624 



SCIENCE 



[N. S. Vol. LII. No. 1357 



.we recall that the original toxic protein used 

 to immunize is detoxicated in the course of the 

 immune reaction and the original non-toxic 

 protein used to sensitize is endowed with the 

 ■property of intense toxicity in course of the 

 latter reaction. 



1 As in the instance of the immune state, a 

 still undecided controversy is going on as to 

 whether the hypersensitive condition depends 

 upon humoral or upon cellular factors. There 

 is no doUbt that the anaphylactic antibody 

 exists free in the blood, and hence that a nor- 

 mal animal can be rendered passively sensitive 

 by the infusion of blood derived from a sensi- 

 tized animal. It is equally true that the ana- 

 phylactic response is in part a cellular one, as 

 in the instance mentioned of the bronchial 

 ■musculature stimulated to contraction. By 

 appropriate experiments it can be shown that 

 prgans containing smooth muscle taken from 

 (Sensitive animals, exhibit the equivalent of the 

 anaphylactic reaction even outside the living 

 ibody; and also that co incidentally with the 

 appearance of the " shock " of the reaction in 

 ithe guinea pig, the blood becomes incoagulable. 

 Hypersensitiveness may exist independently 

 of purposive artificial sensitization, and some 

 ,of the most important examples of that con- 

 dition have been observed in man. Because of 

 jtheir size, perhaps for other reasons, human 

 jbeings even when sensitive react to the pa- 

 renteral injection of native proteins less se- 

 verely than the smaller animal species. And 

 yet lamentable instances, if very few in num- 

 ber, of serious or even fatal anaphylactic ef- 

 fects have been observed in man. These have 

 occurred especially in connection with the 

 ■therapeutic employment of curative serums de- 

 rived from the horse. The greatest danger 

 from this source is at the time of the first in- 

 jection, for while severe effects do sometimes 

 ■follow upon a second or subsequent injection, 

 they have never been attended by fatal conse- 

 quences. Luckily, means are known for antici- 

 pating these even infrequent accidents, and 

 of guarding against their dangers without at 

 the same time depriving those in need of the 

 benefits of serum protection or therapy, 

 y Beside the active state of sensitization 



another is known which may be termed nega- 

 tive. Thus it has been found that when a 

 sensitive animal is given an injection of a 

 protein which produces a certain degree of 

 anaphylactic effect, but not a fatal outburst, 

 the treated animal can for a time be rendered 

 insensitive. And thus human beings who are 

 sensitive, say to horse serum, may be desensi- 

 tized by means of successive small inocula- 

 tions of the diluted serum, and while in the 

 ^refractory state thus induced receive without 

 risk larger injections of the serum. 

 j On the other hand, lesser states of anaphy- 

 laxis in man are by no means infrequent. To 

 them belong the rashes of " serum sickness " 

 following the injection of curative serums 

 which while annoying are not dangerous, and 

 the very disagreeable manifestations of hay 

 ^ever and its allied conditions, now attributed 

 ito the action of vegetable materials, pollens 

 chiefly, upon the sensitized mucous membranes 

 ,of the nose and throat. Recent studies by 

 Auer have shown that animals sensitized with 

 harmless proteins, such as horse serum, develop 

 severe local inflammations when from any 

 local cause an extrusion of the antigen-con- 

 taining fluid of the blood is enabled to pene- 

 trate the extravascular tissues; and on the 

 basis of this observed fact he has suggested 

 ^that functional disturbances of many organs 

 pi the body in sensitive human subjects may 

 be brought about in a similar manner. 

 I In a related field the hypersensitive reaction 

 |has been employed to aid in the diagnosis of 

 important diseases of man and animals. It is 

 apparent from what has been stated of the site 

 of the fatal anaphylactic shock in the guinea 

 pig, and as stated a moment ago of the sensi- 

 tiveness of tissue cells in general to the circu- 

 lating anaphylactic antigen, that a visible local 

 reaction might be obtainable by introducing 

 the protein to which the animal or person is 

 sensitive into a visible portion of the body, as 

 say the skin. In this way sensitiveness is 

 looked for before serum injections are given, 

 .tuberculin is employed to disclose hidden foci 

 ,of active tuberculosis, luetin is used to expose 

 evidences of latent syphilis, and, in a modified 

 manner, the Schick test is applied to determine 



