THE NATURE OF COMPLEMENT 229 



plement. And it should be noted that this insusceptibility is not due to any 

 failure of the sensitized cell to combine with complement (see Buxton 1905a, h, c, 

 Muir and Browning 1909). 



The Nature of Complement. 



We have seen that complement is a non-specific substance present in all normal 

 sera, and not increased in amount as the result of immunization. It does not 

 follow that complement is a single substance, or a single system. Different kinds 

 of antibodies, for instance the antibodies acting on different species of red cells, 

 might require different kinds of complement, all, or many of which, might be 

 present in any specimen of normal serum. ■ This question may be analysed into 

 at least three components. (1) As regards one kind of lysis, for instance that of 

 red cells, is the complement present in a given specimen of serum a single entity, 

 or are there separate complements corresponding to the different hsomolytic anti- 

 bodies ? (2) If only one kind of complement is concerned in haemolysis, is it the 

 same, or a different complement, which brings about the lysis of bacteria, or of 

 other organized cells 1 (3) If the complement in a given specimen of serum is one 

 and the same, irrespective of the kind of cells which are lysed, or of the particular 

 antibodies which are sensitizing them, is the complement in different sera, and 

 particularly in sera from different animal species, always the same 1 



This problem afforded one of the most closely debated points in the long con- 

 troversy between Ehrlich and Bordct, and the question has been investigated 

 by many other workers. Space does not allow us to reproduce the arguments 

 employed, nor the experimental evidence on which these arguments were based. 

 For this reference is best made to the original papers, which contain interesting 

 examples of the complexity of the hypothetical receptor-apparatus employed by 

 Ehrlich to describe his experimental results. The provisional answers to these 

 questions which are, in our view, afforded by the available evidence, are as follows : 



There is no evidence that more than one kind of complement is concerned in 

 haemolysis. 



The evidence strongly suggests that the complement, in a given serum, which 

 causes lysis of one type of cell, for instance the red cell, is identical with that 

 which causes lysis of another type of cell, for instance a bacterium. 



It is clear that sera derived from different animal species show qualitative 

 differences in their complementary activities ; and the available evidence indicates 

 that the differences are due to both qualitative and quantitative variations in the 

 components of the complement concerned. 



Accepting the view that there is little, if any, evidence in favour of the existence 

 of a multiplicity of complements in the sense employed above, it remains to inquire 

 whether complement is a single chemical substance, or is a name for a property 

 of normal serum that is dependent on a number of different factors. Here the 

 answer is not in doubt. The complementary action of fresh, unheated serum 

 depends on the interaction of a number of separate components, of which there 

 appear to be four. 



Complement becomes inactive if the euglobulins are precipitated by removal 

 of electrolytes. The remaining fluid is inactive. If the precipitate is removed, 

 and dissolved in saline, it also is inactive, but a mixture of the two fluids will 

 cause haemolysis of sensitized red cells (Ferrata 1907, Brand 1907, Liefmann 

 1909, Skwirsky 1910, Amako 1911, Gengou 1911.) The "globulin" fraction is 

 known as " mid-piece," and the soluble albumin fraction as " end-piece," because 



