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Biomedical subjects

T Lehner

Publications and source records attributed to T Lehner.

At least 217 records · Page 12Linked to original sources

Immunisation with a purified protein from Streptococcus mutans against dental caries in rhesus monkeys.

A purified protein antigen, molecular weight 185,000, was prepared from Streptococcus mutans and used in the immunisation of monkeys against dental caries. 1 mg of this antigen, mixed with adjuvant and injected subcutaneously, elicited serum IgG and to a lesser extent IgA antibodies. Compared with sham-immunised monkeys, those receiving this antigen had a 70% reduction in dental caries and a smaller growth of Strep. mutans from dental plaque. The results suggest that the defined protein material isolated from Strep. mutans may be one of the antigens eliciting a protective immune response against dental caries. This antigen seems to be a suitable candidate for consideration as a vaccine for man.

Animals↗

Protein antigens of Streptococcus mutans: purification and properties of a double antigen and its protease-resistant component.

A surface protein antigen of Streptococcus mutans having two sets of antigenic determinants (antigens I and II) was purified by column chromatography from culture supernatants of S. mutans serotype c. The protease-resistant component, antigen II, was purified from pronase-digested antigen I/II. The antigens were analyzed chemically and immunologically, and their physicochemical properties were investigated. Antigen I/II consisted of more than 80% protein, and its peptide chain molecular weight was estimated to be 185,000. Antigen II consisted of approximately 60% protein, with a peptide chain molecular weight of 48,000. Antisera to antigens I/II and II were raised in rabbits and used to investigate the presence of the antigens in cells of other streptococci. This indicated that not only serotype c but also serotypes e and f possessed antigen I and II determinants, whereas serotypes a, d, and g possessed a determinant related to antigen I but not one related to antigen II.

Amino Acids↗

Affinity purification and characterization of protease-susceptible antigen I of Streptococcus mutans.

An antigenic component (antigen I) of the cell surface of Streptococcus mutans has been purified from culture supernatants and shown to be immunologically identical to the protease-susceptible moiety of antigen I/II. Ion-exchange and gel filtration chromatography failed to yield a physicochemically homogeneous product. Immunoasbsorbent chromatography on single and tandem columns containing immobilized antibodies to antigens I/II and II yielded identical products which were homogeneous in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and which when injected into rabbits induced monospecific antisera to antigen I. This antigen consisted of approximately 70% protein. Its molecular weight was estimated as 150,000, and the isoelectric point was estimated to be 5.1. Immunofluorescence microscopy using monospecific antiserum to antigen I showed that a similar antigen was present on cells of S. mutans serotypes a, c, d, e, f, and g, but not b.

Animals↗

Immunochemical properties of antigen-specific monkey T-cell suppressor factor induced with a Streptococcus mutans antigen.

Antigen-specific suppressor factor could be released from monkey suppressor T cells induced in vitro with a protein antigen isolated from the carcinogenic bacterium Streptococcus mutans. The suppressor activity was due to the factor itself and not to carryover of free antigen. Characterization of the monkey factor revealed it to have a molecular weight of ca. 70,000, and to contain a constant region and determinants encoded by the major histocompatibility complex. The presence of immunoglobulin determinants could not be demonstrated. However, by virtue of its adsorption to specific antigen, an antigen-combining site was shown to be present. The possible regulatory role of streptococcal antigen-specific suppressor factor in protection against dental caries is discussed.

Animals↗

Acute phase proteins, C9, factor B, and lysozyme in recurrent oral ulceration and Behçet's syndrome.

The concentrations and sequential changes of some acute phase proteins, factor B, and lysozyme have been assayed in recurrent oral ulceration and Behçet's syndrome. C9 was elevated in both groups of patients and was the sensitive index of disease activity; however, it failed to discriminate between the three types of recurrent oral ulcers and four types of Behçet's syndrome. The level of alpha 1 acid glycoprotein and lysozyme were significantly increased predominantly in the ocular type, whereas factor B was significantly increased especially in the neurological type of Behçet's syndrome. It is suggested that the changes in the concentrations of some plasma proteins may help our understanding of tissue involvement in Behçet's syndrome, as well as in the selection of therapeutic agents in this disease.

Azathioprine↗

A comparative investigation of the generation of specific T cell-helper function induced by Streptococcus mutans in monkeys and mice.

Antigen-specific helper cells were induced in vitro in monkeys and mice by using an antigen preparation from Streptococcus mutans. These helper cells were T cells on the basis of their sensitivity to anti-Thy. I and complement, and were not retained on nylon wool. Upon further in vitro culture the helper cells release mediators of help, "helper factor" in the supernatant. The release of helper factor as well as its augmentation of the immune response was antigen specific. Monkey and murine helper factors were similar in their induction, function, and specificity.

Animals↗

Partial characterization of murine and monkey helper factor to a streptococcal antigen.

Helper factors specifically stimulating cooperative antibody responses by normal mouse spleen cells to a dinitrophenylated protein antigen from Streptococcus mutans (DNP-SA) were produced in vitro from monkey peripheral blood leucocytes and mouse spleen cells. The factors were partially characterized by gel filtration on Sephadex G-75, isoelectric focusing, treatment with heat and degradative enzymes and binding to specific immunoadsorbents. Gel filtration of both the monkey and mouse factors showed coelution with human serum albumin, suggesting a molecular weight of approximately 70,000. The isoelectric points fell within the range of 4.9-5.2 for monkey and 6.4-6.7 for the mouse helper factors. The glycoprotein nature of both factors was suggested by their lability to heat and sensitivity to pronase and neuraminidase. The factors carried a small fragment of the stimulating antigen and showed specific binding to SA but not to keyhole limpet haemocyanin (KLH). Monkey factor bound to rabbit antisera directed against the Fc portion of monkey IgM, but not to the IgG or IgA isotypes. The mouse factor contained determinants coded for by the I-Ak but not I-Jk subregion of the MHC. Both factors were absorbed by an antiserum to helper factor raised in rabbits against a KLH-specific mouse helper factor as immunogen. A corresponding antiserum to suppressor factor failed to adsorb either factor. This emphasizes the specific identities of helper and suppressor factors and suggests an evolutionary relationship between those derived from monkey and mouse leucocytes.

Animals↗

Specificity of antibodies induced by Streptococcus mutans during immunization against dental caries.

Protection against smooth surface dental caries was investigated in fifteen young rhesus monkeys which were immunized subcutaneously with Streptococcus mutans serotype c in Freund's incomplete adjuvant. Monkeys immunized with killed whole organisms developed significantly less caries than control animals. Monkeys immunized with pronase-treated cell walls developed significantly more caries than control animals while monkeys immunized with untreated cell walls showed no such enhancement of caries. Haemagglutinating and complement-fixing antibodies to cell walls and culture supernatant antigens (SN Ag) of S. mutans developed in the sera of all immunized animals to a similar degree. Antibodies to lipoteichoic acid and to an insoluble dextran preparation were found in all immunized animals and showed no relationship to the prevalence of caries. Antibodies to the serotype c polysaccharide were also found in animals immunized with whole cells and pronase-treated cell walls. However, precipitating antibody levels to partially purified antigens I/II and II, derived from SN Ag, but present also in cells, were related to the development of caries. Animals immunized with whole cells and with untreated cell walls developed a brisk antibody response to antigen I/II, while those immunized with pronase-treated cell walls responded more slowly. The results suggest that immunization may induce both caries reduction and enhancement, depending on the antibody response which is developed.

Animals↗

Oral immunization with Streptococcus mutants in rhesus monkeys and the development of immune response and dental caries.

The oral route of immunization with Streptococcus mutants was compared with the subcutaneous route in rhesus monkeys. Significant levels of serum IgG, IgM and IgA antibodies in Strep. mutans were elicited only in monkeys immunized subcutaneously. Similarly, the skin delayed hypersensitivity reaction to Strep. mutans was elicited only in the subcutaneously immunized monkeys. Oral immunization induced a modest increase in salivary IgA antibodies to Strep. mutans, though a slight increase in IgA antibodies was also found in the saliva of all other groups of immunized and control monkeys. A small though not significant reduction in dental caries was found in the monkeys immunized orally, whereas subcutaneous immunization with Strep. mutans consistently elicited a significant reduction in caries. Oral feeding of Strep. mutans failed to induce tolerance to a subsequent subcutaneous challenge by the same organism. Furthermore, sequential subcutaneous followed by oral immunization had little effect on the titre of salivary or serum antibodies.

Administration, Oral↗

Generation of specfic T-cell suppressor function induced by Streptococcus mutans in monkeys and mice.

Specific suppressor cells in mice and monkeys can be induced with high doses of Streptococcus mutans antigen. When these cells are further cultured with a low dose of S. mutans antigen in vitro, they secrete specific suppressor factors which decrease the cooperative responses to this antigen. In view of the sensitivity of these cells to anti-Thy 1 and complement, and as they are not retained on nylon-wool, these suppressor cells are T cells. The suppressor factor exerts its effect on T helper cells and not on B cells. Suppressor cells and factors may regulate antibody responses to S. mutans and might be of significance in determining the dose and frequency of immunization and the type of adjuvant to be used.

Animals↗

Bacterial and strain specificities in opsonization, phagocytosis and killing of Streptococcus mutans.

Opsonization of Streptococcus mutans, followed by phagocytosis and killing by polymorphonuclear leucocytes has been postulated as an effector mechanism in protection against dental caries. Opsonization was studied by using sera from monkeys immunized with killed Strep. mutans (sero-type c) and compared with sera from sham-immunized monkeys. Antibodies to Strep. mutans (sero-type c) induced maximal phagocytosis and killing of serotypes c and e, and this was significantly greater than with serotypes a and d; there was no significant phagocytosis or killing of serotype b. There was little or no opsonization with Actinomyces viscosus, Lactobacillus casei, Strep, sanguis and Strep. salivarius. The exception was Strep. CHT which showed significant phagocytosis and killing. The results suggest that immunization with the serotype c strain of Strep. mutans might offer protection against four of the five common serotypes of this organism.

Animals↗

Cryoglobulins in Behçet's syndrome and recurrent oral ulceration: assay by laser nephelometry.

The presence of cryoglobulins was investigated in ninety patients with recurrent oral ulcers (ROU) and sixty-one patients with Behçet's syndrome (BS). The immunodiffusion method was compared with Laser nephelometry for the analysis of IgG, IgM, IgA and C3 in cryoglobulins. Although the two methods of assessment showed a very significant agreement. Laser nephelometry was more sensitive than the double diffusion precipitation method and was used for quantitative analysis of cryoglobulins. The prevalence of any type of cryoglobulins was 64% in ROU and 75% in BS, as compared with controls (15%). In ROU significant levels of IgA were found in minor (P = 0.0196) and major (P = 0.0114) aphthous ulcers and to a lesser extent in herpetiform ulcers (P = 0.0624). Among the four types of BS signficant increases in C3 were found in the arthritic type (P = 0.0068) and ocular type (P = 0.0275), whereas IgM (P = 0.0031) and IgG (P = 0.0369) were increased only in the muco-cutaneous type. Sequential studies showed that disease remissions or exacerbations were correlated with a decrease or increase in IgM or IgG classes of cryoglobulins. However, the converse was found with IgA which may inhibit some functions of polymorphonuclear leucocytes, and this may be responsible for the failure to remove damaging IgG, IgM and C3 complexes from the circulation.

Behcet Syndrome↗

An immunogenetic basis for the tissue involvement in Behçet's syndrome.

The multifocal involvement in Behçet's syndrome was grouped into a spectrum of four types, three of which appeared to have an immunogenetic basis. HLA-B5 was related to the ocular type of Behçet's syndrome (relative risk 7.3), HLA-B27 to the arthritic type (relative risk 12.1) and HLA-B12 to the muco-cutaneous type (relative risk 3.9). The concept that recurrent oral ulceration and Behçet's syndrome may belong to a disease spectrum is substantiated by the natural course of the disease. Furthermore, patients with recurrent oral ulcers share with the muco-cutaneous type of Behçet's syndrome a significantly increased frequency of HLA-B12 (relative risk 2.6). The HLA markers may also prove to be significant in the differential diagnosis and prognosis of a disease which may present under a confusing variety of clinical manifestations.

Adolescent↗

Passive immunisation with serum and immunoglobulins against dental caries in rhesus monkeys.

Active immunisation with Streptococcus mutans induced protection against dental caries in rhesus monkeys, and this was associated with serum antibodies. Passive transfer of immune serum with IgG, IgM, and IgA antibodies to Strep. mutans failed to induce protection against dental caries. However, when separated IgG, IgM, and IgA sera were given, IgG induced significant protection but IgA or IgM antibodies to Strep. mutans did not. IgA and IgM may compete or interfere with the protective effect of IgG antibodies, and the ratio of IgG/IgA and IgG/IgM antibodies might be an important factor in immunisation against dental caries.

Animals↗