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At least 19 recordsLinked to original sources
PubMed2003

Mucosal immunity--mucosal tolerance. A strategy for treatment of allergic diseases.

The mucosal surfaces of the respiratory, the gastrointestinal and the urogenital tract, covering a total of 300 m2, are the largest areas within the body in contact with the external environment and thus are major sites of antigen exposure. Discriminating between pathogenic antigens, towards which a protective immune response has to be established, and harmless antigens--such as food, airborne antigens or the commensal bacterial flora--that should be ignored is the most challenging task of the mucosal immune system. In order to handle these challenges the mucosal immune system has generated two arms of adaptive defenses: (1) antigen exclusion performed by secretory IgA and secretory IgM antibodies to modulate or inhibit adherence or colonization of microorganisms and prevent penetration of potentially dangerous antigens (toxins, etc.), and (2) suppressive mechanisms to avoid local and peripheral overreaction against innocuous substances contacting the mucosal surfaces. The latter arm is referred to as oral or mucosal tolerance. A breakdown or a failure of induction of long-lasting tolerance to environmental and food antigens or components of the indigenous microflora is believed to lead to allergic diseases or food enteropathies. Based on the physiological situation to prevent hypersensitivity reactions, tolerance induction via the mucosa has been proposed as a treatment strategy against human inflammatory diseases, such as allergies.

Antigen-Presenting Cells↗
PubMed1996

History of oral tolerance and mucosal immunity.

Mucosal immunity depends on antigen stimulation in specialized lymphoepithelial structures such as the Peyer's patches. Although these inductive compartments were discovered more than 300 years ago, their functional role has become clear only over the last few decades. Research on homing of primed lymphoid cells to the intestinal mucosa began with animal experimentation in the 1960s and 1970s and has recently been brought to the molecular level. The major effector substance of mucosal immunity is secretory IgA (SIgA). The first evidence for its local antibody activity was obtained in humans in 1922, but its unique properties were not defined until the mid-1960s. Several models were subsequently proposed for selective external transport of IgA involving the secretory component (SC). In the early 1970s SC was suggested to act as a transmembrane polymeric Ig receptor common for dimeric IgA and pentameric IgM; this transport mechanism has now been confirmed by detailed studies at the level of cellular/molecular biology. Although SIgA antibodies performing immune exclusion are the main goal for exploitation of the mucosal immune system by oral vaccination, little is known about the precise mechanisms for induction of mucosal immunity against soluble proteins and chemicals. A peripheral immunosuppressive effect of oral immunization with such substances was apparently exploited by ancient people, and "oral tolerance" has since 1910 been subjected to numerous feeding experiments in rodents. The basis for the whole phenomenon appears to be intact epithelial barrier. Mucosal induction of suppression may in the future be exploited not only to modulate autoimmune diseases through the gut but also to prevent the development of IgE-mediated allergy and other untoward immune reactions by way of the respiratory tract.

Administration, Oral↗
PubMed2001

Suppository-mediated DNA immunization induces mucosal immunity against bovine herpesvirus-1 in cattle.

Mucosal surfaces are the primary sites for the transmission of infectious agents including viruses, so effective vaccines generally should induce mucosal immunity. Furthermore, noninvasive delivery is desirable because of the ease of application, the high degree of patient compliance, and the improved safety for patients and clinicians due to the elimination of needles. Unfortunately, most of the conventional vaccines are parenterally administered and result in systemic rather than mucosal immunity. Here we present the first report of mucosal immunity by noninvasive DNA immunization in a target species. As an approach to induce mucosal immunity against bovine herpesvirus-1, cows were immunized intravaginally with suppositories containing plasmid coding for glycoprotein D. Serum IgG, as well as IgA both in the serum and in the nasal fluids, were detected, which supports the contention of a common mucosal immune system. This level of immunity was of sufficient magnitude to minimize weight loss and significantly reduce the duration of virus shedding after intranasal viral challenge, which demonstrates the efficacy of suppository-based administration of DNA vaccines to target species. As this is a very practical method of delivery, it has great potential to be applied as vaccine or therapy in a variety of species.

Administration, Intravaginal↗
PubMed1991

Mucosal immunity following oral poliovirus vaccine and enhanced potency inactivated poliovirus vaccine immunization.

Mucosal immunity is considered to be an important barrier for inhibiting person-to-person transmission of naturally occurring (wild type) poliovirus infection. This review briefly summarizes the results of a previously published study in which 79 oral poliovirus vaccine (OPV) vaccinated children and 93 enhanced-potency inactivated poliovirus vaccine (IPV) children were challenged with one of two doses of type 1 OPV virus to test the oropharyngeal and gastrointestinal mucosal immunity conferred by each type of poliovirus vaccine. Although both OPV and IPV produced excellent oropharyngeal immunity, OPV was clearly superior in decreasing fecal shedding of the challenge virus.

Child, Preschool↗
PubMed1995

The gut as a lymphoepithelial organ: the role of intestinal epithelial cells in mucosal immunity.

Mucosal surfaces covered by a layer of epithelial cells represent the largest and most critical interface between the organism and its environment. The barrier function of mucosal surfaces is performed by the epithelial layer and immune cells present in the mucosal compartment. As recently found, epithelial cells, apart from their participation in absorptive, digestive and secretory processes perform more than a passive barrier function and are directly involved in immune processes. Besides the well known role of epithelial cells in the transfer of polymeric immunoglobulins produced by lamina propria B lymphocytes to the luminal content of mucosals (secretory Igs), these cells were found to perform various other immunological functions, to interact with other cells of the immune system and to induce an efficient inflammatory response to microbial invasion: enzymic processing of dietary antigens, expression of class I and II MHC antigens, presentation of antigens to lymphocytes, expression of adhesive molecules mediating interaction with intraepithelial lymphocytes and components of extracellular matrix, production of cytokines and probable participation in extrathymic T cell development of intraepithelial lymphocytes. All these functions were suggested to influence substantially the mucosal immune system and its response. Under immunopathological conditions, e.g. during infections and inflammatory bowel and celiac diseases, both epithelial cells and intraepithelial lymphocytes participate substantially in inflammatory reactions. Moreover, enterocytes could become a target of mucosal immune factors. Mucosal immunosurveillance function is of crucial importance in various pathological conditions but especially in the case of the most frequent malignity occurring in the intestinal compartment, i.e. colorectal carcinoma. Proper understanding of the differentiation processes and functions of epithelial cells in interaction with other components of the mucosal immune system is therefore highly desirable.

Adult↗
PubMed2004

Molecular adjuvants for mucosal immunity.

Mucosal surfaces represent the entry route of a multitude of viral pathogens. For many of these viruses, such as the herpes simplex viruses and human immunodeficiency virus, no effective vaccine exists. Hence, it is important that prospective vaccines engender maximal immunity at these susceptible sites. Genetic vaccines encoding adjuvant molecules represent one approach to optimize mucosal as well as systemic immunity. Promising candidates include various inflammatory cytokines and chemokines that might be used to enhance the primary response to a level sufficient for protection. Encouraging studies involving cytokines such as granulocyte/macrophage colony-stimulating factor, interleukin-2 (IL-2), IL-12, IL-18, and many others are examined. Notable chemokines that may offer hope in such efforts include IL-8, RANTES, CCL19, CCL21, and a few others. Combinatorial approaches utilizing several cytokines and chemokines will most likely yield the greatest success. In addition, as more is discovered regarding the requirements for memory development of T cells, boosters involving key cytokines such as IL-15 and IL-23 may prove beneficial to long-term maintenance of the memory pool. This review summarizes the progress in the use of genetic vaccines to achieve mucosal immunity and discusses the needed strategies to maximize long-term prospective immunity at this vulnerable entry site.

Adjuvants, Immunologic↗
PubMed1983

Mucosal immunity.

Mucosal defense is provided by a number of host factors countering the specific virulence factors of the many microorganisms infecting the mucous membranes. Secretory IgA antibodies presumably play an important role. Increase of the sIgA antibodies may most advantageously be attained by parenteral immunization, following mucosal priming. This was demonstrated in a rat model, where it was also noted that antigen injection into PP induced high milk IgA antibody levels. In man, parenteral vaccination against polio increased the sIgA antibody levels in the milk of mothers previously exposed naturally to the poliovirus. The response was relatively short-lived. In the previously unexposed, there was little or no response. By contrast peroral immunization with live poliovirus vaccine did not increase, or even decrease, the milk sIgA poliovirus antibody levels. Although salivary sIgA antibodies against antigens of colonizing E. coli appear during the first days of life, they are slow to increase. This deficiency is richly compensated for by all the sIgA antibodies that are provided the baby through the milk. No transfer of dimeric IgA into the milk could be shown in lactating rats, in contrast to what has been reported in mice. There is no evidence for a contribution to milk sIgA from serum in man. Close to parturition, human milk often contains some 7S IgA and various sizes of free SC, in addition to the dominating 11S sIgA. A few days later there is almost exclusively monomeric SC and 11S sIgA. IgG antibodies also play a role at the mucosal level. IgG2 antibodies against the bacterial polysaccharide capsule are as slow to appear as sIgA in ontogeny, possibly explaining the prevalence of infections with encapsulated bacteria and the poor response to polysaccharide vaccines in early childhood. Other defense factors preventing infections by way of mucous membranes may be important. Thus, oligosaccharides present in human milk seem to specifically prevent pneumococcal attachment to retropharyngeal cells. This anti-attachment capacity, in addition to that provided by milk and salivary IgA antibodies, may explain why breast-fed babies have less otitis media than formula-fed ones.

Adult↗
PubMed2006

IgG transport across mucosal barriers by neonatal Fc receptor for IgG and mucosal immunity.

Mucosal secretions of the human gastrointestinal, respiratory, and genital tracts contain significant quantities of IgG. The neonatal Fc receptor for IgG (FcRn) plays a major role in regulating host IgG levels and transporting IgG and associated antigens across polarized epithelial barriers. The FcRn can then recycle the IgG/antigen complex back across the intestinal barrier into the lamina propria for processing by dendritic cells and presentation to CD4(+) T cells in regional organized lymphoid structures. FcRn, through its ability to secrete and absorb IgG, thus integrates luminal antigen encounters with systemic immune compartments and, as such, provides essential host defense and immunoregulatory functions at the mucosal surfaces.

Antigens↗
PubMed1994

Antimicrobial peptides as agents of mucosal immunity.

Mucosal surfaces are continually exposed to a wide range of potentially pathogenic organisms, yet the incidence of infectious disease resulting from these encounters is relatively low. This suggests the presence of highly effective defence mechanisms in these tissues. Antimicrobial peptides have recently been discovered in mucosal tissues and may play a significant role in host defence. Several mucosal peptides (andropin, magainin, tracheal antimicrobial peptide, enteric defensins and PR-39) all fulfil minimal criteria for a role in mucosal host defence, including potent in vitro antimicrobial activity and accumulation at the mucosal surface. Most of these mucosal peptides are encoded by members of large gene families that contain members found in other biological contexts more classically associated with antimicrobial defence. The abundance, activity and evolutionary history of several epithelial peptides suggest that antimicrobial peptides play a key role in host defence at mucosal surfaces.

Amino Acid Sequence↗
PubMed1999

The effect of route of immunization on mucosal immunity and protection.

In macaques, the route of immunization has a profound effect on the immune response. Augmenting rectal or vaginal immunization with oral or nasal immunization enhanced the secretory IgA, serum IgG, and T cell responses. However, targeted iliac lymph node (TILN) immunization with recombinant simian immunodeficiency virus (SIV) gp120 and p27 elicited the most consistent mucosal antibody responses in the rectum, vagina, urine, seminal fluid, and blood. Both mucosal and TILN immunization induced specific CD4+ T cell proliferative responses in the iliac lymph nodes, which drain these mucosal surfaces, and in the splenic and circulating T cells. Rectal mucosal challenge with cell-free SIV induced total protection in 4 of 7 macaques that were immunized by the TILN route, and, compared with unimmunized macaques or those immunized by the mucosal route (P<.001), it induced a >90% decrease in virus load in 3 of them. Protection from mucosal rectal infection with SIV was significantly associated with an increase in the CD8 suppressor factor (which was generated by the iliac lymph node), RANTES, and MIP-1beta (P<.01).

Animals↗
PubMed1997

Mucosal immune responses associated with polynucleotide vaccination.

A variety of gene delivery technologies can be used to express antigens within somatic tissues, resulting in systemic humoral and cellular immune responses. This observation has led to the development of polynucleotide vaccine preparations for stimulation of systemic immunity. Mucosal immune responses are functionally distinct from systemic immune responses, and are stimulated by antigen presentation within specialised mucosal-associated inductor tissues. We hypothesize that mucosal genetic vaccine will require gene transfer methods which target mucosal-associated inductor tissues such as the oropharyngeal Waldeyer's ring or intestinal Peyer's patches. We have tested this hypothesis by expressing a test antigen using a replication-defective recombinant Semliki Forest Virus (SFV) preparation. Mice treated with recombinant SFV via an intravascular or intratracheal route generated systemic immune responses against the test antigen. In contrast, intranasal inoculation resulted in the production of IgA within pulmonary fluids, one hallmark of a mucosal immune response. These results indicate that transfection of mucosal effector tissues may not be sufficient for the generation of a universal mucosal immune response. Furthermore, the results predict that techniques which target transfection or transduction to mucosal inductor tissues will enable the development of a new class of polynucleotide vaccines which exploit current concepts in mucosal immunology.

Animals↗
PubMed2001

Systemic immunity and mucosal immunity are induced against human immunodeficiency virus Gag protein in mice by a new hyperattenuated strain of Listeria monocytogenes.

Vaccines designed to control chronic infections by intracellular agents such as human immunodeficiency virus type 1 (HIV-1) require the induction of cell-mediated immune responses to rid the host of pathogen-infected cells. Listeria monocytogenes has characteristics that make it an attractive vaccine vector for use against such infections. Here we show that parenteral immunization with a new highly attenuated strain of this organism provided complete protection against systemic and mucosal challenges with a recombinant vaccinia virus expressing HIV-1 gag. Immunization also generated a strong, long-term memory cytotoxic-T-lymphocyte (CTL) response in spleen, mesenteric lymph nodes, and Peyer's patches directed against the gag protein. Oral immunization with this attenuated strain also produced complete, long-lasting protection against the recombinant virus but only against mucosal virus challenge. Curiously, oral immunization was associated with a transient CTL response in the three lymphoid tissues examined.

AIDS Vaccines↗
PubMed2006

The postnatal development of the mucosal immune system and mucosal tolerance in domestic animals.

The mucosal immune system is exposed to a range of antigens associated with pathogens, to which it must mount active immune responses. However, it is also exposed to a large number of harmless antigens associated with food and with commensal microbial flora, to which expression of active, inflammatory immune responses to these antigens is undesirable. The mucosal immune system must contain machinery capable of evaluating the antigens to which it is exposed and mounting appropriate effector or regulatory responses. Since the immune system is likely to have evolved initially in mucosal tissues, the requirement to prevent damaging allergic responses must be at least as old as the adaptive immune system, and studies of the mechanisms should include a range of non-mammalian species. Despite the importance for rational design of vaccines and for control of allergic reactions, the mechanisms involved are still largely unclear. It is not clear that the classical experimental protocol of "oral tolerance" is, in fact, measuring a biologically important phenomenon, nor is it clear whether tolerance is regulated in the evolutionarily recent organised lymphoid tissue (the lymph nodes) or the more ancient, diffuse architecture in the intestine. The capacity of the immune system to discriminate between "dangerous" and "harmless" antigens appears to develop with age and exposure to microbial flora. Thus, the ability of an individual or a group of animals to correctly regulate mucosal immune responses will depend on age, genetics and on their microbial environment and history. Attempts to manipulate the mucosal immune system towards active immune responses by oral vaccines, or towards oral tolerance, are likely to be confounded by environmentally-induced variability between individuals and between groups of animals.

Aging↗
PubMed2006

Innate immunity in the mucosal immune system.

The mucosal immune system is equipped with unique innate and acquired defense mechanisms which provide a first line of protection against ingested and inhaled infectious agents. Peyer's patches (PPs) and nasopharynx-associated lymphoid tissue (NALT) have been shown to be important inductive sites for the initiation of the acquired phase of antigen-specific immune responses. In addition, the mucosal innate immune system acts as both a physical and an immunological boundary, playing a key role in the sensing and eliminating of pathogens and in the creating of symbiosis. The mucus layer covering the mucosal epithelium acts as a first physical and biochemical barrier. An additional layer of physical protection against microorganisms is provided by a tightly interlaced cell-to-cell network of epithelial cells and intraepithelial lymphocytes. Various antimicrobial peptides produced by the epithelium and secreted into the mucosal lumen can directly kill the invading pathogenic bacteria. Finally, Toll-like receptors (TLRs) associated with the mucosal compartment have been shown to recognize the pathogen-associated molecular patterns (PAMPs) of a variety of pathogenic and commensal microorganisms. Therefore, a greater understanding of the immunological progression from mucosal innate to acquired immune systems should facilitate the development of new generation of mucosal vaccines to prevent and control infectious diseases.

Animals↗
PubMed1997

[Mucosal immune system and mucosal vaccine].

In the recent years, mucosal immune system is recognized as the new world in the area of immunology. The host is continuously exposed to the numerous numbers of environmental antigens via the mucosa and the skin. A total surface area of the mucosa is approximately 200 times larger than that of the skin, and the former surface area contains a large numbers of lymphoid cells (> 10(11)). In order to provide an effective defence for the host by vaccine, it is logical to consider the mucosal immune system. According to the new informations obtained by the modern cellular and molecular immunobiological knowledges and approaches, the concept of the mucosal immune system has been rapidly proceeded to apply for the development of mucosal vaccine. In this report, we have reviewed and discussed the recent progress in the characterization of mucosal immune system and the development of mucosal vaccine.

Animals↗
PubMed1990

[Mucosal immunity].

The mucosal immune system protects against infections that enter the body via the mucosae. This article describes how the mucosal immune system functions and how mucosal immune responses can be induced by vaccination. It also discusses various vaccination regimens that maximize the induction of mucosal immune responses against bacterial and viral infections. One paragraph of the article discusses the possibilities of developing vaccines that induce a mucosal immune response against parasite infections.

Animals↗
PubMed2000

Systemic and mucosal immune responses in mice after mucosal immunization with group B streptococcus type III capsular polysaccharide-cholera toxin B subunit conjugate vaccine.

Group B streptococci (GBS) colonize the female genital and rectal tracts and can cause invasive infection in susceptible newborns. An optimally effective GBS vaccine should induce mucosal and systemic immunity. In this study, we investigate the local and systemic immune responses to GBS type III capsular polysaccharide (CPS) after mucosal vaccination of mice via intranasal, peroral, rectal, and vaginal routes, with GBS type III CPS conjugated with recombinant cholera toxin B subunit (GBS III CPS-rCTB). Cholera toxin (CT) was added as an adjuvant. Immunoglobulin G (IgG) and IgA antibodies to the CPS were tested in serum, lungs, and intestinal, rectal, and vaginal extracts by enzyme-linked immunosorbent assay. The conjugated CPS administered by intranasal, peroral, rectal, and vaginal routes was much more effective at inducing both mucosal and systemic antibody responses to GBS III CPS than was unconjugated CPS. The CPS-specific immune responses in various organs were dependent on the route of immunization. Generally, the highest levels of IgA and IgG were generated in the regions or sites of the conjugate exposure. Thus, intranasal vaccination elicited the highest anti-CPS IgA and IgG antibody levels in the lungs, whereas peroral administration in the intestinal site and vaginal vaccination elicited the highest antibody levels in the vagina. Rectal vaccination was superior to the other routes in inducing high antibody levels in the rectum. The four routes of mucosal vaccination also induced distant antibody responses to CPS. Rectal vaccination induced high specific IgA levels in the vagina and intestine, and oral administration induced high specific IgA levels in the lungs and rectum. All four routes of vaccination with the conjugate elicited similarly high levels of anti-CPS IgG in serum. Intranasal vaccination with different doses of the conjugate (10, 30, and 80 microg of CPS) did not have a significant influence on the anti-CPS specific antibody responses. Intranasal immunization induced better antibody responses when one dose of the conjugate was divided and given on three consecutive days compared to administration of the full dose on one occasion. In conclusion, rectal and vaginal vaccination may be the best way of stimulating anti-CPS immune responses in the rectal and vaginal tracts, while high levels of anti-CPS antibodies in the lungs can be achieved after intranasal administration. The vaccination regimen thus might influence the mucosal immune response to CPS. This conjugate may serve as an effective mucosal vaccine for preventing mucosal colonization and invasive infection caused by GBS.

Animals↗