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M Mannik

Publications and source records attributed to M Mannik.

125 records · Page 7Linked to original sources
PubMed1972

In vitro adherence of soluble immune complexes to macrophages.

The adherence of soluble immune complexes to stimulated alveolar macrophages was studied in vitro using HSA-anti-HSA complexes prepared in antigen excess. Those complexes containing more than two molecules of antibody preferentially adhered to macrophages in the absence of complement. Free gammaG in less than physiological concentrations inhibited the adherence of complexes, and the presence of complement did not significantly alter this inhibition. Complexes prepared with reduced and alkylated antibodies showed a decreased adherence. The strength of binding of soluble complexes to macrophages and their efficiency in fixing complement were greater than seen with small aggregates of homologous gammaG. These differences in biological properties were observed even though the immune complexes and aggregates contained comparable numbers of gammaG molecules. The gammaG receptor on rabbit macrophages exhibited species specificity. Pretreatment of macrophages with proteolytic enzymes led to adherence of larger amounts of soluble complexes. These observations suggest that the strength of binding of soluble immune complexes to macrophages and their efficiency in fixing complement are not determined solely by a random summation of individual binding sites. It is proposed that conformational changes in the gammaG antibodies or a specific molecular arrangement in the lattice work of complexes containing large protein antigens may influence the biological properties of the soluble complexes.

Animals↗
PubMed1971

The distribution of antigenic determinants in rat skin collagen.

Immunological studies of rat skin collagen were carried out with a sensitive and quantitative radioimmunoassay. Hyperimmune rabbit antisera to rat skin collagen and isolated alpha2 chains were used. Iodine-labeled alpha chains and CNBr-produced peptides served as test antigens, and native collagen, alpha chains, and CNBr peptides were employed as inhibitors in the assay. The alpha1 and alpha2 chains were immunologically distinct. Although the alpha1 chain was not immunogenic, antibodies to alpha1 were detected in antisera to the intact collagen molecule. The major antigenic determinant of the alpha1 chain was located in alpha1-CB6 which constitutes the carboxy-terminal region of the chain. The alpha2 chain contained two non-cross-reacting antigenic determinants, one in the amino-terminal region (alpha2-CB1) and the other in the carboxy-terminal region (alpha2-CB5) of the chain. The native collagen molecule was less effective than isolated alpha chains in inhibiting binding of labeled peptides to antisera, indicating that antigenic determinants were less accessible in the triple helical molecule. These immunologic studies are consistent with preliminary comparative biochemical data which indicate that interspecies structural differences in collagen predominate at both the amino- and carboxy-terminal ends of the chains.

Animals↗
PubMed1971

Studies on antigen-antibody complexes. I. Elimination of soluble complexes from rabbit circulation.

Solid phase immunoadsorbents were prepared by coupling antigens to agarose. With this technique specific antibodies were easily isolated in large amounts. The gammaG-globulin class of antibodies isolated in this manner were not denatured as judged by their normal biological half-life in rabbits. Soluble immune complexes at fivefold antigen excess were prepared from isolated specific antibodies and HSA, human lambda-chains, human lambdaG-globulins, and a Waldenström's macroglobulin as antigens. In all these preparations a characteristic immune complex was encountered that represented the smallest stable antigen-antibody union. In the HSA-anti-HSA system they were found to be AgAb(2) complexes, and Ag(2)Ab complexes in the gammaG-anti-gammaG system. These stable complexes fixed complement ineffectively. Also, a spectrum of larger complexes was present in each system, and these complexes fixed complement effectively. With intact antibodies the disappearance curves of immune complexes from the circulation were composed of three exponential components. The immune complexes larger than AgAb(2) were quickly removed from the circulation with half-lives of 0.09-0.37 hr. Their clearance was not dependent on complement components, in that depletion of complement by cobra venom factor and aggregated gammaG-globulin did not alter the pattern of their removal from the circulation. However, when the interchain disulfide bonds of antibodies were reduced and alkylated, the removal of the lambda-anti-lambda, HSA-anti-HSA, and gammaG-anti-gammaG complexes was altered. In these experiments the disappearance curves were composed of two exponential components and the rapid removal of the greater than AgAb(2) complexes did not occur. The immune complexes prepared from reduced and alkylated antibodies fixed complement ineffectively. The presented data indicate that the rapid removal of circulating immune complexes, containing gammaG-globulin molecules as antibodies, depends primarily on the number of antibodies involved. Furthermore, complement fixation is not involved in the rapid removal of such complexes. Nevertheless, the rapid removal of immune complexes and their ability to fix complement have similarities for optimal function in that both processes require intact interchain disulfide bonds of antibodies and complexes that exceed the AgAb(2) combination.

Adsorption↗
PubMed1965

Specificity of recombination of H and L chains from human gamma-G-myeloma proteins.

Dissociated H and L chains of human gammaG-myeloma proteins were recombined by removal of conditions interrupting non-covalent interactions. In the process of recombination 7S molecules were formed. It was demonstrated that the H chains from individual gammaG-myeloma proteins recombine with their own L chains but also with L chains derived from other myeloma proteins. In some instances, however, the L chains from other myeloma proteins did not recombine as avidly with the H chains as the autologous L chains. The specificity of the non-covalent interactions of H and L chains was particularly well brought out by competitive recombination experiments where an individual H chain had a choice of recombining with its own L chain or with the L chain obtained from another myeloma protein. In this manner a spectrum of affinities between individual H chains and several L chains was demonstrated. In the vast majority of recombinations there was a clearcut preference for recombination to take place between the H and L chains derived from the same protein. It is postulated that this specificity is related to differences in the primary structure, which cause differences in configuration of these homogeneous H and L chains and that these configurations then dictate on thermodynamic grounds the pairing of H chains with particular L chains.

Humans↗
PubMedDate not supplied

The hyperviscosity syndrome in rheumatoid arthritis due to intermediate complexes formed by self-association of IgG-rheumatoid factors.

Three patients with rheumatoid arthritis and abundant circulating intermediate complexes were studied. Two of these patients presented with the hyperviscosity syndrome. All 3 patients had markedly elevated plasma and blood viscosity, and the intermediate complexes were thought to be responsible for the increased viscosity. Studies on the isolated intermediate complexes revealed that they were formed by self-association of IgG-rheumatoid factors.

Adult↗
PubMedDate not supplied

Immunoblastic lymphadenopathy presenting as respiratory insufficiency.

The clinical course of a patient is described who experienced respiratory insufficiency as the primary manifestation of immunoblastic lymphadenopathy. Respiratory symptoms preceded the enlargement of lymph nodes, improved spontaneously at first and then after steroid therapy. Subsequently these symptoms reappeared concurrent with lymph node enlargement. Hypergammaglobulinemia was noted with marked elevation of polyclonal immunoglobulin M.

Adult↗