424 COLLECTED STUDIES IN IMMUNITY. 



In the deflection of methylene blue by means of orange we thus 

 have presented a phenomenon which in its essential features reminds 

 us of the mode of action of the antitoxins. 



The opposite hehavior, however, also occurs, namely, that the 

 localization of a certain substance in a particular tissue becomes 

 possible only through the simultaneous introduction of a second 

 combination, even though the latter effects no union whatever with 

 the first combination. Naturally these complicated phenomena can 

 be demonstrated with certainty only by the aid of vital stainings, foj 

 in these can the microscopical distribution be positively determined. 

 The following examples are the result of this method of investigation: 



Bismarck brown, the well-known basic azo dye, exhibits a certain 

 amount of neurotropy manifested especially in the staining of the 

 gray matter of the brain. This affinity, however, is insufficient to 

 give rise to a staining of the peripheral nerve endings in a frog, 

 particularly a staining of the taste bulbs. If, however, a frog is 

 injected with a mixture of methylene blue and Bismarck brown 

 it will be found that the terminal apparatus is stained a mixed 

 shade. The blue very readily loses its color through reduction, and 

 in a preparation mounted on a slide and sealed with a cover-glass 

 the blue color can be seen to disappear rapidly, leaving only a pure 

 brown stain. 



The other example is still more striking: If a rabbit is infused 

 with a solution of methylene blue, one always finds well-marked stain- 

 ing of the pancreas, due especially to a staining of the granules and 

 protoplasm of the islands of Langerhans. In no case have I ob- 

 served a staining of the nerve endings under these conditions. If, 

 however, one adds certain dyestufTs of the triphenylmethane series 

 to the fluid infused, dyes which in themselves do not stain the nerve 

 endings, a truly beautiful staining of the nerve apparatus frequently 

 occurs. In these and other similar cases I believe that we can 

 only assume that the favoring substances cause a modification of the 

 function of the apparatus in question, and that this carries with it a 

 change in the "chemical milieu" defined above, and so in the ab- 

 sorbing power. It is possible that similar factors also play a certain 

 r61e in many abnormal actions of drugs, especially in inherited or 

 acquired hypersensitiveness. 



(i.e. the neutral stain) will come into play, a fact which is so well observed in 

 the staining of the neutrophilic granules. 



