Antipneumococcus Serum Research Articles

Inhibition of Immune Phagocytosis of Diplococcus Pneumoniae by Human Neutrophiles with Antibody against Complement

Summary Treatment of normal human blood with rabbit antibody against human complement completely blocks the phagocytosis by the neutrophiles of Diplococcus pneumoniae in the presence of its type-specific antibody. The effect is observed whether the incubation period of blood with organisms is as short as 15 min or as long as 4 hr. The addition of fresh, untreated serum to cells from treated blood does not reverse the inhibition, nor does the addition of fresh complement-containing serum in amounts 4 times that of the original serum present. Bactericidal studies indicate that antipneumococcal serum is capable of the destruction of the organism even when the complement is inactivated by anticomplement and the phagocytes appear to be inactive.

Immunochemical Studies on Cross-Reactions of Antipneumococcal Sera

Summary A series of dextran fractions of graded molecular weight cross-react with a horse and a rabbit type II antipneumococcal serum. The lower molecular weight fractions precipitate less anti-SII than do the higher molecular weight fractions and none of the fractions removes as much antibody N as does the native dextran from which they were derived. Quantitative inhibition studies with oligosaccharides of the cross-reaction of the lowest molecular weight dextran fraction with horse anti-SII showed that an upper limit in inhibiting power was reached with isomaltopentaose, as had been found for the cross-reaction of this antiserum with native dextran.

Immunochemical Studies on Cross-Reactions of Antipneumococcal Sera

Summary A variety of dextrans cross-react with Types IX and XII antipneumococcal sera and, to the extent of their cross-reactivity, remove the same fraction of anti-SIX or anti-SXII. Dextrans with high proportions of 1,6 linkages cross-react poorly with anti-SIX whereas some dextrans with high proportions of 1,3-like linkages precipitate the largest quantitites of antibody N and three dextrans with high proportions of 1,2 linkages precipitate about two-thirds of this cross-reacting antibody. Inhibition studies of the cross-reaction of anti-SIX with a dextran with 38% 1,2 linkages and 12% 1,4 linkages (B1299-S-3) show that a trisaccharide, 4-O-α-d-glucopyranosyl-3-O-α-d-glucopyranosyl-d-glucopyranose (T2), was the best inhibitor tested; maltose, kojibiose and nigerose were the best disaccharide inhibitors of this cross-reaction, all three being poorer than T2 and about equal to one another. Inhibition studies of the cross-reaction of anti-SIX with a dextran with a high proportion of 1,3-like linkages (B1355-S-4) show that nigerose is a much more effective inhibitor than either maltose or kojibiose and as good, on a molar basis, as either T2 or 3-O-α-d-glucopyranosyl-4-O-α-d-glucopyranosyl-d-glucopyranose, indicating a heterogeneity in the specificity of the anti-SIX involved in the cross-reactions. Dextrans with high proportions of 1,2 linkages precipitate the most antibody N from anti-SXII whereas dextrans with high proportions of 1,6 linkages precipitate the least and kojibiose was found to be the best inhibitor of the cross-reaction of anti-SXII with a dextran with a high proportion of 1,2 linkages (B1299-S-3). Trehalose was almost as effective as kojibiose in inhibiting the cross-reaction of anti-SXII with B1355-S-4 (no 1,2 linkages), also indicating heterogeneity in the specificity of the cross-reacting fraction of anti-SXII. The results of the dextran-anti SXII cross-reaction closely parallel findings in the reaction of dextran with human antidextran of specificity involving the 1,2 linkage. The data are discussed in relation to the information provided concerning the structural units on SIX and SXII involved in the cross-reactions. N-acetylglucosamine and glucuronic acid may be involved in the specificity of the cross-reacting fraction of anti-SIX and N-acetylglucosamine may be involved in the specificity of the cross-reacting fraction of anti-SXII.

Immunochemical Studies on Blood Groups

Summary The nondialyzable residue of mild acid treated blood group A or B substance (P1 fractions) can give rise in human beings to precipitins specific for the A P1 and B P1 fractions respectively. A P1 fractions differ from untreated A substance in that they are able to stimulate the formation of A P1 specific precipitins in group A as well as group O individuals. Similarly B P1 fractions differ from untreated B substance since they may give rise to B P1 specific precipitins in group AB as well as group O subjects. Anti-B P1 precipitins are specific for groupings present in B substance which are exposed by mild acid hydrolysis since untreated B preparations show little or no reactivity with anti-B P1 sera but acquire this capacity following mild acid treatment. Hog A substances likewise show no capacity to remove anti-A P1 precipitins unless subjected to mild acid treatment. A single human A substance tested, however, was found to possess A P1 specificity prior to treatment. Quantitative oligosaccharide inhibition studies indicate that B P1 specificity is partially determined by terminal nonreducing α-galactosyl residues. These α-galactosyl determinants of B P1 specificity appear to be involved in a linkage different from that of α-galactosyl determinants of blood group B specificity since melibiose which is very effective in inhibiting B-anti-B precipitation, is a poor inhibitor of B P1 anti-B P1, being even less effective in this system than galactose. Thus the galactosyl residues of B P1 determinant groupings are probably not in 1 → 6 linkage. Limited inhibition studies show anti-A P1 to differ in specificity from anti-A since N-acetyl-glucosamine is able to inhibit A P1-anti-A P1 precipitation but shows no inhibitory effect on A-anti-A precipitation. The ability of B and B P1 fractions to precipitate anti-B is independent of the capacity of the same preparation to remove anti-B P1 precipitins. In agreement with inhibition studies this suggests that groupings determining B P1 specificity are distinct from those groupings conferring blood group B activity. In addition, time-hydrolysis studies of human B substance at pH 1.62, 1.32 and 1.10 show that reactivity with type XIV horse antipneumococcal sera as well as reactivity with human anti-B and anti-B P1 sera are affected in a different way for each specific antiserum further indicating distinct structural groupings to be associated with B, B P1 and type XIV cross reactivity.

Cross Reactions of Polyglucoses in Antipneumococcal Sera

Summary A synthetic polyglucose fraction is shown to precipitate more antibody nitrogen from Types II, IX, XII, XX, and XXII antipneumococcal horse sera than do various glycogens, amylopectins, and other natural polyglucoses. Quantitative data are given. Various features of these cross reactions and the compositions of certain of the precipitates are discussed. Use is made of the action of amylase on glycogen-antibody precipitates for the partial purification and concentration of cross-reactive antibody. Preliminary results are given with an analytical method which appears to provide a new criterion of homogeneity for carbohydrates composed of a single sugar or polysaccharides not fractionated by a single precipitation with an antiserum.

Cross Reactions of Polyglucoses in Antipneumococcal Sera

Summary The cross reactivity of Types IX and XII antipneumococcal rabbit sera toward glycogen, a limit dextrin, and a fraction of synthetic polyglucose is described and related in a measure to the chemical constitution of these carbohydrates. The precipitation of antibody by glycogen and limit dextrin is reversed by the action of amylase present in the sera, but conditions are given for minimizing the effects of the enzyme.

Cross Reactions of Polyglucoses in Antipneumococcal Sera

Summary Quantitative data are given on the precipitation of antibody nitrogen from a variety of antipneumococcal horse sera by various glycogens and dextrins derived from them. The data are shown to be in accord with predictions made from a quantitative theory of the precipitin reaction and with the requirements of the chemical structures of the carbohydrates involved. Inferences are drawn regarding probable details of composition and structure of the specific polysaccharides of pneumococcal Types IX, XII, XX, and XXII.

Acute pericarditis associated with serum sickness.

ALTHOUGH carditis has been described as a manifestation of serum sickness in man, reports of acute pericarditis are uncommon. Davidson1 described an increase in cardiac dullness in 72 per cent of 50 cases of serum sickness, with an average increase of 1 cm. in transverse diameter of the heart. No subjective or objective evidence of heart disease was found in any of these patients, and it was assumed that the cardiac enlargement resulted from edema of the muscular wall of the heart. Clark and Kaplan2 reported 2 cases with endocardial and myocardial lesions, without pericardial involvement, after antipneumococcus serum. Clark . . .

A method for the quantitative measurement of agglutinin nitrogen in antisera to Hemophilus pertussis, phase I.

A method for the measurement, in weight units, of the agglutinin nitrogen in antisera to Hemophilus pertussis, Phase I, is described. The procedure and techniques are essentially the same as those first published by Heidelberger and Kabat for the measurement of agglutinin nitrogen in antipneumococcal sera. However, it was found that unusually large amounts of bacterial nitrogen were required to absorb pertussis agglutinins completely, even when the antibodycontent of the antisera was low. The accuracy of this method is limited to ± 1-2%, the error involved in the Kjeldahl procedure for measuring nitrogen. Thus, the large amounts of bacterial nitrogen necessary for absorption and the relatively low agglutinin nitrogen content of the antisera indicated that the results of one, or at the most two, absorptions be used to calculate values with some meaning in terms of quantitative analytical chemistry. Analysis of an unknown antiserum can now be accomplished in one or two absorptions if 1.0 ml. volumes of appropriate dilutions of serum are absorbed with approximately 2 mgm. of bacterial nitrogen. The antibody content is calculated from the dilution of serum which was completely absorbed.

Infectious diseases; seventeenth annual review of significant publications.

THE ADVANCES made in the field of infectious diseases during the last two decades are reflected in these annual reviews by the prominence given them. Indeed, the history of these years can be divided into distinct periods based on a succession of epochal therapeutic discoveries. After the first review published in 1935, pneumococcic pneumonias and their treatment with specific antipneumococcic serum held the chief interest up to 1939, when serum was displaced by sulfapyridine. Sulfonamide chemotherapy for many infections dominated interest until 1944. Penicillin was referred to briefly in 1942, the year that serotherapy last was mentioned. Two years later penicillin treatment rendered sulfonamide chemotherapy almost obsolete. Penicillin and the discovery of a surprising variety of other antibiotic agents placed them as leading subjects since 1944. At present, effects of adrenocorticotropic hormones on infectious diseases are under intensive study. So far, however, aside from immediate beneficial effects in rheumatic disease

Antihyaluronidase antagonistic to pneumococcus hyaluronidase in the serum of normal human beings and patients with pneumococcic pneumonia; rise of titer in bacteremic pneumococcic pneumonia.

Abstract Antihyaluronidase in the serum of fifty normal human beings antagonistic to Type 2 pneumococcus hyaluronidase was compared with the same antihyaluronidase in the serum of Patient A. T. who was six months convalescent from Type 2 pneumococcus endocarditis. All of the fifty normal subjects tested had some degree of this antihyaluronidase. Since subsequent experiments demonstrated that serum antihyaluronidase antagonistic to pneumococcus hyaluronidase is not type specific, these observations upon the sera of normal human beings pertain to hyaluronidase elaborated by all types of pneumococci. Serial sera of twenty-six patients with primary pneumococcic pneumonia were tested for antihyaluronidase by titration against hyaluronidases in culture filtrates of Type 1, Type 2, and Type 7 pneumococci. Seven patients with negative blood culture and no purulent complication exhibited no change of antihyaluronidase titer. Eight of eleven patients with pneumococcus bacteremia and no purulent complication exhibited rises of antihyaluronidase titer which were fourfold or greater. All of eight patients with pneumococcus bacteremia and purulent complication exhibited rises of titer of fourfold or greater. The rises of antihyaluronidase titer which were observed were not specific for pneumococcus type. Therapeutic antipneumococcic rabbit serum exhibited less antagonism of pneumococcus hyaluronidase than did a majority of the sera from fifty normal human beings. High therapeutic concentrations of penicillin and sodium sulfadiazine exhibited no antagonism of pneumococcus hyaluronidase. A rise of serum antihyaluronidase titer could not be brought about in one patient with pneumococcic pneumonia by the intravenous administration of therapeutic antipneumococcic serum, but a progressive rise of serum agglutinin titer for the homologous pneumococcus was produced.

IMMUNOCHEMICAL STUDIES ON BLOOD GROUPS

It has been possible, by employing a new color reaction for methylpentoses, to determine the fucose content of individual hog and human blood group A, B, and O substances. The data indicate an inverse correlation between fucose content of the hog A and O substances and ability to cross-react with Type XIV antipneumococcus serum. The human A, B, and O substances display no correlation between their fucose content and ability to cross-react with Type XIV antipneumococcus serum.

Reactions to antipneumococcal rabbit serum

Abstract Additional studies of reactions to antipneumococcal rabbit serum are presented which show: 1. 1. Shocking doses of antiserum can be reduced to an ineffectual level when sensitizing doses of polysaccharide and the interval between sensitizing and shocking doses are constant. The intensity of the reactions decreased (as antiserum doses were reduced) from uniformly severe to uniformly mild reactions before ineffectual doses were reached. 2. 2. Different lots of the same type and of different types of antipneumococcal rabbit serum vary widely in their effectiveness in producing reversed passive anaphylaxis. 3. 3. Reasons are given for the suggestion that the presence or absence of circulating polysaccharide should be determined before giving antipneumococcal rabbit serum.

ACUTE PHASE SERUM IN RABBITS

Acta Medica ScandinavicaVolume 128, Issue S196 p. 575-578 ACUTE PHASE SERUM IN RABBITS THE CAPACITY OF PNEUMOCOCCUS STRAINS WHICH REACT SPECIFICALLY WITH TYPE 16 ANTIPNEUMOCOCCUS SERUM TO CAUSE NON-SPECIFIC CAPSULAR SWELLING WITH ACUTE PHASE SERUM FROM RABBITS1 GUNNAR LÖFSTRÖM, GUNNAR LÖFSTRÖMSearch for more papers by this author GUNNAR LÖFSTRÖM, GUNNAR LÖFSTRÖMSearch for more papers by this author First published: January/December 1947 https://doi.org/10.1111/j.0954-6820.1947.tb14693.x 1 State Bacteriologic Laboratory, Stockholm. AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Volume128, IssueS196January/December 1947Pages 575-578 RelatedInformation

Studies of Antipneumococcal Serum

Summary The complement-fixing activities of fractions of one pooled normal and three pooled antipneumococcal rabbit sera (types 2, 3, and 7) have been studied quantitatively in the presence and absence of homologous type-specific carbohydrate antigen. Considered in relation to total nitrogen content, the water-insoluble globulin was, of these fractions, the most anticomplementary; the concentrated water-soluble globulin fraction had about the same degree of anticomplementary activity as the original serum; the albumin fraction had a negligible effect on complement. In titrations of the activities of the various fractions of antipneumococcal sera with homologous type-specific carbohydrate, a somewhat better agreement was noted between W, the maximally reactive dose of antigen, and η, the amount of antibody nitrogen present, than between η and K', the number of units of complement required for 50-per-cent hemolysis. Although individual preparations differed in this respect, this observation suggested that the procedures of fractionation might have affected the combining activity of antibody with antigen less than its complement-fixing capacity in the presence of the same antigen.

Anaphylactic Properties of Photo-Oxidized Rabbit-Antisera (vs Sheep-Erythrocytes and Pneumococci) and Horse-Antiserum (vs Diphtherial Toxin) Containing ‘Univalent’ Antibodies

Summary Photo-oxidation of antisheep-erythrocyte rabbit-serum to the point of maximal titer of ‘univalent’ antibody (243 mm3 O2 uptake per ml serum) gives a more than fifty-fold reduction in its direct anaphylactic action on guinea pigs. It is concluded that the ‘univalents’ are ineffective in inducing shock in this system. Antipneumococcal rabbit-serum photo-oxidized to 150 mm3 O2/ml (at which point precipitating ability is first lost) and 304 mm3 O2/ml (maximal titer of ‘univalents’) shows progressively decreased ability to produce passive sensitization of guinea pigs. The evidence shows the ‘univalents’ to be incapable of effecting such sensitization and indicates some inhibitory action on their part. The ability of photo-oxidized antipneumococcal rabbit-serum to induce shock in guinea pigs actively sensitized to untreated serum shows a reduction of between two- and five-fold for the “150” sample and between 50- and 1000-fold for the “304” sample. The reductions in protective value (12) are two-fold and twelve-fold respectively for these samples. Both of these photo-oxidized samples of antipneumococcal serum can actively sensitize guinea pigs to the action of untreated serum and of the treated serum. The results with the “304” sample give evidence of the presence of an active antigen of altered specificity. Photo-oxidation of equine diphtheric antitoxin to 448 mm3 O2/ml, gives an approximately 50-fold reduction in its action on guinea pigs actively sensitized to the untreated serum, as compared with a two-fold reduction in its ability to neutralize toxin. The photo-oxidized horse-serum can actively sensitize guinea pigs to the action of both the untreated serum and the treated material. A small number of tests show desensitization of horse-serum-sensitized guinea pigs by non-shocking doses of the photo-oxidized material. The more favorable ratio of reduction in anaphylactic action to reduction in protective value obtained with the antitoxic than with the antibacterial serum is interpreted on the basis of the loss of protective ability when antibacterial antibodies are converted into the ‘univalent’ form.

Conversion of Agglutinins and Precipitins into ‘Univalent’ (Non-Agglutinating or Non-Precipitating) Antibodies by Photodynamic Irradiation of Rabbitantisera vs Pneumococci, Sheep-Red-Cells and Sea-Urchin Sperm

Summary Photo-oxidation of rabbit-antisera against sea-urchin sperm, pneumococci and sheep-erythrocytes converts the antibodies into a non-precipitating or non-agglutinating (‘univalent’) form which still combines specifically with the antigen and inhibits the action of the control antiserum. The inhibitive titers are found to increase initially with increased photooxidation beyond the point when loss of precipitating power of the antiserum is first obtained. High maximal values are reached and differences are observed in the values obtained by precipitative and agglutinative tests with the same system. From a non-precipitating antipneumococcal serum produced by moderate photo-oxidation, precipitating antibody is obtained by fractional salting-out with ammonium sulphate. Determinations of the antibody-nitrogen content of photo-oxidized anti-pneumococcal serum show no significant difference from that of the control antiserum. In anti-sheep-cell sera, photo-oxidized to various degrees, the hemolytic titer falls off rapidly while the agglutination-inhibiting titer rises, indicating that the ‘univalents’ do not function as hemolysin. The results are interpreted on the basis of the mutual-multivalence theory which they tend to support.

IRITIS, RETINAL HEMORRHAGE AND CHANGES IN THE LENS FOLLOWING INJECTION OF TYPHUS VACCINE

Ocular manifestations following injections of serum have not been common, although cases have been reported. Mason 1 reported 3 cases in which measurable blurring of the optic disks developed during serum sickness, with gradual return to normal. Brown 2 reported 5 cases in which elevation of the disk and edema of the retina developed after administration of diphtheria antitoxin. These signs subsided in a few days. Bedell 3 described severe and extensive bilateral edema of the retina with superficial hemorrhages, which he attributed to serum sickness following the injection of tetanus antitoxin. This condition cleared up rapidly, leaving few vestiges. Theodore and Lewson 4 reported 1 case of iritis following antipneumococcic serum. The case reported here is unusual because it involved damage to the iris, lens, optic nerve and retina without any serum sickness or other prodromal symptoms. A white soldier aged 22 walked into the ophthalmic clinic complaining of

Torantil (histaminase) in urticaria following serum administration

B EST and McHenry, 1 in 1930, reported ttmt histaminase could be neutralized in vitro by a substance extracted from certain viscera, particularly the gastrointestinal tract and kidney. Since this substance displayed the properties an enzyme, they called it histaminase. They prepared it as a stable powder and defined 1 unit as the amomlt necessary to neutralize 1 mg. histamine after twenty-four hours incubation at 37 ~ C. at a pH 7.2. tIistaminase was subsequently manufactured ior clinical use from porcine gastrointestinal tract. It was given the trade name Torantil and distributed in the form tablets or capsules, each containing 5 units. It has been frequently suggested that a sudden release histamine might be the mechanism whereby the various clinical signs an allergic state are produced. Were this true, it would be logical to assume that a substance capable destroying histamine in the body might be therapeutic value. A number investigators have, therefore, tested histaminase experimentally and clinically in a wide variety conditions. The results have been diverse and difficult to interpret. The only reports pertinent to our work were those concerned with use histaminase in serum sickness after antitoxin or antiserum administration. Foshay and Hagebusch 2 reported marked relief in twenty twenty-two cases, with prevention serum sickness in six eight patients treated prophylactically. Roth and Horten 3 noted relief in from twelve to thirty-six hours in fourteen seventeen patients; and Vaisberg ~ had good results in one patient. Cherry and Prickman 5 used Torantil to prevent and treat selann sickness in twentytwo patients with good results. Many patients treated with serums and antitoxins develop serum sickness. I t was decided to note the effect Torantil in such patients i n the Division Contagious Diseases, City Hospital, Cleveland, following the administration of scarlet fever antitoxin, diphtheria antitoxin, pneumococcus antiserum or meningococcus antitoxin. In the first clinical experiment, thirteen patients who developed urticaria were given four tablets Torantil four times a day until the serum sickness had subsided. This procedure seemed worthless, since

A Simplified Procedure for Detecting Cross Reactions in Diagnostic Antipneumococcic Serum

A Simplified Procedure for Detecting Cross Reactions in Diagnostic Antipneumococcic Serum