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Vaccines against sexually transmitted diseases.

Corbeil LB, Campero CM, Rhyan JC, BonDurant RH - Reprod. Biol. Endocrinol. (2003)

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Infectious Diseases, University of California, San Diego Medical Center, 200 West Arbor Drive, San Diego, CA, 92103-8416, USA. lcorbeil@ucsd.edu

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Human sexually transmitted infections are prevalent throughout the world... Several have been associated with adverse pregnancy outcome and increased susceptibility to HIV infection, in addition to the discomfort of inflammation of the genital tract... IgA antibodies immobilized C. fetus better than IgG antibodies at a standardized agglutination titer... Conversely, IgG antibodies mediated opsonization and intracellular killing of C. fetus by macrophages and neutrophils, whereas IgA antibodies did not... This same research group has also demonstrated lymphoid nodules in human uterine epithelium... Therefore, it can be concluded that cells taking up antigen likely present that antigen to T helper cells, that antigenic stimulation leads to the formation of mucosally associated lymphoid tissue in the genital tract and that IgA responses result... IgG1 in protection was not clear from these studies, however... IgA is usually thought to be the major Ig class in protection of mucosal surfaces, but both IgA and IgG1 pathogen specific antibodies were found in vaginal secretions in both the local immune response of infected heifers and after systemic immunization... In spite of this, however, local immunity eventually clears the infection and local or systemic vaccination with appropriate antigens and adjuvants can enhance the response enough to clear infection before inflammation and reproductive failure result... In both C. fetus and T. foetus infection of the bovine female genital tract, convalescent immunity associated with mucosal IgA antibody is partially protective... Studies with trichomoniasis showed that antigen uptake by the genital epithelium is followed by formation of mucosally associated lymphoid tissue... A local IgA and IgG1 response results... Since systemic immunization protects in both bovine trichomoniasis and genital campylobacteriosis, it may be protective against other extracellular pathogens causing STDs in other animal species and in humans... It may be even more protective against pathogens which invade across the genital mucosa becoming more accessible to systemic immune responses.

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Higher magnification of Figure 1, showing plasma cells below the uterine glandular epithelium.
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Figure 2: Higher magnification of Figure 1, showing plasma cells below the uterine glandular epithelium.

Mentions: Convalescent immunity is partially protective against T. foetus as with C. fetus. We studied this response in order to understand how to enhance protection by vaccination. Skirrow and BonDurant [17] showed that clearance of vaginal infection occurred when antibodies to whole trichomonads increased in vaginal secretions. There was little detectable systemic antibody response. Later studies showed that IgG1 and IgA antibodies correlated with clearance of the vaginal infection [18]. Only IgG1 and IgA antibody to TF1.17 antigen (LPG/protein complex) were detected in uterine secretions also [19]. IgG1 is a Th2 type response in cattle [20], so it may be that this antigen induces a very skewed response. The production of any local immune response to genital tract infection raised a question since a mucosally associated lymphoid tissue is not seen in histologic sections, especially in the uterus. Histopathologic studies of reproductive tracts of experimentally infected heifers, however, showed lymphoid accumulations under the uterine surface and glandular epithelium [19,21,22]. This was especially true around infected glands. Some lymphoid nodules even had germinal centers (Figure 1). Plasma cells below the glandular epithelium (Figure 2) were consistent with secretion of antibodies across the uterine epithelium. Subsequent immunohistochemical studies, with mAbs specific for T. foetus LPG, demonstrated antigen uptake by uterine epithelial cells (Figure 3). This figure also demonstrates abundant intraepithelial and subepithelial lymphocytes, suggesting recruitment of immune cells. We have detected similar lymphoid nodules and antigen uptake in the vaginal mucosa of heifers (Rhyan, BonDurant and Corbeil, unpublished data) and the preputial epithelium of bulls [25] infected with T. foetus. Both bulls and heifers had IgA responses in genital secretions [18,19,21,22,25]. Others [23] have shown that both human uterine epithelial and stromal cells can present antigen to T cells. This same research group has also demonstrated lymphoid nodules in human uterine epithelium [24]. Therefore, it can be concluded that cells taking up antigen likely present that antigen to T helper cells, that antigenic stimulation leads to the formation of mucosally associated lymphoid tissue in the genital tract and that IgA responses result.


Vaccines against sexually transmitted diseases.

Corbeil LB, Campero CM, Rhyan JC, BonDurant RH - Reprod. Biol. Endocrinol. (2003)

Higher magnification of Figure 1, showing plasma cells below the uterine glandular epithelium.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC305334&req=5

Figure 2: Higher magnification of Figure 1, showing plasma cells below the uterine glandular epithelium.
Mentions: Convalescent immunity is partially protective against T. foetus as with C. fetus. We studied this response in order to understand how to enhance protection by vaccination. Skirrow and BonDurant [17] showed that clearance of vaginal infection occurred when antibodies to whole trichomonads increased in vaginal secretions. There was little detectable systemic antibody response. Later studies showed that IgG1 and IgA antibodies correlated with clearance of the vaginal infection [18]. Only IgG1 and IgA antibody to TF1.17 antigen (LPG/protein complex) were detected in uterine secretions also [19]. IgG1 is a Th2 type response in cattle [20], so it may be that this antigen induces a very skewed response. The production of any local immune response to genital tract infection raised a question since a mucosally associated lymphoid tissue is not seen in histologic sections, especially in the uterus. Histopathologic studies of reproductive tracts of experimentally infected heifers, however, showed lymphoid accumulations under the uterine surface and glandular epithelium [19,21,22]. This was especially true around infected glands. Some lymphoid nodules even had germinal centers (Figure 1). Plasma cells below the glandular epithelium (Figure 2) were consistent with secretion of antibodies across the uterine epithelium. Subsequent immunohistochemical studies, with mAbs specific for T. foetus LPG, demonstrated antigen uptake by uterine epithelial cells (Figure 3). This figure also demonstrates abundant intraepithelial and subepithelial lymphocytes, suggesting recruitment of immune cells. We have detected similar lymphoid nodules and antigen uptake in the vaginal mucosa of heifers (Rhyan, BonDurant and Corbeil, unpublished data) and the preputial epithelium of bulls [25] infected with T. foetus. Both bulls and heifers had IgA responses in genital secretions [18,19,21,22,25]. Others [23] have shown that both human uterine epithelial and stromal cells can present antigen to T cells. This same research group has also demonstrated lymphoid nodules in human uterine epithelium [24]. Therefore, it can be concluded that cells taking up antigen likely present that antigen to T helper cells, that antigenic stimulation leads to the formation of mucosally associated lymphoid tissue in the genital tract and that IgA responses result.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Infectious Diseases, University of California, San Diego Medical Center, 200 West Arbor Drive, San Diego, CA, 92103-8416, USA. lcorbeil@ucsd.edu

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

Human sexually transmitted infections are prevalent throughout the world... Several have been associated with adverse pregnancy outcome and increased susceptibility to HIV infection, in addition to the discomfort of inflammation of the genital tract... IgA antibodies immobilized C. fetus better than IgG antibodies at a standardized agglutination titer... Conversely, IgG antibodies mediated opsonization and intracellular killing of C. fetus by macrophages and neutrophils, whereas IgA antibodies did not... This same research group has also demonstrated lymphoid nodules in human uterine epithelium... Therefore, it can be concluded that cells taking up antigen likely present that antigen to T helper cells, that antigenic stimulation leads to the formation of mucosally associated lymphoid tissue in the genital tract and that IgA responses result... IgG1 in protection was not clear from these studies, however... IgA is usually thought to be the major Ig class in protection of mucosal surfaces, but both IgA and IgG1 pathogen specific antibodies were found in vaginal secretions in both the local immune response of infected heifers and after systemic immunization... In spite of this, however, local immunity eventually clears the infection and local or systemic vaccination with appropriate antigens and adjuvants can enhance the response enough to clear infection before inflammation and reproductive failure result... In both C. fetus and T. foetus infection of the bovine female genital tract, convalescent immunity associated with mucosal IgA antibody is partially protective... Studies with trichomoniasis showed that antigen uptake by the genital epithelium is followed by formation of mucosally associated lymphoid tissue... A local IgA and IgG1 response results... Since systemic immunization protects in both bovine trichomoniasis and genital campylobacteriosis, it may be protective against other extracellular pathogens causing STDs in other animal species and in humans... It may be even more protective against pathogens which invade across the genital mucosa becoming more accessible to systemic immune responses.

Show MeSH