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Results for “mucosal immunization”

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Bacillus anthracis edema toxin acts as an adjuvant for mucosal immune responses to nasally administered vaccine antigens.

Anthrax edema toxin (EdTx) is an AB-type toxin that binds to anthrax toxin receptors on target cells via the binding subunit, protective Ag (PA). Edema factor, the enzymatic A subunit of EdTx, is an adenylate cyclase. We found that nasal delivery of EdTx enhanced systemic immunity to nasally coadministered OVA and resulted in high OVA-specific plasma IgA and IgG (mainly IgG1 and IgG2b). The edema factor also enhanced immunity to the binding PA subunit itself and promoted high levels of plasma IgG and IgA responses as well as neutralizing PA Abs. Mice given OVA and EdTx also exhibited both PA- and OVA-specific IgA and IgG Ab responses in saliva as well as IgA Ab responses in vaginal washes. EdTx as adjuvant triggered OVA- and PA-specific + T cells which secreted IFN-gamma and selected Th2-type cytokines. The EdTx up-regulated costimulatory molecule expression by APCs but was less effective than cholera toxin for inducing IL-6 responses either by APCs in vitro or in nasal washes in vivo. Finally, nasally administered EdTx did not target CNS tissues and did not induce IL-1 mRNA responses in the nasopharyngeal-associated lymphoepithelial tissue or in the olfactory bulb epithelium. Thus, EdTx derivatives could represent an alternative to the ganglioside-binding enterotoxin adjuvants and provide new tools for inducing protective immunity to PA-based anthrax vaccines.

Adenylyl Cyclases↗

Nomenclature of immunoglobulin A and other proteins of the mucosal immune system. IUIS/WHO subcommittee on IgA nomenclature.

The predominant immunoglobulin found in exocrine secretions of humans and most other mammals is secretory IgA, a polymeric form of IgA containing an additional glycoprotein chain designated "secretory component". In this article recommended abbreviations are proposed for the following forms of human IgA and other proteins of related interest: secretory IgA, secretory IgM, secretory component, polymeric immunoglobulin receptor, polymeric IgA, monomeric IgA, IgA subclass 1, IgA subclass 2, A2 allotype marker 1, and A2 allotype marker 2.

Animals↗

Role of intraepithelial lymphocytes in mucosal immune responses of mice experimentally infected with Cryptosporidium parvum.

In order to investigate the role of intestinal intraepithelial lymphocytes (IELs) in host defense against Cryptosporidium parvum infection, conventionally bred immunocompetent (ImCT) ICR mice and immunosuppressed (ImSP) littermates were infected orally with 10(6) C. parvum oocysts. Then fecal oocyst excretion, the number and location of IELs, and their T lymphocyte subsets were observed on days 4, 7, 10, 13, 16, and 20 postinfection (PI). Uninfected ImCT and ImSP mice were used as controls. The starting point of oocyst excretion was day 4 PI in both ImCT- and ImSP-infected mice. The highest oocyst excretion occurred on day 7 PI in both groups, though the number of oocysts excreted was 3 times greater in ImSP than in ImCT mice. In ImCT mice, IELs greatly increased in number on days 16 and 20 PI (P < 0.05), but the increase was minimal in ImSP mice. IELs changed their location from the basal area to intermediate and apical areas of villous epithelial cells during the early stage of infection. In ImCT-infected mice, IEL phenotypes also changed; whereas CD4+ cells increased temporarily on day 7 PI (P < 0.05), CD8+ cells increased significantly on days 16 and 20 PI (P < 0.05). The results strongly suggest that IELs play a significant role in host defense against C. parvum infection, with helper T cells initiating control of the infection and cytotoxic T cells eliminating the parasites.

Animals↗

Intestinal microflora and homeostasis of the mucosal immune response: implications for probiotic bacteria?

The intestinal microflora can be considered a postnatally acquired organ that is composed of a large diversity of bacteria that perform important functions for the host and can be modulated by environmental factors, such as nutrition. Specific components of the intestinal microflora, including lactobacilli and bifidobacteria, have been associated with beneficial effects on the host, such as promotion of gut maturation and integrity, antagonisms against pathogens and immune modulation. Beyond this, the microflora seems to play a significant role in the maintenance of intestinal immune homeostasis and prevention of inflammation. The contribution of the intestinal epithelial cell in the first line of defense against pathogenic bacteria and microbial antigens has been recognized. However, the interactions of intestinal epithelial cells with indigenous bacteria are less well understood. This review will summarize the increasing scientific attention to mechanisms of the innate immune response of the host towards different components of the microflora, and suggest a potential role for selected probiotic bacteria in the regulation of intestinal inflammation.

Animals↗

Mucosal immunity.

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Enzyme-Linked Immunosorbent Assay↗

Genetic and spontaneous models of inflammatory bowel disease in rodents: evidence for abnormalities in mucosal immune regulation.

A number of models of spontaneous chronic intestinal inflammation in mice and rats have recently been developed. A characteristic of the majority of these models is that disease developed as a consequence of immune manipulations, suggesting a central role for the immune system in the regulation of intestinal inflammation. Analysis of cytokine patterns in disease showed elevations in TNF-alpha and IFN-gamma, characteristic of the T-helper-1 (Th1) pathway, implicating Th1 cells and their cytokines in disease pathogenesis. Strikingly, inflammation did not develop in mice maintained in germ-free conditions, suggesting disease may develop due to a dysregulated inflammatory response to components of the normal flora. Evidence from a number of these models suggests that this potentially pathogenic inflammatory response does not develop in normal animals as it is actively inhibited by a population of CD4+ alpha beta + regulatory T cells and immunosuppressive cytokines such as IL-10 and TGF-beta 1. These new models will allow further investigation into the mechanisms of natural immune regulation and protection in the intestinal tract and how these mechanisms relate to the etiopathogenesis of inflammatory bowel disease (IBD). Furthermore, these models should provide useful insights for the design of effective immunomodulatory therapies for the treatment of IBD in humans.

Animals↗

In vivo antiinfluenza virus activity of Kampo medicine Sho-seiryu-to through mucosal immune system.

The Kampo (Japanese herbal) medicine, Sho-seiryu-to, which has traditionally been used for the treatment of colds and bronchial asthma, showed potent antiinfluenza A and B virus activity through augmentation of production of antiviral IgA antibody in the nasal and bronchoalveolar cavities of mice when administrated orally before viral infection. Sho-seiryu-to also showed antiinfluenza virus activity against A virus H1N1 subtype infected in aged mice (approximately 6 months old) with an increase of antiviral IgA antibody in the bronchoalveolar wash of the treated mice by similar administration. When mice infected with mouse nonadapted influenza A virus H3N2 subtype before 14 days were secondarily infected with mouse adapted A/PR/8 (H1N1) virus and administered Sho-seiryu-to orally after the second infection, replication of the virus in both nasal and bronchoalveolar cavities was significantly inhibited. Sho-seiryu-to had no effect on the mice which were not primed with mouse nonadapted virus when administered after the infection of mouse-adapted A/PR/8 virus. Oral administration of Sho-seiryu-to caused increment of viral-specific IgA antibody secreting cells in mouse nasal lymphocyte. Sho-seiryu-to also augmented IL-2 receptor beta chain+ T-cells in Peyer's patch of the infected mice. Sho-seiryu-to also significantly reduced viral titer in the nasal washes of the infected ovalbumin-sensitized bronchial asthma model mice. Oral administration of Sho-seiryu-to before and after vaccination significantly augmented hemagglutination-inhibiting antibody in the serum by nasal inoculation of influenza HA vaccine, and significantly augmented nasal antiviral IgA antibody and bronchoalveolar and serum antiviral IgG antibodies even after secondary vaccination although induction of antiviral antibody by intranasal vaccination was insufficient without Sho-seiryu-to. These results suggest that Sho-seiryu-to is able to prevent influenza virus infection by cross-protection of subtypes of influenza A virus and B virus. Sho-seiryu-to is also useful for the treatment of influenza virus infection in hosts with a history of influenza virus infection and/or influenza vaccination and allergic pulmonary inflammation, such as bronchial asthma, and can be used as an adjuvant to nasally inoculated influenza HA vaccine.

Animals↗

Mucosal immunity and bacteriology of the eustachian tube.

The pathogenesis of otitis media is a multifaceted process that is not completely understood. Eustachian tube dysfunction plays a central but uncertain role, as do viral and bacterial microorganisms. Of the latter, the three most important are Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. This article reviews the various mechanisms of infection and the immune system's response to them.

Eustachian Tube↗

Specific mucosal immunity in the pathophysiology of bacterial prostatitis in a rat model.

Mucosal immunity was established in the rat prostate by stimulating the common mucosal system through serosal exposure of formalin-killed Escherichia coli. Immunized but not sham-immunized rats developed bacterial specific IgG and IgA in prostatic fluid, and IgA in urine. Immunized (n = 21) and sham-immunized control rats (n = 30) were challenged by transurethral injection of E. coli into the prostate ducts. Mortality, gross and microscopic pathology, tissue bacterial counts, bacterial associated immunoglobulins, and antibody titers in serum and urine were assessed at 7 days following the challenge. Increased E. coli specific immunoglobulin titers were seen in immunized rats, and E. coli, but not Proteus, found in the prostates of immunized animals were coated with IgG and IgA. Immunization protected against toxaemia and septicemia, seen as a rare complication of acute prostatitis, but did not protect against acute prostatitis, nor alter the degree of tissue damage seen in the rat model.

Acute Disease↗

Mucosal immunity--a major adaptive defence mechanism.

The epithelial glycoprotein called secretory component (SC) is quantitatively the most important receptor of the immune system because it is responsible for external transport of locally produced polymeric IgA (pIgA) to generate remarkably large amounts of secretory IgA. Antibodies of this type constitute the major mediators of specific humoral immunity. Transmembrane SC belongs to the Ig supergene family and functions as a common pIg receptor, also translocating pentameric IgM externally to form secretory IgM. The B cells responsible for mucosal pIg production are initially stimulated in organized mucosa-associated lymphoepithelial structures, particularly the Peyer's patches in the distal small intestine; from these inductive site they migrate as memory cells to exocrine tissues all over the body. Mucous membranes are thus furnished with secretory antibodies in an integrated way, ensuring a variety of specificities at every secretory effector site. There is currently great interest in exploiting this integrated or "common" mucosal immune system for oral vaccination against pathogenic infectious agents and also to induce tolerance in T cell-mediated autoimmune diseases. However, much remains to be learned about mechanisms for antigen uptake and processing necessary to elicit stimulatory or suppressive mucosal immune responses. Moreover, evidence is emerging for the existence of considerable regionalization with regard to functional links between inductive sites and effecter sites of mucosal immunity.

Animals↗

Evidence for early aging in the mucosal immune system.

Despite recent advances in the cellular and molecular analysis of induction and regulation of mucosal immune responses, little is yet known about differences which occur in aging. To address this important issue, we have compared the mucosal and systemic immune responses of aged (12- to 14-mo- or 2-year-old) and young adult (6- to 8-wk-old) C57BL/6 mice. Both aged and young mice were immunized weekly with three oral doses of 1 mg of OVA and 10 microg of cholera toxin (CT) as mucosal adjuvant. Both groups of mice over 1 or 2 years of age showed reduced levels of Ag-specific mucosal or systemic immune responses at day 21. An Ag-specific B cell enzyme-linked immunospot assay confirmed these results at the cellular level. When the Ag-induced cytokine responses were examined at both protein and mRNA levels, CD4(+) T cells from spleen and Peyer's patches of young adult mice revealed elevated levels of IL-4 production; however, these cytokine responses were significantly diminished in aged mice. In contrast to mucosal immunization, mice s. c. immunized with OVA plus CT resulted in impaired OVA-specific but intact CT B subunit-specific immune responses in 12- to 14-mo-old mice although the responses to both Ags were depressed in 2-year-old mice. These results provide the first evidence that the development of age-associated alterations possibly occurs earlier in the mucosal immune system than in the systemic immune compartment.

Adjuvants, Immunologic↗

Mucosal immunity in the brushtail possum (Trichosurus vulpecula): detection of antibody in serum and at female reproductive sites after intranasal immunization.

Vaccination strategies for the brushtail possum, which rely upon stimulation of mucosal immunity, are being developed for biocontrol purposes. As little is known about how to stimulate possum immune responses via a mucosal site, groups of possums were immunized intranasally with keyhole limpet haemocyanin (KLH) alone or in combination with known or novel mucosal adjuvants. Antigen-specific antibody titres in female reproductive secretions were measured by ELISA and compared with antibody titres in the serum. Antigen-induced lymphocyte proliferative responses were measured as an indicator of cell-mediated responses. Intranasal immunization with KLH alone stimulated a weak serum antibody response that was significantly increased when KLH was given with cholera toxin subunit B (CTB), recombinant possum tumour necrosis factor alpha (TNF alpha) or live Mycobacterium bovis bacillus Calmette Guerin (BCG). Antibody titres in secretions from ovarian follicles and the uterus were very low in animals administered KLH alone. Significantly higher antibody titres to KLH were present in the reproductive secretions of possums immunized with KLH plus CTB, BCG or heat-killed Mycobacterium vaccae. Antibody titres were lower in mucosal secretions than in the serum, but there was a significant correlation between the two. In addition, coadministration of live BCG with KLH produced a strong antigen-specific cell-mediated response to KLH. This study has shown that an immune response to a protein antigen can be stimulated in possums by intranasal immunization and that antigen-specific antibodies can be detected in secretions from the female reproductive tract.

Adjuvants, Immunologic↗