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S J Challacombe

Publications and source records attributed to S J Challacombe.

At least 127 records · Page 7Linked to original sources

The detection and specificity of class specific antibodies to whole bacterial cells using a solid phase radioimmunoassay.

A solid phase radioimmunoassay has been developed which can be used for the detection of isotype specific antibodies to whole bacteria and other particulate antigens, and is applicable to a variety of species. Bacteria are bound to the solid phase by the use either of antibodies, or of methyl glyoxal. Both methods result in a sensitive and reproducible assay, and bacteria do not appear to desorb from the solid phase. The specificity of antibodies to whole bacteria was examined by absorption of antisera with various species of bacteria and retesting, or by determining the binding of antisera to various bacteria bound to the solid phase. Both methods revealed specificity for the bacteria examined. Inhibition studies showed that antibodies to Streptococcus mutans whole cells could be inhibited by purified cell surface antigens glucosyltransferase and antigen I/II, but only minimally by lipoteichoic acid, c polysaccharide or dextran. In murine antisera antibodies of the IgG, IgM, and IgA classes could be detected at amounts of less than 1 ng/ml.

Actinomyces↗

Systemic tolerance and secretory immunity after oral immunization.

Diminished systemic immune reaction after ingestion of antigen has been reported in several animal models. Conversely, it has been reported recently that oral immunization may lead to the production of secretory antibodies. To determine whether these events could occur concurrently, CBA/J mice were immunized intragastrically with varying doses of ovalbumin (OVA) and Streptococcus mutans. After 7 d, the animals were challenged systemically with antigen in complete adjuvant and 8 d later serum and saliva taken, and the draining lymph nodes assayed for a proliferative response. Intragastric doses of 1 mg OVA or 10(9) S. mutans led to significant suppression of the proliferative response, and intragastric doses of 10 mg OVA or 2.5 X 10(9) S. mutans led to the production of detectable salivary antibodies using hemagglutination. Serum antibodies were not detected after intragastric administration of OVA or S. mutans. Suppression of the proliferative response could be detected from 2-60 d after intragastric administration of OVA, and 2-21 d after S. mutans. Prior intragastric immunization with heterologous antigens did not suppress the response to OVA or S. mutans. Transfer of 40 X 10(6) mesenteric lymph node cells from mice given 20 mg OVA or 10(9) S. mutans led to suppression of the proliferative response in syngeneic recipients. Salivary antibodies wer removed by absorption with anti-IgA, but not anti-IgG or IgM, indicating that they were of the IgA class. It appears that intragastric administration of soluble or particulate antigens in mice may lead to the concurrent induction of salivary antibodies and systemic suppression.

Administration, Oral↗

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↗

Estimation of the intravascular half-lives of normal rhesus monkey IgG, IgA and IgM.

Rhesus monkey IgG, IgA and IgM were purified from pooled normal serum and labelled with 125I. Four monkeys were injected intravenously with approximately 50 microgram of each purified immunoglobulin containing between 25 muCi and 50 muCi of 125I. Iodination was approximately 1 atom per 14 molecules of IgG and IgA and per 2.5 molecules of IgM. Samples of serum were taken for up to 22 days after injection and radioactivity compared with that in a sample taken within 30 min of injection. Sucrose density ultracentrifugation of serum samples revealed that in animals given IgG or IgA, radioactivity was associated with 7S protein peaks, and in animals given IgM radioactivity was associated predominantly with a 19S protein peak. Most of the radioactivity could be precipitated from serum samples with the appropriate monospecific antiserum. The mean half-life of rhesus monkey IgG was estimated as 8.3 days, IgA as 4.5 days and IgM as 4.7 days.

Animals↗

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↗

Passive immunization with antisera to Streptococcus mutans in the prevention of caries in rhesus monkeys.

1) The immunological mechanism of protection against dental caries has been investigated by passive immunization with antisera to S. mutans in the rhesus monkey. 2) Passive immunization with separated IgG, IgM and IgA from sera of immunized monkeys supports the concept that IgG, unlike IgA or IgM antibodies are protective. 3) The role of cell-mediated immunity has been explored by the use of transfer factor. This showed that protection against dental caries can be elicited by passive transfer of whole immune serum and cellular immunity, but not by cellular immunity or immune serum alone. 4) The results of active and passive immunization suggests that immuno-regulation of T and B cell interactions plays an important part in the effector mechanism of opsonization, phagocytosis and killing of S. mutans.

Animals↗

Salivary IgA antibodies to antigens from Streptococcus mutans in human dental caries.

1) Subjects of low caries experience (DMF 7) had significantly lower IgA antibody titers to antigens from S. mutans serotype c than subjects of high caries experience (DMF 13). 2) Subjects with carious lesions and a high DMF had significantly lower salivary antibody titers than subjects without carious lesions. 3) Sequential studies revealed that in the absence of caries salivary antibody titers decreased over a 9 month period. 4) Treatment of caries was associated with a rise in salivary IgA antibodies. No significant changes were associated with the development of caries. 5) No relationship with caries experience was found with antibodies to S. mutans BHT (serotype b), S. sanguis OMZ-9 or S. mitis CHT. 6) The results do not support the hypothesis that salivary antibodies in man play a role in protection against caries.

Antibodies, Bacterial↗

Immunoradiometric assay of salivary anti-c3 antibodies.

By an immunoradiometric assay IgA and IgG anti-C3 antibodies were found in adult parotid salivas. The binding of the IgA antibodies to complement coated red cells could be reversed by washing in buffer containing 0.01 M EDTA but IgG antibodies were unaffected. The binding of IgA antibodies was inhibited by small quantities of purified C3. This assay may prove useful in the detection of anti-C3 antibodies in other body fluids.

Adult↗

Passage of immunoglobulins from plasma to the oral cavity in rhesus monkeys.

The passage of immunoglobulin from plasma to the oral cavity was studied in rhesus monkeys. Immunoglobulins G, A and M were purified from pooled rhesus monkey serum, radiolabelled with 125I and injected intravenously into twelve monkeys. Sequential samples of oral fluids were taken over a 24 h period and were assayed for radioactivity. Radioactivity could be detected in crevicular fluid washings after 0.5 h in monkeys injected with IgG and IgA, and after 2 h in monkeys given IgM. Maximal levels were found after 4 h with each immunoglobulin. Radioactivity in parotid and mixed saliva could be detected in all animals after 30 min, reaching a maximal level after 4 h. Ultracentrifugation on sucrose density gradients revealed that most of the radioactivity in crevicular fluid washings was in the 7S zone in the animals given IgG and IgA, and in a 19S zone in animals given IgM. The radioactivity in partoid saliva did not represent intact immunoglobulin molecules, since all the activity was present in zones of low molecular weight in animals given IgG, IgA or IgM. In mixed saliva a small amount of radioactivity was found in the immunoglobulin zones. The results suggest that intact molecules of IgG, IgA and IgM can pass from plasma to the oral cavity via crevicular fluid, and could contribute to oral defence mechanisms particularly in the crevicular domain. The volume of crevicular fluid in the approximal space of deciduous molars of rhesus monkeys was estimated to be approximately 0.3 microliter.

Animals↗