REINJECTION OF THE HOMOLOGOUS PROTEIN 133 



with one twenty-millionth of a gram of crystallized egg albumen. 

 Usually 0.001 to 0.1 c.c. of serum is an effective sensitizing dose. 



A latent period intervenes between the initial injection of the 

 animal with sensitizing protein and sensitization on the average 

 this is about ten to fourteen days. Gay and Southard 1 showed, how- 

 ever, that the time necessary to effect sensitization depends somewhat 

 upon the size of the sensitizing dose, larger amounts requiring longer 

 periods than smaller amounts. White and Avery 2 have found that a 

 relation exists between the minimum sensitizing and the maximum 

 intoxicating dose, larger amounts of protein being required on rein- 

 jection to elicit a reaction when the sensitizing dose is very small, and 

 vice versa. 



Reinjection of the Homologous Protein. Repeated injections of the 

 homologous protein spaced at intervals less than ten days do not, 

 as a rule, cause symptoms of acute anaphylaxis after a third or a 

 fourth injection, however, there appears at the site of the first injec- 

 tion a swelling, usually indurated and more or less edematous, which 

 may lead to extensive necrosis and sloughing. These local reactions, 

 the so-called Arthus 3 phenomenon, are closely related phylogenetically 

 to the anaphylactic symptoms described below. 



If the second parenteral injection is made after sensitization is 

 established usually after ten to fourteen days symptoms follow 

 almost immediately, which vary somewhat according to dosage and 

 the site of inoculation. A very large dose frequently results in rapid 

 death, the Theobald Smith phenomenon. 4 Very broadly speaking, 

 it requires 200 to 2000 times as much protein to cause acute anaphy- 

 laxis as to effect sensitization. 



Intravenous or intracerebral injections of moderate doses are fol- 

 lowed very soon by a period of excitement (in dogs, followed by a 

 period of depression), 5 the animal is restless and moves about in a 

 bewildered manner and shows signs of respiratory embarrassment. 

 It coughs (a normal guinea-pig rarely or never coughs) and scratches 

 the corners of its mouth. This state is followed by dyspnea, with 

 involvement of the diaphragm and bronchial musculature leading to 



1 Jour. Med. Res., 1908, xviii, 407. 



2 Jour. Inf. Dis., 1913, xiii, 103. 



3 Compt. rend. Soc. Biol., 1903, Iv, 20; 1906, Ix, 1143. 



4 Theobald Smith, Jour. Med. Res., 1905, xiii, 341; Otto, Leuthold-Gedenkschrift, 

 1096, i, 153. 



6 Guinea-pigs in general react most strikingly to anaphylactic stimuli; man is less 

 sensitive. Rabbits, sheep, goats, horses, and birds, in the order mentioned, are less, 

 susceptible than man. Cold-blooded animals appear to be refractory. 



