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Results for “mucosal immunization”

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PubMed1994

Mucosal immune responses in calves orally vaccinated with a live auxotrophic aroA Salmonella dublin strain.

The mucosal immune responses were studied in two calves orally vaccinated with the live aroA mutant strain, Salmonella dublin SL5631, and in two non-vaccinated control calves. Intestinal secretions were collected through a permanent fistula in place during a 5-week period. Vaccinated calves responded with high IgM and IgA titres against the S. dublin lipopolysaccharide. Both IgA and the IgM titres appeared already after 3 days and IgM somewhat earlier than the IgA titres. Both antibody titres remained high for 2 weeks after the third and final vaccine dose. The calves also showed marked T-cell responses in lymphocytes collected from mesenterial lymph nodes and the spleen.

Animals↗
PubMed1997

Induction of HIV-1 specific mucosal immune responses by DNA vaccination.

DNA vaccination has been shown to induce immunity against several different pathogens including HIV-1. The authors demonstrate here that administration of DNA vaccines via the intranasal route is sufficient to induce immune responses both at distal mucosal sites and systemically. Since transmission of HIV-1 occurs largely across mucosal surfaces, the intranasal route provides a further means of application for DNA immunization.

Administration, Intranasal↗
PubMed1998

Current concepts in mucosal immunity. IV. How epithelial transport of IgA antibodies relates to host defense.

The humoral arm of the mucosal immune system is principally composed of locally synthesized polymeric IgA, whose Fc portion is adapted for binding to the polymeric immunoglobulin receptor that is expressed on the basolateral surface of mucosal epithelial cells, including enterocytes. This receptor mediates the endocytosis and transcytosis of polymeric IgA, which allows IgA to function in host defense at three anatomic levels in relation to mucosal epithelium: IgA antibodies in the lamina propria can bind antigens and excrete them through the epithelium into the lumen; antiviral IgA antibodies in transit through epithelial cells can inhibit virus production by an intracellular action; and IgA antibodies secreted into the lumen can prevent antigens and microbes from adhering to and penetrating the epithelium. The ways in which IgA antibodies function in mucous membranes provide challenging investigative opportunities for cell physiologists and cell biologists.

Animals↗
PubMed2006

Anatomical route of invasion and protective mucosal immunity in Trypanosoma cruzi conjunctival infection.

Trypanosoma cruzi is a protozoan parasite that can initiate mucosal infection after conjunctival exposure. The anatomical route of T. cruzi invasion and spread after conjunctival parasite contamination remains poorly characterized. In the present work we have identified the sites of initial invasion and replication after contaminative conjunctival challenges with T. cruzi metacyclic trypomastigotes using a combination of immunohistochemical and real-time PCR confirmatory techniques in 56 mice between 3 and 14 days after challenge. Our results demonstrate that the predominant route of infection involves drainage of parasites through the nasolacrimal duct into the nasal cavity. Initial parasite invasion occurs within the ductal and respiratory epithelia. After successive waves of intracellular replication and cell-to-cell spread, parasites drain via local lymphatic channels to lymph nodes and then disseminate through the blood to distant tissues. This model of conjunctival challenge was used to identify immune responses associated with protection against mucosal infection. Preceding mucosal infection induces mucosal immunity, resulting in at least 50-fold reductions in recoverable tissue parasite DNA in immune mice compared to controls 10 days after conjunctival challenge (P < 0.05). Antigen-specific gamma interferon production by T cells was increased at least 100-fold in cells harvested from immune mice (P < 0.05). Mucosal secretions containing T. cruzi-specific secretory immunoglobulin A harvested from immune mice were shown to protect against mucosal parasite infection (P < 0.05), demonstrating that mucosal antibodies can play a role in T. cruzi immunity. This model provides an important tool for detailed studies of mucosal immunity necessary for the development of mucosal vaccines.

Animals↗
PubMed2001

Mucosal immunization against hepatitis B virus by intranasal co-administration of recombinant hepatitis B surface antigen and recombinant cholera toxin B subunit as an adjuvant.

Recombinant cholera toxin B subunit (rCTB) produced by Bacillus brevis carrying pNU212-CTB has been previously found to be a potent mucosal adjuvant to aluminium-non-adsorbed tetanus toxoid (nTT) and diphtheria toxoid (nDT) co-administered intranasally, and the possibility of needle-free inoculation of these vaccines with rCTB has been suggested. In this paper we examined the potentiality of rCTB as a mucosal adjuvant to aluminium-non-adsorbed yeast-derived recombinant hepatitis B surface antigen (rHBs) being a particulate antigen when administered intranasally with rCTB. In-house ELISA showed that a mixture of rHBs (1 or 5 microg) and rCTB (10 microg) elevated not only systemic responses but also mucosal immune responses at the nasal cavity, the lung, the saliva, the small intestine and the vagina against rHBs, and these could be further increased with higher doses of antigen. With antibody isotypes of IgG, there were equally high levels of serum HBs-specific IgG1, IgG2a and IgG2b antibodies and induction of mixed Th1- and Th2-type responses was considered to occur in combination of rHBs and rCTB. Serum anti-HBs titres in almost all mice obtained from sandwich EIA using a commercial kit were higher than 1000 milli-international units ml(-1) (mIU ml(-1)). These results show that rCTB is also very effective as a mucosal adjuvant for a particulate antigen like rHBs, as well as soluble antigens like nTT and nDT reported previously, suggesting the possibility of intranasal immunization with rHBs plus rCTB in humans.

Adjuvants, Immunologic↗
PubMed2004

Viral macrophage-inflammatory protein-II: a viral chemokine that differentially affects adaptive mucosal immunity compared with its mammalian counterparts.

Chemokines play a profound role in leukocyte trafficking and the development of adaptive immune responses. Perhaps due to their importance in host defense, viruses have adopted many of the hallmarks displayed by chemokines. In particular, viral MIP-II (vMIP-II) is a human chemokine homologue that is encoded by human herpes virus 8. vMIP-II is angiogenic, selectively chemotactic for Th2 lymphocytes, and a homologue of human I-309 and mouse TCA-3, which also differentially attracts Th2 cells. To better understand the effect of viral chemokines on mucosal immunity, we compared the affects of vMIP-II, I-309, and TCA-3 on cellular and humoral immune responses after nasal immunization with OVA. These CCR8 ligands significantly enhanced Ag-specific serum and mucosal Abs through increasing Th2 cytokine secretion by CD4+ T cells. These alterations in adaptive humoral and cellular responses were preceded (12 h after immunization) by an increase in CD4+ T and B cells in nasal tracts with decreases of these leukocyte populations in the lung. Interestingly, vMIP-II increased neutrophil infiltration in the lung and Ag-specific IL-10-secreting CD4+ T cells after immunization. Although I-309 increased the number of CD28-, CD40L-, and CD30-positive, Ag-stimulated naive CD4+ T cells, vMIP-II and TCA-3 decreased the number of CD28-, CD40L-, and CD30-positive, resting naive CD4+ T cells. Taken together, these studies suggest that CCR8 ligands direct host Th2 responses, and vMIP-II up-regulates IL-10 responses and limits costimulatory molecule expression to mitigate host immunity.

Adjuvants, Immunologic↗
PubMed1998

The role of sympathetic innervation of the gut in regulating mucosal immune responses.

The effects of chemical sympathectomy on the mucosal compartments of the immune system were examined in adult rats. Ablation of the sympathetic nervous system using 6-hydroxydopamine in recipient animals reduced the migration into Peyer's patches and mesenteric lymph nodes (MLN) of adoptively transferred cells from MLN of normal donors. The mucosal immune response to ovalbumin (OVA), assessed by enumeration of anti-OVA antibody containing cells (AOCC) in the lamina propria after intestinal immunisation, was reduced in animals sympathectomized prior to immunization. In order to identify whether this reduction in AOCC response in intestinally immunized sympathectomized animals was due to a defect in migration of AOCC precursors to the intestinal lamina propria, the effect of chemical sympathectomy on the appearance of AOCC in the gut of immunized animals after adoptive transfer of AOCC precursors was investigated. The IgA-specific AOCC response was significantly reduced in sympathectomized recipients compared to the control group. Taken together these results demonstrate that the peripheral sympathetic nervous system influences the migration and accumulation in vivo of both naive and memory/effector lymphocytes in mucosal lymphoid tissues.

Animals↗
PubMed1979

Protein deprivation causes reversible impariment of mucosal immune response to cholera toxoid/toxin in rat gut.

Scretory antibodies may be the major defence against mucosal infections, especially those due to viruses and non-invasive pathogens such as Vibrio cholerae and toxinogenic Escherichia coli. The high incidence of mucosal infections in malnourished protein-deficient children may result from defective antibody production, but evidence for this is conflicting. We report here that protein deficiency markedly impairs the mucosal immune reponse to cholera toxiod/toxin (CT), a protein antigen, in rats and that this impairment is rapidly reversed by refeeding.

Animals↗
PubMed1998

[Mucosal immune system of the intestine].

Gut-associated lymphoid tissue is the major inductive site of mucosal immune system, functionally independent of the systemic immune system. Particulate antigens are mainly uptaken from M cell of Peyer's patches, inducing IgA production in the intestinal mucosa. Lymphocytes are continuously recirculating through the intestinal mucosa to facilitate intestinal immune response. Dysregulation of lymphocyte migration and cytokine imbalance in the intestinal mucosa may be largely involved in the pathogenesis of inflammatory bowel diseases including intestinal allergy and Crohn's disease. There is also a possibility that dietary components especially long chain fatty acid could influence immune cell function of the intestinal mucosa. Because dietary components are closely associated with immunological function of intestinal mucosa, the importance of dietary manipulation for the management of inflammatory bowel diseases should be concerned.

Animals↗
PubMed2005

The effects of long-term total parenteral nutrition on gut mucosal immunity in children with short bowel syndrome: a systematic review.

BACKGROUND: Short bowel syndrome (SBS) is defined as the malabsorptive state that often follows massive resection of the small intestine. Most cases originate in the newborn period and result from congenital anomalies. It is associated with a high morbidity, is potentially lethal and often requires months, sometimes years, in the hospital and home on total parenteral nutrition (TPN). Long-term survival without parenteral nutrition depends upon establishing enteral nutrition and the process of intestinal adaptation through which the remaining small bowel gradually increases its absorptive capacity. The purpose of this article is to perform a descriptive systematic review of the published articles on the effects of TPN on the intestinal immune system investigating whether long-term TPN induces bacterial translocation, decreases secretory immunoglobulin A (S-IgA), impairs intestinal immunity, and changes mucosal architecture in children with SBS. METHODS: The databases of OVID, such as MEDLINE and CINAHL, Cochran Library, and Evidence-Based Medicine were searched for articles published from 1990 to 2001. Search terms were total parenteral nutrition, children, bacterial translocation, small bowel syndrome, short gut syndrome, intestinal immunity, gut permeability, sepsis, hyperglycemia, immunonutrition, glutamine, enteral tube feeding, and systematic reviews. The goal was to include all clinical studies conducted in children directly addressing the effects of TPN on gut immunity. RESULTS: A total of 13 studies were identified. These 13 studies included a total of 414 infants and children between the ages approximately 4 months to 17 years old, and 16 healthy adults as controls; and they varied in design and were conducted in several disciplines. The results were integrated into common themes. Five themes were identified: 1) sepsis, 2) impaired immune functions: In vitro studies, 3) mortality, 4) villous atrophy, 5) duration of dependency on TPN after bowel resection. CONCLUSION: Based on this exhaustive literature review, there is no direct evidence suggesting that TPN promotes bacterial overgrowth, impairs neutrophil functions, inhibits blood's bactericidal effect, causes villous atrophy, or causes to death in human model.The hypothesis relating negative effects of TPN on gut immunity remains attractive, but unproven. Enteral nutrition is cheaper, but no safer than TPN. Based on the current evidence, TPN seems to be safe and a life saving solution.

Journal Article↗
PubMed2002

Calcium phosphate nanoparticles induce mucosal immunity and protection against herpes simplex virus type 2.

Previously we reported that calcium phosphate nanoparticles (CAP) represented a superior alternative to alum adjuvants in mice immunized with viral protein. Additionally, we showed that CAP was safe and elicited no detectable immunoglobulin E (IgE) response. In this study, we demonstrated that following mucosal delivery of herpes simplex virus type 2 (HSV-2) antigen with CAP, CAP adjuvant enhanced protective systemic and mucosal immunity versus live virus. Mice were immunized intravaginally and intranasally with HSV-2 protein plus CAP adjuvant (HSV-2+CAP), CAP alone, phosphate-buffered saline, or HSV-2 alone. HSV-2+CAP induced HSV-specific mucosal IgA and IgG and concurrently enhanced systemic IgG responses. Our results demonstrate the potency of CAP as a mucosal adjuvant. Furthermore, we show that systemic immunity could be induced via the mucosal route following inoculation with CAP-based vaccine. Moreover, neutralizing antibodies were found in the sera of mice immunized intranasally or intravaginally with HSV-2+CAP. Also, the results of our in vivo experiments indicated that mice vaccinated with HSV-2+CAP were protected against live HSV-2 infection. In conclusion, these preclinical data support the hypothesis that CAP may be an effective mucosal adjuvant that protects against viral infection.

Adjuvants, Immunologic↗
PubMedDate not supplied

Changes in mucosal immune cells of bladder tumor patient after BCG intravesical immunotherapy.

The Bacillus Calmette-Guerin (BCG) is considered to be at least as effective, and perhaps superior to chemotherapy in the prophylaxis of recurrent superficial tumors. However, the mechanism of the antitumor effect of BCG is still not exactly known. We have conducted investigations to examine changes in bladder mucosal immune cells in patients with superficial bladder carcinoma treated with a first cycle of BCG. The study group included 15 BCG and 5 doxorubicin instillation patients, most in the intermediate or high risk group for recurrent tumor. Grossly normal bladder mucosal cold cup biopsies were performed at initial TUR and one week after six consecutive weekly instillations of BCG or doxorubicin. All specimens underwent immunohistochemical staining, both pre-treatment and post-treatment, including CD20, CD45RO, CD8, CD4 and CD57. Immunoreactive cell counts were evaluated from three different microscopic fields (x400) under the grid. The mean duration of follow-up was 52.8 months. The post-treatment bladder mucosal B-cells (CD20) and T-cells (CD45RO, CD4, CD8) were significantly increased compared to pre-treatment in patients treated with BCG instillation, but NK-cells (CD57) were not changed. However, there was no change in B-cells or T-cells in patient treated with doxorubicin. The CD20 cells in pre-treatment specimens did not correlate with any other cells. However, it was a statistically significant correlation with CD45RO in post-treatment specimens. The CD4 correlated with CD45RO and CD8 in pre-treatment, but it was correlated with CD45RO and CD57 in post-treatment specimens. There was no tumor recurrence in cases with significantly increased B-cells after BCG instillation. The results of these studies suggest that intravesical BCG immunotherapy for superficial bladder tumor induces a significant increase in T-cells as well as B-cells and that B-cells have a preventive effect on tumor recurrence. Further studies with a larger number of patients are needed to confirm the value of the B-cell increment after BCG instillation as a clinically independent prognostic factor.

Administration, Intravesical↗
PubMed2006

Induction of systemic and mucosal immune response and decrease in Streptococcus pneumoniae colonization by nasal inoculation of mice with recombinant lactic acid bacteria expressing pneumococcal surface antigen A.

Mucosal epithelia constitute the first barriers to be overcome by pathogens during infection. The induction of protective IgA in this location is important for the prevention of infection and can be achieved through different mucosal immunization strategies. Lactic acid bacteria have been tested in the last few years as live vectors for the delivery of antigens at mucosal sites, with promising results. In this work, Streptococcus pneumoniae PsaA antigen was expressed in different species of lactic acid bacteria, such as Lactococcus lactis, Lactobacillus casei, Lactobacillus plantarum, and Lactobacillus helveticus. After nasal inoculation of C57Bl/6 mice, their ability to induce both systemic (IgG in serum) and mucosal (IgA in saliva, nasal and bronchial washes) anti-PsaA antibodies was determined. Immunization with L. lactis MG1363 induced very low levels of IgA and IgG, possibly by the low amount of PsaA expressed in this strain and its short persistence in the nasal mucosa. All three lactobacilli persisted in the nasal mucosa for 3 days and produced a similar amount of PsaA protein (150-250 ng per 10(9) CFU). However, L. plantarum NCDO1193 and L. helveticus ATCC15009 elicited the highest antibody response (IgA and IgG). Vaccination with recombinant lactobacilli but not with recombinant L. lactis led to a decrease in S. pneumoniae recovery from nasal mucosa upon a colonization challenge. Our results confirm that certain Lactobacillus strains have intrinsic properties that make them suitable candidates for mucosal vaccination experiments.

Adhesins, Bacterial↗
PubMed1988

Passive acquired mucosal immunity to group A streptococci by secretory immunoglobulin A.

We present a model in which animals are passively immunized at a mucosal site, allowing one to evaluate immunological protection at the mucosal level only. Affinity-purified, anti-M protein sIgA administered intranasally protected mice against systemic infection after intranasal challenge with group A streptococci. In contrast, anti-M protein serum Ig administered intranasally was not protective at this site, although it neutralized the antiphagocytic property of M protein and promoted phagocytosis. Protection by sIgA occurred despite the lower immunoreactivity of sIgA to purified M protein compared with serum Ig. The data suggest that sIgA can protect at the mucosa and may preclude the need for opsonic IgG in preventing streptococcal infection.

Animals↗
PubMedDate not supplied

The liver: an integral part of the enteric mucosal immune system.

The inclusion of the liver and biliary tract as an integral part of the enteric mucosal immune defense has come about in the past 5 years as a result of experimental studies in laboratory animals. The importance of secretory IgA and IgA immune complexes in the generation of an immune response and their participation in the immune exclusion of potentially pathogenic molecules and organisms are areas of active investigation. The transport of IgA and IgA immune complexes by the liver from serum to bile may provide another means of immune-mediated host defense against enteric pathogens.

Animals↗
PubMed1995

The bone marrow as a site of antibody production after a mucosal immunization.

To study the importance of the bone marrow in the production of specific antibodies after a mucosal immunization with cholera toxin, the IgG, IgA and IgM specific antibody forming cells were evaluated by ELISPOT in Peyer patches, mesenteric lymph node (MLN), spleen, blood and bone marrow (BM). When 50-day-old rats were immunized intra-Peyer patches, a similar number of IgG and IgA antitoxin antibody forming cells (AFC) were found in the BM, whereas in the other lymphoid tissues a higher number of IgG antitoxin AFC were found. In all sites the peak of AFC was obtained 2 weeks after immunization. The administration of CT to 35-week-old rats resulted in a stronger immune response in all lymphoid tissues studied, but the proportion of antitoxin AFC contributed by the BM had not changed. One oral dose of cholera toxin resulted in a low number of antitoxin AFC, whereas when two or three doses of CT were administered orally an increase in the number of AFC was observed in the BM, reaching similar or higher numbers of IgG and IgA AFC than in the spleen. In all cases the highest number of AFC/10(6) cells was observed in the MLN, whereas antitoxin AFC were not found in the blood. The total number of AFC recovered from each organ was calculated taken into account that the BM of one femur represents 9% of the total BM. So, it was found that the BM is an important site in the production of IgG antitoxin antibodies, being the main site in the IgA antitoxin antibody production.

Administration, Oral↗
PubMed1998

Cytokine- and T helper-dependent lung mucosal immunity in mice with invasive pulmonary aspergillosis.

The role of cytokine- and T helper (Th)-dependent lung mucosal antifungal immunity in murine invasive pulmonary aspergillosis (IPA) was investigated. Intact or leukopenic DBA/2 mice were resistant or highly susceptible, respectively, to infection caused by multiple intranasal injections of viable Aspergillus fumigatus conidia. Resistance was associated with unimpaired innate antifungal activity of pulmonary phagocytic cells, concomitant with high-level production of tumor necrosis factor (TNF)-alpha and interleukin (IL)-12 and the presence of interstitial lymphocytes producing interferon-gamma and IL-2. Conversely, production of TNF-alpha and IL-12 was down-regulated in highly susceptible mice, which also had defective innate antifungal immunity and high-level production of IL-4 and IL-10 by lung lymphocytes. Resistance was increased in susceptible mice upon local IL-4 or IL-10 neutralization or IL-12 administration. These results indicate that, similar to observations in mice with disseminated aspergillosis, innate and Th1-dependent immunity play an essential role in host defense against IPA.

Animals↗