[Intestinal epithelial cell-derived IL-7 mediated immune responses in mucosal immunity and intestinal inflammation].
Explore the source record for details and available documents.
Animals↗
SEARCH · Search PubMed
Results for “mucosal immunization”
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.
Long-term persistence and recall of immune responses in aged mice after mucosal immunization.
To evaluate the retention of memory in the mucosal immune system of aged animals, 2-year-old mice that had been immunized intragastrically at 3 months of age with Streptococcus mutans protein AgI/II coupled to the B subunit of cholera toxin (CTB) were evaluated by ELISA for antibodies to AgI/II and CT in serum, saliva, and vaginal wash. To evaluate recall responses, mice were then immunized intragastrically with AgI/II-CTB, in comparison with previously unimmunized controls. Those that had been primed in their youth showed a more rapid antibody response in serum (immunoglobulin G (IgG)) and secretions (IgA), but all animals eventually responded to a similar degree after the third dose. Mice immunized at 3 months also retained for 2 years spleen cells capable of proliferating in vitro in response to AgI/II. These data show that aged mice retain the ability to mount immune responses to mucosally presented immunogens and that memory to mucosally presented immunogens can persist for almost the whole lifetime of a mouse.
Adjuvants, Immunologic↗
Influence of bedding type on mucosal immune responses.
The mucosal immune system interacts with the external environment. In the study reported here, we found that bedding materials can influence the intestinal immune responses of mice. We observed that mice housed on wood, compared with cotton bedding, had increased numbers of Peyer's patches (PP) visible under a dissecting microscope. In addition, culture of lymphoid organs revealed increased production of total and virus-specific IgA by PP and mesenteric lymph node (MLN) lymphocytes from mice housed on wood, compared with cotton bedding. However, bedding type did not influence serum virus-specific antibody responses. These observations indicate that bedding type influences the intestinal immune system and suggest that this issue should be considered by mucosal immunologists and personnel at animal care facilities.
Animal Husbandry↗
Current concepts in mucosal immunity. V Role of M cells in transepithelial transport of antigens and pathogens to the mucosal immune system.
Specialized epithelial M cells, a phenotype that occurs only in the epithelium over organized lymphoid follicles, deliver samples of foreign material by transepithelial transport from the lumen to organized lymphoid tissues within the mucosa of the small and large intestines. Mounting evidence indicates that a complex interplay of mucosal lymphoid cells and luminal microorganisms with epithelial cells underlies differentiation of the M cell phenotype. The cellular and molecular features of M cells that promote adherence and transport of antigens and microorganisms are crucial for the design of mucosal vaccines and for understanding the strategies that pathogens use to exploit this pathway.
Animals↗
Oral DNA vaccination in utero induces mucosal immunity and immune memory in the neonate.
Infectious diseases are responsible for a significant number of deaths during the first weeks of life. Some of the salient pathogens include HSV, HIV, hepatitis B virus, group B streptococcus, Haemophilus sp., and Chlamydia sp. The vertical transmission of many of these pathogens significantly increases the risk of neonatal infection. We recently reported that oral DNA immunization in utero induced high serum Ab titers and cell-mediated immunity in fetal lambs. In this study, we demonstrate immune memory and mucosal immunity in newborn lambs following oral DNA immunization of the fetus. A single oral exposure in utero to plasmid DNA encoding a truncated form of glycoprotein D of bovine herpesvirus-1 induced detectable immune responses in 80% (12 of 15) of newborn lambs. There was no evidence for the induction of immune tolerance in nonresponding lambs. Responding lambs displayed both systemic and mucosal immune responses and reduced virus shedding following intranasal challenge. Furthermore, strong anamnestic responses were evident for at least 3 mo after birth. The efficacy of in utero oral DNA immunization was further demonstrated with the hepatitis B surface Ag, and protective serum Ab titers occurred in 75% of immunized lambs. Thus, the present investigation confirms that oral DNA immunization in utero can induce both mucosal and systemic immune responses in the neonate and that this immunity has the potential to prevent vertical disease transmission.
Administration, Oral↗
Nasal lymphoid tissue, intranasal immunization, and compartmentalization of the common mucosal immune system.
Mucosal application of vaccines with an appropriate adjuvant can induce immune responses at both systemic and mucosal sites, and therefore may prevent not only infectious disease, but also colonization of mucosal surfaces. Intranasal is more effective than intragastric immunization at generating earlier and stronger mucosal immune response. Nasal lymphoid tissue (NALT) and its local draining lymph nodes may retain long-term immune memory. IgA isotype switching, and the differentiation and maturation of IgA antibody-secreting cells (ASC) may occur before these cells migrate out of NALT, whereas IgG ASC responses require passage of the cells through draining lymph nodes of the NALT. Knowledge of whether immune memory cells can recirculate to and reside in the inductive sites other than their origin after encountering antigen will be helpful for understanding the compartmentalization of the common mucosal immune system as well as for determining the best route for delivering a mucosal vaccine against a particular pathogen.
Administration, Intranasal↗
The common mucosal immune system: from basic principles to enteric vaccines with relevance for the female reproductive tract.
The realization that induction of immune responses at mucosal surfaces may prevent colonization, invasion or dissemination of pathogenic microorganisms has spurred intensive efforts to develop vaccines which elicit effective mucosal immunity. In this paper, recent results are discussed for mice given cholera toxin as both an immunogen and as an adjuvant for inducing both humoral and gastrointestinal mucosal immune responses. Oral administration of cholera toxin alone or with a co-administered protein vaccine tetanus toxoid induces a strong T helper type 2 (TH2) cell response in both Peyer's patches and spleen. Both serum IgG and secretory IgA antibodies specific for cholera toxin or for the co-administered protein tetanus toxoid were induced. When administered parentally, however, no mucosal antibody responses were evident and a mixed TH1- and TH2-type CD4+ T cell response was noted in the spleen. Various vectors are being employed in an effort not only to induce mucosal immune responses but also to direct the response to a TH1-type response, thought to promote strong cell-mediated immune responses, or to a TH2-type response for maximum B cell antibody responses. The ability to manipulate the TH cell responses may provide a more rational approach for the design of vaccines. Although lymphoid tissues of the female reproductive tract differ from that of the gut, many of the strategies and evolving principles may be directly applicable to the development of vaccines designed to prevent sexually transmitted diseases.
Administration, Oral↗
Development of mucosal immunity in the first year of life and relationship to sudden infant death syndrome.
The common mucosal immune system (CMIS) is an interconnecting network of immune structures that provides effective immunity to mucosal surfaces. The structures of the mucosal immune system are fully developed in utero by 28 weeks gestation, but in the absence of intrauterine infection, activation does not occur until after birth. Mucosal immune responses occur rapidly in the first weeks of life in response to extensive antigenic exposure. Maturation of the mucosal immune system and establishment of protective immunity varies between individuals but is usually fully developed in the first year of life, irrespective of gestational age at birth. In addition to exposure to pathogenic and commensal bacteria, the major modifier of the developmental patterns in the neonatal period is infant feeding practices. A period of heightened immune responses occurs during the maturation process, particularly between 1 and 6 months, which coincides with the age range during which most cases of sudden infant death syndrome (SIDS) occur. A hyper-immune mucosal response has been a common finding in infants whose death is classified as SIDS, particularly if in association with a prior upper respiratory infection. Inappropriate mucosal immune responses to an otherwise innocuous common antigen and the resulting inflammatory processes have been proposed as factors contributing to SIDS.
Child, Preschool↗
Intranasal immunization with liposome-formulated Yersinia pestis vaccine enhances mucosal immune responses.
The induction of mucosal immune responses by a liposome-formulated Y. pestis vaccine (formaldehyde-killed whole cell vaccine; KWC) was evaluated. We demonstrated that intranasal immunization of mice with Y. pestis KWC vaccine, formulated with liposomes, significantly enhanced mucosal immune responses in the lung when compared to the responses induced with KWC vaccine alone. These immune responses were characterized by increased titres of specific IgA and IgG in mucosal secretions (lung and nasal washes), and an increased frequency of specific antibody-secreting cells in the lungs. In addition, antigen-specific proliferative responses and IFN-gamma-secreting cells were also significantly enhanced in the spleens of mice immunized with the KWC vaccine formulated in liposomes. Animals that were immunized intranasally with the KWC vaccine showed significant protection against an intranasal challenge with Y. pestis. These results highlight the importance of mucosal administration of vaccine antigens to stimulate immunity in the respiratory tract and demonstrate that liposome formulations can improve the effectiveness of conventional vaccines.
Administration, Intranasal↗
Oral administration of the adenovirus vector induces systemic immunity rather than intestinal mucosal immunity.
Explore the source record for details and available documents.
Adenoviridae↗
CpG DNA, a novel immune enhancer for systemic and mucosal immunization with influenza virus.
Bacterial DNA causes B cell proliferation, immunoglobulin secretion, and Th1-like cytokine secretion, due to unmethylated CpG dinucleotides in particular base contexts (CpG motifs), which are far more common in bacterial DNA than in vertebrate DNA. Synthetic oligodeoxynucleotides (ODN) containing CpG motifs also trigger immune activation, suggesting possible utility as vaccine enhancers. Mice systemically primed with formalin-inactivated influenza virus mixed with CpG ODN, generated virus-specific serum antibodies at titres approximately seven times higher than mice immunized without CpG; the titres were further increased following an identical second injection. To determine whether CpG could be absorbed through mucosae and enhance vaccination responses, mice were immunized intranasally (IN) with the same preparation of virus with or without CpG ODN or Escherichia coli DNA. Following IN immunization, CpG ODN or E. coli DNA promoted increased production of influenza-specific antibodies in serum, saliva and the genital tract, compared with the control groups. These studies indicate that stimulatory CpG ODN are promising new immune enhancers for vaccination applications.
Administration, Intranasal↗
The mucosal immune system: from specialized immune defense to inflammation and allergy.
The mucosal immune system is a first line of defense against foreign antigens, including microbial and dietary antigens. Under normal circumstances, the mucosal immune system employs tightly regulated dynamic mucosal intra- and internets consisting of inductive and effector sites for the induction of an appropriate immunological homeostasis between the host and mucosal environments. The common mucosal immune system (CMIS), which interconnects between inductive (e.g. Peyer patch) and effector (e.g. intestinal lamina propria) tissues for the induction of the IgA response, is well characterized. Recent results provide strong evidence for the presence of a CMIS-independent IgA induction pathway. Two distinct subsets of mucosal IgA-committed B cells termed B-1 and B-2, are associated with CMIS-independence and CMIS-dependent cascades respectively. In some cases, the breakdown of this tightly regulated mucosal immune system leads to pathological responses to different gut environmental antigens. As a result, disorders such as inflammatory bowel disease (e.g. IBD) and allergic gastroenteropathy can be evoked in the gastrointestinal tissues. Recently, many studies have described possible molecular and cellular mechanisms for this dysfunction in the gastrointestinal tissues by using murine models with specific gene manipulation. In this review we summarize recent findings from our group concerning the CMIS-dependent and CMIS-independent IgA induction pathways and gastrointestinal diseases (IBD and intestinal allergic diseases). These observations may provide useful information for the development of new mucosal immune therapy.
Animals↗
Cells and cytokines in mucosal immunity and inflammation.
The mucosal immune system consists of a number of compartments that are populated with a different assortment of cells and serve different functions. The cytokines produced by the cells in each of these compartments are currently being defined. This is best understood in relation to B cells, whose proliferation and maturation is guided by a sequence of cytokines. PP are inductive sites that preferentially stimulate IgA production. At least in part, this preference seems to be due to the T cells located in PP, which have been shown to stimulate switching to IgA production by cognate interactions and production of TGF-beta. Postswitch B cells expressing surface IgA respond to IL-5, a cytokine produced by T cells in GALT. Terminal differentiation to IgA-producing plasma cells in the lamina propria may be driven by IL-6, which can be produced by a variety of cells in the lamina propria and by epithelial cells. T cells in the lamina propria have an assortment of surface markers consistent with both activation and memory and appear to produce a variety of cytokines in the local environment that presumably act in normal host defense. IEL consist mainly of CD8+ T cells. They have been shown to produce IFN-gamma and, very likely, other cytokines that presumably act in a paracrine fashion on local enterocytes. How these cells and cytokines are perturbed during intestinal inflammation is currently being defined. A certain assortment of cytokines are greatly increased in IBD. This assortment, including IL-1, IL-6, and IL-8, is elevated in a wide variety of chronic inflammatory states in other tissues as well. A critical requirement for cytokines to exert their effects is the expression of specific receptors on target cells. Virtually nothing is known about this aspect of mucosal immunity, but receptor expression on mucosal cells must be defined before we will be able to understand the complex interactions among lymphoid cells, the cytokines they produce, and the local stromal and epithelial cells.
Animals↗
Application of polyethyleneglycol (PEG)-modified liposomes for oral vaccine: effect of lipid dose on systemic and mucosal immunity.
To examine the systemic and mucosal immunity towards a liposomal antigen in an oral vaccine, we prepared ovalbumin (OVA)-encapsulating polyethyleneglycol (PEG)-modified liposomes and unmodified ones, and orally administered two different concentrations of them to mice. Unmodified liposomes tended to induce a stronger systemic immune response than the PEG-modified ones especially at the higher concentration of liposomes. Whereas at the lower liposome concentration the mucosal immune response was stronger for the PEG-modified liposomes than for the unmodified ones but nearly the same at the higher concentration. The relative amount of immunoglobulin G (IgG) against OVA in the plasma was 1.7-fold higher for a 12.5 micro mol phospholipid dose of PEG-liposomes encapsulating OVA than for a 5.0 micro mol one encapsulating the same amount of OVA. On the contrary, the relative amount of IgA in the intestinal wash was 2.6-fold higher for the 5.0 micro mol phospholipid dose than for the 12.5 micro mol one. These results indicate that OVA encapsulated in a small number of liposomes, especially the PEG-modified ones, is favorable for inducing a mucosal immune response and that the same amount of OVA in a large number of liposomes tends to improve the systemic immune response. A possible explanation for this tendency is the differential release rate of OVA from the liposomes at the intestinal mucosa. Our present study suggests that the dose of liposomes containing antigen is an important factor for controlling the response of systemic and mucosal immune systems.
Administration, Oral↗
Antigen processing in the mucosal immune system.
The mucosal immune system is concerned with host defense along the moist surfaces of the body which have contact with the external environment. These sites contain specialized lymphoid structures which contain precursors for IgA-synthesizing B lymphocytes and immunoregulatory T lymphocytes which will determine whether oral tolerance or a strong immune response develops against antigens administered orally. The key step to antigen processing in the gastrointestinal tract involves its initial uptake from the gut lumen by specialized follicle associated epithelium called 'M' cells. M cells originate from adjacent crypt epithelium and are interspersed between the absorptive epithelial cells in the follicle-associated epithelium. M cells cells have short, irregular microvilli, are closely associated with lymphocytes, do not have a prominent terminal web, and have only weak alkaline phosphatase activity but strong nonspecific esterase activity. M cells do not express surface MHC class II (HLA-DR) antigens. These cells take up macromolecules, viruses, bacteria and protozoa within 30 minutes from the initial presentation of the antigen to the intestinal lumen. After the initial uptake of antigen by M cells, the antigens are transported into the follicular areas to be processed by dendritic cells and brought into close contact with the antigen-specific precursors for IgA secreting plasma cells. The final result of M cell processing is the production of a vigorous secretory IgA response and local cell-mediated immunity with suppression of a systemic IgG, IgE and delayed-type hypersensitivity to orally-administered antigens.
Animals↗
Neonatal gastrointestinal mucosal immunity.
The gastrointestinal mucosal immune system is a complex system with multiple interacting cells, which express different markers and elaborate a variety of mediators in response to noxious stimuli and pathogens. At birth this system is quite immature, putting the newborn mammal at risk for a variety of infectious and noninfectious diseases. With age and antigenic stimulation, maturation occurs and intestinal host defense then functions quite effectively to protect the host from ingested noxious substances and microorganisms.
Aging↗
Regulation of mucosal immune responses by T lymphocytes: the effect of chronic CD4+ T cell deficiency on IgA synthesis.
Mechanisms of immune defence at the mucosal surface has been elucidated by recent advances in molecular and cellular immunology. IgA is undoubtedly the most important defense factor in the mucosal immune system. It has been shown that T cells are essential for the induction and regulation of IgA synthesis. In T cell regulation of IgA synthesis, various cytokines (e.g., TGF-beta, IL-2, IL-5, and IL-6) which are secreted by CD4+ T cells, play important roles for the induction and regulation of IgA isotype switching and terminal differentiation of sIgA+ B cells to become IgA producing cells. The chronic treatment of mice with anti-CD4 mAb induced a market deficiency of CD4+ T cells in both mucosal and systemic tissues. IgA plasma cells were significantly reduced in treated mice when compared with normal mice (greater than 80% reduction), while the numbers of sIgA+ B cells in IgA inductive sites (e.g., PP) remained normal. CD4+ Th cells are a critical element for the induction of appropriate IgA responses in mucosal associated tissues. Elucidation of the precise cellular and molecular network for the regulation of mucosal immune defense system is important and useful for the consideration of prevention of infectious diseases. In this regard, the effective and sophisticated mucosal administration of vaccines using the concept of the common mucosal immune system should induce effective immune responses which prevent the pathogen from entering the host through large surface areas of mucosal membranes. This goal cannot be achieved without a more complete understanding of regulatory T cells and cytokines for mucosal immune responses.
Animals↗
The systemic immune response is more prominent than the mucosal immune response in the pathogenesis of periodontal disease.
BACKGROUND/AIM: The diseased periodontium appears to express features of a systemic and a mucosal immune response. Our aims were to determine differences in immunoglobulin expression between gingivitis and periodontitis lesions and to ascertain whether immune and inflammatory cells were recruited into the diseased periodontium by the mucosal addressin adhesion molecule (MAdCAM-1). METHODS: In situ hybridization and immunohistochemistry were used to detect the expression of chemokines, adhesion molecules and immunoglobulins in tissue sections of gingival and granulation tissues excised from periodontitis-affected sites and of healthy tissue and gingivitis-affected tissue excised during crown-lengthening procedures. RESULTS: Greater numbers of plasma cells were observed in periodontitis gingival/granulation tissue lesions compared with gingivitis lesions. While IgA1 were predominant in all lesions, IgA2 and J-chain expressing plasma cells were present in increased proportions in gingival tissues compared with granulation tissue. Intracellular adhesion molecule-1 (ICAM-1) was higher in periodontitis than in gingivitis and interleukin-8 mRNA was higher in lesions with a pronounced neutrophil infiltrate. Vascular cell adhesion molecule-1 (VCAM-1) localized to the deep connective tissue and indicated the presence of a systemic type of immune response in this region. Periodontal tissues (n=71 biopsies) did not appear to express MAdCAM-1, in positive control sections of small intestine where it was detected. CONCLUSION: Overall, the systemic-type immune response is predominant, and although the mucosal immune response is minor and limited to the superficial tissues it may have an important role in the host defense to periodontal pathogens.
Adult↗