158 THE PRINCIPLES OF IMMUNOLOGY 



limits appears to have no influence whatever on the phagocytic activity 

 of their cells. Calderone and Runfola have recently studied the in- 

 fluence of temperature upon phagocytosis in the frog and find that 

 phagocytosis proceeds actively between 5 and 40 C, but ceases when 

 a temperature of 42 C. is reached. 



OPSONINS 



Introduction. Early in the study of phagocytosis it was noted 

 that immune animals respond to the introduction of the antigenic 

 bacteria by a greater degree of phagocytic activity than normal animals. 

 This was interpreted by Metchnikoff as being due to " stimulins " 

 which were supposed to augment the activity of the phagocytic cells. 

 The first study of importance in contraindication of MetchnikorFs con- 

 ception of stimulins was that of Denys and Leclef in 1895. They 

 showed in a study of streptococcus immunity in rabbits that the leuco- 

 cytes of normal and immune animals took up the bacteria equally 

 well, but that both varieties of leucocytes acted much more powerfully 

 when immune serum was added. They indicated that the process of 

 immunization did not augment the phagocytic power of the leucocytes 

 and concluded that in their opinion the antitoxic substance acts not 

 upon the leucocyte but upon a poison enclosed within the bodies of the 

 microbes or dissolved in the medium, the poison acting to protect the 

 bacteria against the attacks of the leucocyte until neutralized by the 

 immune substance in the serum. The observations were confirmed by 

 other investigators and later Denys and Leclef showed that whereas 

 extremely virulent bacteria are taken up by leucocytes in normal serum 

 to only a slight degree, the addition of an immune serum markedly 

 increases the phagocytosis. Little progress was made until after the 

 discovery by Leishman whereby the study of phagocytosis could be 

 carried out in vitro. Modifying this method, Wright and Douglas in 

 1903 published the first of a series of experiments which have built up 

 in large measure our modern conception of the influence of serum on 

 phagocytosis and the practical use of bacterial vaccination in the treat- 

 ment of disease. They showed conclusively that it is the activity upon 

 the bacteria of some substance in the blood which favors phago- 

 cytosis and they named the substance opsonin. By treating the bacteria 

 with serum, then washing them to remove the serum, from the sur- 

 rounding medium and finally mixing with a leucocyte emulsion in salt 

 solution they showed that phagocytosis proceeds actively. Similar 

 treatment of the leucocytes by serum produces no augmentation of their 

 phagocytic activity. Thus it was shown that the serum does not stimu- 

 late the leucocytes but rather prepares the bacteria so that they may 

 more readily be ingested, hence the term opsonin (Gr. opsono to pre- 

 pare food). There is some variation, however, in the way the serum 

 operates in the case of different bacteria. Tunnicliff and Davis have 

 shown that fusiform bacilli and influenza bacilli can be taken up readily 

 independently of the presence of serum. There are, of course, different 

 degrees of facility with which bacteria can be taken up, varying from 



