin which causes an urticarial wheal when applied 

 to the skin, nor does it interfere with the reactivity of the tissues towards 

 histamin. The local, rapid, and specific exhaustion of the tissue to the 

 application of a substance to which the individual is hypersensitive prob- 

 ably explains the beneficial results which have been obtained both by the 

 feeding of egg white in gradually increasing doses to children who are 

 susceptible to egg white, as well as the prevention of hay fever and asthma 

 by the subcutaneous injection of gradually increasing amounts of the 

 extract of pollens or other substances to which these individuals may be 

 hypersensitive. 



It may thus be seen that considerable variations occur both in the 

 degree of hypersensitiveness of different individuals and of the participa- 

 tion of different mucous and cutaneous surfaces as regards the hypersensi- 

 tiveness to a given protein in the same individual. 



