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Biomedical subjects

A Belehu

Publications and source records attributed to A Belehu.

At least 37 records · Page 2Linked to original sources
PubMed1982

Thymus-dependent lymphocytes in leprosy. II. Effect of chemotherapy on T-lymphocyte subpopulations.

The basis of the immunological unresponsiveness seen in leprosy patients is unknown. Untreated lepromatous leprosy patients display an unspecific cellular anergy which disappears with treatment, leaving an anergy specific for Mycobacterium leprae. These patients suffer from a complication, erythema nodosum leprosum, characterized by a recurrent eruption of tender skin nodules disappearing in 2 to 3 days. These nodules show a histological picture reminiscent of an Arthus reaction. Erythema nodosum leprosum can occur in untreated patients but it is more frequent in those receiving effective chemotherapy, and this has been thought to be due to massive release of antigen from the bacilli. By using monoclonal antibodies detecting different subpopulations of human peripheral blood T lymphocytes, we have shown that both borderline lepromatous leprosy patients had increased circulating suppressor cells (P less than 0.001) while the total number of T cells was within the normal range. The suppressor-cell population decreased with the duration of treatment, the change being evident at as early as 21 days. Five patients developed erythema nodosum leprosum during the study period. In all these patients the number of suppressor cells was decreased prior to the complication, increasing to original values with clinical recovery from this syndrome. There was no significant effect on T-lymphocyte subpopulations during chemotherapy of borderline tuberculoid leprosy patients. It seems that antileprosy chemotherapy precipitates erythema nodosum leprosum by interfering with immunoregulatory T cells.

Antibodies, Monoclonal↗
PubMed1982

Studies on the defect in cell-mediated immunity in lepromatous leprosy using HLA-D-identical siblings. Absence of circulating suppressor cells and evidence that the defect is in the T-lymphocyte, rather than the monocyte, population.

Sixteen healthy siblings were identified as HLA-D-identical to 12 borderline lepromatous or polar lepromatous leprosy patients by the absence of a mixed lymphocyte reaction (MLR). The peripheral blood mononuclear cells (PBM) of the healthy siblings showed a lymphoproliferative response (delta cpm) to Mycobacterium leprae antigens which was about fivefold or more greater than that of the lepromatous patients. Lepromatous PBM, with or without mitomycin C treatment, were co-cultured with a constant number of normal PBM. In other experiments the two cell types were co-cultured in various proportions, with the total cell number kept constant. Neither approach revealed suppressor cells in lepromatous PBM capable of suppressing the lymphoproliferative response to M. leprae. On the contrary, we found that lepromatous PBM can respond to M. leprae antigens if the sensitized lymphocyte is provided by mitomycin-C treated normal PBM. Additionally, experiments in which isolated adherent cells and non-adherent cells of sibling pairs were recombined failed to reveal a defect in the M. leprae antigen-presenting function of lepromatous adherent cells. Since we found no evidence that sensitized cells are present in lepromatous PBM with their function unexpressed (due to a monocyte defect) or suppressed (due to suppressor cells), we conclude that lepromatous patients simply lack sufficient numbers of antigen-specific T lymphocytes to initiate a lymphoproliferative response to M. leprae antigens. The reason for their absence remains an important unanswered question.

Adolescent↗
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

Humoral immunity in leprosy: immunoglobulin G and M antibody responses to Mycobacterium leprae in relation to various disease patterns.

A solid-phase radioimmunoassay, applying whole Mycobacterium leprae as antigen and radiolabeled protein A from Staphylococcus aureus as antibody-detecting reagent, was used for the determination of specific immunoglobulin G (IgG) and IgM antibody responses in leprosy patients. High IgG anti-M. leprae antibody levels were found in lepromatous leprosy patients, whereas the antibody response in tuberculoid leprosy patients varied from negative, i.e., comparable with responses measured in normal individuals, to strongly positive. In tuberculoid leprosy patients, a significant increase in IgG anti-M. leprae antibody levels was observed in the more widespread forms of the disease, but positive antibody responses were especially predominant among patients with active lesions. Lepromatous leprosy patients generally demonstrated high levels of both IgG and IgM anti-M. leprae antibodies, but no relation was found between the antibody responses and bacillary load or other clinical parameters. A marked decrease in specific IgG and IgM antibody levels was observed in lepromatous leprosy patients during their first year of treatment. Differences in mechanisms regulating the humoral immune response in tuberculoid and lepromatous leprosy patients were indicated, and the application of antibody assessments in leprosy control programs is discussed.

Antibodies, Bacterial↗
PubMed1982

Thymus dependent lymphocytes in leprosy. I. T lymphocyte subpopulations defined by monoclonal antibodies.

Monoclonal antibodies recognizing different human T lymphocyte subpopulations were used to characterize peripheral blood T lymphocytes in patients with leprosy. An increase in the suppressor T lymphocyte subpopulation was seen only in lepromatous leprosy (BL-LL) patients. In contrast, patients who had erythema nodosum leprosum (ENL) showed a disturbance in immunoregulation seen as a decrease of the suppressor cell percentage and manifested by an increase in in vitro lymphoproliferative responses to both PPD and PHA. This imbalance was seen to normalize as patients improved clinically. There was no deviation from the normal values of the total T lymphocyte population. It is suggested, therefore, that ENL may be associated with an acute imbalance of T lymphocyte subpopulations. Since the suppressor T lymphocyte identified by the mononuclear antibody used is antigen nonspecific, the significance of these suppressor cells in the pathogenesis of leprosy remains unclear.

Antibodies, Monoclonal↗
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↗
PubMed1982

Immunoglobulin class specific antibodies to M. leprae in leprosy patients, including the indeterminate group and healthy contacts as a step in the development of methods for sero-diagnosis of leprosy.

IgA, IgM and IgG anti-M. leprae antibody activity was quantitated by solid phase radioimmunoassay in groups of untreated leprosy patients throughout the spectrum, in lepromatous leprosy patients treated for more than 10 years, in an indeterminate leprosy group, and in a non-leprosy control group. IgA, IgM and IgG anti-M. leprae antibody activity increased from the group of healthy individuals exposed to M. leprae but without clinical signs of leprosy to tuberculoid (BT and BT/TT) and further to lepromatous (BL to LL) leprosy. There was a considerable overlap in IgA antibody activity, while the overlap between controls and tuberculoid and lepromatous leprosy was less than 20% in the IgM and IgG assays. After more than 10 years of treatment, the IgG anti-M. leprae activity had decreased markedly, whereas there was less effect in the IgA assay and no significant change in the IgM assay. In contrast to earlier findings, the group of 'strictly indeterminate leprosy' showed signs of an active humoral immune response against M. leprae. The IgM anti-M. leprae activity was higher in indeterminate leprosy than in the control group with virtually no overlap. IgA anti-M. leprae was higher in indeterminate leprosy, but with considerable overlap with the controls. No difference between these two groups was found in the IgG assay. The results are discussed in relation to the value of the various immunoglobulin specific anti-M. leprae assays for different purposes, including development of techniques for sero-diagnosis of leprosy.

Antibodies, Bacterial↗
PubMed1982

Demonstration of mycobacterial antigens in leprosy tissues.

Biopsies from 69 patients with leprosy were stained to demonstrate mycobacterial antigens using immunoperoxidase methods. The same biopsies were cut and stained using Fite-Faraco, TRIFF and hematoxylin-eosin for classifying the patients and to demonstrate mycobacteria. Since M. leprae and BCG show extensive antigenic cross reactions, anti-BCG antibodies were used as primary antisera to demonstrate cross-reacting antigens of M. leprae. Cross-reacting mycobacterial antigens were, thus, found in all LL and BL leprosy patients. Eight out of 10 patients with indeterminate leprosy had mycobacterial antigens and 17 out of 19 BT leprosy patients were positive for antigens. In general, in the BT patients the presence of the antigen was related to the host tissue reaction; this relationship was found in only half of the patients with indeterminate leprosy studied. During ENL mycobacterial antigens were found both intra- and extra-cellularly in the inflammatory infiltrate, but the polymorphonuclear leukocyte infiltration was seen only around the extracellular perivascular antigen. In reversal reaction, the inflammatory response was towards extracellular mycobacterial antigens. After this reaction there were no antigens demonstrable.

Animals↗
PubMed1981

Borderline tuberculoid leprosy following BCG vaccination. A case report.

Borderline tuberculoid leprosy was diagnosed clinically and histologically in a four year-old boy about 6 months after intradermal vaccination with BCG. His mother reported that a lesion began to appear above the vaccination site on the arm 2 weeks after the vaccination, and a second lesion appeared on the chin 2 months later. Responses in the lymphocyte transformation test to sonicated Mycobacterium leprae, BCG, and to PPD were consistent with a tuberculoid leprosy infection. Precipitation of BT leprosy by intradermal BCG infection may possibly represent the overcoming of a phase of primary suppression in an individual who might otherwise have progressed toward lepromatous leprosy. The implications of this hypothesis for the planning of a controlled trial of an anti-leprosy vaccine are discussed.

BCG Vaccine↗
PubMed1980

Effect of Mycobacterium leprae on lymphocyte proliferation: suppression of mitogen and antigen responses of human peripheral blood mononuclear cells.

Evidence is presented that Mycobacterium leprae suppresses the in vitro proliferative response of human peripheral blood mononuclear cells (PBM) to antigen and mitogen. Lymphoproliferation induced by PPD or alloantigen stimulation was inhibited by concentrations of M. leprae which were not cytotoxic for lymphoblasts. In contrast, the inhibition of mitogen-stimulated PBM was seen only at higher concentrations of M. leprae which proved to be cytotoxic for lymphoblasts. The inhibitory effect was found not to be dependent on a particular cell population present in leprosy patients, as PBM from normal were inhibited similarly. These findings may explain some of the immunological aberrations observed in lepromatous leprosy patients who harbour large numbers of M. leprae bacilli in their tissues.

Antigens, Bacterial↗
PubMed1980

An assay for antibodies in leprosy sera reacting with ribonucleoprotein (RNP), a mycobacterial ribosomal antigen, using crossed immunoelectrophoresis with intermediate gel.

The technique of crossed immunoelectrophoresis with intermediate gel has been adapted to provide a quantitative assay for antibodies to a mycobacterial ribosomal antigen termed ribonucleoprotein (RNP) antigen. This antigen is no. 1 in the M. smegmatis reference system and corresponds to antigen no. 5 of M. leprae. The assay method measures changes in the rate of migration of the reference precipitin peak caused by the addition of serum in the intermediate gel and utilizes a lepromatous serum pool (LSP) both in the reference gel and as a standard in the intermediate gel. The anti-RNP activity in 24 leprosy sera differentiated the pauci-bacillary tuberculoid group (11 of 12 < 35% LSP) from the multi-bacillary lepromatous group (11 of 12 > 35% LSP). These findings confirm the work of others which indicates that assay of anti-RNP activity may have applications in the classification of leprosy patients and in the serodiagnosis of lepromatous leprosy infections. This method should also be applicable in other systems in which an antigen of high electrophoretic mobility forms a major precipitin in crossed immunoelectrophoresis.

Antibodies, Bacterial↗