bluuebunny/crossref_metadata_2025 huggingface dataset:
Interaction of alphaviruses with human peripheral leukocytes: in vitro replication of Venezuelan equine encephalomyelitis virus in monocyte cultures
Authors: Levitt N H , Miller H V , Edelman R
Published: January 2020

Human peripheral blood leukocytes (PBL) were examined for their ability to support growth of several group A arboviruses in vitro. Cells were refractory to infection with eastern (EEE) and western (WEE) equine encephalitis viruses, whereas Venezuelan equine encephalomyelitis (VEE) virus was shown to infect and replicate to a substantially high titer. When PBL were fractionated into purified subpopulations, only the monocytes were susceptible to predictive VEE virus infection. Lymphocytes treated 24 h before virus inoculation with phytohemagglutinin (10 microgram/ml) were capable of propagating significant amounts of VEE virus. A monocytic cell line, J-111, was also susceptible to infection with VEE, EEE, and WEE viruses, whereas a lymphocytic cell line, Raji, was refractory. Additional information on the participation of PBL during human infection with these viruses may add considerably to our understanding of their differing pathogenicities and clinical pictures.
Neisseria meningitidis bacteremia in association with deficiency of the sixth component of complement
Authors: Lee T J , Snyderman R , Patterson J , Rauchbach A S , Folds J D , Yount W J
Published: January 2020

The serum of a 26-year-old black man with a recent episode of meningococcemia complicated by meningitis and arthritis was found to lack hemolytic complement activity. The sixth component of complement was not detected by functional or immunochemical assays whereas other components were normal by hemolytic assay. His fresh acute-phase serum lacked complement-mediated bactericidal activity against the homologous strain of Neisseria meningitidis, but the addition of fresh normal serum or purified C6 restored bactericidal activity as well as hemolytic activity. The absence of C6 activity could not be accounted for on the basis of an inhibitor. Opsonization and chemotaxis functioned normally. Histocompatibility typing of family members did not demonstrate evidence for genetic linkage of C6 deficiency with the major histocompatibility loci. This report represents the first published case of C6 deficiency associated with bacteremic Neisseria infections in which antimeningococcal bactericidal antibodies have been definitively demonstrated against the homologous strain in the acute phase of the illness.
Suppressive effect of bacterial endotoxin on the expression of cell-mediated anti-Listeria immunity
Authors: Newborg M F , North R J
Published: January 2020

Intravenous injection of bacterial endotoxin into mice at any time during ongoing infection with Listeria monocytogenes resulted in a markedly increased multiplication of this organism in the liver and spleen. Experiments designed to investigate the basis of this infection-enhancing effect revealed that endotoxin was also capable of inhibiting the expression of adoptive T-cell-mediated anti-Listeria immunity if given to normal recipient mice up to 48 h before they were infused with protective T-cells. On the other hand, endotoxin had only a marginal effect on the expression of adoptive immunity if given to donor mice before their spleen cells were harvested for adoptive transfer. Taken together, these results indicate that endotoxin probably interferes with the antibacterial function of macrophages rather than with mediator lymphocytes. The additional finding that the infection-enhancing action of endotoxin could be greatly reduced by making mice "tolerant" to endotoxin suggests that the acquisition of tolerance to this effect of endotoxin may be an important adaptive mechanism in acquired resistance to infection with gram-negative bacteria.
Solid-phase micro-radioimmunoassay to measure immunoglobulin class-specific antibody to Mycoplasma pulmonis
Authors: Taylor G
Published: January 2020

A solid-phase radioimmunoassay (RIA) was used for the detection and quantitation of immunoglobulin class-specific antibodies to Mycoplasma pulmonis in mouse sera. The RIA was found to be more sensitive than the single radial haemolysis (SRH) test for detecting antibodies in sera from mice at intervals after inoculation with M. pulmonis, since antibody was detected in 26 out of 29 serum samples by RIA but in only 8 out of 29 samples by SRH. A method is described for quantitating immunoglobulin class-specific antibody in test sera by reference to a standard serum. The RIA should be useful for the study of the relative importance of various immunoglobulin classes in resistance to mycoplasma infections.
Host defenses in murine malaria: analysis of the mechanisms of immunity to Plasmodium berghei generated in response to immunization with formalin-killed blood-stage parasites
Authors: Murphy J R
Published: January 2020

Syngeneic B6D2F1 (C57Bl/6 x DBA/2) mice were immunized with a nonliving antigen prepared from mixed blood forms of Plasmodium berghei strain NYU-2. Consistently greater than 80% of the vaccinated mice survived virulent challenge, and protective immunity was demonstrable from 1 week through at least 4 months after immunization. However, vaccination did not prevent the development of patient infection after challenge. Instead, infections in vaccinated mice progressed to about 10% parasitemia and were then subsequently cleared. In contrast, infections initiated in nonvaccinated mice progressed beyond 10% parasitemia and were uniformly fatal within 4 weeks. Sera collected from normal mice, nonvaccinated mice infected with P. berghei, or vaccinated mice before challenge failed to passively protect recipients against virulent infection. On the other hand, sera collected from vaccinated mice after recovery from a challenge infection conferred upon passively immunized recipients protection from homologous virulent challenge, which was manifest as a delay in the onset of overt infection. It was concluded, therefore, that vaccination altered the immunological potential of the host in such a way as to allow the production of a protective humoral factor, probably specific antibody, in response to infection with the virulent parasites.
Comparison of Enzyme-Linked Immunosorbent Assay and Passive Hemagglutination Method for Quantification of Antibodies to Lipopolysaccharide and Tetanus Toxoid in Rats
Authors: Vos J. G. , Buys J. , Hanstede J. G. , Hagenaars A. M.
Published: January 2020

In a comparative study, the enzyme-linked immunosorbent assay, using peroxidase labeled anti-rat immunoglobulin M and immunoglobulin G, and the passive hemagglutination test were applied to determine the primary and secondary antibody response to lipopolysaccharide and tetanus toxoid in rats. In the enzyme-linked immunosorbent assay, the antigens were bound to the wells of polystyrene microplates, tetanus toxoid directly, and lipopolysaccharide after complexing it with methylated bovine serum albumin. After incubation with dilutions of the rat sera, the amount of antibody bound to the solid phase was quantified by means of peroxidase-labeled anti-immunoglobulin. The specificity of the enzyme immunoassay was tested by absorption of the sera with their respective antigens. The enzyme-linked immunosorbent assay proved to be more sensitive than the hemagglutination reaction, except when titers were determined during the secondary response to tetanus toxoid. Besides its specificity and sensitivity, the enzyme-linked immunosorbent assay is a convenient method for measuring both immunoglobulin M and immunoglobulin G antibodies. At low serum dilutions of lipopolysaccharide antisera, inhibition of the reaction in the enzyme-linked immunosorbent assay occurred. This phenomenon could be prevented by heating the sera at 56°C for 30 min. Lipopolysaccharide was immunogenic in rats over an extremely wide dose range (from 10 pg to 1 mg); the optimal immunogenic dose of lipopolysaccharide for young adult rats was 0.1 to 1,000 μg when administered intravenously, and that of tetanus toxoid was 5 to 10 lines of flocculation, as determined by the Ramon flocculation test.
Phosphoenolpyruvate-dependent sucrose phosphotransferase activity in Streptococcus mutans NCTC 10449
Authors: Slee A M , Tanzer J M
Published: January 2020

A phosphoenolpyruvate-dependent sucrose phosphotransferase system (PTS) has been demonstrated, by an enzyme-coupled reaction and product isolation, in decryptified cell suspensions of the cariogenic microorganism Streptococcus mutans NCTC 10449. The apparent sucrose PTS reaction for sucrose-adapted, sucrose-challenged cells displayed saturation kinetics with an apparent Km of 7.14 x 10(-5) M, which was distinct from the Km of the glucose PTS activity of glucose-adapted, glucose-challenged cells. Both the sucrose and the glucose PTS activities appear to be inducible and under separate genetic control. The sucrose PTS reaction demonstrated in decryptified cells had an absolute requirement for phosphoenolpyruvate. Only 2-phosphoglycerate, the immediate glycolytic precursor of phosphoenolpyruvate, was found to substitute for phosphoenolpyruvate in this reaction in the absence of fluoride. The sucrose PTS activity of sucrose-adapted cells was competitively inhibited by raffinose and lactose; these same sugars had no effect on the apparent glucose PTS activity. Fructose was the only carbohydrate tested other than sucrose which elicited an apparent PTS reaction in sucrose-adapted cells. The product of the sucrose PTS reaction was isolated and behaved chromatographically on a Dowex-1-X8 column like a monophosphate ester. Alkaline phosphatase treatment of the presumptive sucrose monophosphate liberated a component which behaved chromatographically like free sucrose. Subsequent acid hydrolysis of this component produced moieties which behaved chromatographically like glucose and fructose.
Inactivators of fibroblast interferon found in human serum
Authors: Cesario T , Vaziri N , Slater L , Tilles J
Published: January 2020

Investigation of the inactivators of fibroblast interferon has shown that those substances could be identified in every specimen of serum taken from normal individuals. These inactivators were found to destroy a mean of 82% of the interferon antiviral activity beyond that caused by the effects of temperature alone. The inactivators exerted no effect at 4 degrees C but were found in a variety of animal as well as human sera. Although slight differences were found to exist in the extent of inactivation when comparing normal human serum to serum from patients (i) receiving chronic hemodialysis, (ii) with jaundice, or (iii) with underlying malignancies, the differences did not appear to be clinically significant. In exploring the nature of the substances, we found that both dialyzable and non-dialyzable inactivators exist, but the former appear to be the major factors responsible for the unwanted process.
Shigella infection of Henle intestinal epithelial cells: role of the bacterium
Authors: Hale T L , Bonventre P F
Published: January 2020

Epithelial cell infection by Shigella flexneri 2a was studied in an in vitro model system. Using the Henle 407 human intestinal epithelial cell line as host cells, a standardized experimental protocol which allowed quantitative measurement of infection was developed. Intravellular residence of infecting organisms was confirmed by indirect fluorescent-antibody staining of unfixed and methanol-fixed (Henle 407) cells and by quantitative bacteriological culture of disrupted host cells after infection. The process of shigella entry into cells was evaluated by chemical or physical modulation of the bacterium under controlled experimental conditions. Shigella were subjected to mild heat, ultraviolet radiation aminoglycoside antibiotics, and immunoglobulins raised against S. flexneri 2a. The data show that heat-stable antigens on the bacterial surface are not solely responsible for infectivity of S. flexneri 2a. Furthermore, it was shown that physiological and synthetic functions of shigellae are required for entry into host cells.
Aberrant secondary antibody responses to sheep erythrocytes in rabbits with experimental syphilis
Authors: Baughn R E , Musher D M
Published: January 2020

Rabbits infected with Treponema pallidum have strikingly depressed in vivo immunoglobulin G responses to sheep erythrocytes. To gain further insight into the nature of this suppression, the immune responses of splenic and peripheral blood lymphocytes from infected rabbits to sheep erythrocytes were studied in vitro. Spleen cells from rabbits that had been sensitized with sheep erythrocytes during active syphilis had greatly decreased immunoglobulin M and G responses after in vitro incubation with sheep erythrocytes, when compared to the results obtained with cells from sensitized uninfected animals. Suppressor cells could be demonstrated in peripheral blood lymphocytes of control rabbits 6 months after sensitization with sheep erythrocytes; these cells could be removed by nylon wool filtration. When primary sensitization with sheep erythrocytes was carried out during active syphilis, these suppressor cells were not detectable in peripheral blood lymphocytes 6 to 9 months later. These findings provide further evidence that induction of immune responses may be abnormal early in treponemal infection and may help to explain the failure of the host to produce antibodies which eradicate the organism during the first 2 to 3 months of infection.
Interactions between human serum proteins and oral streptococci reveal occurrence of receptors for aggregated beta 2-microglobulin
Authors: Ericson D , Bratthall D , Björck L , Myhre E , Kronvall G
Published: January 2020

A total of 31 strains of oral streptococci representing Streptococcus mutans, Streptococcus sanguis, Streptococcus mitior, Streptococcus salivarius, and Streptococcus milleri were tested for possible binding of human immunoglobulins G, G1, G2, G3, G4, A1, A2, M1, and M2 and haptoglobin, hemoglobin, fibrinogen, and aggregated beta 2-microglobulin. Radiolabeled beta 2-microglobulin in aggregated form showed affinity for 20 of the 31 strains tested. Binding activity for the protein was found in strains belonging to all five species. The bacterial receptor was resistant to trypsin. Monomeric, unlabeled beta 2-microglobulin did not interfere with the binding of the aggregated form. Of the other proteins tested, only the immunoglobulin A1 protein showed positive binding, and that was only with a single strain of S. milleri. beta 2-Microglobulin is present on all nucleated cell membranes in vivo. The reaction between aggregated beta 2-microglobulin and oral streptococci is a new type of human-bacterium interaction which should be considered in studies of bacterial adherence.
Immunosuppressive activity of BCG: effects of adjuvant disease, lymphocyte subpopulations, and homing of thoracic duct cells in rats
Authors: Sutherland R I , Spadaro-Antonelli M A , Lawrence V J , Quagliata F
Published: January 2020

Administration of BCG by various dosage schedules suppressed adjuvant disease in rats. BCG administration produced an initial increase, followed by a depression, of the phytohemagglutinin response of purified blood lymphocytes. An increase in absolute and relative numbers of bursa-equivalent (B)-cells followed BCG administration, concurrent with a decrease in the phytohemagglutinin responsiveness. With adjuvant alone, there was a diminution in phytohemagglutinin response and an increase in number of B-cells; the latter occurred immediately after adjuvant injection and also when the generalized disease appeared. When both BCG and adjvant were present, parallel increases of phytohemagglutinin responsiveness and B-cell numbers resulted. The pattern of tissue localization of radioactively labeled thoracic duct cells from normal or BCG-treated donors given to normal, BCG-treated, adjuvant-injected, and BCG-treated + adjuvant-injected syngeneic recipients indicated significantly greater homing to the thymus and decreased localization to the bone marrow when BCG had been given to either donors or recipients. When labeled thymus cells were used, only the decreased bone marrow localization was noted. These observations suggest that the suppressive effect of BCG may be mediated through modification of the lymphocyte recirculation pattern, possibly resulting from alterations in lymphocyte recognition sites.
Enhancement of generation of monocyte tissue thromboplastin by bacterial phagocytosis: possible pathway for fibrin formation on infected vegetations in bacterial endocarditis
Authors: van Ginkel C J , Thörig L , Thompson J , Oh J I , van Aken W G
Published: January 2020

The deposition of fibrin on infected vegetations and the presence of mononuclear phagocytes that have phagocytized bacteria are remarkabe features in experimental bacterial endocarditis. In a study in vitro, we show that phagocytosis of bacteria by human monocytes enhances thromboplastin generation by these cells. Maximal enhancement of the generation of thromboplastin by monocytes was about six times compared with that in the control experiment without bacteria, and it was obtained by preincubation of the monocytes with 5 to 10 bacteria per monocyte. No quantitative difference was observed between Staphylococcus epidermidis and Streptococcus sanguis as to the enhancement of the monocyte thromboplastin generation. An enhancement of the procoagulant activity generation was also observed after addition of bacteria to human or rabbit whole blood. Probably, this generation was also due to synthesis of thromboplastin by monocytes. It is conceivable that fibrin deposition on infected vegetations during bacterial endocarditis is mediated by thromboplastin synthesis by monocytes.
Interaction of Mycoplasma pneumoniae with human lung fibroblasts: role of receptor sites
Authors: Gabridge M G , Taylor-Robinson D
Published: January 2020

The biochemical nature of the neuraminidase-sensitive Mycoplasma pneumoniae receptor site on human lung fibroblast cells was studied. Purified, mixed sialoglycolipid (ganglioside) preparations from human and bovine tissues did not bind to M. pneumoniae organisms and block their subsequent attachment to fibroblasts. Fibroblasts incubated for 24 h in sialoglycolipid solutions to increase the ganglioside content of their membranes did not show increased pathogen attachment when later incubated with mycoplasmas. HeLa cells grown in the presence of sodium butyrate to increase GM3 ganglioside levels likewise did not have significantly increased uptake of M. pneumoniae organisms. Treatment of fibroblasts with enzymes indicated that the mycoplasma receptor site is trypsin and papain resistant but Pronase sensitive. Pronase digests of fibroblast membranes contained a product(s) which combined with M. pneumoniae cellls and cosedimented with them during centrifugation. Glycoproteins, purified from fibroblast membranes by a lithium diiodosalicylate solubilization technique, similarly bound to M. pneumoniae organisms. Collectively, these data suggest that the major component of the M. pneumoniae receptor site is a sialoglycoprotein with little or no lipid.
Use of HeLa cell guanine nucleotides by Chlamydia psittaci
Authors: Ceballos M M , Hatch T P
Published: January 2020

Exogenous guanine was found to be incorporated into the nucleic acids of Chlamydia psittaci when the parasite was grown in HeLa cells containing hypoxanthine guanine phosphoribosyltransferase (EC 2.4.2.8) activity but not when the parasite was grown in transferase-deficient HeLa cells. No evidence for a chlamydia-specific transferase activity was found in either transferase-containing or transferase-deficient infected HeLa cells. It is concluded that C. psittaci is incapable of metabolizing guanine, but that the parasite can use host-generated guanine nucleotides as precursors for nucleic acid synthesis.
B-lymphocyte activation with an extract of Nocardia brasiliensis
Authors: Ortiz-Oritz L , Parks D E , Lopez J S , Weigle W O
Published: January 2020

An extract from the pathogenic actinomycete Nocardia brasiliensis was mitogenic for murine lymphocytes. This deoxyribonucleic acid-synthetic response of whole spleen cells peaked after 48 h in culture at concentrations of Nocardia extract ranging from 10 to 200 micrograms/ml. The extract appeared to be a mitogen for B lymphocytes since cultures of spleen cells from congenitally athymic nude (nu/nu) mice and of antithymocyte serum plus complement-treated spleen cells from conventional (+/+) mice responded as well as untreated spleen cells from normal +/+ mice. Furthermore, thymocytes did not respond mitogenically to the extract. Mitogenic responses were stimulated in spleen cells from H-2(a), H-2(b), H-2(d), and H-2(k) mice, including lipopolysaccharide-nonresponder C3H/HeJ mice. This Nocardia extract also stimulated polyclonal B-cell activation to the hapten trinitrophenyl, serum protein human gamma globulin, and several mammalian erythrocytes in cultures of cells from both euthymic and nude mice. Additionally, the requirement for helper T cells in the primary in vitro immune response to sheep erythrocytes could be circumvented by the addition of this Nocardia extract. These results indicate that an extract from the pathogen N. brasiliensis can nonspecifically activate murine B lymphocytes and raise the possibility that polyclonal activation of B lymphocytes may contribute to the pathogenesis of nocardiosis.
Interferon production: variation in yields from human cell lines
Authors: Meager A , Graves H E , Shuttleworth J , Zucker N
Published: January 2020

A survey of human diploid, aneusomic, transformed and tumor fibroblast or fibroblastoid cell lines for their capacity to produce interferon after polyriboinosinic acid:polycytidylic acid induction showed considerable variation in responsiveness. There was no apparent correlation between karyotype or phenotype and interferon production. Pretreating or "priming" the cells with human interferon generally led to increased yields of interferon after polyriboinosinic acid:polycytidylic acid induction in all cell lines tested. All the cells also showed the "super-induction" phenomenon, although to varying degrees. The combination of priming and superinduction conditions led to the production of very high yields of interferon in some cell lines, but in other lines, yields less than either the primed or superinduced amounts were found. A more limited survey of human cell lines for their capacity to produce interferon after Newcastle disease virus induction also showed that yields varied from line to line. However, there was little evidence to suggest that ability to produce interferon after Newcastle disease virus induction correlated with that after polyriboinosinic acid:polycytidylic acid induction.
Adsorption and growth of Vibrio cholerae on chitin
Authors: Nalin D R , Daya V , Reid A , Levine M M , Cisneros L
Published: January 2020

Incubation of Vibrio cholerae of O-group serotype 1 with chitin particles resulted in adsorption of vibrios onto chitin; chitin-adsorbed V. cholerae survived exposure to acid better than nonadsorbed vibrios. V. cholerae multiplied in dialyzed chitin suspended in 4.2% NaCl, suggesting that adherence to ingested chitin of crustacea might be of epidemiological significance by providing a substrate for vibrio multiplication as well as protection from gastric acid during stomach transit.
Liposomal enhancement of the immunogenicity of adenovirus type 5 hexon and fiber vaccines
Authors: Kramp W J , Six H R , Drake S , Kasel J A
Published: January 2020

Immunogenicity of adenovirus capsid proteins carried in liposomes was comparable to that with equivalent doses administered in Freund adjuvant, and both forms were more potent than aqueous vaccines.
Immune labeling of certain strains of Actinomyces naeslundii and Actinomyces viscosus by fluorescence and electron microscopy
Authors: Lai C H , Listgarten M A
Published: January 2020

A total of 12 well-characterized strains of Actinomyces viscosus and A. naeslundii grown on Trypticase soy agar plates supplemented with sheep erythrocytes were examined by light microscopy and transmission electron microscopy after treatment with appropriately labeled antisera to homologous and heterologous strains. Cells incubated with homologous rabbit antisera followed by fluorescein-isothiocyanate (FITC)-conjugated goat anti-rabbit immunoglobulin G (IgG) exhibited a completely smooth fluorescent outline in the case of A. naeslundii and and interrupted, irregular fluorescent outline in the case of human strains of A. viscosus. The different labeling patterns appeared to be related to the presence at the ultrastructural level of long, unevenly distributed strands of "fuzz" on the surface of human A. viscosus cells, whereas A. naeslundii cells had a narrower layer of fuzz, or more even thickness. The immunocoating reaction revealed homologous antibody binding to the irregular strands of fuzz on the surface of human A. viscosus cells, whereas homologous antisera to A. naeslundii coated A. naeslundii cells with a moderately electron-dense coating of antibody of even thickness. Human strains of A. viscosus incubated with heterologous antiserum to A. naeslundii followed by FITC-labeled goat anti-rabbit IgG exhibited a segmented fluorescent outline, which differed from that produced with homologous antisera. A. naeslundii incubated with heterologous rabbit antisera to human A. viscosus strains and FITC-labeled anti-rabbit IgG exhibited a completely smooth fluorescent outline similar to that produced with homologous antiserum. A. viscosus strains of hamster origin differed from A. viscosus strains of human origin by the absence of a surface fuzz and the comparatively smooth, even fluorescence produced by incubating these cells with homologous rabbit antiserum followed by FITC-labeled goat anti-rabbit IgG. Antiserum to a hamster strain did not cross-react with A. naeslundii or human strains of A. viscosus. Under the growth conditions of this experiment, ultrastructural features and labeling patterns with the indirect fluorescent technique may be useful in differentiating these serotypes from one another.
Nonspecific T-lymphocyte mitogenesis by pyrogenic exotoxins from group A streptococci and Staphylococcus aureus
Authors: Schlievert P M , Schoettle D J , Watson D W
Published: January 2020

Group A streptococcal pyrogenic exotoxins types A, B, and C and staphylococcal pyrogenic exotoxin were shown to be potent nonspecific T-lymphocyte mitogens. Adherent cell populations did not significantly affect the nonspecific mitogenicity.
Lipid composition and activity of a lytic factor isolated from Plasmodium berghei
Authors: Boyer J M , D'Antonio L E , Schiavone W A
Published: January 2020

A fraction was obtained from Plasmodium berghei which induced hemolysis of the erythrocytes of mice and hamsters. This fraction, called lytic factor (LF), was found to be composed of a large amount of lipid material. An examination of the lipids showed the major lipids to be monoglycerides, diglycerides, triglycerides, fatty acids, long-chain alcohol, sterol, sterol ester, sterol glycoside, and two cerebrosides. The most abundant component found in the LF was sterol ester, followed in order by cerebrosides, sterol, and sterol glycoside. Lytic activity was found to be lost when samples were boiled for 5 min. An examination of the lipid composition of LF before and after boiling showed changes which may be useful in studies on the mechanism of activity of this factor. The fatty acid composition of the total lipid fraction of LF was examined by gas-liquid chromatography. The major fractions were 18:1 and 16:0 in unheated LF and 16:0 in the heated LF.
Guinea Pig Lung Lavage Cells After Intranasal BCG Sensitization
Authors: Terai T. , Ganguly Rama , Waldman Robert H.
Published: January 2020

Recent studies have suggested that intranasal administration of antigen can induce local cell-mediated immunity in lung lavage cells. The present study was designed to examine the changes in composition of lung lavage cells and their capacity to produce the lymphokine migration inhibitory factor after intranasal immunization with BCG in guinea pigs. Results indicate that guinea pigs responded to respiratory tract BCG infection with an increase in immunocompetent cells in the bronchoalveolar tract and with production of migration inhibitory factor. After local pulmonary BCG administration, the total number of cells increased as compared with that of the uninfected animals, the increase being statistically significant within 2 weeks. This marked increase in the total cell population is due to a more than doubling of the number of macrophages in the lavage fluid. Animals also developed at this time positive delayed hypersensitivity to intradermally administered purified protein derivative. A significant increase in the total lymphoid cells and macrophage population was observed again at 6 weeks after sensitization, suggesting that the response is biphasic in nature. At 6 weeks, however, there was also a significant rise in total lymphocytes and T cell population in addition to macrophage numbers. This increase in T cells correlated with an increase in production of migration inhibitory factor in the presence of purified protein derivative. These data suggest that the immune response of the respiratory tract after BCG challenge involves increased recruitment of immunocompetent cells locally at the site of infection and that these cells are capable of producing effector molecules in terms of the elaboration of migration inhibitory factor.
Outer membrane antigens of Neisseria meningitidis group B serotype 2 studied by crossed immunoelectrophoresis
Authors: Hoff G E , Frasch C E
Published: January 2020

This study shows that the capsular polysaccharide, protein, and lipopolysaccharide antigens from the outer membrane of Neisseria meningitidis group B serotype 2 may be identified by crossed immunoelectrophoresis. By using this technique, seven precipitates were resolved when outer membrane preparations were reacted against goat anti-whole cell group B type 2 antiserum. Most of these precipitates were identified by comparison with purified reference preparations. Different outer membrane preparations, reflecting different growth conditions, varied in their compositions of lipopolysaccharide, protein, and polysaccharide. Detergent treatment altered the protein and lipopolysaccharide precipitation patterns. In the presence of detergent, the lipopolysaccharide did not precipitate, and the electrophoretic migration of the protein antigens decreased. Crossed immunoelectrophoresis is a useful qualitative method for analysis of the antigenic components of the meningococcal outer membrane. The crossed immunoelectrophoresis with intermediate gel technique is presently being used to measure the human immune response to the different cell surface components.
Immune response to Escherichia coli B surface antigens
Authors: Taplits M , Michael J G
Published: January 2020

The cell surface antigens of Escherichia coli B were investigated. We found that mice immunized with live bacteria responded with an immune response directed mainly against the protein structure of the cell surface. The lipopolysaccharide component of the bacterium was immunogenic, but its contribution to the overall response was only secondary. It is suggested that when considering the immune response to gram-negative bacteria, more attention should be given to the protein antigens.
Appearance of Rosette-Forming Macrophages in the Lungs of Influenza Virus-Infected Mice
Authors: Wyde Philip R. , Cate Thomas R.
Published: January 2020

Approximately one fifth of the macrophages obtained from the lungs of mice infected 2 to 5 days with influenza A/HK virus were found to rosette well with either unmodified human, chicken, or guinea pig erythrocytes, but not with erythrocytes from hamsters, sheep, or mice. Rosette-forming macrophages were seldom seen in suspensions from uninfected mice (3±3%) or mice infected 24 h previously (3±3%). Rosette formation was not due to virus hemadsorption, as indicated by the failure of specific antiserum to influenza virus to block rosette formation; by the induction of comparable levels of rosette-forming macrophages in the lungs of mice infected with herpes simplex virus type 2, a nonhemadsorbing virus; and by the inhibition of rosette formation at 4°C. Instead, rosette formation appeared to be directly related to macrophage elicitation or activation since nonstimulated macrophage populations such as peripheral blood monocytes, macrophages from uninfected lungs, or noninduced peritoneal macrophages were not observed to rosette to any significant extent. Furthermore, peritoneal macrophages induced with filter-sterilized normal horse serum rosetted at levels comparable to that observed with cells from infected lungs. These results indicate that hemadsorption alone can not be used as a criterion of virus infection of macrophages. However, rosette formation may serve to identify macrophage subpopulations which are active in host defense against viral infections.
Hemagglutinin mutants of swine influenza virus differing in replication characteristics in their natural host
Authors: Kilbourne E D , McGregor S , Easterday B C
Published: January 2020

In two mutant clones (L and H) of A/NJ/11/76 (Hsw 1N1) influenza viruses which differ slightly antigenically and markedly in replication characteristics in chicken embryos and Madin Darby canine kidney cells, these pleiotropic differences are mediated by mutation in the hemagglutinin gene (E. D. Kilbourne, Proc. Natl. Acad. Sci. U.S.A. 75:6258--6262, 1978). Experimental infection of swine with either the mutant L and H clones or recombinant viruses differing genetically only with respect to the presence of L or H hemagglutinin demonstrated greater infectivity for the natural host of viruses bearing the L hemagglutinin. Introduction of the L but not the H hemagglutinin gene into the human influenza virus A/PR/8/34 rendered it infective for swine. Both L and H variants were isolated from pigs naturally infected with contemporary swine influenza viruses when selective conditions for the suppression of the more prevalent L mutant were employed. The L and H mutants of swine influenza virus are yet another example of viral dimorphism in nature and probably are not mere artifacts of laboratory selection. In any event, the frequent apparent allelic appearance of the two forms suggests frequent mutation and/or reversion involving a point mutation in the hemagglutinin gene. The present studies demonstrate the importance of a single gene in the pathogenesis of an influenza viral infection in its natural host.
Immunogenicity of Soluble Versus Cellular Glycerol Teichoic Acid
Authors: Chorpenning Frank W. , Cooper Harold R. , Oldfather John W. , Lynch John J.
Published: January 2020

Guinea pigs which were injected with either whole bacilli or purified soluble glycerol teichoic acid (GTA) usually exhibited a rise in hemolysin titer to GTA-coated erythrocytes. The only exceptions were those animals having high baseline titers of natural anti-GTA antibodies. Rats yielded better responses than guinea pigs and produced significantly higher responses to the soluble antigen than to the cellular GTA. Rats reared on a GTA-free diet were predominantly free of natural antibodies to GTA and furnished a more clear-cut model for assaying immune responses. Using this model, it was shown that adsorption of GTA to homologous erythrocytes before injection resulted in poor responses, suggesting that such spontaneous adsorption does not account for the good responses to soluble antigen. In GTA-deprived rats, positive skin tests were induced only with bacilli, whereas migration inhibitory factor was induced with both bacilli and soluble antigen. Hemolytic plaques in immunized rats were increased over controls with both kinds of immunogen, but the GTA-deprived rats responded better than conventional ones, and hemolytic plaque responses to bacilli were better than those to soluble antigen. This reversal of the serum hemolysin results may be due to delayed suppression by soluble GTA or to antibody cycling. The guinea pig data, combined with results from GTA-deprived rats, suggest that high antibody levels resulted in depressed antibody synthesis, perhaps because antibody cycling was initiated. No evidence was found to explain the superior responses to soluble antigen, but it did not seem related to formation of immune complexes or adsorption to erythrocyte membranes.
Cell-mediated immunity to cytomegalovirus in immunocompromised patients: effect of radiation or chemotherapy
Authors: Agatsuma Y , Fitzpatrick P , Kaul A , Kaul R , Kohli R , Paves A V , Ogra P L
Published: January 2020

Using the techniques of complement fixation, immunofluorescence, and in vitro lymphocyte transformation (LTF), we studied the humoral antibody and cell-mediated immunity to cytomegalovirus (CMV) in normal subjects, in patients with cancer receiving localized or nonlocalized radiation, and in renal transplant recipients on immunosuppressive chemotherapy. The LTF activity was determined by the whole blood microassay, using four strains of CMV (AD-169, Davis, Veca, and Towne), AD-169 early antigen, and phytohemagglutinin (PAH). The renal transplant subjects manifested significantly depressed LTF responses to PHA and CMV and frequent presence of immunoglobulin M and early antigen-specific antibody response. The depressed LTF response to CMV recovered significantly 2 years after transplantation. The cancer patients were also characterized by a profound drop in LTF responses to PHA and CMV and in immunoglobulin M and early antigen-specific antibody response after nonlocalized radiation. LTF responses to AD-169 and Towne strains were found to be higher than those to Davis and Veca strains. The LTF response to PHA declined with age. However, LTF responses to specific CMV antigens were found to be somewhat increased with advancing age. These observations suggest that transplantation-associated suppression of CMV-specific cell-mediated immunity may improve a few years after transplantation despite continued immunosuppressive therapy.
Group B streptococcal type Ia sepsis in mice after intranasal inoculation and the effect of infection on lungs
Authors: Wennerstrom D E
Published: January 2020

The intranasal inoculation of adult mice with saline suspensions of virulent group B streptococci serotype Ia resulted in septicemia which was lethal. Decreasing the inoculation dose of streptotocci increased the time required for their appearance in the blood and the mean time to death of the mice. Before the appearance of septicemia, the number of organisms in the lungs decreased to about 1% of the inoculation dose, and the majority could be recovered by lavage of the lungs through the trachea. In contrast, most of the organisms remained in the lavaged lungs of bacteremic mice after intranasal or intravenous inoculation. Lung surfactant obtained from infected mice was altered by a reduction in lipid and by an increase in protein. The organisms in vitro did not attack surfactant lipid labeled with [1-14C]palmitic acid, but their pathogenesis in vivo affected the permeability of the air-blood barrier, as shown by the leakage into the air spaces of plasma albumin labeled by the intravenous injection of Evans blue dye.
Behavior of a surface antigenic determinant of lateral flagella of Vibrio parahaemolyticus
Authors: Shinoda S , Nakahara N , Ono B I
Published: January 2020

The behavior of a surface antigenic determinant (SA) of lateral flagella of Vibrio parahaemolyticus was studied. SA, located on the surface of flagellar filaments, is responsible for H-agglutination and specific for serotype. Results of H-agglutination inhibition tests demonstrated that SA could not be detected on the flagellin molecule when the flagellar filaments were dissociated to flagellin monomers by heating or treatment with urea, sodium dodecyl sulfate, HCl, or acetone, although SA could be detected on short flagellar fragments obtained by milder heat treatment. When flagellar filaments were reconstituted from flagellin monomers, SA was detected on the surface of the filaments. These results suggest that SA is buried in the flagellin molecule with dissociation of flagellar filaments to flagellin monomers or steric configuration of SA itself is altered to a different form which cannot react with the responsible antibody.
Ia antigens in serum during different murine infections
Authors: Parish C R , Freeman R R , McKenzie I F , Cheers C , Cole G A
Published: January 2020

There exists in the mouse a family of I-region-controlled (Ia) antigens which carry carbohydrate-defined determinants. These antigens appear in serum as glycolipids and seem to be actively secreted by antigen-activated T-cells. This paper describes the ability of selected viral, bacterial, and protozoal infections of mice to markedly alter the serum levels of these Ia antigens. All the infectious agents examined induced substantial augmentation or suppression of serum Ia concentrations or both. Lymphocytic choriomeningitis (LCM) virus first enhanced and then suppressed serum Ia levels during the course of acute infection. Enhancement occurred during the time of ongoing virus replication and splenic lymphoproliferation while suppression coincided with the peak of the cytotoxic T-cell response and virus clearance. Listeria monocytogenes infection induced a substantial reduction in Ia levels at a time just after marked depletion of T-cells in the spleen. In contrast, Brucella abortus caused a significant increase in Ia levels 7 days postinfection, which correlates with the appearance of peak numbers of bacteria in tissues. Finally, Plasmodium yoelii, a nonlethal malarial parasite which stimulates prolonged T-cell proliferation, augmented serum Ia levels, whereas P. berghei, a lethal parasite which tends to inhibit. T-cell division, suppressed Ia secretion. Possible interpretations of these different results are presented.
Regression of a murine fibrosarcoma after intralesional injection of a synthetic C39 glycolipid related to cord factor
Authors: Yarkoni E , Rapp H J , Polonsky J , Varenne J , Lederer E
Published: January 2020

Intratumoral injection of ultrasonically prepared emulsions of the synthetic glycolipid methly 6-O-(2-tetradecyl-3-hydroxyoctadecanoyl)-alpha-D-glucopyranoside (designated C39) induced complete regression of transplants of a syngeneic murine fibrosarcoma in most of the treated animals as did 6,6'-di-O(2-tetradecyl-3-hydroxyoctadecanoyl)-alpha,alpha,-trehalose (designated C76) in a previous study. The C76 compound, about twice the molecular weight of C39, was more effective therapeutically than the smaller molecule. Ultrasonically prepared emulsions of C39 and C76 were not toxic when given intravenously. Intravenously administered emulsions of C39 prepared by mechanical grinding were more toxic, but less granulomagenic, than those containing C76. Squalane and squalene, but not peanut oil, were effective substitutes for mineral oil as carriers of C39 in the treatment of the tumor.
Role of interferon in mice in protection against influenza A virus by bacterial ribosomes together with membranal glycoproteins of Klebsiella pneumoniae as adjuvant
Authors: Robert D , Quillon J P , Ivanoff B , Beaudry Y , Fontanges R , Normier G , Pinel A M , D'hinterland L D
Published: January 2020

Nonspecific protection against infectious aerosols of influenza A virus was obtained in Swiss mice after vaccination by aerosols of bacterial ribosomes together with membranal glycoproteins extracted from Klebsiella pneumoniae as the adjuvant. It was shown that repeated stimulant aerosols were necessary to obtain this protection. Routine estimation of serum interferon levels after administration of the association of ribosomes plus membranal glycoproteins to the animals by aerosol or intravenous route showed that there was no correlation between protection and the presence of serum interferon. It was shown that the serum interferon-inducer activity was due to ribosomes. No induction of serum interferon was obtained with membranal glycoproteins used separately. Local liberation of interferon in the mucous membrane of the upper respiratory tract was not investigated.
Suppression of In Vitro Lymphocyte Transformation During an Experimental Dermatophyte Infection
Authors: Green Frederick , Balish Edward
Published: January 2020

During primary
Trichophyton mentagrophytes
infection of strain 2 guinea pigs, the colony-forming units (CFU) of fungi present within the lesion peaked between days 7 and 14, whereas the severity of the lesion itself peaked between days 11 and 16. Concomitant with the latter peak, a pronounced depression in the in vitro mitogenic activity of spleen cells (SPC) and lymph node cells (LNC) was observed. Only after resolution of the primary infection (day 21) did LNC show increased deoxyribonucleic acid (DNA) synthesis in the presence of fungal antigens. During cutaneous reinfection, there was no distinct peak fungal load and CFU appeared to decrease steadily during the accelerated course of a reinfection disease. LNC from guinea pigs with severe, ulcerated reinfection lesions generally exhibited a heightened response to fungal antigen in vitro. LNC from guinea pigs with mild reinfection dermatophytosis had depressed in vitro reactivity to mitogens and dermatophyte antigen. The suppression of blastogenic activity during dermatophyte infection appeared to be associated with autologous serum components, since increased DNA synthesis resulted when SPC or LNC were cultured with fetal calf serum. The depressed in vitro DNA synthesis of lymphocytes (cultured with dermatophyte antigens) that were harvested during reinfection was not accompanied by an impaired ability of infected guinea pigs to respond with a delayed-type hypersensitivity skin test in vivo. These results support the hypothesis that experimental
T. mentagrophytes
dermatophytosis is a cell-mediated hypersensitivity disease that can be modified by immunosuppressive control mechanisms elaborated or induced by the fungus.
Immunostimulant activities of a lipophilic muramyl dipeptide derivative and of desmuramyl peptidolipid analogs
Authors: Parant M A , Audibert F M , Chedid L A , Level M R , Lefrancier P L , Choay J P , Lederer E
Published: January 2020

The immunostimulant properties of a new muramyl dipeptide (MDP) derivative bearing a lipophilic moiety on the C-terminal end of the peptide chain are described. It is shown, in particular, that 1,O-(acetylmuramyl-L-alanyl-D-isoglutamine-L-alanyl)-glycerol-3-mycolate had increased immunostimulant activity in comparison with MDP. It induced hypersensitivity even when administered with an antigen in saline, and it gave higher protection against bacterial infections than did MDP. A quite unexpected finding was obtained with the corresponding desmuramyl compound 1,O-(L-alanyl-D-isoglutamine-L-alanyl)-glycerol-3-mycolate, which had no activity in producing humoral antibodies but was just as active as the muramic acid-containing compound in stimulating nonspecific resistance to bacterial infections. It was not pyrogenic. Modifications of the peptide moiety or the lipid moiety of this peptidolipid led to decrease, or even loss, of activity. These results show the importance of the N-acetylmuramyl moiety in MDP for humoral antibody production. The peptidolipid 1,O-(L-alanyl-D-isoglutamine-L-alanyl)-glycerol-3-mycolate is the first member of a new category of nonspecific immunostimulants.
Effect of Treponema pallidum-infected testis supernatants on the cellular response of normal rabbit lymphocytes
Authors: Wicher K , Wicher V , Kaminski D
Published: January 2020

This report presents evidence indicating that both Treponema pallidum and the T. pallidum-free supernatant from T. pallidum-infected rabbit testes exert an immunosuppressive effect on the spontaneous proliferation and mitogenic response of normal rabbit lymphocytes. This effect seemed to be on the level of clonal expansion since antigenic recognition and blastogenic factor production occurred in spite of the presence of the immunosuppressive substance(s). The implication of this finding for T. pallidum multiplication in rabbit testes is discussed.