8o6 THE FUNCTIONAL ROLE OF AGGLUTININS 



the process occurs and becomes evident in vitro is its almost instantaneous occurrence 

 in vivo. Also agglutination within the body seems to take place with dilutions of an 

 antiserum which are wholly ineffective in the test tube, while the specificity of in vivo 

 agglutination is as strict as in vitro. Organisms like Bacillus mucosus capsulatiis which 

 are agglutinated only slightly even by highly immune serum in the test tube are rapid- 

 ly and completely agglutinated in immune animals. Bull studied first the mechanism 

 of bacterial immunity, both natural and acquired, in the rabbit. This animal may be 

 regarded as possessing a high degree of natural immunity to such organisms as ty- 

 phoid baciUi, dysentery bacilli of the Flexner group, and non-virulent influenza 

 bacilli, while it is very susceptible to virulent pneumococci, dysentery bacilli of the 

 Shiga type, and virulent influenza bacilli. It was shown that the degree of agglutina- 

 tion and opsonization of the bacteria within the body is inversely parallel to the in- 

 fectiousness of the particular micro-organism for the host. When typhoid bacilli are 

 injected into the circulation of normal rabbits the micro-organisms are promptly 

 agglutinated, quickly removed from the blood stream, and accumulated in the internal 

 organs where they are taken up by the polymorphonuclear leukocytes and fixed-tissue 

 cells, especially in the lungs, liver, and spleen. The rapidity with which the agglutina- 

 tion takes place is remarkable. In fact, it was shown that the bacilli are agglutinated 

 within a few seconds after entering the blood stream. This was proved by making 

 smears from the blood by heart puncture and from the crushed organs. The same 

 was found true for all organisms investigated to which the rabbit is naturally resistant, 

 while slight or no agglutination was observed for bacteria with which the animal may 

 be infected. 



It appears, therefore, that agglutination may be an important factor in the fore- 

 going instances of natural immunity. That this is probable is supported by indica- 

 tions that typhoid bacilli, for example, do not undergo intra vitani destruction by 

 bacteriolysis as is the case in vitro. It was shown that the unagglutinated and un- 

 phagocyted bacilli in the organs resist longest and stain best. It is known that ty- 

 phoid bacilli may appear and survive in the blood of typhoid fever patients at a time 

 when the shed blood is highly bacteriolytic for the bacilli. Since the organisms in the 

 blood may also become inagglutinable, they cannot be remov'ed by the organs and 

 hence are not phagocyted and destroyed. 



Bull showed that in actively or passively immunized animals agglutination is 

 still more noticeable. His observations in regard to the action of pneumococcus-im- 

 mune serum in pneumococcus-infected rabbits is particularly interesting. As is well 

 known, virulent pneumococci in the blood stream of normal rabbits soon begin to mul- 

 tiply and a fatal septicemia soon develops from an exceedingly small number of or- 

 ganisms. The virulent pneumococci are neither agglutinated nor opsonized by normal 

 rabbit serum. On the other hand, the non-virulent strains are agglutinated instantly 

 after injection into the circulation of normal rabbits and are opsonized by the serum 

 of such rabbits. It was found that the injection of a small amount of antipneumococ- 

 cus serum into septicemic rabbits resulted in a rapid clumping of the virulent pneu- 

 mococci in the blood stream. An immediate heart puncture revealed clumps of the 

 bacteria which had been evenly distributed in smears prepared just before the in- 

 jection. Three to five minutes after the serum injection it was impossible to find any 



