INTRODUCTION 13 



and in a different species, as heterotoxins. The chemical nature of the latter 

 is distinct from that of the syngenesio- and homoiotoxins. 



Furthermore, these substances, the organismal differentials, diffuse not only 

 into the area directly surrounding the transplanted piece, but they also enter 

 the circulation and are carried by the blood and lymph to more distant organs. 

 This may be concluded from the observation, already stated, that transplanta- 

 tion of a normal piece of grafted tissue induces changes in the relative pro- 

 portions of the circulating blood cells, which are parallel to the degree of 

 relationship or strangeness between host and transplant and which depend 

 therefore on the nature of the organismal differentials of host and graft. Such 

 substances, corresponding to individuality and species differentials, enter the 

 blood and exert their effects in distant parts and thus resemble hormones in 

 their action. 



When they have reached and are retained in certain organs, such as spleen 

 and bone marrow, they may, in addition, stimulate the formation of immune 

 substances, since they are strange to the individual or to the species in which 

 they circulate. It is especially the organismal differentials derived from a 

 different species, or even from a different individual, which initiate defensive 

 processes of immunity ; being strange to the new host they disturb his equilib- 

 rium, which is attuned to substances possessing his own specific organismal 

 differentials. These strange substances act, therefore, as antigens. Organ 

 differentials as such may not be strange to the host, in this sense, and as a rule 

 they function as antigens only in combination with a strange organismal 

 differential. 



If, then, we may consider it an established fact that when tissues are trans- 

 planted from one to another individual of the same species, including even 

 nearly related individuals such as brother or sister, substances are given off by 

 these tissues which call forth noticeable reactions on the part of the host cells, 

 might it not be possible, or even probable, that such substances, acting on 

 nearby tissues as contact substances or on farther distant tissues as hormones, 

 are also given off in the animal's own organism ; but that, here, instead of 

 operating as disturbers of the tissue equilibrium, on the contrary, they serve 

 as instruments by means of which the tissue equilibrium is maintained and 

 regulated in such a manner that it is best adapted to the normal cooperation of 

 the various tissues in the interest of the entire organism, and thus to the 

 normal functioning of the organism as a whole? Such substances, represent- 

 ing the individuality differential, if discharged into an animal's own organism 

 may then be designated as autogenous substances. If two tissues, possessing 

 two different individuality differentials, adjoin each other, signs of disharmony 

 develop, which are partly or largely due to the action of disharmonious in- 

 dividuality differentials. This applies, for instance, to homoiogenous skin 

 transplants. Conversely, may we not assume that since the epithelial cells in 

 the normal skin remain at rest, this is due at least partly to the action of the 

 autogenous substances which keep the neighboring epithelial cells as well as 

 the underlying connective tissue and lymphocytes in a quiescent state? 



