272 MEDICAL BACTERIOLOGY 



When produced by other substances it is referred to as anaphylaxis. 



As commonly thought of, allergy or anaphylaxis is a state of hypersensitive- 

 ness to a foreign protein, produced by the primary dose of that protein and 

 manifest only after a second dose. 



This phenomenon was first observed by Theobald Smith when studying the 

 effect of repeated subcutaneous injections of horse serum into guinea-pigs. He 

 found that, in practically all cases the first injection of horse serum into a guinea- 

 pig is innocuous; the animal shows no subsequent discomfort, illness or injury. 

 A second injection, somewhat less in quantity, equal to, or greater than the 

 first, in a few minutes, always less than 10, and sometimes almost instantly, 

 produces signs of great distress and usually death. 



The animal shows difficulty in breathing, air hunger, throws up its head 

 falls paralyzed and expires. Occasionally the animal does not die but lies on its 

 side breathing rapidly for several minutes or hours and then quickly recovers 

 completely. 



Guinea-pigs that have manifested these signs of hypersensitiveness and have 

 recovered are thereafter non-sensitive, a subsequent injection or injections of 

 horse serum causes no illness or injury the animals are immune. 



The state of hypersensitiveness does not develop immediately after the first 

 injection; it develops gradually, does not reach its fastigium until 2 or 3 

 weeks after the first injection and may be deferred. There is a minimum quan- 

 tity of horse serum which will produce anaphylaxis and larger quantities having 

 the same effect. The larger the quantity used for the first injection the longer 

 the interval before hypersensitiveness develops. 



During the period of incubation the interim between the first injection and 

 the development of hypersensitiveness a second injection causes no disturbance, 

 but somewhat lengthens the period of incubation beyond what it otherwise 

 would be. Multiple injections during the period of incubation have the same 

 effect. A guinea-pig sensitized to horse serum continues hypersensitive to it 

 throughout life unless immunized, so that a second injection given a year after 

 the first will be followed by a typical anaphylactic attack. 



As small a quantity as i/iooo cc. of horse serum subcutaneously has caused 

 a fatal reaction in sensitized guinea-pigs and 1/50,000,000 cc. of pollen extract 

 has induced a violent attack of hay fever. 



Many investigators throughout the world have confirmed the observations 

 of Smith. 



Recent studies have shown that anaphylaxis, like immunity, may be pas- 

 sive or active, passed from mother to progeny or acquired, and may be due to 

 the blood serum alone, fixed tissue cells alone or both. 



The phenomena of anaphylaxis and allergy sensitization by a primary non- 

 toxic dose after a period of incubation, sudden onset of respiratory disturbance 

 and paralysis following a second injection and terminating in death or complete 

 recovery with subsequent immunity has been produced in guinea-pigs and 

 other animals with extract of oats, egg albumin, other proteins and bacteria. 



From these observations and certain similarities to what has been well 



