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At least 613 records · Page 34Linked to original sources
PubMed1999

Mucosal immunity to influenza without IgA: an IgA knockout mouse model.

IgA knockout mice (IgA-/-) were generated by gene targeting and were used to determine the role of IgA in protection against mucosal infection by influenza and the value of immunization for preferential induction of secretory IgA. Aerosol challenge of naive IgA-/- mice and their wild-type IgA+/+ littermates with sublethal and lethal doses of influenza virus resulted in similar levels of pulmonary virus infection and mortality. Intranasal and i.p. immunization with influenza vaccine plus cholera toxin/cholera toxin B induced significant mucosal and serum influenza hemagglutinin-specific IgA Abs in IgA+/+ (but not IgA-/-) mice as well as IgG and IgM Abs in both IgA-/- and IgA+/+ mice; both exhibited similar levels of pulmonary and nasal virus replication and mortality following a lethal influenza virus challenge. Monoclonal anti-hemagglutinin IgG1, IgG2a, IgM, and polymeric IgA Abs were equally effective in preventing influenza virus infection in IgA-/- mice. These results indicate that IgA is not required for prevention of influenza virus infection and disease. Indeed, while mucosal immunization for selective induction of IgA against influenza may constitute a useful approach for control of influenza and other respiratory viral infections, strategies that stimulate other Igs in addition may be more desirable.

Adoptive Transfer↗
PubMed2003

T-cell-mediated mucosal immunity is attenuated in experimental necrotizing enterocolitis.

In premature infants with necrotizing enterocolitis (NEC) the gastrointestinal mucosal barrier is immature, but little is known about the immune response of immature bowel. The aim of this study was to evaluate the intestinal mucosal immune response in experimental NEC. In general anaesthesia, NEC was induced in six newborn piglets by injection of bovine casein into terminal ileum. Six controls received an equal amount of saline. Four hours later, samples were taken from the macroscopically most affected part of the treated loop and from the macroscopically healthy untreated intestine. Monoclonal antibodies to porcine CD1, CD2, CD4, CD8, CD45 and IgM were used for immunohistochemical staining. Casein-treated bowel showed typical macro- and microscopic findings of NEC. No changes were found in the saline-treated bowel. In both groups the bowel outside the treatment sector was normal. In casein-treated animals, treated samples showed significant decrease in density of CD4+ cells when compared with saline-treated controls. Similar trend was found in CD2+ and CD8+ cells but without statistical significance. Macroscopically healthy proximal untreated samples showed significant decrease in densities of CD2+, CD4+ and CD8+ lymphocytes in casein-treated group when compared with control samples. In casein-treated animals the density of CD45+ cells in the non-injected bowel was also decreased, but this did not reach statistical significance. Densities of CD1+ and IgM+ cells did not differ between casein-treated and saline-treated groups. A significant T-cell decrease was found in the present NEC model. Surprisingly, this was most prominent in the macroscopically healthy bowel outside the casein injection segment. The reason for T-cell decrease remains unclear, but bovine casein is known to contain peptide fractions that can modulate immune function. These findings may have implications in the design of neonatal milk formulas.

Animals↗
PubMed1994

Epithelial transcytosis of monomeric IgA and IgG cross-linked through antigen to polymeric IgA. A role for monomeric antibodies in the mucosal immune system.

We recently demonstrated that the polymeric IgR (pIgR) mediates epithelial transcytosis of immune complexes (IC) containing dimeric IgA (dIgA). In vivo, this "excretory" pathway could allow direct elimination of IgA IC at the mucosal sites where they are likely to form. In contrast, IC containing only monomeric IgA (mIgA) were not transported, consistent with the specificity of pIgR for polymeric IgA. However, the potential exists in vivo that monomeric Ig like mIgA or IgG could become associated through binding to multivalent Ag with IC containing dIgA, and that such mixed IC could act as ligands for pIgR. In the present work, using Madin-Darby canine kidney epithelial cells that express pIgR, we showed that 125I-labeled anti-DNP mIgA or IgG in the same IC with unlabeled dIgA antibody and DNP-BSA Ag was vectorially transported from the basolateral to the apical surface and then released. However, 125I-mIgA IC or 125I-IgG IC (without dIgA) and 125I-mIgA or 125I-IgG in the presence of dIgA antibody (but without Ag) were not transported, demonstrating the necessity for monomeric Ig to be in an IC with dIgA to be transported. Transcytosis of mixed mIgA/dIgA or IgG/dIgA IC was mediated by pIgR because no transport was observed in untransfected, wild-type Madin-Darby canine kidney cells lacking pIgR. The data demonstrate that mIgA and IgG can participate along with dIgA in the "excretory" pathway for local elimination of IgA IC, thus providing a means by which monomeric antibodies have the potential to participate in the mucosal immune system.

Animals↗
PubMedDate not supplied

Immunization of the gastrointestinal tract with bacterial and viral antigens: implications in mucosal immunity.

The effects of oral immunization with Pseudomonas aeruginosa (PAOI), Chlamydia trachomatis or respiratory syncytial virus (RSV) on the development of specific antibody responses in the intestine, respiratory tract and genital secretions was studied in several animal models. Oral immunization resulted in the development of specific immunity in distant mucosal sites. However, its role in influencing the outcome of reinfection challenge at the distant site varied with the antigen. Little or no protection was observed against infection with Pseudomonas aeruginosa in the respiratory tract. Limited protection was observed against respiratory tract infection with RSV. On the other hand oral immunization appeared to be quite effective in preventing respiratory or genital infection with Chlamydia trachomatis. Finally, preliminary studies have suggested that intestinal immunization via the process of breast feeding can also be employed as an effective means to induce anti-idiotypic immunity against RSV in the breast feeding neonates.

Animals↗
PubMed2001

The immuno-inflammatory mechanism for tissue injury in inflammatory bowel disease and Helicobacter pylori-infected chronic active gastritis. Roles of the mucosal immune system.

The gastrointestinal mucosa is exposed to myriads of infectious and food antigens, and a unique barrier mechanism handles them on the mucosal surface, and specific immune responses to these antigens call on the mucosal immune system in the mucosal tissues to maintain homeostasis of gastrointestinal functions and structure. Abrogation of these mucosal defense mechanisms may lead to alter immunologic homeostasis in the gastrointestinal tract and to induce pathological features of inflammatory bowel disease (IBD) and Helicobacter pylori-infected chronic active gastritis, including chronic active inflammation, mucosal atrophy and tissue injuries. Regardless of the initiating cause of these long-standing chronic active mucosal inflammations, characteristic immuno-inflammatory mechanisms are involved in their pathogenesis, that is, similar and/or different specific prolonged impaired and excessive immuno-inflammatory responses following the abrogation of the mucosal barrier system are present in the diseased mucosa with IBD and H. pylori infection, respectively.

Apoptosis↗
PubMed2006

Immunoglobulin A and CD8 T-cell mucosal immune defenses protect against intranasal infection with Chlamydia pneumoniae.

Chlamydia pneumoniae initiates infection in humans via the mucosal epithelia of the respiratory tract; therefore, immunity at this mucosal site is believed to be important to control infection with this pathogen. We compared the protective capacity of immunization in mice with two C. pneumoniae antigens, namely the major outer membrane protein (MOMP) and the heat shock protein 60 (HSP-60), against intranasal (i.n.) infection with the bacteria when given as protein or DNA and when administered by i.n. or intraperitoneal (i.p.) routes. Our data showed that i.n. immunizations with both antigens delivered as DNA were protective against C. pneumoniae infection, probably due to induction of cell-mediated immune responses. Our study also revealed that i.n. immunizations with MOMP, but not with HSP-60, given as protein induced protective local immune responses in the respiratory tract against C. pneumoniae infection. Moreover, no protection was induced by either antigen when the i.p. route of immunization was used. We further investigated in immunoglobulin (Ig)A-deficient mice whether the reduction in the bacterial loads observed when MOMP was administered intranasally was related to the strong local IgA responses induced by this route of immunization. Our data showed that IgA-deficient mice were more susceptible to infection than wild-type mice, suggesting that the induction of local IgA responses may play a role in the protection of the respiratory tract against C. pneumoniae infections.

Administration, Intranasal↗
PubMed2002

Mucosal immunization with live recombinant bovine respiratory syncytial virus (BRSV) and recombinant BRSV lacking the envelope glycoprotein G protects against challenge with wild-type BRSV.

Recombinant bovine respiratory syncytial virus (rBRSV) and an rBRSV deletion mutant lacking the G gene (rBRSVDeltaG) were characterized in calves with respect to replication competence, attenuation, and protective efficacy as live-attenuated BRSV vaccines. Both recombinant viruses were safe and induced protection against a BRSV challenge infection. rBRSV replicated efficiently in the upper respiratory tract. Intranasal immunization with rBRSVDeltaG led to infection but not to mucosal virus replication. Neutralizing antibodies were induced by rBRSV and rBRSVDeltaG. Thus, the BRSV attachment glycoprotein G seems to be dispensable in vaccinating calves against BRSV.

Administration, Intranasal↗
PubMed2004

Induction of a mucosal immune response to the streptococcal M protein by intramuscular administration of a PADRE-ASREAK peptide.

In a previous study, it was shown that an intramuscular administration of amino acid PADRE-ELDKWA sequence induced a mucosal immune response to a conserved epitope of human immunodeficiency virus in mice. In the same model, here it is shown that this method can be used with a selected peptide from the M protein of group A streptococci. The PADRE-ASREAK sequence was injected in mice by the intramuscular route. Antibodies against M protein were detected in extracts of mucosal tissues and in serum. The repertoire isotypes of serum immunoglobulin G (IgG) and mucosal IgA and IgG antibodies varied, according to the dose of injected peptide. The highest mucosal IgA antibody response was obtained with 0.01 micro g of antigen per injection, whereas the systemic IgG antibody response increased with 10 micro g of antigen. Mucosal antibody production against streptococci was confirmed by immunofluorescence analysis. These results provide evidence that this novel approach of mucosal vaccination may be of advantage for bacterial systems and suggest a new field of investigation based on synthetic peptide analogues.

Amino Acid Sequence↗
PubMed1994

Mucosal immunization via M cells for production of protective secretory IgA antibodies.

Transepithelial transport of antigens by M cells in the epithelium associated with lymphoid follicles in the intestine delivers immunogens directly to organized mucosal lymphoid tissues, the inductive sites for mucosal immune responses. We have exploited M cell transport to generate and characterize specific monoclonal IgA antibodies that can prevent the interaction of pathogens with epithelial surfaces. The relative protective capacities of specific monoclonal IgA antibodies have been tested in vivo by generation of hybridoma tumors that result in the secretion of monoclonal IgA into the intestine. Using this method, we have established that the secretion of IgA antibodies recognizing a single surface epitope on enteric pathogens can provide protection against colonization or invasion of the intestinal mucosa.

Animals↗
PubMed2003

Enteral feeding preserves mucosal immunity despite in vivo MAdCAM-1 blockade of lymphocyte homing.

OBJECTIVE: To determine the influence of route of nutrition on gut mucosal addressin cellular adhesion molecule-1 (MAdCAM-1) expression and the effect of MAdCAM-1 blockade on gut-associated lymphoid tissue (GALT) lymphocyte populations and established respiratory antibacterial immunity. SUMMARY BACKGROUND DATA: Lymphocytes, sensitized to antigens in Peyer's patches, migrate via mesenteric lymph nodes and home to intestinal lamina propria. MAdCAM-1 located on endothelial cells regulates this trafficking. Experimentally, parenteral nutrition (PN) decreases GALT cell mass and mucosal immunity when compared with enteral feeding. METHODS: In experiment 1, MAdCAM-1 expression was quantified in 32 mice after 4 days of feeding chow, a complex diet, intragastric (IG)-PN, or PN. In experiment 2, MAdCAM-1 was measured in 102 mice 0, 4, 8, 12, 24, 48, or 72 hours after starting PN and at 0, 4, 8, 12, 24, or 48 hours after reinstituting chow following 5 days of PN. In experiment 3, 56 mice received chow, PN, chow + MECA-367 (anti-MAdCAM-1 mAb), or chow + Isotype control Ab (IsoAb) for 5 days, followed by Peyer's patches, lamina propria, and intraepithelial lymphocyte yield with respiratory and intestinal IgA levels. In experiment 4, 10 days after Pseudomonas immunization, mice received chow + MECA-367 or chow + IsoAb for 4 days followed by 1.2 x 108 Pseudomonas intratracheally. RESULTS: Diet and route affect MAdCAM-1 expression (chow > complex diet > IG-PN > PN). Decreased MAdCAM-1 expression occurred within hours of starting PN in Peyer's patches, but not mesenteric lymph nodes or the intestine, and recovered quickly with enteral refeeding. MAdCAM-1 blockade reduced all GALT populations. Blockade had little effect on IgA levels and partially impaired the late response of established respiratory immunity. CONCLUSIONS: Enteral feeding affects MAdCAM-1 expression. Complete MAdCAM-1 blockade reduces GALT lymphocytes to PN levels, but the chow feeding stimulus preserves IgA and early antibacterial resistance, implying the existence of non-MAdCAM-1 mechanisms to preserve mucosal immunity.

Animals↗
PubMed1999

Surgical stress, bacteria, and mucosal immune function.

Bacteria share a benign coexistence with host mucosal surfaces in the gastrointestinal tract during periods of health. Both host epithelial defense function and bacterial virulence phenotypes are significantly affected by stress. Via discreet and specific sensory input signals to bacteria, the molecular machinery of otherwise commensal strains of bacteria can shift the phenotypes of residential colonizers to more virulent and invasive strains. This occurs at a time when the host may be relatively immunosuppressed by the injury. This adaptive response demonstrates the duplicitous nature of bacteria residing on mucosal surfaces whose ability to shift their virulence characteristics may play an important role in infectious-related morbidity following surgical stress.

Animals↗
PubMed1996

Mucosal immunization with a measles virus CTL epitope encapsulated in biodegradable PLG microparticles.

The immunogenicity of a cytotoxic T cell epitope (CTL) representing residues 52-60 from measles virus (MV) nucleoprotein, encapsulated in poly(lactide-co-glycolide) (PLG) microparticles was evaluated after mucosal immunization. After intranasal administration of the encapsulated CTL epitope linked at the carboxyl terminus of two copies of a T-helper epitope (TT-NP6), peptide-specific and MV-specific CTL responses were detected in splenocytes. However, these responses were lower than the responses observed when the TT-NP6 peptide was administered intranasally in saline or using CTB as an adjuvant. Intranasal coadministration of the encapsulated TT-NP6 peptide with CTB did not result in any significant potentiation of the CTL responses. The effectiveness of biodegradable PLG microparticles for mucosal delivery of CTL epitopes, combined with their excellent tissue compatibility and biodegradability suggests that they represent a valuable delivery system for synthetic immunogens. However, further work is needed to define the requirements for effective absorption by the nasal epithelium.

Animals↗
PubMed1998

The mucosal immune system in the human female reproductive tract: potential insights into the heterosexual transmission of HIV.

Using isolated cell suspensions and in situ techniques, we have partially characterized the organization, functional capacity, and sex hormone regulation of the mucosal immune system in the human female reproductive tract. Isolated cells suspensions have been used to demonstrate that the uterus contains antigen-presenting cells that are functionally able to present antigen to autologous tetanus toxoid-specific T cells. Immunophenotypic analyses of the female reproductive tract by three-color immunofluorescent staining has been used to show that lymphoid aggregates, which are absent in postmenopausal women, develop in the uterine endometrium during the menstrual cycle in premenopausal women. Lymphoid aggregates are composed of a B lymphocyte core surrounded by numerous CD8+CD4- T lymphocytes and an outer halo of macrophages. Macrophages, CD4+ and CD8+ T cells, and CD56+ NK cells are distributed throughout the uterine endometrium. In contrast, the Fallopian tube, cervix, and vagina, which lack lymphoid aggregates, contain CD8+ and CD4+ T cells as well as macrophages. The female reproductive tract has also been analyzed for the presence of antigen-independent CD3+ T lymphocyte cytolytic function by an anti-CD3 MAb-mediated redirected lysis assay. High levels of CD3+ T lymphocyte cytolytic activity were demonstrated in cervix and vagina and independent of stage of the menstrual cycle. In the uterus, cytolytic activity changed with endocrine state. In postmenopausal women the uterine endometrium had CD3+ T lymphocytes with high cytolytic activity, whereas premenopausal women had CD3+ T lymphocytes with moderate cytolytic potential during the proliferative phase to low/no cytolytic activity during the secretory phase of the menstrual cycle. In studies to determine whether the upper reproductive tract could be infected with HIV-1, we found on the basis of nef expression and p24 release that epithelial cells from the Fallopian tube, and from the uterus and cervix, are infectable. These studies demonstrate that the human female reproductive tract is an inductive site for immune responses and the cell-mediated immunity is present throughout the female reproductive tract. These studies further indicate that the Fallopian tube and uterus are potential entry sites for HIV-1 infection and that uterine immune cell architecture as well as cytolytic activity are under hormonal control.

Antigen Presentation↗
PubMed2003

Evidence for naturally acquired T cell-mediated mucosal immunity to Neisseria meningitidis.

Naturally acquired protective immunity against Neisseria meningitidis is thought to partially explain the disparity between the high levels of carriage in the human nasopharynx and the rare incidence of disease. To investigate this immunity to Neisseria meningitidis at the mucosal level, in vitro cellular responses to outer membrane vesicle preparations derived from this pathogen were examined using mononuclear cells from the palatine tonsils of adults and children. Characterization of these responses was achieved by depletion of CD45RA(+), CD45RO(+), and CD19(+) populations and outer membrane vesicles derived from isogenic mutants expressing different serosubtypes of the major outer membrane protein, porin A (PorA), no PorA and membrane preparations from a mutant with no LPS (LpxA(-)). The magnitude of cellular proliferative responses against the outer membrane vesicles were strongly associated with age and were largely T cell mediated, involving both CD45RO(+) and CD45RA(+) T cell phenotypes. Responses were not dependent on LPS but consisted of both PorA cross-specific and non-PorA-dependent responses. Cellular immunity against Neisseria meningitidis was found to be frequently associated with systemic IgG Abs but was not associated with serum bactericidal Abs. For the first time our results demonstrate an age-associated acquisition of mucosal T effector/memory cell responses to Neisseria meningitidis. This mucosal cellular immunity can be present in the absence of serum bactericidal Abs, a classical marker of protective immunity.

Adolescent↗
PubMed1996

Immunity at mucosal surfaces.

The mucosae form a barrier between our bodies and a hostile external environment. Diseases and extrinsic factors which impair mucosal function may lead to serious consequences. The mucosal immune system is the primary mediator of specific immunity at mucosal surfaces. As such, it is responsible for maintaining homeostasis and for defense against both overt and opportunistic pathogens. For this reason, it is also the target of many new vaccine strategies for the induction of mucosal immunity. This brief review will examine the mucosal immune system, its role in maintaining the integrity of the mucosa, and some of the strategies aimed at enhancing specific immunity.

Administration, Oral↗
PubMed2005

Novel bacterial delivery system with attenuated Salmonella typhimurium carrying plasmid encoding Mtb antigen 85A for mucosal immunization: establishment of proof of principle in TB mouse model.

Tuberculosis (TB), the leading killer of young adults worldwide, newly affects one person every second and kills one in every 15 seconds. The recent increase of TB in developing countries has been exacerbated by many causes including pandemic HIV, war and political instability, drug resistance, and increasing poverty. Genetic immunization has emerged with tremendous potential in vaccination against TB with success in animal models with naked DNA encoding different genes such as Ag85A, Pst3, and hsp65. However, there are shortcomings in translating this success into reality in human clinical trials due to limitations at the level of delivery, quality, and quantity of DNA to be administered, which can be circumvented by using an attenuated bacteria delivery system for transgene vaccination for mucosal immunization targeting the inductive sites of the immune system. We compare this novel delivery system using an attenuated Salmonella delta aroA strain through a mucosal route with classic intramuscular DNA delivery using a potential protective antigen, Ag85A, of Mycobacterium tuberculosis in a mouse infection virulent challenge model. We show an immune response and superior protection in the mice at the level of the lungs as well as the spleen against a virulent challenge after intranasal immunization by recombinant Salmonella typhimurium carrying a eukaryotic expression plasmid encoding Ag85A rather than the classic DNA immunization and at par with the protection conferred by BCG. This study establishes the proof of principle of this system for further exploitation of this platform for vaccine development, which is being pursued for postexposure vaccine development for TB.

Acyltransferases↗
PubMed1980

A common mucosal immune system. Antibody expression in secretions following gastrointestinal stimulation.

Isoelectric focusing was used to probe the expression of IgA anti-DNP antibodies in secretions of rats receiving gastrointestinal immunization. The identity of the IgA antibody spectrotypes suggest that cells with identical clonotype potential seed various secretory surfaces following gastrointestinal stimulation. The data are discussed in terms of a common mucosal immune system linked by migrating populations of IgA precursor cells.

Animals↗
PubMed2005

The importance of mucosal immunity in defense against epithelial cancers.

Many cancers arise in epithelial mucosa. These mucosal surfaces are characterized by the induction of divergent immune responses, as they are both the main portal of entry for pathogens and a large niche of commensal bacteria and tolerized antigens. In addition, mucosa located in different anatomical sites harbor distinct typical features. Exploiting the different requirements for inducing an effective immune response at mucosal sites might help to define new immunotherapeutic approaches against epithelial cancers, at least in the case of differentiated tumors that have retained their mucosal characteristics.

Cancer Vaccines↗