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1. Sera from individuals acutely ill with lobar pneumonia possess the capacity to precipitate in high titre a non-protein somatic fraction derived from pneumococci (Fraction C). Following crisis the reaction is no longer demonstrable. 2. Sera obtained from cases of pneumococcus pneumonia during illness and convalescence have been tested for antibodies specifically reactive with three chemically distinct constituents of Pneumococcus. The results, when correlated with the course of disease, demonstrate differences in the occurrence of each qualitatively distinct antibody. 3. The precipitation of pneumococcus Fraction C is not limited to the sera of individuals ill with pneumococcus infection. But in the few other cases available for comparative tests, definite reactions have been obtained only in streptococcus and staphylococcus infections and in acute rheumatic fever.

THE OBSERVATIONS RECORDED IN THIS PAPER ON THE INFECTIVITY OF TYPE III PNEUMOCOCCI FOR RABBITS MAY BE SUMMARIZED AS FOLLOWS: 1. Of eleven strains of Type III isolated from human sources, ten were found to possess low virulence for rabbits. This was true despite the fact that all the strains tested possessed large capsules and a high degree of virulence for mice. 2. One strain of Type III pneumococcus was rendered highly virulent for rabbits. Since it possessed no other biological property demonstrably different from the other strains, its virulence must reside in some additional property. 3. An initial decrease in the number of circulating organisms following the injection of virulent bacteria is a well known occurrence, and it was observed in rabbits injected with the rabbit virulent strain of Type III. However, the extent of the reduction was in inverse proportion to the degree of virulence of the strain; a fact which makes mechanical explanations of the phenomenon insufficient. 4. The bacteremia produced in rabbits by Type III pneumococci, avirulent for this species, runs a characteristic course. It differs from that produced by non-encapsulated R forms of pneumococci although in both instances survival of the infected animal ensues. This is evidence that the mechanism of resistance against encapsulated and non-encapsulated pneumococci is not identical. 5. Phagocytosis of Type III pneumococci by circulating rabbit leucocytes was not demonstrable by a vital stain technique, whereas under the same conditions the ingestion of non-encapsulated R forms occurred. This is further evidence that the process whereby non-encapsulated pneumococci are disposed of, is insufficient to explain the natural resistance of rabbits to infection with encapsulated Type III pneumococci.

1. Guinea pigs passively sensitized with the serum of rabbits immunized with an artificially prepared sugar-protein (gluco-globulin) exhibit typical anaphylactic shock when subsequently inoculated with gluco-albumin; the serum of rabbits immunized with a second synthetic sugar-protein (galacto-globulin) similarly sensitizes guinea pigs to galacto-albumin. The reactions, in each instance, are specific and depend for their specificity on the carbohydrate component, and not on the protein fraction of the synthesized sugar-protein. 2. Guinea pigs actively sensitized with gluco-globulin or galacto-globulin are similarly subject to anaphylactic shock, when injected, after 21 days, with sugar-proteins containing carbohydrate identical with that present in the sensitizing antigen, regardless of the kind of protein with which it is combined. 3. The unconjugated glucosides, although themselves not capable of inducing shock, inhibit the anaphylactic reaction when injected immediately prior to the introduction of the toxigenic sugar-protein. The protective action of the glucosides disappears within two hours after injection. In order to elicit the phenomenon, the carbohydrate must be the same as that combined in the sugar-protein complex. 4. Anaphylactic shock may be induced by uncombined globulin in guinea pigs passively sensitized with either antigluco-globulin serum or antigalacto-globulin serum; globulin is similarly effective in animals actively sensitized with gluco-globulin or galacto-globulin. The reactions elicited by globulin alone are dependent upon the common protein present in the antigens, and exhibit only species specificity.

Small areas of skin infiltrated with immune serum proved refractory to the injurious action of a filterable rabbit virus inoculated 24 to 48 hours later. Infiltrations of normal serum did not appreciably protect the skin against the virus. The local protection afforded by the infiltrations of immune serum appears to constitute an example of local passive immunity. Small areas of skin infiltrated with either normal serum or meat infusion broth proved more refractory than normal skin to infection with hemolytic streptococci inoculated 24 hours later. The refractory state induced in the tissues was non-specific in character. A greater amount of local protection against hemolytic streptococci was afforded by infiltrations with a homologous immune serum than by infiltrations with normal serum. The difference in the amount of protection afforded by immune serum over that induced by normal serum may be thought of as representative of the degree of local passive immunity conferred.

The majority of patients convalescent from pneumonia due to Types I, II and III Pneumococcus develop at the time of recovery circulating antibodies for the homologous type of organisms. At the same time an immediate wheal and erythema reaction followed the intradermal injection of the homologous type-specific polysaccharide in 100 per cent of Type I patients, 58.8 per cent of Type II patients, and 44 per cent of Type III patients. In a group of 18 patients repeatedly tested with the type-specific polysaccharides, 10 developed in the second or third week of convalescence circulating antibodies for one or more heterologous types. In none of 21 control patients was this phenomenon observed. It is suggested that the development of circulating antibodies for heterologous types of Pneumococcus was associated with the previous intradermal injections of the type-specific polysaccharides.

The injection of the type-specific capsular polysaccharides of Pneumococcus Types I, II and III into the skin of rabbits, actively or passively immunized to one of these types of Pneumococcus, elicits a type-specific cutaneous reaction. The form of reaction resembles that described by Arthus. The reaction is produced only when type-specific precipitins for the homologous polysaccharide are demonstrable in the blood of the rabbit. In 84 per cent of actively immunized rabbits, the serum of which contained type-specific precipitins, a reaction was elicited. A positive result was obtained in 100 per cent of rabbits passively immunized with antipneumococcus horse serum whereas, attempts passively to transfer reactivity from immune rabbit to normal rabbit were unsuccessful. The recipients, in the latter group, possessed no demonstrable circulating type-specific precipitins. The reaction produced by specific capsular carbohydrates is always associated with a well grounded type-specific immunity. A brief summary of the relation of hypersensitiveness and immunity to pneumococcus is given.

Although sera derived from patients at the time of acute, active infection were found to be capable of destroying hemolytic streptococci under aerobic conditions, the organisms retained viability when the tests were performed in the environment of anaerobiosis afforded by a vaseline seal or an anaerobic jar. Within the limitations of the experimental procedures which were employed, the aerobic or anaerobic effect was found to be a reversible reaction. Heating sera at 60 degrees C. for 1 hour inactivated the streptococcidal element in most instances, but not in every case; heating at 56 degrees C. for 1 hour impaired the killing power of half of the specimens which were tested. Sera retained the capacity to destroy hemolytic streptococci when kept in the ice box for 3 weeks; a slight diminution in killing power was noted after 4 weeks. By the methods which were employed, the streptococcidal property of sera could not be correlated with either true antibacterial agglutination or with pseudo-agglutination. The significance of the findings as a basis for analyzing the mechanism of the streptococcidal phenomenon is discussed.

THE ACTIVE FIBRINOLYTIC PRINCIPLE PRESENT IN CULTURES OF HEMOLYTIC STREPTOCOCCI CAN BE ISOLATED IN STABLE FORM, AND PARTIALLY PURIFIED BY THE FOLLOWING METHODS: 1. Precipitation of culture filtrate with 3 volumes of 95 per cent ethyl alcohol. 2. Adsorption upon polyaluminum hydroxide B of Willstätter (5) followed by elution with M/10 sodium phosphate buffer, pH 7.3. Concentration can be best accomplished by vacuum dialysis (4) of either culture filtrates or preparations obtained by adsorption and elution. The streptococcal fibrinolysin is characterized by the following properties: 1. It may resist heating to 100 degrees C. for 60 minutes; variations in thermal resistance are described. 2. Partially purified preparations give positive tests for protein. Activity is rapidly and completely destroyed by trypsin or papain. 3. The active principle is demonstrable in dissolved fibrin even after 18 hours incubation.

The fibrinolysin of hemolytic streptococci exerts no hydrolytic action upon casein, gelatin, or peptone. The action on solid human fibrin is characterized by a small and gradual increase in the amino nitrogen content of the solution. The specific and special enzymatic action of fibrinolysin is contrasted with trypsin and with streptococcal peptase (4). Solutions of human fibrinogen, after brief incubation with fibrinolysin, lose the capacity to form fibrin. Solutions of rabbit fibrinogen, on the other hand, retain the property of transformation into fibrin, even after prolonged exposure to fibrinolysin. Qualitative tests, with solutions resulting from the action of streptococcal fibrinolysin on human fibrin, indicate that the end-product may be protein and that the degradation of the molecule is not great.