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Biomedical subjects

A F Geczy

Publications and source records attributed to A F Geczy.

At least 73 records · Page 4Linked to original sources

Characterization of a factor(s) present in Klebsiella culture filtrates that specifically modifies an HLA-B27-associated cell-surface component.

It has been shown that HLA-B27 lymphocytes from healthy individuals (B27+ ankylosing spondylitis [AS]-), which are not lysed by an antiserum against Klebsiella K43, can be rendered susceptible to lysis after incubation in the culture filtrate of Klebsiella K43. This finding is compatible with a specific modification by a Klebsiella K43-derived soluble factor of a B27-associated lymphoid cell component. Preliminary characterization of the factor has indicated that it is nondialyzable, but it is heat labile at 56 degrees C for 30 min and has a 35,000-50,000 mol wt. The modifying factor activity of the filtrate is destroyed by neuraminidase but not by trypsin and alpha-chymotrypsin. Furthermore, the ability of the factor to convert B27+AS- lymphocytes can be specifically absorbed by B27+AS- lymphocytes, but not by B27+AS+, B27-AS+, or by B27-AS- lymphocytes, which suggests that B27+AS- cells carry a hypothetical receptor which can specifically bind a Klebsiella K43 antigenic determinant. These results imply that the modification by environmental agents of specific major histocompatibility complex-associated gene products may be an important element in the pathogenesis of the HLA-B27-linked seronegative arthropathies.

Antigens, Bacterial↗

Search for Klebsiella cell wall components cross-reactive with lymphocytes of B27+ AS+ individuals.

It has been suggested that some Klebsiella sp may cross-react with a cell surface determinant on the lymphocytes of B27+AS+ individuals. Studies were undertaken to identify culture filtrates capable of rendering the lymphocytes of B27-positive healthy controls susceptible to lysis by the anti-Klebsiella antiserum. Polyacrylamide gel electrophoresis of cell wall material of Klebsiella K43 prepared by sonication, high-speed centrifugation, and nonidet solubilization, demonstrated the presence of four major protein bands. When antisera raised in rabbits to each of these were tested for their cytotoxic effect on the lymphocytes of B27+AS+ individuals, an antiserum to one component only, of 40-52 K daltons molecular weight, reproduced the activity of the whole serum. Studies on the K43 filtrate indicated that the 'modifying' factor appeared to reside in a 25-50 K dalton component. Immunoelectrophoresis against anti-K43 serum demonstrated overlapping bands in the culture filtrate and the 40-52 K dalton cell wall fraction and these appeared to be identical on immunodiffusion. Antibody to the cell wall component removed both the 'modifying' activity and the appropriate protein band from the filtrate. The results suggest that a 40-52 K dalton component of the Klebsiella K43 cell wall is cross-reactive with a determinant on the lymphocytes of B27+AS+ individuals and is similar to or identical with a modifying factor in K43 culture filtrate which renders the lymphocytes of B27-positive healthy controls susceptible to lysis by anti-Klebsiella antiserum.

Cell Wall↗

The guinea-pig I-region. III. Distribution of Ia antigens in inbred and partially inbred strains.

We have used a combined serologic and structural approach to study the distribution of I-region associated (Ia) antigens in nine strains of inbred and partially inbred guinea-pigs. All of the inbred strains studied with the exception of strain 2 animals were found to share one or more I-subregions with inbred strain 13 animals. The BIOAD, R9, OM3, and BIOAC strains have the same I-region as strain 13 animals; the B/Lac strain has two subregions in common with strain 13, while the BIOB strain has a single subregion in common with strain 13. The availability of a number of different guinea-pig strains with well-characterized major histocompatibility complexes should facilitate the continuing use of this species in studies of immunogenetics, transplantation, and tumour immunology.

Animals↗

The role of Klebsiella in the pathogenesis of ankylosing spondylitis. II Evidence for a specific B27-associated marker on the lymphocytes of patients with ankylosing spondylitis.

Although the strong association of HLA-B27 with ankylosing spondylitis (AS) is well documented, the significance of this association is largely unknown. It has recently been reported that Klebsiella pneumoniae was present in the faeces of patients with AS more frequently than in healthy individuals, and that there appeared to be some cross-reactivity between HLA-B27 and Klebsiella. We have therefore attempted to gain an insight into the possible role of Klebsiella in the pathogenesis of AS. The results presented here indicate that HLA-B27 positive individuals with AS have a significantly lower in vitro lymphocyte responsiveness to Klebsiella antigens, as compared with B27 positive and B27 negative healthy controls. By contrast, B27 positive patients with AS as well as B27 positive and negative controls respond equally well to phytohaemagglutinin, Staphylococcus, Streptococcus, Yersinia and Shigella. To investigate a possible cross-reactivity between Klebsiella and HLA-B27, antisera were raised in rabbits against various isolates of Klebsiella. An antiserum to one isolate (427) of Klebsiella lysed the lymphocytes of B27 positive AS patients but not of B27 positive or B27 negative controls. These observations strongly suggest that some Klebsiella antigens cross-react with a gene product closely associated with HLA-B27 or possibly with a modified B27 antigen in patients with AS.

Animals↗

Suppression of reaginic antibody formation in guinea pigs by anti-idiotypic antibodies.

Syngeneic immunization of strain 2 and strain 13 guinea pigs with purified antibodies against benzyl-penicilloyl bovine IgG (BPO-BGG) produces anti-idiotypic antibodies which specifically inhibit antigen-induced T cell proliferation in vitro. In sensitized guinea pigs, passive administration (either intravenously or subcutaneously in complete Freund's adjuvant [CFA] of these anti-idiotypic antibodies has a reversible suppressive effect on IgG and IgM responses. In addition, preimmunization with idiotypes effects a long-term and specific suppression of the production of homocytotropic antibodies against a hapten-protein conjugate (BPO-BGG). The suppression of the homocytotropic antibody response in already sensitized outbred guinea pigs was attampted by immunization with autologous serum, autologous antibodies, or autologous lymphoid cells. With all immunization procedures used so far, no significant suppressive effects could be demonstrated. The significance of these findings, in terms of the practical potential of autoanti-idiotypic immunization for the management of allergic diseases, is briefly discussed.

Animals↗

The guinea pig I region. I. A structural and genetic analysis.

The Ia antigens of the guinea pig have been shown to play a central role in the regulation of the immune response. We have previously partially characterized the chemical structure of these antigens. In this communication, we further characterize the structure of the five Ia antigens already described, as well as two new Ia antigens. Evidence is presented which shows that these seven Ia antigens can be organized into three distinct groups, each with a characteristic structure. The Ia.2 determinant of strain 2 and the Ia.3 and Ia.5 determinants of strain 13 animals are found on molecules composed of a 25,000 dalton chain and a 33,000 dalton chain in noncovalent association, or else are individually expressed on nonlinked 33,000 and 25,000 dalton molecules. The Ia.4 and Ia.5 determinants of strain 2 and the Ia.7 determinant of strain 13 are borne on 58,000 dalton molecules in which two chains are linked by disulfide bonds. The Ia.1 and Ia.6 determinants of strain 13 are found on a molecule of 26,000-27,000 daltons. Ia.6 of strain 2 has yet to be definitively assigned. Furthermore, in strain 13 animals the Ia.3 and Ia.5 determinants are borne on the same molecule, as are the Ia.1 and Ia.6 determinants. In strain 2 animals, the Ia.4 and Ia.5 determinants are found on the same molecule. On the basis of chemical structure, we have divided the guinea pig I region into three subregions. The accompanying paper presents evidence of associations between particular Ia genes and Ir genes.

Animals↗

The guinea pig I region. II. Functional analysis.

We have examined whether an association exists between specific Ia antigen genes and Ir genes which are encoded within the same haplotype. Functionally monospecific sera to the Ia antigens of the guinea pig MHC were selective in their ability to inhibit antigen-specific T-cell proliferation and we were thus able to demonstrate an association between individual Ia specificities and specific Ir genes. The results of these studies in inbred animals were confirmed by examining the association of Ir genes and Ia antigens in the outbred guinea pig population. Of great interest was the observation that antisera made against cross-reactive Ia antigens of strains lacking specific Ir genes would still inhibit immune responses of strains possessing the Ir gene, if the Ir gene was associated with that Ia antigen in the responder strain.

Albumins↗

Histocompatibility antigens and genetic control of the immune response in guinea pigs IV. Specific inhibition of lymphocyte proliferation by auto-anti-idiotypic antibodies.

The in vitro T-cell proliferation induced by penicilloylated bovine IgG (BPO-BGG) in sensitized strain 2 guinea pigs could be specifically blocked by the serum of guinea pig (*305) which had been repeatedly immunized with BPO-BGG over a period of 9 mo. The antibodies which appeared in the serum of this animal (*305) were functionally similar to the strain 2 anti-idiotypic antibodies (a strain 2 BPO-BGG) raised by immunizing strain 2 guinea pigs with immuno-adsorbent column-purified BPO-BGG. Animal *305 had no detectable antibodies to BPO-BGG and failed to give a delayed hypersensitivity skin response when challenged with BPO-BGG.

Animals↗

Histocompatibility antigens and genetic control of the immune response in guinea-pigs. V. Evidence from further breeding studies for the polygenic control of the cellular immune response to structurally unrelated antigens in the guinea-pig.

Further breeding studies were carried out to investigate the polygenic control of the cellular immune response in the guinea-pig to low doses of aspirin anhydride (ASAN), penicilloylated bovine immunoglobulin (BPO-BGG) and to the multi-chain copolymer (T, G)-A-L. Although responsiveness to these three antigens is controlled by three independently segregating loci, at least one gene required for these responses is linked to the strain 13 haplotype.

Animals↗

Immunogenicity of p-phenetidine, 2-hydroxy-p-phenetidine and their protein conjugates in guinea pigs, rabbits and man.

Guinea pigs were sensitized by p-phenetidine (PT), 2-hydroxy-p-phenetidine (HPT) as well as by conjugates prepared by reacting PT and HPT with proteins in vitro. Sensitization was evaluated by delayed skin reactivity and in vitro antigen-induced lymphocyte proleferation. HPT and HPT-protein conjugates were found to be the most effective sensitizing agents. Reaginic antibodies could be raised in both guinea pigs and rabbits by immunizing with PT- and HPT-protein conjugates but not by PT and HPT alone: these PCA antibodies showed strong cross-reactivity and could be elicited equally well with either the PT- or HPT-protein derivatives. By contrast, no precipitating antibodies could be raised in either species even after repeated immunizations over a period of 4 months. Peripheral blood lymphocytes, from a few patients who gave a positive patch test with PT, could be stiumlated in vitro with phenacetin and to a lesser degree with PT and with a HPT-derivative of human serum albumin.

Aniline Compounds↗