^.Y.l/'//r/,.lA7.S' OR ALLERGY 195 



more of such amino-acids as glycocoll, tryptophane, or lysine, pro- 

 duce typical reactions. Some compound proteins are efficient ana- 

 phylactoprens (mucin,*"" casein) but with alpha-nucleoproteins which 

 have been thoroughly purified I have obtained only negative results ; **• 

 as also with histon and nucleic acid, the isolated components of nu- 

 eleins. Bacterial substances, extracts of plant tissues, purified plant 

 proteins, and proteins obtained from invertebrates and cold-blooded 

 vertebrates, have all been found to be anaphylactogens, if they can 

 be introduced by any means into the blood or tissues in a soluble 

 unaltered condition. 



If the proteins are rendered insoluble by coagulation they become 

 inert, but proteins which cannot be made insoluble by heating (e. g., 

 casein, ovomucoid) withstand boiling temperatures. Trypsin destroys 

 anaphylactogens in just the same proportion as it splits the protein 

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

 regards coagulability and anaphylactic activity. Acids, alkalies and 

 other chemical agents may modify the reactivity of proteins in propor- 

 tion to the changes in solubility or constitution which they produce.^ 



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- 

 ]5hylactie. 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. 

 Wliite and Avery ^^ 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. 



It is now generally accepted 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 



?■! Elliott, Jour. Infect. Dis., 1914 (15), 501. 



sb See review in Zeit. Immunitat., 101.3 (10), 500. conrernino- alplia-nucleopro- 

 teins. Avhicli is the type nsiially desip:natofl as "niirlooproteins." T have found 

 beta-nnoleoproteins to be more effective antigens (Jour. Biol. Cliem., 1016 (28), 

 11). 



9 See Dold and Aoki. Cent. f. Bakt., Ref. Bellage, 1912 (54), 246. 



9a Jour. Infect. Dis., 1013 (13), 103. 



