216 THE PRINCIPLES OF IMMUNOLOGY 



peritoneal injections may require three or four hours for results, 

 whereas intravenous injections may be effective in a few minutes. An 

 experiment quoted from Besredka illustrates the rapidity and extent 

 of the process. Guinea-pigs sensitized with egg-white exhibited fatal 

 reactions with a toxic dose of 0.002 c.c. egg-white. An animal of this 

 group was given 0.0005 c - c - egg-white intravenously without reaction. 

 It did not react to 0.005 c - c -> tne ^ ata ^ dose, given two minutes after 

 the first injection nor to doses of 0.02' c.c., or 0.2 c.c., given at ten- 

 minute intervals. Ten minutes later it was given 2.0 c.c. and, although 

 visibly uncomfortable for a time, recovered. Desensitization may also 

 be practised by four or five repeated subcutaneous or intraperitoneal 

 injections at intervals of about two hours, the subcutaneous route 

 requiring a longer time to be effective than the intraperitoneal route. 

 We have found relatively large, but still sub-lethal, single doses to be 

 most effective by intravenous injections, but less so by intraperitoneal 

 and least by subcutaneous injection. Besredka also reports desensitiza- 

 tion by introducing the protein into the gastro-intestinal tract but as 

 yet this has not received widespread confirmation. Desensitization may 

 be effective at any period during the hypersusceptible state. If a second 

 dose be given before hypersusceptibility appears, the condition may, 

 by subsequent injections, become one of increased resistance 

 or immunity. 



Other methods of preventing shock include the use of atropin as 

 suggested by Auer and Lewis, of adrenalin, of chloral hydrate, admin- 

 istration of ether, alcohol, atoxyl and numerous other drugs. Pelz and 

 Jackson found adrenalin most satisfactory in dogs. Karsner and Nutt 

 found that atropin sulphate is satisfactory in guinea-pigs provided the 

 toxic dose of serum is not too large. The use of adrenalin in guinea- 

 pigs is unsatisfactory because of the pulmonary hemorrhage and 

 edema which it produces. Drugs which depress the excitability of 

 the smooth muscle of the bronchioles, those which depress nerve activity 

 generally as the anesthetics, and those which tend to maintain blood 

 circulation, are pharmacologically adapted to the prevention of ana- 

 phylactic shock. They do not operate as effectively after the toxic dose 

 of protein has been given, as they do when given in time to produce 

 physiologic effects before the onset of shock. Thomson found that 

 exposure to the X-ray inhibits anaphylactic shock. Friedberger and 

 Mita have suggested that anaphylactic shock may be inhibited by very- 

 slow administration of the protein. Lewis has investigated this problem 

 experimentally and by the use of the Woodyat pump has found that 

 " acute anaphylactic shock can be prevented in sensitized experimental 

 animals by giving otherwise fatal doses of diluted antigen intravenously 

 at very slow rates." 



Passive Anaphylaxis. As was shown in 1907 by the independent 

 investigations of Nicolle, Richet, Otto and Friedemann, the serum of 

 a hypersusceptible animal, when injected into a normal animal, will 

 render the latter also hypersusceptible. This condition is transferred 

 in the serum rather than in corpuscles or tissue cells. Passive ana- 



