The Fundamentals of Bacteriology

by Charles Bradfield Morrey

COMPLEMENTS.

As to whether complements are numerous, as Ehrlich claims, or there is only one complement, according to Buchner and others, need not be discussed here. In the practical applications given later as means of diagnosis it is apparent that all the complement or complements are capable of uniting with at least two kinds of amboceptors.

If complement be injected into an animal it may act as an antigen and give rise to the formation of anticomplement which may combine with it and prevent its action and is consequently analogous to antitoxin. If amboceptors as antigen are injected into an animal there will be formed by the animal’s cells antiamboceptors. As one would expect, there are two kinds of antiamboceptors, one for each of its combining groups, since it has been stated that it is always the combining group of any given antigen that acts as the cell stimulus. Hence we may have an “anticytophil amboceptor” or an “anticomplementophil amboceptor.” These antiamboceptors and the anticomplements are analogous to antitoxin, antiagglutinin, etc., and hence are receptors of the first order.

ANTISNAKE VENOMS.

A practical use of antiamboceptors is in antisnake venoms. Snake poisons appear to contain only amboceptors for different cells of the body. In the most deadly the amboceptor is specific for nerve cells (cobra), in others for red corpuscles, or for endothelial cells of the bloodvessels (rattlesnake). The complement is furnished by the blood of the individual bitten, that is, in a sense the individual poisons himself, since he furnishes the destroying element. The antisera contain antiamboceptors which unite with the amboceptor introduced and prevent it joining to cells and thus binding the complement to the cells and destroying them. With this exception these antibodies are chiefly of theoretical interest.

FAILURE OF CYTOLYTIC SERUMS.

The discovery of the possibility of producing a strongly bactericidal serum in the manner above described aroused the hope that such sera would prove of great value in passive immunization and serum treatment of bacterial diseases. Unfortunately such expectations have not been realized and no serum of this character of much practical importance has been developed as yet (with the possible exception of Flexner’s antimeningococcus serum in human practice. What hog cholera serum is remains to be discovered).

The reasons for the failure of such sera are not entirely clear. The following are some that have been offered: (1) Amboceptors do not appear to be present in very large amount so that relatively large injections of blood are necessary, which is not without risk in itself. (2) Since the complement is furnished by the blood of the animal to be treated, there may not be enough of this to unite with a sufficient quantity of amboceptor to destroy all the bacteria present, hence the disease is continued by those that escape. (3) Or the complement may not be of the right kind to unite with the amboceptor introduced, since this is derived from the blood of a heterologous (“other kind”) species. In hog-cholera serum, if it is bactericidal, this difficulty is removed by using blood of a homologous (“same kind”) animal. Hence Ehrlich suggested the use of apes for preparing bactericidal sera for human beings. The good results which have been reported in the treatment of human beings with the serum of persons convalescing from the same disease indicate that this lack of proper complement for the given amboceptor is probably a chief factor in the failure of sera from lower animals. (4) The bacteria may be localized in tissues (lymph glands), within cavities (cranial, peritoneal), in hollow organs (alimentary tract), etc., so that it is not possible to get at them with sufficient serum to destroy all. This difficulty is obviated by injecting directly into the spinal canal when Flexner’s antimeningococcus serum is used. (5) Even if the bacteria are dissolved it does not necessarily follow that their endotoxins are destroyed. These may be merely liberated and add to the danger of the patient, though this does not appear to be a valid objection. (6) Complement which is present in such a large excess of amboceptor may just as well unite with amboceptor which is not united to the bacteria to be destroyed as with that which is, and hence be actually prevented from dissolving the bacteria. Therefore it is difficult to standardize the serum to get a proper amount of amboceptor for the complement present.

COMPLEMENT-FIXATION TEST.

Although little practical use has been made of bactericidal sera, the discovery of receptors of this class and the peculiar relations between the antigen, amboceptor and complement have resulted in developing one of the most delicate and accurate methods for the diagnosis of disease and for the recognition of small amounts of specific protein that is in use today.