Biomedical subjects

G Filipp

Publications and source records attributed to G Filipp.

At least 19 recordsLinked to original sources

PubMed1987

Antigen-gelonin conjugates. Preparation and application in experimental myasthenia gravis.

The antigen-specific immune suppression by gelonin-antigen conjugates was tested in two different systems: (i) the horseradish-peroxidase-stimulated T-cell proliferation in vitro and (ii) in vivo with experimental autoimmune myasthenia gravis (EAMG) in the rat. For this, the phytotoxin gelonin, a glycoprotein from Gelonium multiflorum, was purified and linked to the respective antigens. For the in-vitro assay a lymph node cell suspension from rats immunized with horseradish peroxidase was cultured in the presence of this protein and proliferation was measured by [3H]thymidine uptake. In-vitro proliferation was significantly inhibited by adding gelonin-horseradish peroxidase conjugates. The therapeutic effects of antigen-gelonin conjugates were tested in the rat model EAMG. For these experiments rats were immunized with purified nicotinic acetylcholine receptor from electric fish in order to develop EAMG. The success of the immunization was monitored by the change in physical performance tests, the change in anti-acetylcholine receptor antibody titer, and by the change in the number of ionic endplate channels using a novel electrophysiological method. The latter method permits a very accurate assay of functional damage of acetylcholine receptor at the endplate and correlates well with the clinical severity of the disease. Rats were conventionally immunized with acetylcholine receptor from electric fish. After the onset of EAMG as measured by physical performance tests and rise in antibody titer a group of the animals was injected with an acetylcholine receptor-gelonin conjugate and this treatment was repeated seven days later. The loss in functional acetylcholine receptor was significantly smaller in the therapy group than in the untreated EAMG group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1985

Experimental autoimmune myasthenia gravis: can pretreatment with 125I-labeled receptor prevent functional damage at the neuromuscular junction?

Rats were immunized with purified receptor from electric fish to induce experimental autoimmune myasthenia gravis (EAMG). It is implied by the clonal selection theory that antigens react only with receptors on specific immunocompetent cell subpopulations. In an attempt to damage these specific cells with the aid of highly radioactive antigen, one group of rats was pretreated with an additional injection of radiolabeled receptor of high specific activity 3 days before the basic immunization. The success of the immunization was monitored by measuring changes in the following three parameters: antibody titers against nicotinic acetylcholine receptor; number of alpha-bungarotoxin-binding sites at endplates; and number of acetylcholine-operated ionic endplate channels, using quantitative electrophysiologic methods. Conventionally immunized animals showed the classical signs of EAMG: elevated antibody titers against nicotinic acetylcholine receptor and a reduction of the number of alpha-bungarotoxin-binding sites, as well as reduction of the number of acetylcholine-operated ionic channels. The same symptoms were found in animals pretreated with unlabeled receptor and in animals pretreated with radioactive albumin. Animals pretreated with radioactively labeled receptor showed far less reduction of functional nicotinic acetylcholine receptor and only slightly raised antibody titers. This study suggests that preimmunization with radioactive antigen selectively eliminates immunocompetent cells, thus precluding the production of antibodies by a subsequent immunization procedure. The same protective effect cannot be obtained by either preimmunization with unlabeled antigen or by radioactively labeled unspecific antigen.

Animals↗

PubMed1984

Effect of highly radiolabelled 2,4-dinitrochlorobenzene (DNCB) on experimental DNCB contact dermatitis in guinea pigs.

With the aid of epicutaneous application of 2,4-dinitrochlorobenzene (DNCB) solution in acetone, we induced a cutaneous allergic reaction of the delayed type. Our question was whether the development of the DNCB cutaneous sensitivity could be suppressed by highly radiolabelled DNCB. On the basis of the clonal selection theory and our own results with other in vivo-experimental animal models, one could suppose that the highly radiolabelled DNCB as haptens binds to the Ig-membrane receptors of the genetically determined T-lymphocyte clone, and that the conjugated radioactivity (125I) causes a selective radioactive damage to this competent T-lymphocyte subpopulation. By means of intracardially applied radiolabelled DNCB, we are able to induce either complete or very significant suppression of the cutaneous DNCB immune response. In the second experiment, the highly radiolabelled DNCB was not able to inhibit sensitization to a simultaneously applied 4-ethoxy-methylene-2-phenyl-oxazolone (oxazolone). This result clearly demonstrates the antigen specificity of this form of immune suppression.

Animals↗

PubMed1984

Inhibition of autoimmune hepatitis with hot labelled liver specific antigen.

In accordance with the clonal selection theory the authors intended to prevent the development of autoimmune hepatitis in rabbits with the aid of radiolabelled liver specific membrane (LSP) antigen administered prior to the antigen immunization. The autoimmune hepatitis was produced in rabbits by allogen LSP antigen. The inflammatory reaction was characterized by the serum glutamic oxaloacetic transaminase activity in the sera, by the parameters of immune reaction as well as by lysosomal membrane alterations in the liver and by morphological findings. The process was inhibited by pre-treatment with hot labelled LSP antigen. Neither the radioactively labelled growth hormone pre-treatment, nor the application of hot labelled antigen at the last week of the experiment were able to prevent the humoral and lysosomal, as well as the morphological data characteristic for autoimmune hepatitis. The results obtained may be understood considering the mechanism of clonal selection.

Animals↗

PubMed1981

Selective suppression of antibody production with the aid of radiolabelled birch pollen allergen.

In accordance with the clonal selection theory we intended to prevent the development of artificially induced birch pollen allergy in rabbits with the aid of the radiolabelled pollen allergen (75-1000 microCi125 I-pollen/animal) intravenously administered prior to pollen sensitization. The birch pollen allergen, is accordance with Burnet's working hypothesis, reacts only with a genetically determining B cell subpopulation. The fixation of the radiolabelled birch pollen allergen to the receptors of the competent B cell clone causes the lesion of the latter. Compared with the control group, this group of rabbits showed an extensive suppression of anaphylactic reagin-like PCA-antibodies, and haemagglutinating antibodies in the blood as well as in nasal secretion. In addition, we tried to influence the already ongoing synthesis of the antibodies with the aid of subsequent intravenously administered radiolabelled birch pollen allergen (750-100 microCi 125 I-pollen/animal). An intensive suppression of the synthesis of antibodies could also be proved in this case. The simultaneous immunization of the control rabbits with birch pollen and egg albumin resulted in the production of antibodies against both antigens, as expected. The hot-labelled birch pollen antigen intravenously injected before or after immunization with egg albumin and birch pollen led selectively to suppression of anti-birch-pollen PCA antibodies. The synthesis of anti-egg albumin PCA antibodies was unaffected.

Allergens↗

PubMed1980

Aortic and hepatic changes in guinea pigs after immunization with vascular tissue antigens. Immunological and immune electron microscopic studies.

Human vascular tissue antigens were administered to guinea pigs for the study of humoral immune responses and of the microscopic and ultrastructural features of the changes produced in the aorta and liver. Immunization was followed by a definite humoral reaction. The passive haemagglutination test gave a cross reaction between the two antigenic effects. Histologic, immunofluorescent and electron microscopic studies revealed changes in the intima and the liver structure. IgG-containing immunocomplexes were demonstrable by means of ferritin-labelled monospecific antiserum in the aortic endothelium and hepatocytes.

Animals↗

PubMed1977