Significance of immune responses to oral antigens in dental diseases.
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Antibodies, Bacterial↗
Biomedical subjects
M A Taubman
Publications and source records attributed to M A Taubman.
Anti-peptide antibodies reactive with epitopic domains of porcine amelogenins at the C-terminus.
This was an immunological investigation of the processing of porcine amelogenins in situ. Rabbit and rat anti-peptide sera reacted specifically with the hydrophilic segment of the intact amelogenins at the C-terminus. The immunogens used were the synthetic peptides: (a) C13 composed of PATDKTKREEVDC and (b) C25 composed of MQSLLPDLPLEAWPATDKTKREEVD. These peptides correspond to the C-terminal 12- and 25-residue segments of porcine amelogenin, respectively. Cystine was introduced at the C-terminus of C12 for KLH-binding (C13). Western blot analysis disclosed that: (i) both rabbit and rat anti-C13 sera reacted selectively with the 25-kDa porcine amelogenin and three other minor components (27, 22 and 18 kDa); (ii) anti-C25 peptide sera, additionally, reacted with the 23-kDa amelogenins (a degradation derivative of the 25-kDa protein, lacking the 12-residue segment at the C-terminus) and as trace components, 20-, 16- and 14-kDa moieties. Importantly, all the proteins reactive with the anti-C13 serum were concentrated in the outer secretory enamel adjacent to the ameloblasts, decreasing significantly in the underlying inner secretory enamel. Immunohistochemical studies applying the anti-peptide sera to the developing tooth germs of a minipig also confirmed the localization of reactivity in the outer secretory region. Neither anti-peptide serum reacted with porcine non-amelogenins, serum proteins nor dentine matrix proteins at the dilutions tested. however, it was found that both the anti-C13 and C25 sera reacted with human keratin.(ABSTRACT TRUNCATED AT 250 WORDS)
Amelogenin↗
Longitudinal monitoring of humoral antibody in subjects with destructive periodontal diseases.
Fifty-one subjects (16-61 years old) with evidence of prior destructive periodontal disease were monitored clinically and immunologically at bi-monthly intervals for up to 5 yr. Periodontal disease activity, determined as new attachment loss, was detected in 33 of these subjects. Only 4 of 51 subjects failed to show an elevated serum antibody level to any of the 18 subgingival species tested. The antibody level threshold established for periodontally healthy subjects was exceeded most often in diseased subjects with serum antibody to Actinobacillus sp., P. gingivalis, E. corrodens, C. concisus, F. nucleatum and P. intermedia in that order. In general, most serum antibody levels to subgingival species remained relatively consistent for periods as long as 5 yr. However, major increases and decreases in antibody could be detected to at most one or two species in individual subjects. In addition, prolonged, steady increases and decreases in antibody to specific species could be detected in certain subjects. These findings suggest that major changes occurring in serum antibody may reflect fluctuations in the nature of the infection. Differences were observed in the antibody level to specific species when subjects were divided into subsets on the basis of clinical criteria. These included high levels of antibody to A. actinomycetemcomitans Y4 in LJP and RPP subjects and to A. actinomycetemcomitans 29523 in LJP and GJP subjects.
Adolescent↗
Humoral IgG antibodies to oral microbiota in a population at risk for root-surface caries.
Mutans streptococci have been strongly implicated in the initiation of dental caries on coronal surfaces. Their role in development of root-surface caries is less clear. The etiologic agents of both types of dental caries are likely to elicit systemic immune responses. The objective of the present study, therefore, was to study the association of clinical variables of disease with humoral IgG antibodies to nine oral micro-organisms in 314 adult subjects, aged 45-65 years, who were at risk for root-surface caries. Antibody activity to Streptococcus mutans strain Ingbritt, S. mutans/S. sobrinus GTFs, S. faecalis strain 19433, Actinomyces viscosus strain WVU 626, Actinomyces naeslundii strain 12, Lactobacillus casei, Actinobacillus actinomycetemcomitans strain Y4, Porphyromonas gingivalis strain 381, Eikenella corrodens strain 1073, and Wolinella recta strain 371 was measured by ELISA. Pearson correlation coefficients among log10 antibody levels within subjects revealed marked positive correlations among subgingival bacteria, generally weak positive correlations among supragingival micro-organisms, and no correlations between elements of the supragingival battery with the subgingival battery. IgG antibody levels to mutans streptococcal antigens were significantly correlated with subject DMF scores (r = 0.23; p less than 0.0001). No significant correlation was seen between DMF scores and antibody to any other supragingival micro-organism tested. Further relationships between levels of S. mutans antibody and individual clinical variables were analyzed by step-wise multiple linear regression, resulting in a model that was highly significant (p = 0.0001), with an r2 = 0.14. Numbers of missing teeth, coronal caries, root-surface caries, and root-surface restorations were each positively associated with antibody levels to mutans streptococci.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Effect of age on immunoglobulin content and volume of human labial gland saliva.
Stimulated lower labial (LLGF) and parotid salivary volumes and IgG, IgA, and IgM concentrations were measured in 264 subjects whose ages ranged from 17 to 76 years. A significant (p < 0.001) age-related decline in LLGF output was observed for subjects over this age range. Sixty-three percent of the subjects in the 18-20-year-old group (n = 46) secreted at least 10 microL of labial saliva in a 7-10-minute period, while approximately 70% of the subjects in the two oldest groups (61-70 and 71-76 years old) secreted less than 1 microL of LLGF during this time period (n = 64). No significant gender-based differences occurred in the volumes of labial saliva secreted. Stimulated parotid salivary flow showed no age-related trend in these subjects. Lower labial gland salivary IgA concentrations in an older population (mean age +/- SD = 55.6 yr +/- 1.3) were significantly lower (p < 0.025) than IgA concentrations in a younger population (20.7 yr +/- 0.8), when IgA was expressed as microgram/mL LLGF collected. Immunoglobulin A concentrations in parotid saliva and IgG and IgM concentrations in labial and parotid saliva were not significantly different when the two age populations were compared. These data suggest that the physiological and immunological potential of labial gland saliva may decrease with age.
Adolescent↗
Ontogeny of immunity to oral microbiota in humans.
This article reviews the ontogeny of immune systems in the human oral cavity that may influence the colonization, accumulation, or pathogenesis of oral microbiota. The prenatal development of cellular components associated with the secretory immune system reveals that the initial organization of tissue into Peyer's patches can first be detected immunohistologically at 11 weeks gestation. Epithelial cells positive for secretory component and immunocytes positive for IgM can be detected in salivary gland tissue by 19 to 20 weeks and continue to predominate during gestation. After birth, immunocytes containing IgA begin to dominate. Essentially, no IgA can be detected in saliva at birth. However, salivary IgA and IgM often appear soon thereafter, presumably in response to environmental antigenic and mitogenic challenges. Salivary IgA in young infants has molecular characteristics of secretory IgA and becomes the quantitatively predominate Ig in saliva. Both IgA subclasses are present in proportions characteristic of adult pure glandular salivas in many 1- to 2-month-old infants, although the appearance of IgA2 is delayed in some subjects. Many innate, antibody, and cellular immune components are found in maternal colostrum and breast milk. The antibacterial properties of these maternal factors are diverse and can exert multifaceted protective effects on the infant's alimentary tract. The infant apparently can mount mucosal immune responses quite early in life. For example, salivary antibody activity to organisms that originally colonize the gut (e.g., E. coli) or the oral cavity (e.g., S. mitis, S. salivarius) can be detected by 1 to 2 months of age. Most of this antibody activity has characteristics of secretory IgA, although some IgM antibody can also be initially detected. Salivary IgA1 and IgA2 antibody specificities to S. mitis and S. salivarius components increase qualitatively and quantitatively during the first few years of life. Salivary IgA antibody to components of streptococci that require hard surfaces for colonization (e.g., S. sanguis and mutans streptococci) generally appear after tooth eruption. The loss of placentally derived maternal IgG antibody specificities to these microbiota in the circulation is replaced by de novo synthesis, presumably as a result of the teething process. These IgG antibodies can enter the oral cavity in the gingival crevicular fluid and by the process of teething.(ABSTRACT TRUNCATED AT 400 WORDS)
Bacteria↗
Effect of adoptive transfer of cloned Actinobacillus actinomycetemcomitans-specific T helper cells on periodontal disease.
Previously we isolated several Actinobacillus actinomycetemcomitans-specific T-cell clones from the spleens and lymph nodes of immunized Rowett rats. These clones were characterized as W3/13+, W3/25+, OX8-, and OX22-, suggesting a T helper (Th) phenotype. In the current experiments, 10(6) cells from a single A. actinomycetemcomitans-specific clone (A3) were adoptively transferred to a group (AaTh; n = 13) of normal heterozygous rats (rnu/+) at 28 days of age. A second group received no T cells (AaNT; n = 15), and a third group also received no T cells (NAaNT, n = 11). Beginning 1 day after transfer, the first and second groups were infected orally with A. actinomycetemcomitans for 5 consecutive days. The presence of infection was confirmed immediately after challenge and after 5 months, when the experiments were ended. Significantly higher numbers of lymphocytes were recovered from the gingival tissues of the first group than from those of either of the other groups. Also, this group showed significantly elevated (P less than 0.01) serum immunoglobulin G and immunoglobulin M antibody to A. actinomycetemcomitans in an enzyme-linked immunosorbent assay when compared with both other groups. Bone loss was significantly lower (P less than 0.01) in recipients of A. actinomycetemcomitans-specific cloned cells when compared with the other infected group and was approximately equal to the bone loss of the uninfected group. These results are consistent with the hypothesis that T-cell regulation can affect periodontal disease. In this regulation, T helper cells appear to interfere with periodontal bone loss.
Actinobacillus↗
Immunoglobulin isotypes in human minor gland saliva.
Lower labial, upper labial, palatine (minor), and parotid (major) gland saliva samples from 18 young adult males were quantitatively assayed for the presence of IgA1, IgA2, IgM, and IgG. The mean (+/- standard deviation) concentrations of IgA (sum of IgA1 + IgA2) were 79 +/- 42 micrograms/mL (parotid), 111 +/- 42 micrograms/mL (lower labial), 69 +/- 72 micrograms/mL (upper labial), and 88 +/- 68 micrograms/mL (palatine). Total IgA concentrations were positively correlated among different minor-gland samples from the same subject, although these correlations did not reach significance. Upper-labial-gland saliva samples contained significantly (at least p less than 0.05) lower concentrations of IgA1 than those found in parotid or lower-labial minor-gland secretions. All three minor-gland sources of saliva contained significantly (p less than 0.002) higher levels of IgG than did parotid saliva. Upper-labial fluids had significantly (p less than 0.02) higher IgG concentrations than lower-labial saliva. IgM could be detected in 89% of parotid saliva samples and 75% of the palatine saliva samples. Palatine IgM concentrations (8.2 +/- 17.8 micrograms/mL) were significantly (p less than 0.05) higher than parotid IgM concentrations (0.6 +/- 0.4 micrograms/mL). IgM was detected much less frequently and at lower concentrations in lower- and upper-labial-gland saliva. These data reveal that minor-gland saliva from different oral sites may contain distinctive immunoglobulin isotype patterns, and expressions of host defense may vary within each micro-environment.
Adolescent↗
Effect of local deposition of antigen on salivary immune responses and reaccumulation of mutans streptococci.
In this study glucosyltransferase (GTF) from Streptococcus sobrinus was topically administered onto the lower lips of young adults. The effect of this route of antigenic exposure on labial and parotid gland and serum antibody levels to GTF and on the reaccumulation of indigenous mutans streptococci after a dental prophylaxis was then measured. Young adults between 18 and 42 years of age were screened for levels of antibody activity to GTF in parotid and labial gland salivas and levels of mutans streptococci in their whole saliva. Prior to antigen administration, two groups were formed which had similar distributions of mutans streptococci in their whole saliva. Antigen (GTF) or placebo, each combined with aluminum phosphate (AP), was then administered to the lower lip daily for 5 days. Immediately prior to topical application of GTF or placebo to the labial salivary glands, all subjects were given a dental prophylaxis. Statistically significant differences in anti-GTF IgA antibody activity in parotid or labial salivas were not observed between the GTF-administered and the placebo groups during the 6 weeks following topical application. However, the proportions of indigenous mutans streptococci/total streptococcal flora, or total cultivable flora, were always lower in the whole salivas of the GTF, compared with the placebo group. These differences were statistically significant on days 13, 20, 34, and 41 after initial topical application. Delays in reaccumulation were significantly associated (P less than 0.025) with elevations in parotid saliva IgA antibody levels of all subjects. Seven of 10 of the subjects demonstrating this association were in the group to which GTF was topically administered.(ABSTRACT TRUNCATED AT 250 WORDS)
Administration, Topical↗
Actinobacillus actinomycetemcomitans mitogenicity for B cells can be attributed to lipopolysaccharide.
The purpose of this investigation was to determine the component(s) of whole Actinobacillus actinomycetemcomitans bacteria responsible for B cell mitogenic activity. Congenitally athymic "nude" rats were used as a source of B cells devoid of T lymphocyte activity. Spleen cells were cultured with, or without, whole formalin-killed A. actinomycetemcomitans bacteria or with purified LPS from A. actinomycetemcomitans. Dose-response curves to A. actinomycetemcomitans cells or to A. actinomycetemcomitans-LPS showed that responses were dose dependent. If optimal quantities of both A. actinomycetemcomitans and A. actinomycetemcomitans-LPS were added in combination, the proliferative responses were the same as if either was added alone, i.e., the responses were not additive. Polymyxin B at 2 micrograms/well completely abrogated the proliferative response of athymic rat splenocytes to 10(7) A. actinomycetemcomitans cells or to 1.25 micrograms A. actinomycetemcomitans-LPS/well. Therefore, the in vitro early proliferative response of B cells to A. actinomycetemcomitans can be attributed to the presence of LPS on A. actinomycetemcomitans cells. A considerable portion of the in situ lymphocytic gingival response to A. actinomycetemcomitans infection seen in periodontal disease patients may be a B cell mitogenic response to the LPS of this bacterium.
Actinobacillus↗
Salivary IgA antibody to oral streptococcal antigens in predentate infants.
Salivary IgA antibodies to oral streptococci which colonize the infant oral cavity soon after birth were analyzed in 53 whole salivas of 17 infants who were between three and 27 weeks old. Antibody activities to Streptococcus mitis cells were detected by enzyme linked immunosorbent assay in 78% of the whole salivas by the twelfth week of age. This antibody activity was associated with polymeric IgA as determined after gel filtration of salivas on Superose 6, followed by ELISA. Western blot analyses were used to detect IgA antibodies to Streptococcus mitis and Streptococcus salivarius culture supernatants. Forty one, and 91% of saliva samples contained IgA antibody which reacted in Western blot analyses with S. salivarius and S. mitis culture supernatants, respectively. The youngest infant to show reactive IgA antibody with either oral streptococcal antigen preparation was five week old. Salivary IgA antibody to either bacterial culture supernatant was detected in Western blot only after the isolation of the respective streptococcal species from the oral cavity of these young infants. Some heterogeneity was observed among patterns developed with salivas from different infants. These results suggest that salivary IgA antibody responses may be induced by oral colonization (S. mitis, S. salivarius) by the end of the first month of life.
Age Factors↗
Dental caries in congenitally athymic rats.
The importance of the immune response in dental infection was evaluated in heterozygous (rnu/+) normal and homozygous (rnu/rnu) congenitally athymic "nude" Rowett rats. Animals of both types were infected, or immunized and infected, with mutans streptococci (Streptococcus sobrinus strain 6715). The mean numbers of S. sobrinus cells recovered from the nude rats were higher than those from comparable (immune/nonimmune) normal rats in 10 of 12 possible comparisons. Also, S. sobrinus constituted a greater percentage of the total streptococci in the nude rats compared with normal animals (6 of 6 possible comparisons). Antibody to S. sobrinus whole cells or to S. sobrinus glucosyltransferase from nude rats in serum or in saliva was significantly lower (or absent) than that of comparable normal rats. This was seen after infection, but was most pronounced after immunization (and infection). Dental caries was also significantly elevated in the congenitally athymic animals. Immunologic deficiency of congenitally athymic rats can lead to a greater infection level with mutans streptococci and increased dental caries.
Analysis of Variance↗
Characterization of rat T-cell clones with bacterial specificity.
We have isolated 10 rat T-cell clones from the spleen or lymph nodes of seven different donors. These rats were immunized with 2-5 x 10(8) killed Actinobacillus actinomycetemcomitans (Aa) bacteria, injected either subcutaneously (s.c.) in complete Freund's adjuvant or intraperitoneally (i.p.) in saline. Clones studied to date have demonstrated a T-helper (Th) phenotype W3/13+, W3/25+, OX8- and OX22-. Clones were not stimulated in vitro by purified Aa-lipopolysaccharide (LPS) or heterologous Gram-negative bacteria, but proliferated when stimulated by bacteria representative of each of the three serological groups of Actinobacillus, indicating specificity for an Actinobacillus-common antigen other than LPS. One clone (A4) proliferated vigorously when stimulated with concanavalin A (Con A) in vitro, produced interleukin-2 (IL-2) and was provisionally classified as a Th1 type. This appears to be one of the few Th1-type rat clones reported. All other clones tested did not produce IL-2, exhibited B-cell help to some extent, did not induce delayed-type hypersensitivity (DTH) when injected into the footpads of naive rats along with the specific antigen, and were classified as Th2 type. Adoptive transfer of 10(6) cells of one Th2-type Aa-specific clone into syngeneic recipients resulted in a specific splenocyte in vitro response to Aa 12-14 weeks after cell transfer, indicating survival of cloned cells in recipient animals. The use of such clones in studies of experimental periodontal disease is discussed.
Actinobacillus↗
Oral immunization for the prevention of dental diseases.
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Administration, Oral↗
The specific pathogen-free human: a new frontier in oral infectious disease research.
The indigenous flora acts as a deterrent to the establishment of some pathogenic species. We propose that advances in oral health research will lead to control of oral infections by altering the indigenous microflora to create a specific pathogen-free human. Investigations of important endogenous and exogenous factors which affect the oral flora and the interactions among these parameters, in health and disease, will have to be undertaken for this goal to be achieved. Several approaches to produce a specific pathogen-free human include: (1) introduction of individual or collective moieties which inhibit detrimental interactions on a genetic and molecular level; (2) genetic modification of salivary flow and protein composition by use of transgenic techniques; (3) therapeutic replacement with altered bacterial strains; (4) alteration of host immune responses to produce specific isotype immunity at the most appropriate time in the ontogeny of the oral environment; (5) production of isotype and/or antigen-specific regulatory molecules at the most appropriate time in development; (6) use of synthetic vaccines; (7) genetic alteration or replacement of cells with defective protective capabilities; and (8) use of anti-idiotype vaccines.
Germ-Free Life↗
Isotype, subclass and molecular size of immunoglobulins in salivas from young infants.
Whole saliva samples from 17 infants who were between 3 and 20 weeks of age were analysed for isotype, subclass and molecular size of immunoglobulins. IgA concentrations ranged from 1.7 to over 60 micrograms/ml. IgM concentrations ranged from undetected to 59% of the IgA concentration in the respective saliva. Ratios of salivary IgM to salivary IgA were inversely correlated with the age of the infant. Gel filtration of 31 salivas on calibrated columns of Superose 6 revealed the IgA to elute in a position consistent with that of secretory IgA. IgM eluted in a position consistent with that of the pentameric molecule. IgA1 was the predominating subclass (IgA1/IgA1 + IgA2 = 0.64) in infant whole saliva. Both IgA subclass concentrations were significantly lower than concentrations measured in adult parotid salivas. Several infant salivas initially contained greater than 95% IgA1 but salivary IgA2 concentrations progressively increased as these infants grew older. These observations support the conclusions that essentially all IgA in whole saliva of predentate infants is of secretory origin, that adult salivary IgM/IgA proportions are achieved early in life, but that, at least in some infants, the salivary IgA subclass proportions are still changing during this time.
Female↗
Immune properties of glucosyltransferases from S. sobrinus.
GTF activity was separated into water-insoluble (GTF-I) and water-soluble (GTF-S) polyglucan-synthesizing enzymes. Each preparation demonstrated a single band on 6% SDS PAGE. Only water-insoluble or water-soluble polyglucan was synthesized by the respective enzyme preparation. Rats were immunized, on Days 1 and 14, with either GTF-I or GTF-S in adjuvant. Animals were bled 13, 35 and 54 days after the initial immunization. Individual antisera were tested against either the GTF-I or the GTF-S for inhibition of radioactive glucose incorporation into glucan, and in gel diffusion, and by Western transfer analyses. The respective antisera reacted with the homologous, but not the heterologous enzyme in gel diffusion and Western transfer. GTF-I activity was not inhibited by antibody to GTF-S, but antibody to GTF-I inhibited GTF-I by 68%. GTF-S was inhibited by more than 60% by each of 3 anti-GTF-S sera. Only one anti-GTF-I serum inhibited GTF-S at as much as a modest 30% level. These data support the antigenic and functional distinctiveness of the GTF enzymes of S. sobrinus 6715.
Animals↗