69 



though, by restricting dissemination of the cocci, or in other 

 ways, they may be of subsidiary protective value. 



At this point it may be argued that a sharp distinction should 

 be drawn between active immunity, whether natural or acquired, 

 and passive immunity, i.e., the immunity conferred by admini- 

 stration of an immune serum. About the former, it may be 

 conceded that unknown factors are concerned, but the problem 

 of passive immunity may be regarded as less speculative, the 

 presence of antibodies in the serum being all the explanation 

 that is required. 



There are certain difficulties about this view. The pneumo- 

 coccus may, perhaps, be comparable to certain other parasitic 

 bacteria against which therapeutic sera of undoubted value have 

 been obtained. The mode of action of these sera is not settled ;. 

 but it is at least clear that their value is not due either to preci- 

 pitins and agglutinins or to such antibodies as are usually con- 

 comitants of these. A good example is to be found in the case 

 of anthrax, where numerous investigators have shown that 

 agglutinins and precipitins have nothing to do with the thera- 

 peutic value of the serum. Hence it cannot be accepted as a 

 general principle that the antibodies which may be demonstrable 

 in a serum suffice to explain passive immunity. 



It is, however, possible that pneumococcal antisera are not, 

 and never will be, comparable to anti-anthrax sera. It may be 

 held that the work of the Americans on Type sera has reached 

 the limit of what can be done in the case of pneumococci, that 

 Type I serum, which appears to be effective in very large intra- 

 venous doses, acts in virtue of the known antibodies which it 

 contains, and that the inefficacy of sera for Types II and III is 

 due to the impossibility of producing the corresponding antibodies 

 in sufficient concentration. 



On the other hand, it may be thought that the production 

 of better sera for other bacterial parasites still justifies the hope 

 that the peculiarities of pneumococcal antigens and their corre- 

 sponding antibodies may not prove an insuperable barrier to 

 further progress. 



What method is to be followed in the endeavour to discover 

 some helpful factor ? In addition to precipitins and agglutinins 

 there are other well-accredited types of antibodies, each of 

 which may be considered in turn, to see whether it yields a 

 satisfactory explanation of active immunity against pneumo- 

 cocci. If the search proves unsuccessful, one may turn to other 

 postulated types of antibodies (e.g., anti-endotoxins or anti- 

 aggressins), the existence of which is still a matter of contro- 

 versy ; something may be found in them which yields the desired 

 clue ; or an entirely new kind of antibody may be discovered. 



In this search for a new biological factor, it is often assumed 

 that the new antibody, when its existence is demonstrated, will 

 be a special substance, probably of complex chemical and colloidal 

 constitution, and that this " antibody complex " will differ 



