Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Immunity, Mucosal”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,135 records · Page 63Linked to original sources

Increased production of serum IgA-class antibody to lipid A in Kawasaki disease.

BACKGROUND: The etiology of Kawasaki disease (KD) remains unknown. To investigate whether a conventional bacterial antigen is involved in the pathogenesis of KD, we studied the serum response to lipopolysaccharide (LPS). METHODS: We measured the serum levels of IgG-, IgM- and IgA-class antibodies (Ab) to lipid A, a toxic site of LPS, using enzyme-linked immunosorbent assay in 20 patients with KD, 11 patients with Gram-negative bacterial infection (GNBI), 27 healthy children and 12 healthy adults. RESULTS: The serum levels of anti-lipid A IgG, IgM and IgA tended to increase with advancing age in healthy children older than 6 months of age. The mean level of anti-lipid A IgM in the acute phase of GNBI and the mean levels of anti-lipid A IgM and IgA in the acute phase of KD were found to increase significantly, in comparison to the age-matched controls. Furthermore, the mean level of anti-lipid A IgA also showed a significant increase from the acute to the subacute phases of KD. Regarding the IgA-subclass response, higher titers of anti-lipid A specific Ab were seen in the IgA2 subclass than in the IgA1 subclass. CONCLUSION: These findings indicate that KD patients demonstrate an intense response to lipid A in the IgA, especially IgA2-subclass, thus suggesting that an unusual activation of the mucosal immune response to a ubiquitous antigen derived from Gram-negative bacteria may be involved in the pathogenesis of KD.

Antigens, Bacterial↗

Characterization of ovine nasal-associated lymphoid tissue and identification of M cells in the overlying follicle-associated epithelium.

The distribution of mucosal lymphoid nodules in the ovine nasopharyngeal tract was studied by an acetic acid fixation technique. Nodules, which were concentrated just posterior to the opening of the Eustachian tube, were excised and examined by light microscopy, and scanning and transmission electron microscopy. Immunohistochemical examination revealed that each lymphoid structure consisted of follicles containing discrete B- and T-cell areas, characteristic of a mucosal inductive site of the mucosa-associated lymphoid tissue (MALT). Electron microscopy revealed that specialized epithelial cells, displaying features characteristic of M cells, were present in the follicle-associated epithelium (FAE) that covered the lymphoid nodules. These cells had sparse irregular microvilli and were closely associated with lymphocytes in the underlying tissue. These findings suggest that targeting the nasopharyngeal region may provide a practical and effective route for the stimulation of protective mucosal immune responses.

Acetic Acid↗

Intestinal permeability to mannitol and lactulose in children with type 1 diabetes with the HLA-DQB1*02 allele.

Food antigens and enteroviruses are possible triggers of type 1 diabetes. Because permeability of the intestinal epithelium may facilitate contact of these antigens with the mucosal immune system, we set out to study intestinal permeability in patients with type 1 diabetes. Children with type 1 diabetes (n = 26, mean age 12 years, mean duration of disease 4 years) and 24 healthy age-matched control children were given mannitol and lactulose orally, and their intestinal permeability was measured as a percentage of this dose recovered in urine. Patients with type 1 diabetes did not differ in their permeability to lactulose, nor was their lactulose/mannitol ratio any different from that of controls. However, patients with type 1 diabetes who had the HLA-DQB 1*02 allele and, therefore, a higher risk for celiac disease (CD) absorbed significantly more mannitol (mean + 95% CI): 17.7% (15.2-20.2) than did those negative for this allele: 12.3% (8.2-16.4), p = 0.04. Their lactulose permeability was also higher: 0.30 (0.16-0.44) and 0.09% (0-0.18), respectively, p = 0.02. Although the differences in permeability reach statistical significance, there was still much overlap between the two groups in terms of actual laboratory values. The higher permeability of patients with the HLA-DQB1*02 allele suggests that these patients may be more prone to develop abnormal immune responses to food antigens.

Adolescent↗

New strategies in the management of inflammatory bowel disease.

The incidence and prevalence of IBD increase in our Western populations. Standard therapy with glucocorticosteroids and 5-ASA formulations allow control in only about half of the patients with substantial toxicity for the former drug. Since it became apparent that both UC and Crohn's disease are disorders mediated through abnormalities in the mucosal immune system immunosuppression and immunomodulation have become current practice in the treatment of refractory IBD. In UC cyclosporin is the main immunosuppressive agent. In Crohn's disease azathioprine is the mainstay of therapy for refractory disease. Recently anti-TNF strategies have been developed which hold great promise for the treatment of Crohn's disease.

Adjuvants, Immunologic↗

Essential role for CD103 in the T cell-mediated regulation of experimental colitis.

The integrin CD103 is highly expressed at mucosal sites, but its role in mucosal immune regulation remains poorly understood. We have analyzed the functional role of CD103 in intestinal immune regulation using the T cell transfer model of colitis. Our results show no mandatory role for CD103 expression on T cells for either the development or CD4+CD25+ regulatory T (T reg) cell-mediated control of colitis. However, wild-type CD4+CD25+ T cells were unable to prevent colitis in immune-deficient recipients lacking CD103, demonstrating a nonredundant functional role for CD103 on host cells in T reg cell-mediated intestinal immune regulation. Non-T cell expression of CD103 is restricted primarily to CD11c(high)MHC class II(high) dendritic cells (DCs). This DC population is present at a high frequency in the gut-associated lymphoid tissue and appears to mediate a distinct functional role. Thus, CD103+ DCs, but not their CD103- counterparts, promoted expression of the gut-homing receptor CCR9 on T cells. Conversely, CD103- DCs promoted the differentiation of IFN-gamma-producing T cells. Collectively, these data suggest that CD103+ and CD103- DCs represent functionally distinct subsets and that CD103 expression on DCs influences the balance between effector and regulatory T cell activity in the intestine.

Animals↗

Norwalk virus vaccines: challenges and progress.

Human caliciviruses (HuCVs) are the major cause of outbreaks of acute nonbacterial gastroenteritis throughout the world. An increasing recognition of the clinical significance of these viruses as human pathogens causing foodborne and waterborne disease indicates that an effective vaccine would be useful. This article reviews the current challenges that exist for the development of a vaccine for the HuCVs as well as the status of development of a candidate vaccine. HuCVs are viruses that exhibit a restricted tropism for infection of the gastrointestinal tract of humans, and a volunteer model of infection and disease is available. As pathogens with a restricted host range, the HuCVs are excellent models for understanding the mechanisms that mediate and regulate viral infection of the gastrointestinal tract and mucosal immunity in humans.

Caliciviridae Infections↗

Interactions of the female hormonal environment, susceptibility to viral infections, and disease progression.

Sex hormones influence susceptibility and disease predisposition for many genital tract infections. This review describes the mechanisms by which sex steroids affect mucosal immunity, with particular reference to human immunodeficiency virus (HIV) and genital herpes, and the stage-specific effects of hormonal contraception on human papillomavirus (HPV) infection. Estrogen's role is important in the early stages of several infections as it stimulates antibody- and cell-mediated immune responses. There is increased expression of some cytokines in peripheral blood and vaginal fluids during the follicular phase of the menstrual cycle and with use of hormonal contraception. Whether estrogen exerts a protective or deleterious influence depends on the infecting organism and stage of infection or disease. Estrogen apparently reduces susceptibility to primary HPV infection but in the event of persistent HPV infection, sex steroid hormones (estrogen and/or progesterone) are associated with progression to cervical cancer. It is important that these stage-specific effects are better described because most vaccines will try to prevent either infection or disease. Clinicians with patients at high risk of sexually transmitted infections, especially HIV, require better information on the risks associated with different hormonal contraceptive regimes.

Contraceptives, Oral, Hormonal↗

Isolation of respiratory bacterial pathogens from the throats of healthy infants fed by different methods.

Most bacterial infections are caused by organisms that have already colonized the host. Bacterial attachment to pharyngeal cells and proliferation may be necessary to infect the lower respiratory tract or middle ear. We investigated the incidence of pathogenic bacteria isolated from the throat of healthy infants with different feeding methods. The protecting role of breastmilk is also discussed. The incidence of respiratory bacterial pathogens isolated from the oropharynx of 113 normal infants with different feeding methods was investigated. Group A beta haemolytic Streptococcus, Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis were selected as respiratory bacterial pathogens. No respiratory bacterial pathogens were detected in breastfed and mixed-fed infants. Haemophilus influenzae and Moraxella catarrhalis were isolated from the oropharynx of formula-fed infants. The incidence of respiratory bacterial pathogens did differ among infants with different feeding methods. These results suggest that breastmilk may inhibit the colonization by respiratory bacterial pathogens of the throat of infants, by enhancing mucosal immunity against respiratory tract infection.

Bacteria↗

Cervicovaginal anti-HIV antibodies in HIV-seronegative female sex workers in Abidjan, Côte d'Ivoire.

OBJECTIVE: To detect anti-HIV antibodies in cervicovaginal secretions of HIV-seronegative female sex workers and to evaluate whether the presence of these antibodies is associated with increased sexual exposure. METHODS: A cross-sectional study was carried out at a confidential clinic for female sex workers in Abidjan, Côte d'Ivoire. The participants were 342 HIV-seronegative female sex workers in whom a cervicovaginal lavage was collected. The main outcome measures were the detection of antibodies to HIV-1 in cervicovaginal lavages using an in-house and a commercial (Seradyn Sentinel; Calypte Biomedical Corporation, Berkeley, California, USA) enzyme immunoassay; the detection of semen in cervicovaginal lavages; and the assessment of epidemiological and biological markers of sexual exposure to HIV. RESULTS: Cervicovaginal anti-HIV antibodies were detected in 7.3 and 29.8% of women using in-house enzyme-linked immunosorbent assay (ELISA) and Seradyn Sentinel respectively. All cervicovaginal secretions found to be positive by in-house ELISA were also positive by Seradyn Sentinel. In a minority of women, ranging from 2.9% by in-house ELISA to 12.3% by Seradyn Sentinel, the anti-HIV antibodies were present in vaginal fluids that did not contain semen. Sexual exposure to HIV was similar in women with anti-HIV antibodies in their semen-free cervicovaginal secretions compared with women without anti-HIV antibodies in their cervicovaginal secretions. CONCLUSIONS: Cervicovaginal HIV-specific antibodies were detected in a minority of sexually exposed HIV-seronegative female sex workers in Abidjan. The lack of association between increased sexual exposure to HIV and presence of cervicovaginal HIV-specific antibodies suggests that the production of genital HIV-specific antibodies in exposed seronegative women depends on the ability of individual women to mount specific mucosal immunity to HIV antigens, the determinants of which are currently unknown.

Adult↗

Postoperative nutrition in surgery for major trauma.

Research in the area of the nutritional support of trauma patients has continued to focus on a few main areas: the effect that the route, timing and type of feeding has on patient outcome, nutritional assessment and mucosal immunity. This year a nutritional conference has released a paper, summarizing the current state of research in this area, that generated some controversy.

Humans↗

Intestinal barrier function.

Intestinal barrier function regulates transport and host defense mechanisms at the mucosal interface with the outside world. Transcellular and paracellular fluxes are tightly controlled by membrane pumps, ion channels and tight junctions, adapting permeability to physiological needs. Food and microbial antigens are under constant surveillance of the mucosal immune system. Tolerance against commensals and immunity against pathogens require intact antigen uptake, recognition, processing and response mechanisms. Disturbance at any level, but particularly bacterial translocation due to increased permeability and breakdown of oral tolerance due to compromised epithelial and T cell interaction, can result in inflammation and tissue damage. New therapeutic approaches including probiotics and peptides to restore disrupted barrier function are evolving.

Biological Transport↗

Lamina propria dendritic cells in the physiology and pathology of the gastrointestinal tract.

PURPOSE OF REVIEW: The mucosal immune system constantly surveys the intestinal microbiota. The outcome of this interaction is determined by the functional properties of dendritic cells, which play a key role in immune response by facilitating antigen sampling and pathogen recognition, as well as innate host defenses. RECENT FINDINGS: Recent advances have provided insight into the diverse mechanisms involved in the acquisition of intestinal antigens and led to a new appreciation of organ-specific functional subspecification of dendritic cell subsets. Dendritic cells are not a rare cell type in the intestine but populate the entire lamina propria of the gastrointestinal tract as an extensive network. Distinct dendritic cell subsets may be associated with specific immune functions in the lamina propria and Peyer's patches. Newly discovered routes of antigen acquisition, such as the formation of transepithelial dendrites, allow dendritic cells direct access to the intestinal lumen to obtain information about commensal and pathogenic microorganisms. Dendritic cells emerge as key regulators of the intestinal immune system with their ability to direct intestine-specific migration and control of T cells. SUMMARY: Dendritic cells play a major role in the complex interactions between the gut microbiota and the innate and adaptive immune system, leading to tolerance and immunity. Recent contributions have yielded important information that may aid in the development of novel therapeutic approaches to the treatment of inflammatory bowl disease and intestinal infections and to new immunization strategies.

Animals↗

Type 1 and 2 T helper cell-mediated colitis.

PURPOSE OF REVIEW: Abrogation of mucosal T cell homeostasis by exaggerated not only T helper 1, but also T helper 2 cells is a major problem that leads to intestinal inflammation. In this regard, it is important to understand these different aspects of mucosal inflammation. RECENT FINDINGS: Both T helper 1 and 2 cells play central roles in the induction of mucosal immune responses including secretory IgA antibody production, which would be the most beneficial aspect for the host defense mechanism. T helper 1- and 2-type responses, however, exhibit other roles in the abrogation of intestinal homeostasis. Although it has been shown that T helper 1-type immune responses are key players in the induction of intestinal inflammation in mice colitis models and also in inflammatory bowel diseases in humans, studies in murine colitis models clearly show that T helper 2-type responses are also involved in the pathophysiology of the intestinal inflammation. Both regulatory type T cells and T helper 17 cells are involved to down- or upregulate aberrant T helper 1 and 2 cell responses. SUMMARY: Understanding the cellular and molecular mechanisms of crosstalk among T helper 1, 2, 17 and T regulatory 1 cells is central for the prevention or treatment of inflammatory bowel diseases.

Animals↗

Mucosal B cells: phenotypic characteristics, transcriptional regulation, and homing properties.

Mucosal antibody defense depends on a complex cooperation between local B cells and secretory epithelia. Mucosa-associated lymphoid tissue gives rise to B cells with striking J-chain expression that are seeded to secretory effector sites. Such preferential homing constitutes the biological basis for local production of polymeric immunoglobulin A (pIgA) and pentameric IgM with high affinity to the epithelial pIg receptor that readily can export these antibodies to the mucosal surface. This ultimate functional goal of mucosal B-cell differentiation appears to explain why the J chain is also expressed by IgG- and IgD-producing plasma cells (PCs) occurring at secretory tissue sites; these immunocytes may be considered as 'spin-offs' from early effector clones that through class switch are on their way to pIgA production. Abundant evidence supports the notion that intestinal PCs are largely derived from B cells initially activated in gut-associated lymphoid tissue (GALT). Nevertheless, insufficient knowledge exists concerning the relative importance of M cells, major histocompatibility complex class II-expressing epithelial cells, and professional antigen-presenting cells for the uptake, processing, and presentation of luminal antigens in GALT to accomplish the extensive and sustained priming and expansion of mucosal B cells. Likewise, it is unclear how the germinal center reaction in GALT so strikingly can promote class switch to IgA and expression of J chain. Although B-cell migration from GALT to the intestinal lamina propria is guided by rather well-defined adhesion molecules and chemokines/chemokine receptors, the cues directing preferential homing to different segments of the gut require better definition. This is even more so for the molecules involved in homing of mucosal B cells to secretory effector sites beyond the gut, and in this respect, the role of Waldever's ring (including the palatine tonsils and adenoids) as a regional inductive tissue needs further characterization. Data suggest a remarkable compartmentalization of the mucosal immune system that must be taken into account in the development of effective local vaccines to protect specifically the airways, eyes, oral cavity, small and large intestines, and urogenital tract.

Animals↗

Flow cytometric analysis of leukocytes in the human female reproductive tract: comparison of fallopian tube, uterus, cervix, and vagina.

PROBLEM: The tissues of the human female reproductive tract (Fallopian tube, uterus, cervix, and vagina) may play different roles in the provision of mucosal immunity. The purpose of this study was to develop a uniform method suitable for quantitative comparison of the leukocytes from all these tissues. METHOD OF STUDY: Tissues, typically 0.5-1.0 g, were dispersed by enzyme treatment. A flow cytometric gating procedure based on CD45-positivity and low far-red autofluorescence permitted unfractionated, freshly dispersed cells to be phenotyped with respect to T lymphocytes, B lymphocytes, macrophages, and granulocytes. RESULTS: Reproductive tract tissues contain leukocytes that represent approximately 6-20% of the total number of cells, with the Fallopian tubes and uterus containing a higher proportion of leukocytes than the cervix and vagina. The uterine endometrium from post-menopausal women has fewer leukocytes than does uterine endometrium from pre-menopausal women. T lymphocytes are a major constituent (30-60%) of leukocytes from all tissues. The Fallopian tube contains granulocytes as another major constituent; granulocytes are significantly less numerous in the other tissues. All tissues contain B lymphocytes and macrophages as clearly detectable but minor components. CONCLUSIONS: Three-color flow cytometry is an appropriate method for quantitative comparison of leukocytes from the different tissues of the female reproductive tract, during all phases of the menstrual cycle and within post-menopausal samples. Results indicate that the tissues differ from each other, particularly with respect to the large number of granulocytes in the Fallopian tubes.

Adult↗

Immunocompetent cells in oral candidiasis of HIV-infected patients: an immunohistochemical and electron microscopical study.

OBJECTIVE: The purpose of this study was to elucidate the pathogenesis of oral candidiasis, a common cause of discomfort and social impairment among HIV-infected individuals. STUDY DESIGN, MATERIALS AND METHODS: The oral mucosal immune system cells were analysed by immunohistochemistry and electron microscopy in biopsies from five erythematous and four pseudomembranous candidiasis cases and were compared with those from seven HIV-positive and 10 HIV-negative controls without candidiasis. RESULTS: The superficial lamina propria and basal epithelial layer was populated by CD1a+ Langerhans cells with infiltration of CD8+ lymphocytes. Within the submucosa are CD36+ dendritic macrophages and lymphocytes, although CD4+ subsets were absent from the infiltrate. The expression of human leukocyte antigen system, DR locus (HLA-DR) and leukocyte specific adhesion molecules was low in erythematous, yet more marked in pseudomembranous candidiasis. In the pseudomembranous form, CD14+ leukocytes were found in the basal epithelial layer. Langerhans cells were significantly more numerous and were richer in dendrites and Birbeck granules in erythematous than in pseudomembranous candidiasis. CONCLUSIONS: Candidiasis is associated with alterations in the number and differentiation of lymphocytes and dendritic cells, being more severe in the pseudomembranous than erythematous form. We propose that these alterations play a role in the pathogenesis and evolution of the disease.

AIDS-Related Opportunistic Infections↗

Generation of gut-homing IgA-secreting B cells by intestinal dendritic cells.

Normal intestinal mucosa contains abundant immunoglobulin A (IgA)-secreting cells, which are generated from B cells in gut-associated lymphoid tissues (GALT). We show that dendritic cells (DC) from GALT induce T cell-independent expression of IgA and gut-homing receptors on B cells. GALT-DC-derived retinoic acid (RA) alone conferred gut tropism but could not promote IgA secretion. However, RA potently synergized with GALT-DC-derived interleukin-6 (IL-6) or IL-5 to induce IgA secretion. Consequently, mice deficient in the RA precursor vitamin A lacked IgA-secreting cells in the small intestine. Thus, GALT-DC shape mucosal immunity by modulating B cell migration and effector activity through synergistically acting mediators.

Animals↗

Phenotypic and functional characterization of vaginal dendritic cells in a rat model of Candida albicans vaginitis.

This study analyzes the phenotype of vaginal dendritic cells (VDCs), their antigenic presentation and activation of T-cell cytokine secretion, and their protective role in a rat model of Candida vaginitis. Histological observation demonstrated a significant accumulation of OX62(+) VDCs in the mucosal epithelium of Candida albicans-infected rats at the third round of infection. We identified two subsets of OX62(+) VDCs differing in the expression of CD4 molecule in both noninfected and Candida-infected rats. The OX62(+) CD4(+) subset of VDCs displayed a lymphoid cell-like morphology and expressed the T-cell antigen CD5, whereas the OX62(+) CD4(-) VDC subset exhibited a myeloid morphology and was CD5 negative. Candida infection resulted in VDC maturation with enhanced expression of CD80 and CD134L on both CD4(+) and CD4(-) VDC subsets at 2 and 6 weeks after Candida infection. CD5(-) CD4(-) CD86(-) CD80(-) CD134L(+) VDCs from infected, but not noninfected, rats spontaneously released large amounts of interleukin-12 (IL-12) and tumor necrosis factor alpha, whereas all VDC subsets released comparable levels of IL-10 and IL-2 cytokines. Furthermore, OX62(+) VDCs from infected rats primed naïve CD4(+) T-cell proliferation and release of cytokines, including gamma interferon, IL-2, IL-6, and IL-10, in response to staphylococcal enterotoxin B stimulation in vitro. Adoptive transfer of highly purified OX62(+) VDCs from infected rats induced a significant acceleration of fungal clearance compared with that in rats receiving naive VDCs, suggesting a protective role of VDCs in the anti-Candida mucosal immunity. Finally, VDC-mediated protection was associated with their ability to rapidly migrate to the vaginal mucosa and lymph nodes, as assessed by adoptive transfer of OX62(+) VDCs labeled with 5 (and 6-)-carboxyfluorescein diacetate succinimidyl ester.

Adoptive Transfer↗