G. HOWARD BAILEY 809 



moval of the bacteria from the circulation. This is the so-called "endothelial opsonin." 

 By the application of perfusion methods a thermostable opsonin or bacteriotropin 

 was demonstrated in antipneumococcus serum, so altering pneumococci as to cause 

 their adhesion to the endothelial cells lining the hepatic capillaries. This opsonin was 

 operative in the liver capillaries in many hundred times the dilution necessary to 

 cause agglutination of the pneumococci, but was practically inoperative in the extra- 

 hepatic capillaries. 



It is an interesting fact, then, that in certain instances in which agglutinins in the 

 ordinary sense cannot be demonstrated either in vitro or in vivo, opsonization and 

 phagocytosis of bacteria occur. It is probable, however, that one stage of the process 

 is characterized by a condition of fine aggregation and increased adhesiveness of the 

 sensitized micro-organisms. It has been suggested by Muir and Martin that immune 

 opsonins or bacteriotropins may be identified with agglutinins, inasmuch as they 

 possess resistance to heat and are active without apparent dependence upon alexin. 

 Furthermore, the close similarity of a certain phase of opsonization to agglutination 

 has been emphasized by Ledingham.' This investigator noted that sensitized organ- 

 isms congregate at the periphery of leukocytes, and in the course of experiments on 

 the influence of temperature on phagocytosis found that at low temperatures where 

 little or no phagocytosis occurred this ring distribution of the sensitized bacteria was 

 very evident. This attachment phase was regarded as a physico-chemical phenome- 

 non entirely analogous to agglutination. It was shown that the sensitized bacteria 

 were in a state of fine aggregation, and if the sensitizing fluid also had marked ag- 

 glutinating powers the organisms were frankly clumped. 



Such evidence, therefore, would seem to show that in most instances where im- 

 munity exists, but agglutination in the body in the ordinary sense cannot be observed, 

 either because of low potency of a normal or immune serum, or scarcity of bacteria, 

 effects physically analogous to agglutination are produced. The sensitized micro- 

 organisms are so altered as to become potentially more adhesive to one another, to 

 leukocytes, or to fixed phagocytic cells. Quantitative, and to some extent quahtative, 

 variations in the reaction will depend upon the animal species, the degree of natural 

 or acquired immunity, and the virulence, number, and kind of bacteria. 



The condition of affairs, immunity without the presence of demonstrable anti- 

 bodies such as agglutinins or precipitins, has been referred to as immunity in the ab- 

 sence of antibodies. It is evident, however, that the in vitro tests usually applied are 

 not very sensitive, are somewhat crude, and are certainly artificial. The presence of 

 such antibodies in very small amounts, not demonstrable by ordinary serological 

 methods, may be revealed if the organism be grown in the presence of serum or blood 

 (the thread reaction of Pfaundler). For example, the sera of patients with pneumonia 

 frequently show no agglutinins by the usual methods, but if pneumococci are sown 

 in such sera they grow out in masses with chain formation. It has been shown that 

 growth in immune serum renders pneumococci more agglutinable and less virulent. 

 It is probable that in case of infection with organisms showing such characteristics 

 of growth, phagocytosis would be facilitated and thus the effects of more typical agglu- 

 tination simulated. Bull has demonstrated this to be the case in pneumococcus in- 



' Ledingham, J. C. G.: /. Hyg., 12, 320. 191 2. 



