130 INFECTION AND RESISTANCE 



it ins, while those of the third order, dependent upon the coopera- 

 tion of alexin or complement, for proper functionation, appear as 

 the cytotoxins or lysins. The detailed structure of these various 

 haptines will be discussed in connection with other considerations 

 dealing with their special reactions. 



Limiting ourselves, for the present, to a broad consideration of 

 the theory as a whole, it may be briefly recapitulated as follows: 

 Toxins or other antigens, in order to exert any influence upon the 

 animal body, must enter into chemical relationship with the cells. 

 This they do by virtue of union with chemical units or atom groups 

 of the cells, spoken of as "side chains." These side chains or recep- 

 tors, thrown out of function by this union, and necessary for the 

 metabolic processes of the cell, are regenerated, and under the influ- 

 ence of repetition of this process are produced in excess, to such a 

 degree that they are eventually thrown off by the cells and enter the 

 circulation as antibodies. Thus far the theory, comparing the union 

 of antigen with cells to the processes of nutrition, is eminently log- 

 ical and likely, necessitating the assumption of over-regeneration as 

 the only criterion not directly amenable to experimental proof. 



That the antigen can be bound by the body cells has been vari- 

 ously shown in a large number of investigations, some of which have 

 been reviewed in our section on the action of bacterial poisons. We 

 have there seen that Donitz demonstrated the rapid disappearance 

 of tetanus and diphtheria toxins from the circulation of susceptible 

 animals, and that conversely Metchnikoff showed that the poison may 

 persist unabsorbed and unchanged for weeks and months in the 

 blood of such insusceptible animals as the turtle and the lizard, 

 facts which furnish indirect evidence of the absorption of the toxins 

 by the body cells. More direct evidence has, of course, been possible 

 in the test tube experiments with hemolytic and other cell poisons 

 where a directly specific combination between antigen and antibody 

 has been easily demonstrable. Thus, in his earlier experiments with 

 spider poison, Sachs was able to show that rabbit erythrocytes, which 

 are sensitive to the poison, could absorb it out of solution, while dog 

 and other corpuscles, which were insusceptible to the poison, did not 

 bind or absorb it. This can be easily demonstrated for many anti- 

 gens and antibodies and may be accepted as a fact. 



This point established, and repeatedly confirmed, and the origin 

 of antitoxins from the cells of the body having been rendered likely 

 by the experiments of Salomonsen and Madsen, and by those of Roux 

 and Vaillard just cited, it would follow, by the theory of Ehrlich, 

 that we should find the site of antibody production in the very cells 

 which possessed specific affinity (receptors) for the antigen. This 

 question has been variously investigated, chiefly in the case of the 

 toxins and antitoxins, since this phase of the subject is most easily 

 amenable to experiment. It will be remembered also that Wasser- 



