68
BACTERIOLOGY
[pathological
these bodies, its serum acquires the power of dissolving them. Ehrlich and Morgenroth have shown in the case of red corpuscles that the immune body (specially developed) combines directly with the red corpuscles, and also effects a loose combination with the ferment-like substance, normally present, which he calls “ addiment ” or “ complement.” The development of the immune body with specific combining affinity thus presents an analogy to antitoxin production, the difference being that in lysogenesis another substance is necessary to complete the process. Another property which may be possessed by an antibacterial serum is that of agglutination. By this is meant the aggregation into clumps of the bacteria uniformly distributed in an indifferent fluid; if ination. the bacterium is motile its movement is arrested during the process. The process is of course observed by means of the microscope, but the clumps soon settle in the fluid and ultimately form a sediment, leaving the upper part clear. This change, visible to the naked eye, is called sedimentation. Charrin and Boger first showed in the case of B. jryocyaneus that when a small quantity of the homologous serum (i.e., the serum of an animal immunized against the bacterium) was added to a fluid culture of this bacillus, growth formed a sediment instead of a uniform turbidity. Gruber and Durham showed that sedimentation occurred when a small quantity of the homologous serum was added to an emulsion of the bacterium in a small test-tube, and found that this obtained in all cases where Pfeiffer’s lysogenic action could be demonstrated. Shortly afterwards Widal, and also Griinbaum, showed that the serum of patients suffering succession, the object being to arrive ultimately at a high from typhoid fever, even at an early stage of the disease, dosage, though the details vary in different instances. The agglutinated the typhoid bacillus—a fact which laid the serum of an animal thus actively immunized has powerful foundation of serum diagnosis. A similar phenomenon has protective properties towards another animal, the amount been demonstrated in the case of Malta fever, cholera, necessary for protection being sometimes almost incon- plague, infection with B. coli, “ meat-poisoning ” due to ceivably small. As a rule it has no action on the corre- Gartner’s bacillus, and some other diseases. As regards the sponding toxin, i.e.y is not antitoxic. In addition to the mode of action of agglutinins, Gruber and Durham consider protective action, such a serum may possess properties that it consists in a change in the envelopes of the bacteria, which evidence themselves by producing physical change by which they swell up and become adhesive. This view in the bacterium in question. The first of these has various facts in its support, but Kruse and Nicolle have Ly^genic -s t|ie lysogenic action, which consists in the found that if a bacterial culture be filtered germ-free, an production of a change in the corresponding agglutinating serum still produces some change in it, so bacterium whereby it becomes granular, swells up, and that particles suspended in it become gathered into clumps. ultimately may undergo dissolution. Pfeiffer was the first Duclaux, for this reason, considers that agglutinins are to show that this occurred when the bacterium was coagulative ferments. At present it is not possible to injected into the peritoneal cavity of the animal immunized speak definitely on this question. Of more importance, against it, and also when a little of the serum of such an however, is the relation of agglutinative to protective animal was injected with the bacterium into the peritoneum power. On the other hand a protective serum has not of a fresh, i.e., non-immunized animal. Metchnikoff and always agglutinative action, and the early appearance of Bordet subsequently devised means by which a similar the latter property in the serum, in a disease such as change could be produced in vitro, and analysed the con- typhoid fever, has been considered by some to show that ditions necessary for its occurrence. It has been com- the two properties have no relation to one another. This pletely established that in this phenomenon of lysogenesis conclusion is not justified, as we must suppose that the there are two substances concerned, one specially developed process of immunization begins to be developed at an or developed in excess, and the other present in normal early period in the disease, that it gradually increases, and serum. The former (Immunhorper of Ehrlich, substance ultimately results in cure. It is also doubtful whether a sensibilisatrice of Bordet) is the more stable, resisting a serum with high agglutinating power has been obtained temperature of 60° C., and though giving the specific without possessing protective properties at the same time. character to the reaction cannot act alone. The latter is As regards resistance to heat, agglutinins cannot be ferment-like and much more labile than the former, being separated from protective substances. It should also be readily destroyed at 60° C. It may be added that the stated that agglutinins are used up in the process of protective power is not lost by exposure to the temperature agglutination, apparently combining with some element of mentioned, this apparently depending upon the immune the bacterial structure. In view of all the facts it must be body. Furthermore, lysogenic action is not confined to admitted that the agglutinins and protective bodies are the case of bacteria, but obtains also with other organized the result of corresponding reactive processes, and are probstructures, e.(j., red corpuscles [Boidet, Ehilich and ably related to one another. It may be that some Morgenroth), leucocytes and spermatozoa (Metchnikoff). protective substances, but not all, are agglutinins, oi it That5 is to say, if an animal be treated with injections of I may be that the two are distinct. In the latter case they
though not yet absolutely established, certainly affords the most satisfactory explanation of antitoxin production. In support of it there is the remarkable fact, discovered by Wassermann and Takaki in the case of tetanus, that there do exist in the nervous system molecules with combining affinity for the tetanus toxin. If, for example, the brain and spinal cord removed from an animal be bruised and brought into contact with tetanus toxin, a certain amount of the toxicity disappears, as shown by injecting the mixture into another animal. Further, these molecules in the nervous system present the same susceptibility to heat and other physical agencies as does tetanus antitoxin. There is therefore strong evidence that antitoxin molecules do exist as part of the living substance of nerve cells. In other diseases the evidence obtained is less definite, but in them the toxic action is less limited to a particular tissue. It has, however, been found that the serum of various animals has a certain amount of antitoxic action, and thus the basis for antitoxin production, according to Ehrlich’s theory, is afforded. The theory also supplies the explanation of the power which an animal supplies of producing various antitoxins, since this depends ultimately upon susceptibility to toxic action. The explanation is thus carried back to the complicated constitution of biogen molecules in various living cells of the body. In preparing anti-bacterial sera the lines of procedure correspond to those followed in the case of antitoxins, but the bacteria themselves in the living or dead Anticondition are always used in the injections. bacterial gometimes dead bacteria, living virulent bacteria, serum. an(j living supervirulent bacteria, are used in
