TOXIN AND ANTITOXIN 129 



edly thrust upon the cell, the process of regeneration may be not only 

 sufficient to compensate for the loss of the eliminated receptors, but 

 may follow the general law of overcompensation, formulated by Wei- 

 gert, and receptors of the variety occupied by the antigen are pro- 

 duced in excessive number. 



Here again Ehrlich has called analogy to his aid, and has taken 

 his conception of "overcompensation" from the well-known phe- 

 nomena of pathological anatomy where, for instance, in the restora- 

 tion of cellular elements after injury, there is often an overpro- 

 duction of granulation tissue, far beyond the needs of simple healing. 



Thus the restitution of cell receptors, if sufficiently stimulated 

 by large quantities or repeated administration of the antigen, far 

 exceeds the quantity normal to the cell, and may proceed to such a 

 degree that the cell, becoming as it were "top-heavy" with these 

 elements, sloughs them off into the surrounding lymph and blood, 

 where they circulate as free receptors. These free receptors then, 

 having specific affinity and combining power for the antigen which 

 incited their production, unite with subsequently introduced antigen 

 in the blood stream, diverting it from the cells themselves, and, in 

 the case of the variety of antigens spoken of as toxins, this union 

 with the free receptors in the blood stream would serve to protect 

 the cells from harm, exerting thereby an antitoxic action. 



The antibodies appearing in the blood of immunized animals, 

 therefore, represent atom complexes, normally parts of the body cells 

 and concerned in the metabolic processes, but now produced in ex- 

 cess and extruded into the body fluids under the influence of the 

 stimulation of immunization. The very substances, as Behring has 

 put it, which make possible the poisoning of the cell by the toxins be- 

 come protective when, detached from the cell, they circulate in the 

 blood. Thus the theory, beside explaining the causes leading to anti- 

 body formation, offers a plausible reason for the relatively strict 

 -specificity observed in antibody-antigen reactions. 



Formulated in direct connection with the investigations upon 

 toxins and antitoxins, the side-chain theory has been extended by 

 Ehrlich and his associates to all known phases of antibody-antigen 

 reactions. The differences in the nature and complexity of various 

 antigens would naturally necessitate variation in the receptors capa- 

 ble of assimilating them, and these receptors, appearing subsequently 

 in the blood as antibodies, must, of necessity, differ from each other. 

 On this basis Ehrlich has conceived of three main varieties or "or- 

 ders" of receptors or "haptines," as he calls them. Of these the 

 simplest are those of the first order which attach to the toxins, and 

 by over-regeneration appear in the blood stream as antitoxins. Those 

 of the second order, adapted to the assimilation of more formidable 

 protein molecules, are, of necessity, of greater structural complex- 

 ity, appearing in immunized animals as the agglutinins and precip- 



