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At least 631 records · Page 35Linked to original sources
PubMed1997

Review article: Homing of mucosal immune cells--a possible connection between intestinal and articular inflammation.

An adaptive immune system has developed to protect mucosa, mainly by performing immune exclusion with secretory antibodies (SIgA and SIgM) but also by downregulating pro-inflammatory antibody responses and delayed type hypersensitivity against harmless soluble proteins and the indigenous bacterial flora. In general, mucosal immunopathology appears to represent abrogation of such mucosal tolerance mechanisms. An important consequence is disturbance of the 'gatekeeper' function normally performed by the microvasculature through complementary sets of tightly regulated adhesion molecules on mucosal endothelium and circulating leukocytes. The B cells responsible for local polymeric immunoglobulin (Ig) production (mainly dimeric IgA) are stimulated initially in organized lymphoepithelial structures, particularly the Peyer's patches in the distal small intestine, from which they migrate as memory cells to secretory tissues all over the body. Mucous membranes are thus furnished with primed B cells in an integrated way, ensuring a variety of secretory antibody specificities at every exocrine site. There is currently great interest in exploiting this integrated or 'common' mucosal immune system for topical vaccination against pathogenic infectious agents and also to induce therapeutic peripheral tolerance to ameliorate T-cell-mediated autoimmune diseases. Moreover, homing of immune cells from the gut to the inflamed synovium may represent a modifiable link between intestinal immunity and chronic arthropathies.

Arthritis↗
PubMed1986

Naturally occurring IgA antibodies to ocular and oral microorganisms in tears saliva and colostrum: evidence for a common mucosal immune system and local immune response.

In this study, levels of naturally occurring secretory IgA (sIgA) antibodies to bacterial isolates representative of the microflora of the human eye (Staphylococcus epidermidis and a Corynebacterium species) and the oral cavity (Streptococcus mutans serotypes c and d) were assessed in three different human external secretions. Tears and parotid saliva samples collected at the same time from 22 healthy subjects and colostrum from 11 healthy women (1-14 days post partum) were assessed for sIgA anti-bacterial antibody levels by an enzyme-linked immunosorbent assay. Significantly higher levels (P less than 0.001) of IgA antibodies to Staphylococcus epidermidis and the Corynebacterium sp. were found in tears than in parotid saliva. Furthermore, higher levels of sIgA antibodies to Streptococcus mutans serotype d occurred in parotid saliva than in tears of these subjects. Although levels of salivary sIgA antibodies to S. mutans serotype c were lower than those seen to serotype d, they were not significantly different from those in tears. However, absolute sIgA anti-serotype c antibodies per mg IgA were higher in saliva than in tears. When sIgA antibody levels to the four bacterial strains were assessed in colostrum, the proportion of sIgA antibodies per mg IgA were much lower than seen in tears or saliva. These results suggest that natural sIgA antibodies which occur in human external secretions are induced by antigen ingestion and stimulation of the common mucosal immune system. However, the local presence of antigen at a mucosal site induces greater clonal expression and results in higher levels of sIgA antibodies than at mucosal sites not exposed to local antigenic stimulation.

Adolescent↗
PubMed2001

British Society for Immunology: vaccines and mucosal immunity.

The Annual Congress of the British Society for Immunology was well attended with over 1000 British scientists converging on the small Yorkshire town of Harrogate. Wide-ranging and varied, the topics covered included the biochemistry of signaling as well as sessions examining dietary influences upon mucosal immunity. The plenary session on the morning of Wednesday 6 December focused on immunology at the cell surface, where many speakers discussed the role of lipid rafts in immune cell signaling. A session of particular interest followed the plenary session, hosted by the Vaccine Immunology Group. Discussion centered around a number of novel vaccines currently under development, with the emphasis on finding alternatives to the use of hypodermic needles. A number of interesting posters affiliated to this session reflected the high quality of the research presented at the meeting in general.

Journal Article↗
PubMed2000

Lipopeptides as immunoadjuvants and immunostimulants in mucosal immunization.

In previous studies we have shown that lipopeptides constitute potent immunoadjuvants in mice, rabbits and other species: in parenteral immunization, lipopeptide adjuvants were comparable, or in some cases superior to Freund's adjuvant, and were devoid of the side effects of this additive. Here we demonstrate that lipopeptides also constitute adjuvants for mucosal immunizations. The serum antibody responses against the wheat storage protein gliadin, the bee venom constituent melittin, or the hen egg protein ovalbumin could in most cases be enhanced more than 100-fold by the lipopeptide P3CSK4, applied via the nasal route. An enhanced specific antibody level could also be detected in supernatants of cell cultures prepared from spleens, Peyer's patches, lungs and mesenteric lymph nodes of immunized mice. Moreover, the lipopeptide P3CSK4 enhanced chemiluminescence in mouse spleen cells and peritoneal macrophages in vitro, indicating a macrophage-activating effect. Finally, nasal application of lipopeptide increased protection against a lethal infection of influenza. Our findings are of importance for the improvement of immunizations and might lead to more effective vaccines.

Adjuvants, Immunologic↗
PubMed2005

Characterization of human immunodeficiency virus Gag-specific gamma interferon-expressing cells following protective mucosal immunization with alphavirus replicon particles.

A safe, replication-defective viral vector that can induce mucosal and systemic immune responses and confer protection against many infectious pathogens, such as human immunodeficiency virus type 1 (HIV-1), may be an ideal vaccine platform. Accordingly, we have generated and tested alphavirus replicon particles encoding HIV-1 Gag from Sindbis virus (SIN-Gag) and Venezuelan equine encephalitis virus (VEE-Gag), as well as chimeras between the two (VEE/SIN-Gag). Following intramuscular (i.m.), intranasal (i.n.), or intravaginal (IVAG) immunization with VEE/SIN-Gag and an IVAG challenge with vaccinia virus encoding HIV Gag (VV-Gag), a larger number of Gag-specific CD8+ intracellular gamma interferon-expressing cells (iIFNEC) were detected in iliac lymph nodes (ILN), which drain the vaginal/uterine mucosa (VUM), than were observed after immunizations with SIN-Gag. Moreover, a single i.n. or IVAG immunization with VEE/SIN-Gag induced a larger number of cells expressing HIV Gag in ILN, and immunizations with VEE/SIN-Gag through any route induced better protective responses than immunizations with SIN-Gag. In VUM, a larger percentage of iIFNEC expressed alpha4beta7 or alpha(Ebeta)7 integrin than expressed CD62L integrin. However, in spleens (SP), a larger percentage of iIFNEC expressed alpha4beta7 or CD62L than expressed alpha(Ebeta)7. Moreover, a larger percentage of iIFNEC expressed the chemokine receptor CCR5 in VUM and ILN than in SP. These results demonstrate a better induction of cellular and protective responses following immunizations with VEE/SIN-Gag than that following immunizations with SIN-Gag and also indicate a differential expression of homing and chemokine receptors on iIFNEC in mucosal effector and inductive sites versus systemic lymphoid tissues.

Animals↗
PubMed1999

IL-12 is an effective adjuvant for induction of mucosal immunity.

We addressed the effects of two cytokines, IL-6 and IL-12, derived from APCs, for the development of mucosal IgA Ab responses following their nasal delivery with the protein vaccine tetanus toxoid (TT). Mice treated nasally with IL-6 and TT showed higher TT-specific serum IgG (mainly IgG1 and IgG2b) Ab responses than did control mice, but exhibited no IgE and negligible secretory IgA (S-IgA) Ab responses. In contrast, IL-12 administered nasally with TT not only induced sharp increases in TT-specific serum IgG (mainly IgG1 and IgG2b) and IgA, but also elevated mucosal S-IgA Ab responses. Coadministration of IL-6 and IL-12 with TT did not enhance the mucosal or serum Ab responses over those seen with IL-12 alone. TT-specific CD4+ T cells from mice given TT with IL-6 or IL-12 produced higher levels of IFN-gamma, IL-6, and IL-10 than did those from control mice, but only negligible levels of IL-4 and IL-5. In summary, both intranasal IL-6 and IL-12 induced serum Abs that protected mice from systemic challenge with TT, whereas only IL-12 induced mucosal S-IgA Ab responses. The significance of IL-12-induced Th1-type responses for regulation of both mucosal and systemic immunity is discussed.

Adjuvants, Immunologic↗
PubMed2004

Compartmentalization of the mucosal immune responses to commensal intestinal bacteria.

Mammals coexist with a luxuriant load of bacteria in the lower intestine (up to 10(12) organisms/g of intestinal contents). Although these bacteria do not cause disease if they remain within the intestinal lumen, they contain abundant immunostimulatory molecules that trigger immunopathology if the bacteria penetrate the body in large numbers. The physical barrier consists only of a single epithelial cell layer with overlying mucus, but comparisons between animals kept in germ-free conditions and those colonized with bacteria show that bacteria induce both mucosal B cells and some T cell subsets; these adaptations are assumed to function as an immune barrier against bacterial penetration, but the mechanisms are poorly understood. In mice with normal intestinal flora, but no pathogens, there is a secretory IgA response against bacterial membrane proteins and other cell wall components. Whereas induction of IgA against cholera toxin is highly T help dependent, secretory IgA against commensal bacteria is induced by both T independent and T dependent pathways. When animals are kept in clean conditions and free of pathogens, there is still a profound intestinal secretory IgA response against the commensal intestinal flora. However, T dependent serum IgG responses against commensal bacteria do not occur in immunocompetent animals unless they are deliberately injected intravenously with 10(4) to 10(6) organisms. In other words, unmanipulated pathogen-free mice are systemically ignorant but not tolerant of their commensal flora despite the mucosal immune response to these organisms. In mice that are challenged with intestinal doses of commensal bacteria, small numbers of commensals penetrate the epithelial cell layer and survive within dendritic cells (DC). These commensal-loaded DC induce IgA, but because they are confined within the mucosal immune system by the mesenteric lymph nodes, they do not induce systemic immune responses. In this way the mucosal immune responses to commensals are geographically and functionally separated from systemic immunity.

Animals↗
PubMed1995

Involvement of B-1 cells in mucosal immunity and autoimmunity.

B-1 cells are distinguished from conventional B cells by their anatomical localization, surface phenotypes and functional characteristics. The physiological functions and pathological roles of these cells remain controversial. In this review, Masao Murakami and Tasuku Honjo summarize recent evidence for the involvement of B-1 cells in mucosal immunity and autoimmunity, and discuss the relationship between these phenomena.

Animals↗
PubMed1993

Recent progress in senescence-associated gut mucosal immunity.

The immune response in gut-associated lymphoid tissues (GALT) is altered in the aging process. Senescence-induced quantitative decline and qualitative changes of GALT T and B cells and their subpopulations contribute largely to the impaired gut mucosal immune responses. Thus, not only direct cell-to-cell contact interactions, but also patterns of immuno-regulatory cytokine production and serum-soluble cytokine, such as interleukin-2 receptors are also altered, causing both cellular and humoral immune abnormalities in GALT. One of the characteristic features includes functional defects of suppressor T cells. As a consequence, relative hyperfunction of helper T cells ensures. The defective immune response of both function and control of aged GALT may help to explain the increased incidence of infection and neoplasia in the gastrointestinal tract with age. On the subcellular level, these aged T and B cells impair transmembranous signal transduction. Trials of immune interventions to reduce or reverse immunosenescence in GALT were made in animals. The results of adoptive transfer of in vitro educated helper T cells from aged GALT are encouraging. Further innovative immunologic interventions are indicated.

Aging↗
PubMed1995

Evidence for differential effects of sulphasalazine on systemic and mucosal immunity in rheumatoid arthritis.

OBJECTIVE: To study the effects of sulphasalazine (SASP) on the systemic and mucosal humoral immune systems in patients with rheumatoid arthritis (RA). METHODS: Serum concentrations of interleukin 6 (IL-6), class and subclass specific IgG, IgA and IgM, IgA and IgG antigliadin antibodies and rheumatoid factors (RF) of IgG, IgA (including IgA1 and IgA2 subclasses) and IgM isotypes were measured before and 16 weeks after sulphasalazine (SASP) therapy in 15 female and three male patients with RA. Amounts of immunoglobulins in saliva and jejunal fluid were measured as estimates of mucosal humoral immunity. RESULTS: Serum concentrations of IgA and IgG decreased significantly during SASP therapy and correlated with reduced concentrations of IL-6. In addition, levels of circulating IgA RF, IgA anti-gliadin antibodies and IgM RF decreased significantly after the treatment. In contrast, immunoglobulin levels in saliva and jejunal fluid were unaltered. CONCLUSION: SASP exerts powerful but selective inhibitory effects on systemic immunoglobulin production, whereas no effects on mucosal immunoglobulin production were observed. The decreased systemic B cell activity may be mediated by downregulation of the production of IL-6, a cytokine with Ig switching properties.

Adult↗
PubMed2002

Mucosal immunity in mice immunized with HIV-1 peptide conjugated to Brucella abortus.

We have previously shown that a V3-loop peptide from HIV-1 envelope conjugated to heat-inactivated Brucella abortus (Ba) (V3-Ba) is capable of inducing antibodies that neutralize HIV-1 and cytotoxic T cells (CTL) that kill HIV-1-infected targets, even in mice that lack CD4(+) T cells. In this paper we show that intranasal (i.n.) immunization elicits neutralizing antibodies and IFNgamma-secreting T cells at mucosal surfaces. This approach may protect individuals from HIV-1 infection and reduce transmission from infected individuals to their sexual partners and offspring.

AIDS Vaccines↗
PubMed1989

Adjuvant effect of cholera toxin on the mucosal immune response to soluble proteins. Differences between mouse strains and protein antigens.

We examined the effect of orally administered cholera toxin (CT) on the immune response to keyhole limpet haemocyanin (KLH) and ovalbumin (OVA) in high (C57Bl/6 H2b), medium (CBA H2k), and low (BALB/c H2d) responder I-A haplotypes to CT. Mice were fed OVA or KLH on three occasions at 10-day intervals and the effect of simultaneous feeding of CT determined. Isotype-specific antibody levels were assayed in serum samples collected 7 days after the last immunization. Antibody was also measured in the supernatant of gut explant cultures incubated at either 4 or 37 degrees C. Increased antibody levels in cultures kept at 37 degrees C indicated release of local intracellular antibody. Cholera toxin exerted an adjuvant effect on the mucosal response of all three strains to KLH and OVA. Overall, the responses to CT and the second protein were not correlated; we interpret these findings to indicate that while CT had an effect on the mucosal immune system which enhances the immune response to itself and other protein antigens, the final outcome of the response to the second antigen is dependent on differences in the ability of the strains to process, recognize, and respond to a particular antigen.

Adjuvants, Immunologic↗
PubMed2005

Transgene vaccination using Ulex europaeus agglutinin I (UEA-1) for targeted mucosal immunization against HIV-1 envelope.

Receptor-mediated gene transfer using an M cell ligand has been shown to be an efficient method for mucosal DNA immunization. To investigate further into alternative M cell ligands, the plant lectin, Ulex europaeus agglutinin I (UEA-1), was tested. UEA-1 binds to human intestinal Caco-2 cells, and these cells can be transfected with poly-l-lysine (PL)-conjugated UEA-1 for expression of reporter cDNAs. When tested in vivo, mice nasally immunized with UEA-1-PL complexed to plasmid encoding HIV-1 envelope showed elevated systemic and mucosal antibody responses, and these were supported by tissue antibody-forming cells. Likewise, elevated envelope-specific CTLs were induced. Thus, UEA-1 mediated DNA delivery represents an alternative mucosal formulation for inducing humoral and cellular immunity against HIV-1.

AIDS Vaccines↗
PubMed1991

Ageing and duodenal mucosal immunity.

The production of immunoglobulins by duodenal mucosa in young and old subjects was studied. For 20 elderly people (mean age 85.3 years) and 18 young subjects (mean age 34.5 years) the amounts of the immunoglobulins IgA, IgG and IgM synthesized and secreted by a duodenal biopsy over a 2-day period were compared. There was no significant difference in the immunoglobulin production between the two groups. This suggests that age itself may have no effect on duodenal mucosal immunity.

Adult↗
PubMed1995

Enhanced respiratory clearance of nontypeable Haemophilus influenzae following mucosal immunization with P6 in a rat model.

Nontypeable Haemophilus influenzae (NTHi) is a common cause of infection of the respiratory tract in children and adults. The search for an effective vaccine against this pathogen has focused on components of the outer membrane, and peptidoglycan-associated lipoprotein P6 is among the proposed candidates. This study investigated the immunogenicity of P6 in a rat respiratory model. P6 was purified from two strains of NTHi, one capsule-deficient strain and an H. influenzae type b strain, and assessed for clearance of both homologous and heterologous bacterial strains following mucosal immunization. A protective immune response was determined by enhancement of pulmonary clearance of live bacteria and an increased rate of recruitment of phagocytic cells to the lungs. This was most effective when Peyer's patch immunization was accompanied by an intratracheal (IT) boost. However, the rate of bacterial clearance varied between strains, which suggests some differences in anti-P6 immunological defenses recognizing the expression of the highly conserved P6 lipoprotein on the bacterial surface in some strains. P6-specific antibodies in both serum and bronchoalveolar lavage fluid were cross-reactive and did not differ significantly in strain specificity, demonstrating that difference in clearance was unlikely due to differences in P6-specific antibody levels. Serum homologous and heterologous P6-antibody was bactericidal against NTHi even when enhanced clearance had not been observed. Peyer's patch immunization induced P6-specific CD4+ T-helper cell proliferation in lymphocytes isolated from the mesenteric lymph nodes. An IT boost increased the level of P6-specific antibodies in serum and bronchoalveolar lavage fluid, and P6-specific mesenteric node lymphocyte proliferation. Cells from rats immunized with P6 demonstrated proliferation following stimulation with P6 from nonhomologous strains; however, there was some variation in proliferative responses to P6 from different strains in lymphocytes isolated from animals immunized with killed bacteria. The increase in P6-specific antibodies and T-helper cell responses following an IT boost correlated with an increased rate of recruitment of phagocytic cells and enhanced bacterial clearance of both homologous and heterologous bacteria in the lungs. The data suggests that P6 has the potential to afford protection against pulmonary infection by NTHi following the induction of effective antigen-specific B- and T-cell responses in mucosal tissues.

Animals↗
PubMed2006

Use of recombinant virus-vectored tuberculosis vaccines for respiratory mucosal immunization.

Recombinant virus-vectored TB vaccines represent the most promising vaccine platform for boosting the protective immunity mediated by parenteral BCG prime immunization. A major advantage associated with virus-vectored vaccines is that they are potent respiratory mucosa-deliverable vaccines. A recombinant replication-deficient adenoviral (Ad) vector was engineered to express Mycobacterium tuberculosis (M.tb) Ag85A. Single administration of this Ad vaccine via the intranasal, but not intramuscular, route provided potent immune protection from pulmonary M.tb challenge. Respiratory mucosal boosting immunization with Ad vaccine was effective in enhancing T-cell activation and immune protection following parenteral DNA or BCG prime immunization. We have also recently developed a recombinant vesicular stomatitis virus-vectored (VSV) TB vaccine. Ad and VSV vector systems will be complementary to each other for BCG prime-virus vaccine boost immunization protocols.

Acyltransferases↗
PubMed1998

Leprosy transmission and mucosal immunity: towards eradication?

The declining prevalence of leprosy has not been matched by a declining incidence. Widespread adoption of multiple drug therapy (MDT) in closely monitored control programmes has not prevented transmission of Mycobacterium leprae. Despite the rarity of lepromatous patients, most of those living in endemic areas have immunological evidence of exposure to M. leprae. This paradox could be explained if, for many such individuals, infection was transient, did not result in disease development, but did allow the transmission of infection to other individuals. There is increasing evidence from nasal PCR studies that such sub-clinical transmission may exist and that mucosal immune responses to M. leprae may develop during resolution of initial infection. Sub-clinical infection appears to occur in clusters and may require close contact over a prolonged period for optimal transmission. Control of transmission may be feasible through identification and treatment of individuals within infection clusters, allowing progress towards the eradication of leprosy.

Humans↗