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Biomedical subjects

M Harboe

Publications and source records attributed to M Harboe.

At least 163 records · Page 9Linked to original sources

Antibodies against Mycobacterium leprae antigen 7 from birth to 18 months of age: an indicator of intra-uterine infection in leprosy.

All babies of three non-leprosy mothers and ten tuberculoid leprosy mothers and four of five babies of mothers with inactive lepromatous leprosy showed a decline in serum concentration of antibodies against M. leprae antigen 7 during the first 4 months of life, as expected from catabolism of maternal IgG. By contrast, ten of twenty babies of mothers with active lepromatous leprosy showed a decline in concentration of anti-M. leprae 7 antibodies considerably less than expected. This indicates that these babies have been stimulated by M. leprae antigen 7, either as free antigen or by viable M. leprae before birth, and thus that leprosy may occur as a congenital infection. Studies of anti-M. leprae antibodies in repeated serum samples obtained during the first 18 months of life indicated that children of mothers with bacilliferous leprosy are frequently exposed to M. leprae to a sufficient extent to stimulate the immune system of the baby to production of anti-M. leprae antibodies during this period. The consequences of this exposure to M. leprae should be ascertained by careful clinical studies.

Aging↗

[Nil nocere].

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Antibody Formation↗

Cross-reactions between mycobacteria. II. Crossed immunoelectrophoretic analysis of soluble antigens of BCG and comparison with other mycobacteria.

Cross-reactions between Mycobacterium bovis BCG and various other mycobacteria, Nocardia asteroides, Corynebacterium pyogenes and Listeria monocytogenes were studied by incorporating antibodies against these bacteria in the intermediate gel of a crossed immunoelectrophoretic system with BCG antigen and anti-BCG antibodies. In the BCG reference system forty-four distinct antigenic components were recorded, of which thiryt-three cross-reacted with Mycobacterium tuberculosis, twenty-five with M. avium, twenty-one with M. suvalii, eighteen with M. smegmatis, Fifteen with M. nonchromogenicum, twelve with M. phlei, eight with N. anteroides and two with C. pyogenes, whereas no cross-reaction was detected with L. monocytogenes. The value of the method for characterization of mycobacterial antigens is discussed. A taxonomic system based on this method appears particularly valuable for studies of non-cultivativable mycobacteria such as M. leprae. A majority of twenty-one patients with lepromatous leprosy had anti-BCG antibodies of restricted specificity, affecting only four or five BCG antigens, although one patient had twelve anti-BCG specificities. Most of these antibodies reacted with those BCG antigens that cross-react extensively with other mycobacteria.

Antibodies, Bacterial↗

Antibody response in rabbits to Mycobacterium bovis BCG.

The specificity of the immune response after immunization with Mycobacterium bovis BCG was studied by crossed immunoelectrophoresis with intermediate gel in a BCG/anti-BCG system, in which the reaction against thirty distinct components of BCG was recorded. After a single injection of total sonicate of 3 mg (dry weight) bacilli, the antibody response was markedly similar in eight rabbits. Th earliest and strongest response was directed against nine components of BCG; all but one of these belonged to the group of thirteen components that cross-react extensively with other mycobacteria. After repeated immunization with sonicate from about 0.8 microgram of BCG bacilli, five components still induced a marked antibody response. All but one of these components are among the most widely cross-reacting BCG components, and the observations made after subsequent challenge with the higher dose of BCG indicate that low-zone tolerance was induced against other components of the bacilli. The implication of these findings concerning formation of anti-mycobacterial antibodies in normal individuals and during mycobacterial infection is discussed.

Animals↗

Antigenic analysis of Mycobacterium leprae.

About twenty distinct antigenic components have been demonstrated in Mycobacterium leprae (M. leprae) by crossed immunoelectrophoresis against a rabbit antiserum produced by immunization with concentrated M. leprae antigen. This system allows a more detailed analysis of the antigenic relationship between M. leprae and other mycobacteria and a better characterization of the antigenic content of various M leprae preparations than with previously available anstisera of the antigenic content of various M. leprae preparations than with previously available antisera which reacted with far fewer components. The antibody activity in sera of patients with lepromatous leprosy was studied by incorporating the sera into the intermediate gel of the M. leprae reference system. Antibodies were found against only seven of the components. Since those compared are all known to be cross-reacting widely with antigens of other mycobacteria, it is speculated that cross-immunization may influence the antibody response in lepromatous leprosy.

Animals↗

Cross-reactions between serum proteins and water soluble liver tissue antigens of the nine-banded armadillo (Dasypus novemcinctus Linn.) and man.

Cross-reactions between serum proteins and water soluble liver antigens of the nine-banded armadillo (Dasypus novemcinctus Linn.) and man were studied by crossed immunoelectrophoresis (CIE). Armadillo serum tested with rabbit antiserum against human serum proteins gave twelve components in CIE. Nine of these cross-reacting proteins were identified and showed partial identity with the corresponding human proteins. The electrophoretic mobility of alpha 2-macroglobulin and Gc-globulin differed in the two species. An ultrasonicate of normal armadillo liver gave twenty-eight anodic and eight cathodic components in CIE. By absorption experiments with armadillo serum, twenty of the former and seven of the latter were shown to be liver tissue components. A combination of CIE and crossed-line immunoelectrophoresis (CLIE) revealed the presence of twelve anodic and six cathodic liver tissue components cross-reacting with man. A cathodic armadillo liver antigen called (CALA-17) showed partial identity with that of man both in tandem and fused rocket immunoelectrophoresis. The implications of the findings are discussed in relation to the use of armadillo-grown M. leprae for skin testing and other purposes in man.

Animals↗

Formation of antibody against Mycobacterium leprae antigen 7 in armadillos.

A radioimmunoassay developed to measure antibody against Mycobacterium leprae antigen 7 in man was applied to the nine-banded armadillo (Dasypus novemcinctus). Normal armadillo sera had low but significant antibody activity in the test. Fourteen of 17 armadillos with systemic mycobacterial infection after inoculation with M. leprae showed increased antibody activity in the assay, and in some instances the activity was higher than in a pool of sera from patients with lepromatous leprosy. Crossed immunoelectrophoresis with armadillo serum in the intermediate gel revealed antibodies against five distinct antigenic components of M. leprae. Development of systemic mycobacterial infection after inoculation with M. leprae is thus associated with a distinct humoral immune response. The use of radioimmunosassay for selection of animals for inoculation and for following the development of the infection is discussed.

Animals↗

Mycobacterium leprae specific antibodies detected by radioimmunoassay.

A radioimmunoassay was developed for demonstration of antibodies against M. leprae specific antigenic determinants. The specificity of the assay was tested with hyperimmune rabbit antisera against other mycobacteria and shown to be very high. The titre of M. leprae specific antibodies in a lepromatous serum pool was 10(5). Sixty-one of sixty-two lepromatous sera, all of twelve borderline sera and twenty of forty-eight tuberculoid sera were positive in the assay, whereas all of thirty-eight control sera from tuberculin positive individuals from a leprosy non-endemic area were negative. Aplication as a diagnostic test for subclinical infection with M. leprae is discussed. The principle of the test appears promising for serological distinction between pulmonary infection with M. tuberculosis and other mycobacteria.

Antibodies, Bacterial↗

Characterization of lymphocytes isolated from non-lymphoid human malignant tumours.

Mononuclear cells (MC) were found in suspensions prepared from twenty-one out of twenty-two solid human neoplasms. In three cases it was calculated that more than 1% of the MC could represent contamination by blood MC. Due to technical difficulties and blood lymphocyte contamination, eight cases were excluded from the study. MC could be separated from thirteen of the remaining fourteen tumours and in one tumour no MC were found. On average, 0.44 X 10(6) MC were obtained from each biopsy weighing 1-5 g. The MC were characterized with regard to markers for T and B lymphocytes. On average 41.0% of the MC were T and 18.2% B cells. There was no significant correlation between MC infiltration and tumour size or spread. In all patients blood MC were also isolated and characterized with regard to T (62.0%) and B lymphocytes (14.3%). The T/B ratio of tumour and blood lymphocytes corresponded in most cases. In two cases a markedly depressed T fraction was found within the tumour, whereas the T lymphocyte portions in the blood of these patients were within the normal range.

Aged↗

False spurs in quantitative immunoelectrophoresis.

Antigens which show reactions of identity in double-diffusion tests in gel may cause spur formation in crossed immunoelectrophoretic techniques. To differentiate these misleading spurs from spurs of double-diffusion tests which show the true immunochemical relationship between antigens, we have denoted the former type "false spurs". False spurs are often formed in tandemcrossed immunoelectrophoresis and fused rocket immunoelectrophoresis when antigens with different electrophoretic mobility are compared. On the basis of model experiments, criteria are set up for accepting a spur as a true spur, and procedures are described for avoiding formation of false spurs in quantitative immunoelectrophoresis.

Animals↗

Antibodies against BCG antigen 60 in mycobacterial infection.

A sensitive specific radioimmunoassay was developed to measure antibodies against BCG antigen 60, a prominent antigenic component of BCG bacilli which cross-reacts with similar components in many mycobacterial species including Mycobacterium leprae and M tuberculosis. A lepromatous serum pool had anti-BCG-60 activity with a titre of 10(5) and the tuberculoid pool a titre of 10(4). Testing of individual sera showed striking variations within groups of patients with lepromatous and tuberculoid leprosy. In five of the 20 tuberculoid leprosy sera the anti-BCG-60 activity was above the median for the lepromatous group. The current view that antibody formation against mycobacterial antigens is very low in tuberculoid leprosy thus no longer appears to be tenable. Sera from eight patients with active pulmonary tuberculosis also showed a striking variation in anti-BCG-60 content, and the median value of this group was even higher than in those with lepromatous leprosy.

Antibody Formation↗

Production and assay of antibodies against one antigenic component of Mycobacterium bovis BCG.

Monospecific antisera against BCG antigen 60 were produced by all of four rabbits during immunization with precipitates containing antigen 60 cut out of gels after crossed immunoelectrophoresis. During electrolytic iodination of a crude antigen 60 preparation, preferential labeling of antigen 60 was demonstrated, and a specific radioimmunoassay was established to follow the development of anti-BCG-60 activity during immunization.

Animals↗

Antibody response in rabbits to immunization with Mycobacterium leprae.

Mycobacterium leprae purified from liver tissue of an infected armadillo (the A/10 preparation) was tested for antigenic composition by immunization of rabbits and characterization of the antibody response by crossed immunoelectrophoresis. The rabbit antisera detected seven distinct components in the M. leprae preparation. This number is far lower than in similar experiments with other mycobacteria. The M. leprae sonic extract gave far fewer lines after polyacrylamide gel electrophoresis and staining with Coomassie brillant blue than sonic extracts prepared from BCG, M. smegmatis, and M. phlei adjusted to the same protein concentration based on the Folin assay. The seven components detected in M. leprae cross-reacted extensively with M. avium, BCG, M. lepraemurium, M. smegmatis, and Nocardia asteroides. The seven components are involved in immune reactions in leprosy; antibodies against all of them were demonstrated in sera from patients with lepromatous leprosy, but the specificity of the antibodies varied from patient to patient. The reason for the demonstration of so few antigenic components and some of the implications of these findings for the use of armadillo-grown M. leprae to develop specific skin test reagents and in other aspects of leprosy research are discussed.

Animals↗

Sudden death caused by interaction between a macroglobulin and a divalent drug.

Intravenous injection of the divalent X-ray contrast medium ioglycamic acid ("Biligram") induced intravascular precipitation and sudden death of a patient owing to reaction with his monoclonal macroglobulin. Mice reacted similarly in passive transfer experiments. The corresponding monovalent compound, acetrizoic acid, was also bound to the IgM but did not induce precipitation and had no apparent ill-effects on mice in passive transfer experiments.

Animals↗

Binding of IgA to protein-A-containing staphylococci: relationship to subclasses.

Among 54 human monoclonal IgA proteins, 5 inhibited the binding of labeled human monoclonal IgM (IgM Se and IgM Ba) to protein-A-containing staphylococci, whereas 48 did not have this ability. One protein (IgA Ha) showed discordant findings in the IgM Se and IgM Ba inhibitions assays. Among the 54 IgA proteins, 49 were of the IgA1 and 5 of the IgA2 subclass. All of the 5 IgA2 proteins inhibited the binding of IgM Se and IgM Ba to staphylococci, whereas the 48 proteins that reacted negatively in the two inhibition assays belonged to the IgA1 subclass. These findings show that the ability to react with staphylococci is a property of the IgA2 subclass. IgM proteins may also be divided into two groups based on different reactivities with protein A. It is proposed to call the two IgM subclasses IgM1 and IgM2, where the latter is defined by ability to react with protein A.

Bacterial Proteins↗