of Pfeiffer that there is an essential difference between the agglutinating and the specific bactericidal materials. 1. There are sera which in definite dilutions no longer agglutinate, but yet act as bactericides in the peritoneal cavity (R. Pfeiffer, Deutsch. med. Wochenschr., 1898, No. 31, 489). 2. Often an immune serum, from which all agglutinins have been abstracted by long luxuriant growth of the inoculated bacteria, which after sixteen hours are no longer paralyzed (which, therefore, is devoid of all agglutination), is still active in the peritoneal cavity. The observations may, however, be in part explained by the discovery of Emmerich and Löw, that in the abdominal cavity the action of immune sera is very much increased by the lack of oxygen (see p. 110). The action of agglutinin and specific bactericidal substances is, like that of antitoxin, in a great measure specific. For the bactericidal action R. Pfeiffer has maintained absolute specificity; also other authors, as Dunbar, Sobernheim, Löffler, and Abel, arrived at results that speak very much in favor of specificity (compare typhoid, cholera, etc.). The agglutination phenomenon has been studied by very many investigators, and the standpoint taken by its discoverers has been confirmed as entirely correct. The action of immune sera is strongest upon the variety against which the immunity has been produced; less, but similar, against related varieties (only in high concentration); and fails with varieties that are not related. Thus, for example, a serum from an animal which was immunized against the Bact. typhi was active in a dilution of upon Bact. typhi, and upon Bact. coli at It is evident that this property can be of diagnostic value. 1. If we have serum from an animal which is immunized against true Bact. typhi, then it is employed to identify doubtful bacteria as typhoid bacteria, if the serum dilution of acts distinctly upon the bacteria to be diagnosticated, but not upon related bacteria; for example, Bact. coli. 2. If one has undoubted typhoid bacteria, one can as certain whether a man has had (Gruber and Durham) or still has (Vidal) typhoid fever, if it is demonstrated that the serum from a blood specimen in a dilution of causes marked agglutination of true typhoid bacilli, while it is without effect upon closely related organisms (Bact. coli). (For further details see special part.) In conclusion, we may say that the essential separation of immunity into antitoxic and bactericidal appears today to be entirely warranted, but that in a series of cases it is established that not infrequently antitoxic and bactericidal immunity are both present. Brief reference was made above to the fact that strong diphtheria antitoxin has also some bactericidal action (van de Velde). Wassermann found that an animal protected against pyocyaneum poison also tolerates the virulent Bact. pyocyaneum in large doses, and other similar experiences are contained in the literature (compare under Cholera). APPENDIX. According to investigations by Emmerich and Löw which have just appeared (end of May, 1899) (Z. H. xxxi, 1), the whole doctrine of the bactericidal action of the body fluids and the immunity depending thereon appears in a surprisingly altered light. In every old culture of bacteria, according to the authors, there are found bacteriolytic, remarkably heatresisting enzymes-i. e., ferments, which are able to dissolve and kill bacteria, especially old cells. Agglutination is only the first stage of the solution and depends, as Gruher held, upon a swelling of the external membrane. Thus, in old cultures there is always a sort of agglutination, and then a dying out of the bacterial cells occurs. The enzymes are usually only slightly specific; the pyocy aneum enzyme (pyocyanase) is, for example, active against anthrax. They operate much better if oxygen is excluded than in its presence. Also, certain bacterial poisons-for example, diphtheria toxins-are destroyed by the pyocy aneum enzyme. If an old culture or its "metabolic products" are introduced into the body of animals, within them there occurs a union of the zymase with the body albumin—immunproteïdin (Emmerich). These immunproteïdins have the same solvent action upon bacteria as the bacteriolytic enzymes, but are more durable and, above all, more capable of persisting in the blood. At least in some infectious diseases the immunproteïdins can be produced synthetically in vitro instead of in the animal body, and thus, according to Emmerich and Löw, materials may be produced rapidly and cheaply which possess very high immunizing power. The immunproteïdins operate also much more strongly anaerobically than aerobically. The difference between the Gruber-Durham reaction (agglutination without death) and the R. Pfeiffer reaction (death in the abdominal cavity) is essentially dependent upon the following: In the peritoneal cavity a scarcity of oxygen prevails and the peristalsis mechanically disturbs the agglutination; also, Emmerich and Löw find the bactericidal action of normal blood to be dependent upon enzymes. This mass of observations, which are most worthy of notice, is not to be overlooked to-day, although there has been no opportunity for substantiating them. If they prove true, they render an essential revision of the whole question of immunity necessary. Summarized presentations regarding immunity or of the greater part of the subject are: Buchner, H., Schutzimpfung, etc., in "Handbuch der Therapie," Jena, 1897. Metschnikoff, "Immunität," Jena, 1897. Trumpp, A. H. XXXIII, 70. Dieudonné, "Experimentelle und kritische Beiträge zur Kenntnis deragglutinieren den Stoffe, etc." Habilitationsschrift. Würzburg, 1898. Dieudonné, "Schutzimpfung und Serumtherapie." Leipzig, zweite Aufl., 1899. |