[Current problems in the research on active substances. 13. Fluidity of cell membranes and mobility of cellular receptors, immunological and pharmacological aspects].
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Aspects of acetylcholine receptor immunology and circulating receptor antibodies are reviewed with regard to both human and experimental myasthenia gravis. Receptor antibodies that have negligible cross-reactivity with skeletal muscle receptor can nonetheless cause destruction of the postsynaptic motor endplate area. Antibodies to mammalian skeletal muscle receptor can bind in-situ receptors. Transfer of myasthenic IgG increases neurophysiologic symptoms in rabbits showing slight signs of experimental myasthenia gravis, suggesting a block of in-situ receptors. Determination of receptor antibodies using RIA tests and partially purified human skeletal muscle receptor has been evaluated in the diagnosis of myasthenia gravis. Ninety percent of Swedish myasthenic patients in one study were found to have receptor antibodies. A rough correlation has been found between antibody titer and the severity of disease. Immunosuppressive treatment and thymectomy decrease the titer. In patients with thymoma, high antibody titers remain. When taken together, antibody-titer determination and electrophysiologic tests--particularly single-fiber electromyography--are very valuable diagnostic tools.
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Radiolabelled staphylococcal protein A was used to quantitate the binding of IgG on stored human platelets from human sera containing specific antibodies reactive with platelets and rabbit serum containing immune complexes (IC). Normal human serum (NHS) inhibited the binding of IC onto platelets and to various extents also the binding of specific antibodies. The attachment of inhibitors to platelets seemed to be reversible. The considerable difference in the inhibitory capacities of IgG-deficient sera and monomeric IgG indicates that IgG is the major inhibitory component of NHS. The binding of IgG from NHS onto platelets evidently hampers the detection of weak platelet antibodies even with the most sensitive tests. Purified Clq, known to modify the reactions of IC with fresh platelets did not alter the binding of IC onto stored platelets. A monoclonal, antiglobulin-active rheumatoid factor of IgM class displayed only moderate inhibition. Therefore, the application of RF or Clq for the differentiation of the binding induced by IC or antibodies is not useful in this assay system. The heterogeneity of immunologic receptors of platelets provides an explanation of the inhibitory inefficiency of Clq.
Morphology, lysosomal enzyme activities, and phagocytosis via immunological receptors were tested in peritoneal macrophages from germfree and conventional mice. Nonstimulated macrophages from germfree mice showed less spreading and were more easily detached when seeded on glass than conventional macrophages. The activities of the lysosomal acid phosphatase and cathepsin D were similar in the two cell groups, whereas beta-glucuronidase showed higher activity in macrophages from germfree mice. F(c) receptor-mediated phagocytosis of opsonized sheep erythrocytes was equally effective in germfree and conventional macrophages, and both cell types attached but did not internalize erythrocytes via the C(3)b receptor. Intraperitoneal injections of mineral oil caused a significantly higher influx of macrophages in conventional mice than in germfree mice, whereas the influx of polymorphonuclear cells was enhanced in both animals. Stimulation in vivo with oil or Escherichia coli endotoxin increased cell size, spreading ability, membrane ruffling, and lysosomal enzyme activities in macrophages from both conventional and germfree mice. The Fc-mediated phagocytosis was not influenced by stimulation, whereas the capacity to internalize via C(3)b receptor was triggered in macrophages from conventional mice, but not in corresponding cells from germfree mice. Similar results were obtained after stimulation with endotoxin in vitro. Culture in fetal calf serum for 72 h caused intracellular rises in all three enzyme activities tested in macrophages from conventional mice, whereas only the activity of acid phosphatase was increased in macrophages from germfree mice. Stimulation with zymosan in vitro caused selective release of lysosomal enzyme activity in macrophages from both animal groups. We conclude that peritoneal macrophages from germfree mice share several properties with cells from conventional mice, however, unstimulated beta-glucuronidase activity was increased, whereas spreading on glass, chemotactic response, in vitro induction of lysosomal enzymes, and the capacity to internalize via the C(3)b receptor after stimulation were reduced or absent.
The solubilized rat central nervous system (hypothalamic) nicotinic cholinergic receptor and the Torpedo nicotinic cholinergic receptors are immunologically similar and show greater than 60% immunologic cross-reactivity using a double-antibody technique. Antibodies to the Electrophorus and Torpedo receptors also decrease the rate of alpha-bungarotoxin binding to these membraneous receptors. It is concluded that the Torpedo and hypothalamic nicotinic receptors are immunologically similar and that receptor binding sites for alpha-bungarotoxin and antibodies are physically close. These studies indicate that alpha-bungarotoxin can be used to study the nicotinic cholinergic receptor of the rat hypothalamus.
An immunological surface marker study was performed on 13 patients with a variety of myeloid leukaemias. It was shown that expression of the receptor for the Fc of IgG (gamma FcR) starts to take place at the promyelocyte stage, and that the receptor is present on more mature granulocytic cells, but is absent from myeloblasts. Myeloblasts and promyelocytes are negative for the complement receptor CR2. Monoblasts, unlike myelobasts, were shown to express a gamma FcR and, to a lesser extent, CR2. Receptor expression therefore appears to be an earlier event in monocytic development. The possible diagnostic value of immunological marker studies in myeloid disorders is considered.
The transferrin receptor has been isolated from human placenta using immunochromatography and affinity chromatography. The receptor is a glycoprotein and has a Mr = 90,000 on sodium dodecyl sulfate-gel electrophoresis in the presence of 2-mercaptoethanol. The isolated receptor is immunologically related to the transferrin receptor on the reticulocyte cell surface.
The chemical nature, structural peculiarities, immunological specificity of antigen-binding receptors of various T cell subpopulations and the differences of these receptors from the whole Ig molecule were characterized by using a number of techniques, in particular, the selective absorption of T lymphocytes on corresponding target cell monolayers with the following elution of adherent lymphocytes. Participation of H-antigens, Ia-proteins, Ir-gene and Ig V-gene products in processes related to the specific contact of different T subpopulations with an antigen is discussed and a concept on T cell receptors is outlined. According to this concept, receptor active centres of two antigen-recognizing T subpopulations, antigen-reactive cells and effector cell precursors, differ in their nature, being represented by Ir-gene products and V-gene products, respectively. Each of these products is bound to the cell surface with a H-antigen molecule which functions as a constant portion of the receptor in both cell types. These receptors or their subunits freely moving in the cell membrane probably become stabilized during antigen-driven differentiation. This may be accomplished either by combination of several subunits into one multivalent molecule or by replacing the constant part of the receptor molecule by other plasma cell membrane proteins (Ia-proteins in helpers, differentiation antigens in killers). Three steps of the lethal T killer-target interaction are described, as well as the conditions promoting or inhibiting each of these steps. Possible mechanism of disturbance of cell membrane permeability resulting in lysis of target cells are discussed.
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The induction of a state of immune tolerance is a complex event which can take place at different stages of the immune response since it depends both upon the chemical structure and the experimental manipulation of the antigen. This paper deals mainly with the relationship between antigen structure and the kinds of tolerance induced.
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Sperm receptor sites on the surface of the zona pellucida are believed to be necessary for fertilization on the mammalian egg. Ovary specific antibodies are known to precipitate the zona pellucida and are also responsible for inhibition of sperm binding and subsequent fertilization. The nature of the proposed receptor sites which are blocked by antibodies are discussed relative to comparable studies in which phytoagglutinins and other agents are used to determine the chemical nature of sperm receptor sites.
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