IMMUNOLOGICAL REACTIONS OF PNEUMONIC PLEURAL FLUIDS

Pleuritic exudates from patients with lobar pneumonia may be sterile or infected. Sterile fluids, at or about the time of crisis, contain actively acquired antibodies similar to those in the blood serum. Infected fluids do not contain such antibodies, presumably because of the presence in them of large amounts of soluble specific substance. Sterile fluids from patients treated with immune sera have both horse serum and antibodies similar to those injected. Infected fluids from serum-treated cases contain horse serum and such heterologous antibodies as were contained in the therapeutic sera together with homologous soluble specific substance. The concentration of horse serum and antibodies in pneumonic fluids is usually the same or somewhat less than that of the corresponding blood sera

ANTIPNEUMOCOCCIC IMMUNITY REACTIONS IN INDIVIDUALS OF DIFFERENT AGES

1. The incidence of pneumococcidal power of the whole defibrinated blood in human beings has been shown to vary with age. The age distribution of other type-specific antibodies varies similarly, insofar as they are frequent enough to be compared or technically demonstrable. 2. The incidence of pneumococcidal power of the whole defibrinated blood for Type I, Type II, and Type III differs. Type I is the rarest, Type II is the most frequent, and Type III is of intermediate frequency. The type-specific antibodies responsible for the other tests employed show a similar relative frequency in regard to Types I and II, but some variation in regard to Type III. 3. The skin reactions to the acetic acid-predpitable proteins and autolysates of the pneumococci are negative or rarely positive in infants, infrequently positive in childhood, and positive in a high percentage of adults

SPECIFIC CUTANEOUS REACTIONS AND CIRCULATING ANTIBODIES IN THE COURSE OF LOBAR PNEUMONIA : II. CASES TREATED WITH ANTIPNEUMOCOCCIC SERA

1. Characteristic cutaneous responses to the type-specific protein-free carbohydrates of both Type I and Type II pneumococci have been "produced" in cases of lobar pneumonia due to either of these types by the intravenous injection of concentrated bivalent (Types I and II) antipneumococcic sera (Felton). 2. A positive cutaneous response to the specific polysaccharide of Type II pneumococci has been passively transferred from human cases convalescing from this infection to a patient suffering from pneumonia due to this organism. 3. The cutaneous responses to the type-specific polysaccharides and circulating antibodies were studied in 51 cases of lobar pneumonia. Positive cutaneous reactions were, in most instances, associated with recovery, even when purulent complications were present. Failure to elicit a positive reaction was usually followed by a fatal outcome. 4. The positive reactions in patients who were treated with concentrated sera and recovered were most often elicited within 24 hours after the first dose and after a total of 40 cc. had been given. 5. The positive skin reactions obtained after the administration of specific antisera were associated with the presence of mouse protective antibodies and agglutinins in the sera of the patients. 6. The immune reactions in serum treated cases receiving repeated inoculations with the specific carbohydrates disappeared more rapidly than in similar cases receiving no antiserum. It is suggested that the administration of antisera in someway interferes with the production of antibodies by the intracutaneously injected carbohydrates

SPECIFIC CUTANEOUS REACTIONS AND CIRCULATING ANTIBODIES IN THE COURSE OF LOBAR PNEUMONIA : I. CASES RECEIVING NO SERUM THERAPY

1. A group of 41 non-serum treated patients with Type I, II or III pneumococcus pneumonia were studied during their disease and convalescence with respect to their skin reactions to specific pneumococcus polysaccharides and, in most instances, for the presence of circulating agglutinins and protective antibodies for all these 3 types. 2. One-half of the Type I and two-thirds of the Type II and Type III recovered cases gave the typical immediate "wheal and erythema" response to the homologous polysaccharide at or about the time of recovery. All cases tested showed protective antibodies and almost all showed agglutinins for the homologous pneumococcus. In the fatal cases, in general, positive cutaneous reactions and circulating antibodies were not obtained. 3. In cases of pneumonia receiving repeated cutaneous inoculations with various types of specific polysaccharide, antibodies for pneumococci differing from the infecting type but corresponding to the types of carbohydrate injected were present 1 week or later after such injections. These heterologous antibodies were most frequently demonstrated for Type II and were probably the result of immunization by means of the cutaneous injections. 4. Positive skin responses to homologous polysaccharides and corresponding circulating antibodies were demonstrated with similar frequency in the first 3 weeks after crisis in patients who had not previously received intracutaneous injections. In such patients heterologous antibodies were rarely found. 5. Typical skin reactions with the specific pneumococcus polysaccharides and mouse protective antibodies were demonstrated independently in a number of hospital patients who had had no recent history of pneumonia. 6. Some patients with demonstrable foci of persistent infection or with latent infections which later proved fatal showed positive cutaneous responses to the homologous type polysaccharide and circulating specific antibodies for the corresponding type. 7. The agglutination test, though less sensitive than the mouse protection test for determining the presence of antibody, has many advantages over the latter and is simplest to use in following the course of the untreated pneumonia

IMMUNITY REACTIONS OF HUMAN SUBJECTS TO STRAINS OF PNEUMOCOCCI OTHER THAN TYPES I, II AND III

1. A group of 72 human subjects were studied with respect to the immune reactions of their blood and sera to Types I, II and III pneumococci and to 4 other types (V, VI, VIII and IX) previously included in Group IV. 2. The same general relationships were observed for all of these types as were previously demonstrated for Types I, II and III. Each type was specific in relation to the bactericidal action of normal human blood and the protective action of normal human serum. 3. The frequency with which pneumococcidal action for any pair of types was present for both or absent for both in the same blood samples was slightly greater than that calculated from the frequencies with which each of the types was killed separately. 4. No closer correlation could be demonstrated between the reaction of the blood of these subjects to Types II and V or between Types III and VIII pneumococci, types related in their reaction with artificially prepared immune sera, than was observed between unrelated strains

SPECIFIC ANTIBODY RESPONSE OF HUMAN SUBJECTS TO INTRACUTANEOUS INJECTION OF PNEUMOCOCCUS PRODUCTS

The blood of 63 human subjects selected because of the absence of recent infections, was studied for its content of specific antibodies against virulent strains of Types I, II, and III pneumococci before and after intracutaneous injections of minute amounts of pneumococcus products. The simultaneous injection of the specific polysaccharides of all three types of pneumococci and of proteins and autolysates derived from Types I and II pneumococci was followed by the appearance or increase of pneumococcidal power in the whole defibrinated blood and, in most instances, by the appearance of mouse-protective antibodies and agglutinins for one or more types. A single intracutaneous injection of 0.01 mg. of the protein-free type-specific polysaccharide of either Type I, Type II, or Type III pneumococci or 4 similar daily injections was followed, in most of 29 subjects, by the appearance of antibodies against the homologous, but not against the heterologous type pneumococci. Some subjects showed a simultaneous lowering of a preexisting pneumococcidal power for heterologous or homologous types. A single intracutaneous injection of O.1 mg. of pneumococcus protein in 13 individuals was not followed by the appearance of specific antibodies to any appreciable degree. Single intracutaneous injections of small amounts of autolysates derived from virulent strains of Type I, II, or III pneumococci were followed in 11 subjects by a more or less general rise in the pneumococcidal power with the appearance of homologous type agglutinins and protective antibodies in about one-third of the subjects

AGE AND SUSCEPTIBILITY OF MICE TO COXSACKIE A VIRUSES

Mice varying in age from 1 day to 8 months were inoculated intraperitoneally with Coxsackie A virus, type 9 and studies were made of the quantity of virus in striated muscle and myocardium, the presence of neutralizing antibody in the serum, and the pathological changes in the tissues. The hind limbs of young (1- to 20-day-old) mice yielded high titers of virus and showed diffuse myositis, whereas only low yields of virus and focal myositis were obtained in older mice. In the 20-day-old mice the skeletal lesions were not accompanied by manifest symptoms and histologically showed evidence of regeneration progressing from the 3rd to the 11th day after inoculation. Older mice showed no symptoms and only focal myositis and low yields of virus were found in their hind limbs. Coxsackie A9 virus replicated to relatively low titers in the hearts of young (1- to 40-day-old) mice without producing any demonstrable lesions whereas frank myocarditis with high yields of virus were demonstrated in mice infected at 8 months of age. The data suggest that at least for the 2 strains used, the adult mouse should be considered susceptible to subclinical infection with Coxsackie A9 virus. Neither subclinical infection, nor antibody formation was demonstrable in young adult mice inoculated with a strain of Coxsackie A4 virus

THE EFFECT OF ADRENAL STEROIDS, CORTICOTROPIN, AND GROWTH HORMONE ON RESISTANCE TO EXPERIMENTAL INFECTIONS

Cortisone acetate, hydrocortisone, and hydrocortisone acetate depress the resistance of mice to pneumococcal and influenza viral infections, although hydrocortisone acetate is somewhat less effective than the free alcohol, when given subcutaneously. Pituitary adrenocorticotropin, even in highly purified form and in oil and beeswax, does not significantly alter the resistance of mice to these experimental infections, even when given in doses which may cause profound eosinopenia, lymphopenia, and weight loss, and which are at the limit of tolerance of the animals. Corticosterone depresses resistance to pneumococcal infections significantly, but fails to alter resistance to influenza viral infections. The findings suggest that murine adrenals may produce one of the known adrenal steroids such as corticosterone along with another steroid, or may produce a steroid other than cortisone, hydrocortisone, or corticosterone. When resistance is decreased by adrenal steroids, survival time is invariably shortened, and the effect of the steroid hormones is frequently demonstrable within the 1st day after infection with pneumococci, making it unlikely that the depression of resistance that is seen is primarily due to depression of antibody formation. A single dose of 5 mg. of cortisone may cause depression of resistance and may decrease the survival time for 3 to 6 days afterward. Growth hormone (somatotropic hormone) in highly purified form, and in the doses used, did not overcome the weight loss induced by cortisone, but the animals treated with growth hormone and cortisone regained their lost weight more rapidly than those receiving cortisone alone. Growth hormone alone caused a slight increase in the rate of gain in weight over controls. Growth hormone alone did not increase resistance to infection, and did not increase the survival time, in mice infected with either pneumococci or influenza virus. Growth hormone in various dosages failed to overcome the effect of cortisone in depressing resistance to these infections. Cortisone, hydrocortisone, corticosterone, and corticotropin did not alter significantly the titers of influenza virus attained in the murine lungs during the first 2 days after infection, but cortisone and hydrocortisone markedly delayed the rate at which virus titers declined during the subsequent 6 days. Corticosterone and corticotropin delayed the rate at which the titers declined but slightly, and growth hormone had no apparent effect, as compared with controls. Growth hormone did not overcome the effect of cortisone and hydrocortisone on viral titers. No detectable antibody was found as late as 6 days after infection, in controls or in hormone-treated animals

EFFECTS OF CORTICOSTERONE, HYDROCORTISONE, AND CORTICOTROPIN ON PRODUCTION OF ANTIBODIES IN RABBITS

The effects of hydrocortisone, corticosterone, and pituitary adrenocorticotropin on antibody production were studied immunochemically in rabbits. Hydrocortisone in doses as low as 2.5 mg. per day (approximately 1.0 mg. per kg. per day) markedly depressed antibody production whereas corticosterone in doses four times as large exerted no significant effect. Corticotropin in doses of 15 units daily exerted an effect similar to that of corticosterone, but its effect was more like that of hydrocortisone when given in doses twice as great. This finding is in agreement with observations that the prolonged administration of corticotropin in sufficient dosage leads to increased output of hydrocortisone by the adrenal cortex of the rabbit. Corticosterone did not antagonize the effect of hydrocortisone on antibody production, but seemed to act additively with it. Although each of the hormones tested induced some adverse effect on nitrogen balance as measured by the weights of the animals, and hydrocortisone induced the more striking decreases in weight, there was no direct correlation between the effects of these hormones on antibody production and their effects on weight