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Biomedical subjects

O Closs

Publications and source records attributed to O Closs.

At least 37 records · Page 2Linked to original sources
PubMed1984

Induction of immunity against live Mycobacterium lepraemurium: a requirement for viable bacilli?

Live Mycobacterium lepraemurium (MLM) bacilli, bacilli killed by irradiation or heat, and the water-soluble components of ultrasonicated bacilli (MLMSon) were compared as immunizing and eliciting antigens in C57BL mice which are high-responders to live MLM. The latency period preceding the development of a local granulomatous reaction in normal mice inoculated subcutaneously in the footpad with live MLM was reduced, and the reaction became larger when the dose of bacilli was increased. Immunization with MLMSon induced only weak initial reactivity against an inoculum with live bacilli, but the development of stronger reactivity was accelerated and the magnitude of the local reaction that then developed was increased. MLMSon-immunized mice showed some reactivity also against heat-killed bacilli. Killed bacilli caused the development of a small, late local reaction in normal mice, but no local reactivity was detected upon challenge with live and killed MLM in mice immunized with killed bacilli. However, a local reaction was elicited by MLMSon, which was thus a more potent eliciting antigen than intact bacilli, and MLMSon and whole killed bacilli appeared to induce immune reactivity with overlapping antigen specificities. Subcutaneous inoculation with live bacilli induced reactivity against live MLM but not against MLMSon and not against whole killed MLM, except for a transient early (24 hr) reaction elicited only with a large dose of killed bacilli. The development of a lasting local reaction against killed bacilli was found to be suppressed in mice immunized with live bacilli. Live bacilli and dead MLM antigen appeared to have largely different specificities as inducing as well as eliciting antigens.

Animals↗
PubMed1984

Mouse monoclonal anti rabbit IgG coupled to monodisperse polymer particles. Comparison with polyclonal antibodies in radioimmunoassay for thyroid hormones.

A solid phase second antibody was prepared by covalent coupling of a mouse monoclonal anti rabbit IgG to monodisperse particles. This preparation was compared with immunosorbent purified sheep anti rabbit IgG antibodies coupled to the same particles. The monoclonal antibody bound rabbit IgG with a dissociation constant of 3 X 10(-11) L/mol, and the binding was Fc specific. The sheep antibodies had a similar Kd and about 75% of the activity was directed against the Fc portion of IgG. The binding capacity per mol of both solid phase antibodies was 0.7 mol of rabbit IgG. Monoclonal and polyclonal solid phase antibodies were equally effective as separating agents in various radioimmunoassays. Direct coupling of the rabbit antibodies to the solid phase resulted in a marked loss of binding capacity for the respective thyroid hormones. However, when rabbit anti-thyroxine or anti-triiodothyronine were preadsorbent to second-antibody-coated particles the binding capacities of the former antibodies were well preserved.

Animals↗
PubMed1983

H-2-linked gene(s) influence the granulomatous reaction to viable Mycobacterium lepraemurium in the mouse.

The genetic control of the granulomatous response to viable Mycobacterium lepraemurium (MLM) was studied in C3H and C57BL/6 inbred strains, BXH recombinant inbred strains, (C3H X C57BL) F1 hybrids, and backcross mice. The results indicate that an autosomal dominant gene, or linked complex of genes, has a marked influence on the footpad reaction to viable MLM. The distribution of responders and non-responders among 12 BXH recombinant inbred strains and linkage analysis in C3H X (C3H X C57BL)F1 backcross mice indicated that the response gene(s) are linked to the H-2 complex on chromosome 17. The same gene(s) also influence host restriction of MLM multiplication and thus appear to be the first H-2-linked gene(s) influencing resistance to a bacterial infection.

Animals↗
PubMed1983

Induction of delayed type hypersensitivity against ultrasonicated Mycobacterium lepraemurium bacilli without simultaneous local reactivity against live bacilli or protective immunity.

Delayed type hypersensitivity (DTH) was induced in C3H mice by subcutaneous immunization with Mycobacterium lepraemurium (MLM) antigens in Freund's complete (FCA) or Freund's incomplete (FIA) adjuvant. The total ultrasonicate (MLMSon-P) of MLM bacilli as well as the water soluble fraction (MLMSon-S) of this ultrasonicate was found effective. MLMSon-S was used as the test antigen. Specific DTH also developed after immunization with heat-killed MLM bacilli in FIA, but not with heat-killed bacilli in saline. Some mice were pre-treated with cyclophosphamide (CY) or splenectomized to augment the effect of immunization. In no instance was DTH to MLMSon-S accompanied by detectable local reactivity to live MLM bacilli measured as swelling of the infected footpad or by reduced multiplication or dissemination of the bacilli during the first 11 weeks after inoculation. As determined by testing in the infected footpad 8 weeks after inoculation, MLM infection did not induce DTH to MLMSon-S in non-immunized mice, and MLM infection was found to neither augment nor suppress established DTH to MLMSon-S. The experiments thus demonstrated a clear dissociation between DTH to MLMSon-S and local reactivity to live MLM bacilli, as well as between DTH to MLMSon-S and protective immunity to MLM infection.

Animals↗
PubMed1983

Surface polysaccharide of Moraxella non-liquefaciens identical to Neisseria meningitidis group B capsular polysaccharide. A chemical and immunological investigation.

In whole cell preparations of 27 nonmucoid strains of Moraxella nonliquefaciens neuraminic acid was detected by gas chromatography (GC) in 16 (59%) of the strains. Seven neuraminic-acid-containing strains were tested for agglutination with diagnostic group-specific meningococcal antisera produced in rabbits, and all were positive with group B serum. Counter-immunoelectrophoresis of bacterial suspensions of the three strains with the strongest reaction with such anti-group B serum gave distinct precipitation lines. When tested by double immunodiffusion in agarose with monoclonal antibody to meningococcal group B polysaccharide, suspension of a strain of M nonliquefaciens gave identity reaction with a strain of Neisseria meningitidis, and reacted even more strongly than the latter. Phenol extracts of M nonliquefaciens strains generally contained higher amounts of neuraminic acid than N meningitidis group B strains. Neuraminic-acid-containing polysaccharides of M nonliquefaciens strains sedimented more slowly by ultra-centrifugation than the group-specific B polysaccharide of N meningitidis strains. They also reacted more strongly with a monoclonal anti-group B antiserum than did N meningitidis group B capsular polysaccharide in an antibody binding inhibition test (solid phase radioimmunoassay). Immunological reactivity of the polysaccharides of both species was lost if extraction was performed with unbuffered phenol at 68 degrees C, instead of with neutral phenol at 4 degrees C. The results show that several strains of M nonliquefaciens, often inhabiting the human nose, have high levels of a surface polysaccharide chemically and immunologically closely similar to N meningitidis group B capsular polysaccharide. The cross-reactivity may have immunological implications for meningococcal disease.

Chromatography, Gas↗
PubMed1982

In vitro stimulation of lymphocytes in leprosy patients, healthy contacts of leprosy patients, and subjects not exposed to leprosy. Comparison of an antigen fraction prepared from Mycobacterium leprae and tuberculin-purified protein derivative.

In vitro lymphocyte stimulation was performed on peripheral blood lymphocytes from 48 leprosy patients, 15 healthy contacts of leprosy patients, and 16 normal controls who lived in a leprosy-free area and who had not been exposed to leprosy. Tuberculin PPD and an antigen fraction. MLW 1, prepared from M. leprae, were used as stimulants. The MLW 1 preparation contained one antibody-precipitable component when tested in crossed immunoelectrophoresis against a polyvalent anti-M. leprae immunoglobulin preparation, namely the ML 7 antigen. MLW 1 induced strong lymphocyte responses in patients with tuberculoid leprosy and healthy contacts of leprosy patients, but only a weak or no responses in lepromatous leprosy patients and non-exposed controls. A marked depression of the response to tuberculin PPD was observed in lepromatous leprosy patients. The specificity of the MLW 1 antigen is discussed, and a new estimator of specific lymphocyte stimulation, the delta cpm', is introduced.

Adolescent↗
PubMed1982

Repeated delayed-type hypersensitivity reactions against Mycobacterium lepraemurium antigens at the infection site do not affect bacillary multiplication in C3H mice.

Delayed-type hypersensitivity was induced in cyclophosphamide-pretreated C3H/TifBom mice by subcutaneous immunization in the thorax with ultrasonicated Mycobacterium lepraemurium bacilli in Freund incomplete adjuvant. Seven weeks after immunization, 2.5 X 10(7) acid-fast M. lepraemurium bacilli suspended in diluted sonicate were injected into one hind footpad, and during the next 6 weeks three additional infections of sonicate were given at intervals into the infected footpad. After each injection a strong local reaction developed, which after the first three injections peaked at 24 h. The kinetics of the reaction was accelerated after the repeat injections. Each time the reaction subsided within 1 week. From 2 days to 11 weeks after the inoculation of bacilli there was a 10-fold increase in bacillary numbers in the footpad and a 3,000-fold increase in the draining popliteal lymph node. The degree of bacillary multiplication was the same in animals which had experienced repeated local reactions and in control animals. Thus, repeated strong delayed-type hypersensitivity reactions to M. lepraemurium antigens apparently were without any measurable effect on the bacillary multiplication. This observation provides further evidence for a dissociation in C3H/TifBom mice between delayed-type hypersensitivity to soluble mycobacterial antigens and protective immunity against mycobacteria. Possible explanations for our findings are discussed.

Adipose Tissue↗
PubMed1982

Effect of purified protein derivative and sonicates of Mycobacterium leprae and Mycobacterium bovis BCG on thromboplastin response in human monocytes in vitro.

Human monocytes isolated from peripheral blood responded with increased thromboplastin expression upon stimulation in vitro with three mycobacterial antigens: tuberculin purified protein derivative and sonicates of Mycobacterium boviS BCG and Mycobacterium leprae. The stimulating principle of mycobacteria is probably a cell wall constituent since crude extracts of cell walls were 2.5 to 25 times more potent in stimulating thromboplastin synthesis than were whole sonicates. This thromboplastin response was inhibited by inhibitors of RNA and protein synthesis, dexamethasone, and agents that caused elevation of intracellular cyclic AMP. The presence of lymphocytes did not enhance the monocyte thromboplastin response significantly during the first 24 h of incubation. For M. bovis BCG and M. leprae sonicates, the thromboplastin response correlated with general activating effects measured by determining the release of lysozyme and beta-glucuronidase. The role of thromboplastin in chronic inflammatory reactions is discussed.

Antigens, Bacterial↗
PubMed1982

In vitro lymphocyte stimulation in patients with lepromatous and borderline tuberculoid leprosy. The effect of dapsone treatment on the response to Mycobacterium leprae antigens, tuberculin purified protein derivative and non-mycobacterial stimulants.

Lymphocytes from peripheral blood were isolated from leprosy patients and healthy contacts (HC) of leprosy patients and stimulated in vitro with: Mycobacterium leprae and a M. leprae cell wall antigen, MLW 1; tuberculin purified protein derivative (PPD); antigens prepared from Candida albicans, Entamoeba histolytica, Leishmania aethiopica, and parotitis virus; the non-specific mitogens phytohemagglutinin (PHA) and concanavalin A (Con-A). Lymphocytes from patients with untreated lepromatous leprosy failed to respond to the M. leprae antigens, and the median response to PPD was also significantly (p less than 0.005) lower than in the HC group. They responded almost as well as the other groups to non-mycobacterial antigens, PHA, and Con-A. In LL patients who had been treated with dapsone for several (median 10) years, the failure to respond to M. leprae antigens remained, but the depression of the PPD response and the slight non-specific depression of the lymphocyte stimulation test (LST) responsiveness had been reversed. Our results confirm that the major defect in the cell-mediated immune response of LL patients is M. leprae-specific and permanent. The possibility that the defect may be due to a continuous, antigen-induced suppression of the immune response is discussed. That the defect also affected the response to PPD is important since it points to a clear antigenic relationship between M. leprae and BCG/M. tuberculosis. Evidence is presented suggesting that an antigen induced suppressor mechanism may be operating in vitro with cells from patients with borderline tuberculoid leprosy.

Adolescent↗
PubMed1981

Effect of BCG vaccination on Mycobacterium lepraemurium infection in a highly susceptible inbred mouse strain.

Upon infection with Mycobacterium lepraemurium (MLM) C3H mice develop a disease that has features in common with lepromatous leprosy in man. Intraperitoneal vaccination with a single dose of BCG four weeks before inoculation with MLM in the footpad significantly reduced the total bacillary load of the animals. In vaccinated animals there was a delay in the dissemination of bacilli to the popliteal lymph node, liver, and spleen. The growth rate of MLM in the footpad and the popliteal lymph node was not altered by BCG vaccination. Reduced dissemination of the bacilli seems to be a sensitive parameter of resistance in murine leprosy. The mechanism of the resistance observed is discussed mainly in relation to non-specific macrophage activation and T-cell mediated responses to cross-reactive antigens.

Animals↗
PubMed1981

In vitro lymphocyte stimulation with specific antigen in congenital toxoplasmosis.

The development of specific cell mediated immunity was studied in children with congenital toxoplasmosis and the in vitro lymphocyte stimulation test (LST) evaluated as diagnostic test for congenital infection. The test was performed in 35 children, including 5 with a confirmed or suspected congenital toxoplasmosis and for comparison, in 19 dye test positive and 7 negative women. The development of delayed type hypersensitivity (DTH) seemed to follow approximately the same time course in children with congenital toxoplasmosis as in adults with toxoplasmosis. The lymphocyte responses to toxoplasma antigen were low during the first year, but increased markedly during the second and third years after infection. Chemotherapy during the first year of life did not prevent the later development of DTH. It is concluded that a positive LST during the first year of life may be an indication of congenital toxoplasmosis. A negative test is not decisive.

Adolescent↗
PubMed1981

Demonstration of antibodies reacting with different determinants on Mycobacterium leprae antigen 7.

A purified preparation of M. leprae antigen 7 was used to investigate the specificity of anti-M. Leprae 7 antibodies in leprosy sera in a radioimmunoassay. A solution containing arabinogalactan (AG) and arabinomannan (AM) inhibited the antibodies in some sera to a great extent, whereas the antibody activity was virtually unchanged in other sera under the same conditions. These findings indicate that the antibodies are directed against different determinants on M. leprae antigen 7. Antibodies against determinants other than AG and AM occurred particularly in lepromatous leprosy sera. In 12 out of 14 sera, AG and AM had similar inhibiting capacity. In one serum, AG had markedly higher inhibiting capacity than AM; in the last serum, the reverse was the case, demonstrating variation in anti-polysaccharide specificity in individual sera.

Antibody Formation↗
PubMed1980

The antigens of Mycobacterium bovis, strain BCG, studied by crossed immunoelectrophoresis: a reference system.

A reference system for the soluble antigens of Mycobacterium bovis, strain BCG is described. The system is based on crossed immunoelectrophoresis with intermediate gel. A commercially available immunoglobulin preparation made from rabbit anti-BCG hyperimmune serum was used as reference antibodies, while a concentrated BCG culture filtrate was used as reference antigen. The pattern obtained was highly reproducible, and most of the components were stable when the fiftyfold-concentrated culture filtrate was stored at -20 degrees C. About thirty different antigenic components were selected as reference antigens and numbered. The majority of the reference antigens were present in extracts prepared from BCG by ultrasonication or bacterial press extraction. Use of the system for studies of antigenic relationship between mycobacteria, identification and quantification of antigens, and characterization of antimycobacterial antibodies are illustrated by examples. The antigens of two preparations of tuberculin purified protein derivative (PPD) were identified. The antigen designated BCG60 was found to be a najor constituent of tuberculin PPD. Evidence is presented that this antigen is cell wall associated.

Absorption↗
PubMed1980

Protective immunity and delayed-type hypersensitivity in C57BL mice after immunization with live Mycobacterium lepraemurium and sonicated bacilli.

The immunizing effects of live Mycobacterium lepraemurium (MLM) and bacillary sonic extract (MLMSon) were compared in C57BL mice. MLMSon-immunized mice developed a delayed-type hypersensitivity (DTH) reaction when tested in the footpad with diluted MLMSon. The ability to develop a DTH reaction was transferable with immune cells but not with serum. Footpad testing with live MLM and MLMSon indicated that the specificity of the DTH response induced by MLMSon was different from that induced by infection with live bacilli. Two weeks after footpad inoculation with live MLM, MLMSon-immunized mice developed a strong local reaction to the bacilli. No local reaction developed in these mice after injection of the same number of heat-killed MLM. Studies of bacillary growth after inoculation with live MLM indicated that the bacilli did not multiply in micr previously inoculated with live MLM, but that they multiplied for about 2 weeks in LMLSon-immunized mice versus 4 weeks in the controls. The results suggest that immunization with MLMSon does not by itself induce a protective immune response, but creates a state in which the development of protective immunity is accelerated.

Animals↗