ANAPHYLAXIS OR ALLERGY 193 



molecules; thus, globulins resist trypsin longer than albumins, both 

 as regards coagulability and anaphylactic; activit}'. Acids, alkalies 

 and other chemical agents may modify the reactivity of proteins in 

 proportion to the changes in solubility or constitution which they 

 produce. '2 



The amounts of protein necessary to produce reactions in guinea- 

 pigs are very small. With crystallized egg albumin sensitivity has 

 been produced with one twenty-millionth of a gram (0.000,000,05 

 gm.) and fatal reactions are obtained after sensitization with one- 

 millionth of a gram. No other animal seems to be so sensitive to this 

 reaction as the guinea-pig, however, and rabbits and dogs require 

 larger, and in many instances, repeated doses to render them ana- 

 phylactic. Within certain limits large doses are less effective in sen- 

 sitizing guinea-pigs than small, e. g., one milligram of most proteins 

 will usually be much more effective than one hundred milligrams. 

 White and Averj'^^ found that there is a certain relation between the 

 minimum sensitizing and the minimum intoxicating dose; with ex- 

 tremely minute sensitizing doses a larger intoxicating dose is required 

 to produce fatal reaction than when the sensitizing dose is larger. If 

 too large intoxicating doses are used, however, the degree of reaction 

 may be lowered. ^^ 



It is now generally assumed that both the sensitizing and intox- 

 icating agent are (or are derived from) one and the same protein, 

 but the minimum intoxicating dose is always larger than the mini- 

 mum sensitizing dose; thus, with pure egg albumin the minimum 

 lethal dose for sensitized pigs was one-twentieth to one-tenth milli- 

 gram by intravascular injection, or about one hundred times more 

 than the minimum fatal sensitizing dose. With less soluble proteins 

 the disparity is even greater, for with such the sensitizing dose is not 

 much changed, but the minimum intoxicating dose is relatively much 

 increased. Apparently an animal may be killed by much less antigen 

 than is required to saturate the antibodies present in its body (Weil). 

 The exact fate of the injected antigens is unknown. Manwaring^^ 

 observed no loss in antigen perfused through organs of sensitized 

 animals, but others have found that antigen injected subcutaneously 

 disappears more rapidly in sensitized or immunized than in normal 

 animals.'^ 



The proteins concerned must be foreign to the circulating blood of 

 the injected animal, but they may be tissue proteins of the same ani- 

 mal (e. g., placenta elements, organ extracts, lens proteins) which 

 are not normally present in its blood. Indeed it has been claimed 

 that by injecting a guinea-pig with the dissolved lens of one eye it 



12 See Dold and Aoki, Cent. f. Bakt., Ref. Beilage 1912 (54), 246. 

 "Jour. Infect. Dis., 1913 riS), 103. 



1* Terry and Andrews, Proc. Soc. Exp. Biol. Med., 1915 (12), 176. 

 15 Jour. Immunol., 1917 (2), 511. 



i« G. H. Smith and Cook, Jour. Immunol., 1917 (2), 269. 

 13 



