Activation of the classical complement pathway by homogeneous anti-SIII antibody bound to bivalent or trivalent oligosaccharide antigens.
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Biomedical subjects
Publications and source records attributed to J Gergely.
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Fc-receptor positive peripheral blood mononuclear cells (PMBC) behaved differently after a temperature shift from 4 to 37 degrees. Two types could be distinguished. Type I FcRI+PMBC were transformed to FcR-while type II FcRII+PMBC retained their FcR as measured by EA rosettes. The supernatants of the PMBC or the shed receptor purified on a Sepharose 4B-aggregated human IgG column blocked the EAR formation of FcRI+PMBC but had no effect on EAR information of FcRII+PMBC. An investigation was made into the reason why rosette formation by Fcrii+ cells could not be inhibited by FcRI. As an explanation, the role of differences in affinity or subclass specificity was excluded while the binding site(s) on the IgG molecule for FcRI and II proved to be different. The FcRII+PMBC had a greater cellular avidity for sensitized erythrocytes than FcRI+PMBC. The different states of FcR-s in the cell membrane are discussed as a possible source of heterogeneity.
The increase observed in alpha helix from 20 to 38%, the spectral red shift of the absorption bands of the side chain chromophores, the increase of phenylalanine side chain optical activity and a decrease of cysteinyl side chain reactivity with 5,5'-dithiobis(2-nitrobenzoic acid) are consistent with a coil to helix change in the segment containing Cys-98 and Phe-99 and 102 when the CB9 fragment of troponin C (TnC) with an intact binding site III binds Ca2+. Since similar spectrophotometric observations have been made on the whole molecule the data with CB9 confirm our previous suggestion that binding site III of TnC is one of the strong binding sites for Ca2+. The estimate of the binding constant of Ca2+ for CB9 is about 2 orders of magnitude lower than in whole TnC, indicating further stabilization in the intact molecule.
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Continuous stimulation of a rabbit fast muscle at 10 Hz changes its physiological and biochemical parameters to those of a slow muscle. These transformations include the replacement of myosin of one type by myosin of another type. Two hypotheses could explain the cellular basis of these changes. First, if fibers were permanently programmed to be fast or slow, but not both, a change from one muscle type to another would involve atrophy of one fiber type accompanied by de novo appearance of the other type. Alternatively, preexisting muscle fibers could be changing from the expression of one set of genes to the expression of another. Fluorescein-labeled antibodies against fast (AF) and slow (AS) muscle myosins of rabbits have been prepared by procedures originally applied to chicken muscle. In the unstimulated fast peroneus longus muscle, most fibers stained only with AF; a small percentage stained only with AS; and no fibers stained with both antibodies. In stimulated muscles, most fibers stained with both AF and AS; with increasing time of stimulation, there was a progressive decrease in staining intensity with AF and a progressive increase in staining intensity with AS within the same fibers. These results are consistent with a theory that individual preexisting muscle fibers can actually switch from the synthesis of fast myosin to the synthesis of slow myosin.
Different immunoglobulin preparations of human monoclonal IgM, normal human and rat IgG, as well as purified rabbit antibodies were treated by various methods, fragmentation, aggregation and complexing with antigen. The ability of the treated and untreated preparations to fix isolated human C1, to activate the classical complement pathway (to consume C4 in normal human serum) were compared. It was found that the different methods affected the conformation of the immunoglobulin molecules in different ways and induced changes to a greater or lesser extent in the two capacities of the preparations tested. In the case of the monoclonal IgM preparation a strong C1-fixation was observed without measurable complement activation. Other preparations, interfacially aggregated human IgG, BSA-anti-BSA and OA-anti-OA immune complexes had a very weak C1-fixing but a marked complement activating capacity. Some preparations, e.g. heat-aggregated IgG, both fixed and activated C1 effectively, aggregates with a complement-activating capacity without C1-fixing effect were separated by gel-filtration. It was demonstrated further, that at a given time only a part of the activated C1 molecules could be found fixed to the immunoglobulins, the other part was released into the fluid phase after activation. On the basis of the results of this and previous studies a hypothesis is proposed suggesting three possible results of the interaction between C1 and the different preparations: (1) firm fixation and activation; (2) binding not followed by activation and (3) a transient binding leading to activation. The possible application of this hypothesis for the interpretation of the results of the different methods for detecting immune complexes is discussed.
The shedding and resynthesis of Fc, C3 receptors, and receptors binding SRBC has been studied in normal peripheral lymphocytes, in lymphocytes from CLL patients and in a Raji cell line during 4 h incubation at 37 degrees. During the first part of the incubation, an increased release of receptors was observed. The shed, functionally active, receptors were detectable in the incubating medium on the basis of their ability to inhibit rosette formation specifically. After 4 h incubation the original ratios of the different rosette forming cells were observed, showing that the cells were capable of resynthesizing their shed receptors. This later phenomenon may be the result of an active metabolic process. The shedding was not detectable on Raji cells. Different patterns of receptor shedding and resynthesis were demonstrated by the lymphocytes of CLL patients. The correlations between the reappearance of the receptors on the cells, and the metabolism of the lymphocytes, is discussed.
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Supernatants of human peripheral mononuclear cells containing membrane components shed in consequence of 4--37 degrees temperature shift were used as source for isolation of Fc-receptors (FcR). Aggregated IgG1 myeloma protein and TMV-anti-TMV complexes proved suitable sorbents to adsorb quantitatively and specifically the FcR-s. The isolated FcR interacts only with IgG and not with IgM. No haemagglutination was observed when the isolated FcR was incubated with sensitized human Rh+ red blood cells. Complement dependent lysis of sheep red blood cells was not inhibited by the isolated FcR-s. The interaction between IgG and SpA from Staphylococcus aureus (Cowan I) bacteria was not inhibited when red blood cells sensitized with IgG were preincubated with the isolated FcR-s. The differences between the FcR-like material isolated from supernatants of peripheral human mononuclear cells and those secreted by stimulated T cells or produced by lymphoblastoid cell lines are discussed.
Authors studied the occurrence of antibodies agglutinating IgG determinants with Rh positive red blood cells covered with IgG molecules of anti-Rh(D) activity treated with papain, pepsin, and trypsin. The occurrence of Fab antibodies was studied in the sera of newborn and of 1-6 years old healthy children, further on quantitative immunoglobulin assays were performed in these to determine whether homoreactant antibodies influence IgG production. Based on their results authors conclude that homoreactant antibodies do not influence IgG production. Authors assume a role in the IgG catabolism viz., they are involved in the elimination of antigen-antibody complexes.
A patient with "chronic cold-agglutinin disease" is described. Initially, the process was a benign monoclonal gammopathy. After an intervall of 6 years clinical, cytomorphological and immunochemical studies showed progress towards malignancy. In the bone marrow intranuclear lipid-like inclusions appeared in the plasma cells.
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