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Sample records for boost immune responses

  1. Prime-boost strategies in mucosal immunization affect local IgA production and the type of Th response

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    Fabio eFiorino

    2013-05-01

    Full Text Available Combinations of different delivery routes for priming and boosting represent vaccination strategies that can modulate magnitude, quality, and localization of the immune response. A murine model was used to study T cell clonal expansion following nasal or subcutaneous priming, and secondary immune responses after boosting by either homologous or heterologous routes. T cell primary activation was studied by using the adoptive transfer model of ovalbumin-specific transgenic CD4+ T cells. Both nasal and subcutaneous immunization efficiently elicited, in the respective draining lymph nodes, primary clonal expansion of antigen-specific CD4+ T cells that disseminated towards distal lymph nodes (mesenteric and iliac and the spleen. After boosting, a very high serum IgG response was induced in all groups independent of the combination of immunization routes used, while significant levels of local IgA were detected only in mice boosted by the nasal route. Mucosal priming drove a stronger Th1 polarization than the systemic route, as shown by serum IgG subclass analysis. IFN-gamma production was observed in splenocytes of all groups, while prime-boost vaccine combinations that included the mucosal route, yielded higher levels of IL-17. Memory lymphocytes were identified in both spleen and draining lymph nodes in all immunized mice, with the highest number of IL-2 producing cells detected in mice primed and boosted by the nasal route. This work shows the critical role of immunization routes in modulating quality and localization of immune responses, in prime-boost vaccine strategies.

  2. Per-oral immunization with antigen-conjugated nanoparticles followed by sub-cutaneous boosting immunization induces long-lasting mucosal and systemic antibody responses in mice.

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    Savannah E Howe

    Full Text Available Food or water-borne enteric pathogens invade their hosts via intestinal mucosal surfaces, thus developing effective oral vaccines would greatly reduce the burden of infectious diseases. The nature of the antigen, as well as the mode of its internalization in the intestinal mucosa affects the ensuing immune response. We show that model protein antigen ovalbumin (Ova given per-orally (p.o. induces oral tolerance (OT, characterized by systemic IgG1-dominated antibody response, which cannot be boosted by sub-cutaneous (s.c. immunization with Ova in complete Freund's adjuvant (CFA. Intestinal IgA generated in response to Ova feeding diminished over time and was abrogated by s.c. immunization with Ova+CFA. Humoral response to Ova was altered by administering Ova conjugated to 20 nm nanoparticles (NP-Ova. P.o. administration of NP-Ova induced systemic IgG1/IgG2c, and primed the intestinal mucosa for secretion of IgA. These responses were boosted by secondary s.c. immunization with Ova+CFA or p.o. immunization with NP-Ova. However, only in s.c.-boosted mice serum and mucosal antibody titers remained elevated for 6 months after priming. In contrast, s.c. priming with NP-Ova induced IgG1-dominated serum antibodies, but did not prime the intestinal mucosa for secretion of IgA, even after secondary p.o. immunization with NP-Ova. These results indicate that Ova conjugated to NPs reaches the internal milieu in an immunogenic form and that mucosal immunization with NP-Ova is necessary for induction of a polarized Th1/Th2 immune response, as well as intestinal IgA response. In addition, mucosal priming with NP-Ova, followed by s.c. boosting induces superior systemic and mucosal memory responses. These findings are important for the development of efficacious mucosal vaccines.

  3. Boosting BCG-primed responses with a subunit Apa vaccine during the waning phase improves immunity and imparts protection against Mycobacterium tuberculosis.

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    Nandakumar, Subhadra; Kannanganat, Sunil; Dobos, Karen M; Lucas, Megan; Spencer, John S; Amara, Rama Rao; Plikaytis, Bonnie B; Posey, James E; Sable, Suraj B

    2016-01-01

    Heterologous prime-boosting has emerged as a powerful vaccination approach against tuberculosis. However, optimal timing to boost BCG-immunity using subunit vaccines remains unclear in clinical trials. Here, we followed the adhesin Apa-specific T-cell responses in BCG-primed mice and investigated its BCG-booster potential. The Apa-specific T-cell response peaked 32-52 weeks after parenteral or mucosal BCG-priming but waned significantly by 78 weeks. A subunit-Apa-boost during the contraction-phase of BCG-response had a greater effect on the magnitude and functional quality of specific cellular and humoral responses compared to a boost at the peak of BCG-response. The cellular response increased following mucosal BCG-prime-Apa-subunit-boost strategy compared to Apa-subunit-prime-BCG-boost approach. However, parenteral BCG-prime-Apa-subunit-boost by a homologous route was the most effective strategy in-terms of enhancing specific T-cell responses during waning in the lung and spleen. Two Apa-boosters markedly improved waning BCG-immunity and significantly reduced Mycobacterium tuberculosis burdens post-challenge. Our results highlight the challenges of optimization of prime-boost regimens in mice where BCG drives persistent immune-activation and suggest that boosting with a heterologous vaccine may be ideal once the specific persisting effector responses are contracted. Our results have important implications for design of prime-boost regimens against tuberculosis in humans. PMID:27173443

  4. Co-administration of non-carrier nanoparticles boosts antigen immune response without requiring protein conjugation.

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    Wibowo, Nani; Chuan, Yap P; Seth, Arjun; Cordoba, Yoann; Lua, Linda H L; Middelberg, Anton P J

    2014-06-17

    Nanotechnology promises a revolution in medicine including through new vaccine approaches. The use of nanoparticles in vaccination has, to date, focused on attaching antigen directly to or within nanoparticle structures to enhance antigen uptake by immune cells. Here we question whether antigen incorporation with the nanoparticle is actually necessary to boost vaccine effectiveness. We show that the immunogenicity of a sub-unit protein antigen was significantly boosted by formulation with silica nanoparticles even without specific conjugation of antigen to the nanoparticle. We further show that this effect was observed only for virus-sized nanoparticles (50 nm) but not for larger (1,000 nm) particles, demonstrating a pronounced effect of nanoparticle size. This non-attachment approach has potential to radically simplify the development and application of nanoparticle-based formulations, leading to safer and simpler nanoparticle applications in vaccine development. PMID:24793947

  5. Blocking junctional adhesion molecule C enhances dendritic cell migration and boosts the immune responses against Leishmania major.

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    Romain Ballet

    2014-12-01

    Full Text Available The recruitment of dendritic cells to sites of infections and their migration to lymph nodes is fundamental for antigen processing and presentation to T cells. In the present study, we showed that antibody blockade of junctional adhesion molecule C (JAM-C on endothelial cells removed JAM-C away from junctions and increased vascular permeability after L. major infection. This has multiple consequences on the output of the immune response. In resistant C57BL/6 and susceptible BALB/c mice, we found higher numbers of innate immune cells migrating from blood to the site of infection. The subsequent migration of dendritic cells (DCs from the skin to the draining lymph node was also improved, thereby boosting the induction of the adaptive immune response. In C57BL/6 mice, JAM-C blockade after L. major injection led to an enhanced IFN-γ dominated T helper 1 (Th1 response with reduced skin lesions and parasite burden. Conversely, anti JAM-C treatment increased the IL-4-driven T helper 2 (Th2 response in BALB/c mice with disease exacerbation. Overall, our results show that JAM-C blockade can finely-tune the innate cell migration and accelerate the consequent immune response to L. major without changing the type of the T helper cell response.

  6. The Mycobacterium bovis BCG prime-Rv0577 DNA boost vaccination induces a durable Th1 immune response in mice.

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    Gu, Dongqing; Chen, Wei; Mi, Youjun; Gong, Xueli; Luo, Tao; Bao, Lang

    2016-04-01

    Tuberculosis remains a major global health problem and effective vaccines are urgently needed. In this study, we used the combined DNA- and protein-based vaccines of immunodominant antigen Rv0577 to boost BCG and evaluated their immunogenicity in BALB/c mice. Our data suggest that the booster vaccine may substantially enhance the immunogenicity of BCG and strengthen both CD4+ T cell-mediated Th1 and CD8+ T cell-mediated cytolytic responses. Compared with the protein-based vaccine, the DNA-based vaccine can induce more durable Th1 immune response, characterized by high levels of antibody response, proliferation response, percentages of CD4+/CD8+ and cytokine secretion in antigen-stimulated splenocyte cultures. In conclusion, we for the first time, developed a protein- and plasmid DNA-based booster vaccine based on Rv0577. Our findings suggest that antigen Rv0577-based DNA vaccine is immunogenic and can efficiently boost BCG, which could be helpful in the design of an efficient vaccination strategy against TB. PMID:26922320

  7. Philippine campaign boosts child immunizations.

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    Manuel-santana, R

    1993-03-01

    In 1989, USAID awarded the Philippines a 5-year, US $50 million Child Survival Program targeting improvement in immunization coverage of children, prenatal care coverage for pregnant women, and contraceptive prevalence. Upon successful completion of performance benchmarks at the end of each year, USAID released monies to fund child survival activities for the following year. This program accomplished a major program goal, which was decentralization of health planning. The Philippine Department of Health soon incorporated provincial health planning. The Philippine Department of Health soon incorporated provincial health planning in its determination of allocation of resources. Social marketing activities contributed greatly to success in achieving the goal of boosting the immunization coverage rate for the 6 antigens listed under the Expanded Program for Immunization (51%-85% of infants, 1986-1991). In fact, rural health officers in Tarlac Province in Central Luzon went from household to household to talk to mothers about the benefits of immunizing a 1-year-old child, thereby contributing greatly to their achieving a 95% full immunization coverage rate by December 1991. Social marketing techniques included modern marketing strategies and multimedia channels. They first proved successful in metro Manila which, at the beginning of the campaign, had the lowest immunization rate of all 14 regions. Every Wednesday was designated immunization day and was when rural health centers vaccinated the children. Social marketing also successfully publicized oral rehydration therapy (ORT), breast feeding, and tuberculosis control. Another contributing factor to program success in child survival activities was private sector involvement. For example, the Philippine Pediatric Society helped to promote ORT as the preferred treatment for acute diarrhea. Further, the commercial sector distributed packets of oral rehydration salts and even advertised its own ORT product. At the end of 2

  8. Induction of Boosted Immune Response in Mice by Leptospiral Surface Proteins Expressed in Fusion with DnaK

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    Marina V. Atzingen

    2014-01-01

    Full Text Available Leptospirosis is an important global disease of human and veterinary concern. Caused by pathogenic Leptospira, the illness was recently classified as an emerging infectious disease. Currently available veterinarian vaccines do not induce long-term protection against infection and do not provide cross-protective immunity. Several studies have suggested the use of DnaK as an antigen in vaccine formulation, due to an exceptional degree of immunogenicity. We focused on four surface proteins: rLIC10368 (Lsa21, rLIC10494, rLIC12690 (Lp95, and rLIC12730, previously shown to be involved in host-pathogen interactions. Our goal was to evaluate the immunogenicity of the proteins genetically fused with DnaK in animal model. The chosen genes were amplified by PCR methodology and cloned into pAE, an E. coli vector. The recombinant proteins were expressed alone or in fusion with DnaK at the N-terminus. Our results demonstrate that leptospiral proteins fused with DnaK have elicited an enhanced immune response in mice when compared to the effect promoted by the individual proteins. The boosted immune effect was demonstrated by the production of total IgG, lymphocyte proliferation, and significant amounts of IL-10 in supernatant of splenocyte cell cultures. We believe that this approach could be employed in vaccines to enhance presentation of antigens of Leptospira to professional immune cells.

  9. Skin-Specific Unsaturated Fatty Acids Boost the Staphylococcus aureus Innate Immune Response.

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    Nguyen, Minh Thu; Hanzelmann, Dennis; Härtner, Thomas; Peschel, Andreas; Götz, Friedrich

    2016-01-01

    Antimicrobial fatty acids (AFAs) protect the human epidermis against invasion by pathogenic bacteria. In this study, we questioned whether human skin fatty acids (FAs) can be incorporated into the lipid moiety of lipoproteins and whether such incorporation would have an impact on innate immune stimulation in the model organism Staphylococcus aureus USA300 JE2. This organism synthesized only saturated FAs. However, when feeding USA300 with unsaturated FAs present on human skin (C16:1, C18:1, or C18:2), those were taken up, elongated stepwise by two carbon units, and finally found in the bacterial (phospho)lipid fraction. They were also observed in the lipid moiety of lipoproteins. When USA300 JE2 was fed with the unsaturated FAs, the cells and cell lysates showed an increased innate immune activation with various immune cells and peripheral blood mononuclear cells (PBMCs). Immune activation was highest with linoleic acid (C18:2). There are several pieces of evidence that the enhanced immune stimulating effect was due to the incorporation of unsaturated FAs in lipoproteins. First, the enhanced stimulation was dependent on Toll-like receptor 2 (TLR2). Second, an lgt mutant, unable to carry out lipidation of prolipoproteins, was unable to carry out immune stimulation when fed with unsaturated FAs. Third, the supplied FAs did not significantly affect growth, protein release, or expression of the model lipoprotein Lpl1. Although S. aureus is unable to synthesize unsaturated FAs, it incorporates long-chain unsaturated FAs into its lipoproteins, with the effect that the cells are better recognized by the innate immune system. This is an additional mechanism how our skin controls bacterial colonization and infection. PMID:26502910

  10. Skin-Specific Unsaturated Fatty Acids Boost the Staphylococcus aureus Innate Immune Response

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    Nguyen, Minh Thu; Hanzelmann, Dennis; Härtner, Thomas; Peschel, Andreas; Götz, Friedrich

    2015-01-01

    Antimicrobial fatty acids (AFAs) protect the human epidermis against invasion by pathogenic bacteria. In this study, we questioned whether human skin fatty acids (FAs) can be incorporated into the lipid moiety of lipoproteins and whether such incorporation would have an impact on innate immune stimulation in the model organism Staphylococcus aureus USA300 JE2. This organism synthesized only saturated FAs. However, when feeding USA300 with unsaturated FAs present on human skin (C16:1, C18:1, o...

  11. An adenovirus prime/plasmid boost strategy for induction of equipotent immune responses to two dengue virus serotypes

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    Swaminathan Sathyamangalam

    2007-02-01

    Full Text Available Abstract Background Dengue is a public health problem of global significance for which there is neither an effective antiviral therapy nor a preventive vaccine. It is a mosquito-borne viral disease, caused by dengue (DEN viruses, which are members of the Flaviviridae family. There are four closely related serotypes, DEN-1, DEN-2, DEN-3 and DEN-4, each of which is capable of causing disease. As immunity to any one serotype can potentially sensitize an individual to severe disease during exposure to a heterologous serotype, the general consensus is that an effective vaccine should be tetravalent, that is, it must be capable of affording protection against all four serotypes. The current strategy of creating tetravalent vaccine formulations by mixing together four monovalent live attenuated vaccine viruses has revealed the phenomenon of viral interference leading to the manifestation of immune responses biased towards a single serotype. Results This work stems from the emergence of (i the DEN virus envelope (E domain III (EDIII as the most important region of the molecule from a vaccine perspective and (ii the adenovirus (Ad as a promising vaccine vector platform. We describe the construction of a recombinant, replication-defective Ad (rAd vector encoding a chimeric antigen made of in-frame linked EDIIIs of DEN virus serotypes 2 and 4. Using this rAd vector, in conjunction with a plasmid vector encoding the same chimeric bivalent antigen, in a prime-boost strategy, we show that it is possible to elicit equipotent neutralizing and T cell responses specific to both DEN serotypes 2 and 4. Conclusion Our data support the hypothesis that a DEN vaccine targeting more than one serotype may be based on a single DNA-based vector to circumvent viral interference. This work lays the foundation for developing a single Ad vector encoding EDIIIs of all four DEN serotypes to evoke a balanced immune response against each one of them. Thus, this work has

  12. DNA prime-adenovirus boost immunization induces a vigorous and multifunctional T-cell response against hepadnaviral proteins in the mouse and woodchuck model.

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    Kosinska, Anna D; Johrden, Lena; Zhang, Ejuan; Fiedler, Melanie; Mayer, Anja; Wildner, Oliver; Lu, Mengji; Roggendorf, Michael

    2012-09-01

    Induction of hepatitis B virus (HBV)-specific cytotoxic T cells by therapeutic immunization may be a strategy to treat chronic hepatitis B. In the HBV animal model, woodchucks, the application of DNA vaccine expressing woodchuck hepatitis virus (WHV) core antigen (WHcAg) in combination with antivirals led to the prolonged control of viral replication. However, it became clear that the use of more potent vaccines is required to overcome WHV persistence. Therefore, we asked whether stronger and more functional T-cell responses could be achieved using the modified vaccines and an optimized prime-boost vaccination regimen. We developed a new DNA plasmid (pCGWHc) and recombinant adenoviruses (AdVs) showing high expression levels of WHcAg. Mice vaccinated with the improved plasmid pCGWHc elicited a stronger WHcAg-specific CD8(+) T-cell response than with the previously used vaccines. Using multicolor flow cytometry and an in vivo cytotoxicity assay, we showed that immunization in a DNA prime-AdV boost regimen resulted in an even more vigorous and functional T-cell response than immunization with the new plasmid alone. Immunization of naïve woodchucks with pCGWHc plasmid or AdVs induced a significant WHcAg-specific degranulation response prior to the challenge, this response had not been previously detected. Consistently, this response led to a rapid control of infection after the challenge. Our results demonstrate that high antigen expression levels and the DNA prime-AdV boost immunization improved the T-cell response in mice and induced significant T-cell responses in woodchucks. Therefore, this new vaccination strategy may be a candidate for a therapeutic vaccine against chronic HBV infection. PMID:22718818

  13. Immunological Cross-Reactivity between Malaria Vaccine Target Antigen P48/45 in Plasmodium vivax and P. falciparum and Cross–Boosting of Immune Responses

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    Cao, Yi; Bansal, Geetha P.; Merino, Kristen; Kumar, Nirbhay

    2016-01-01

    In general, malaria immunity has been suggested to be species specific with very little, if any, known cross-reactivity between Plasmodium vivax and P. falciparum, both of which are responsible for >90% of human malaria, and co-endemic in many countries. It is therefore believed that species-specific immunity may be needed to target different species of Plasmodium. Pfs48/45 and Pvs48/45 are well established targets in the sexual stages of the malaria parasites, and are being pursued for the development of transmission blocking vaccines. Comparison of their sequences reveals 61% and 55% identity at the DNA and protein level, respectively raising the possibility that these two target antigens might share cross-reacting epitopes. Having succeeded in expressing recombinant Pfs48/45 and Pvs48/45 proteins, we hypothesized that these proteins will not only exhibit immunological cross–reactivity but also cross-boost immune responses. Mice were immunized with purified recombinant proteins using CFA, Montanide ISA-51 and alum as adjuvants, and the sera were analyzed by ELISA, Western blotting and indirect fixed and live IFA to address the hypothesis. Our studies revealed that Pvs48/45-immune sera showed strong cross-reactivity to full length Pfs48/45 protein, and the majority of this cross reactivity was in the amino-terminal and carboxyl-terminal sub-fragments of Pfs48/45. In cross-boosting experiments Pfs48/45 and Pvs48/45 antigens were able to cross-boost each other in mouse immunization studies. Additionally we also noticed an effect of adjuvants in the overall magnitude of observed cross-reactivity. These studies may have significant implications for immunity targeting transmission of both the species of malaria parasites. PMID:27438603

  14. Mucosal immunization with PLGA-microencapsulated DNA primes a SIV-specific CTL response revealed by boosting with cognate recombinant modified vaccinia virus Ankara

    International Nuclear Information System (INIS)

    Systemically administered DNA encoding a recombinant human immunodeficiency virus (HIV) derived immunogen effectively primes a cytotoxic T lymphocyte (CTL) response in macaques. In this further pilot study we have evaluated mucosal delivery of DNA as an alternative priming strategy. Plasmid DNA, pTH.HW, encoding a multi-CTL epitope gene, was incorporated into poly(D,L-lactic-co-glycolic acid) microparticles of less than 10 μm in diameter. Five intrarectal immunizations failed to stimulate a circulating vaccine-specific CTL response in 2 Mamu-A*01+ rhesus macaques. However, 1 week after intradermal immunization with a cognate modified vaccinia virus Ankara vaccine MVA.HW, CTL responses were detected in both animals that persisted until analysis postmortem, 12 weeks after the final boost. In contrast, a weaker and less durable response was seen in an animal vaccinated with the MVA construct alone. Analysis of lymphoid tissues revealed a disseminated CTL response in peripheral and regional lymph nodes but not the spleen of both mucosally primed animals

  15. Induction of Broad and Potent Anti-Human Immunodeficiency Virus Immune Responses in Rhesus Macaques by Priming with a DNA Vaccine and Boosting with Protein-Adsorbed Polylactide Coglycolide Microparticles

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    Otten, Gillis; Schaefer, Mary; Greer, Catherine; Calderon-Cacia, Maria; Coit, Doris; Kazzaz, Jina; Medina-Selby, Angelica; Selby, Mark; Singh, Manmohan; Ugozzoli, Mildred; zur Megede, Jan; Barnett, Susan W.; O'Hagan, Derek; Donnelly, John; Ulmer, Jeffrey

    2003-01-01

    Several vaccine technologies were evaluated for their abilities to induce anti-human immunodeficiency virus Gag immune responses in rhesus macaques. While no vaccine alone was able to induce broad and strong immune responses, these were achieved by priming with Gag DNA and boosting with Gag protein adsorbed to polylactide coglycolide microparticles. This regimen elicited strong antibodies, helper T cells, and cytotoxic T lymphocytes and thus holds promise as an effective vaccination scheme.

  16. One-prime multi-boost strategy immunization with recombinant DNA, adenovirus, and MVA vector vaccines expressing HPV16 L1 induces potent, sustained, and specific immune response in mice.

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    Li, Li-Li; Wang, He-Rong; Zhou, Zhi-Yi; Luo, Jing; Xiao, Xiang-Qian; Wang, Xiao-Li; Li, Jin-Tao; Zhou, Yu-Bai; Zeng, Yi

    2016-04-01

    Human papillomavirus (HPV) is associated with various human diseases, including cancer, and developing vaccines is a cost-efficient strategy to prevent HPV-related disease. The major capsid protein L1, which an increasing number of studies have confirmed is typically expressed early in infection, is a promising antigen for such a vaccine, although the E6 and E7 proteins have been characterized more extensively. Thus, the L1 gene from HPV16 was inserted into a recombinant vector, AdHu5, and MVA viral vectors, and administered by prime-boost immunization. Virus-like particles were used as control antigens. Our results indicate that prime-boost immunization with heterologous vaccines induced robust and sustained cellular and humoral response specific to HPV16 L1. In particular, sera obtained from mice immunized with DNA + DNA + Ad + MVA had excellent antitumor activity in vivo. However, the data also confirm that virus-like particles can only elicit low levels cellular immunity and not be long-lasting, and are therefore unsuitable for treatment of existing HPV infections. PMID:26821205

  17. Prime-boost vaccination with Bacillus Calmette Guerin and a recombinant adenovirus co-expressing CFP10, ESAT6, Ag85A and Ag85B of Mycobacterium tuberculosis induces robust antigen-specific immune responses in mice.

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    Li, Wu; Li, Min; Deng, Guangcun; Zhao, Liping; Liu, Xiaoming; Wang, Yujiong

    2015-08-01

    Tuberculosis (TB) remains to be a prevalent health issue worldwide. At present, Mycobacterium bovis Bacillus Calmette Guerin (BCG) is the singular anti-TB vaccine available for the prevention of disease in humans; however, this vaccine only provides limited protection against Mycobacterium tuberculosis (Mtb) infection. Therefore, the development of alternative vaccines and strategies for increasing the efficacy of vaccination against TB are urgently required. The present study aimed to evaluate the ability of a recombinant adenoviral vector (Ad5-CEAB) co-expressing 10-kDa culture filtrate protein, 6-kDa early-secreted antigenic target, antigen 85 (Ag85)A and Ag85B of Mtb to boost immune responses following primary vaccination with BCG in mice. The mice were first subcutaneously primed with BCG and boosted with two doses of Ad5-CEAB via an intranasal route. The immunological effects of Ad5-CEAB boosted mice primed with BCG were then evaluated using a series of immunological indexes. The results demonstrated that the prime-boost strategy induced a potent antigen-specific immune response, which was primarily characterized by an enhanced T cell response and increased production of cytokines, including interferon-γ, tumor necrosis factor-α and interleukin-2, in mice. In addition, this vaccination strategy was demonstrated to have an elevated humoral response with increased concentrations of antigen-specific bronchoalveolar lavage secretory immunoglobulin (Ig)A and serum IgG in mice compared with those primed with BCG alone. These data suggested that the regimen of subcutaneous BCG prime and mucosal Ad5-CEAB boost was a novel strategy for inducing a broad range of antigen-specific immune responses to Mtb antigens in vivo, which may provide a promising strategy for further development of adenoviral-based vaccine against Mtb infection. PMID:25962477

  18. Immune Boosting Explains Regime-Shifts in Prevaccine-Era Pertussis Dynamics

    DEFF Research Database (Denmark)

    Lavine, Jennie; King, Aaron A; Andreasen, Viggo; Bjornstad, Ottar N

    2013-01-01

    of large multiannual epidemics interspersed between periods of smaller-amplitude cycles remain an enigma. It has been suggested that recent increases in pertussis incidence and shifts in the age-distribution of cases may be due to diminished natural immune boosting. Here we show that a model that...... permanent or passively-waning immunity. Our results emphasize the importance of understanding the mechanisms responsible for maintaining immune memory for pertussis epidemiology....

  19. Co-administration of Interleukin-2 Enhances Cellular and Humoral Immune Responses to HIV Vaccine DNA Prime/MVA Boost Regime

    Institute of Scientific and Technical Information of China (English)

    JIANG Chun-lai; YU Xiang-hui; WU Yong-ge; LI Wei; KONG Wei

    2005-01-01

    Interleukine-2(IL-2) is a growth factor for antigen-stimulated T lymphocytes and is responsible for T-cell clonal expansion after antigen recognition. It has been demonstrated that DNA vaccine-elicited immune responses in mice could be augmented substantially by using either an IL-2 protein or a plasmid expressing IL-2. Twenty mice, divided into four experimental groups, were immunized with: (1) sham plasmid; (2) HIV-1 DNA vaccine alone; (3) HIV-1 DNA vaccine and IL-2 protein; or (4) HIV-1 DNA vaccine and IL-2 plasmid, separately. All the groups were immunized 3 times at a 2-week interval. Fourteen days after the last DNA vaccine injection, recombinant MVA was injected into all the mice except those in group 1. ELISA and ELISPOT were employed to investigate the effect of IL-2 on DNA vaccine immune responses. The obtained results strongly indicate that the efficacy of HIV vaccine can be enhanced by co-administration of a plasmid encoding IL-2.

  20. Ability of herpes simplex virus vectors to boost immune responses to DNA vectors and to protect against challenge by simian immunodeficiency virus

    International Nuclear Information System (INIS)

    The immunogenicity and protective capacity of replication-defective herpes simplex virus (HSV) vector-based vaccines were examined in rhesus macaques. Three macaques were inoculated with recombinant HSV vectors expressing Gag, Env, and a Tat-Rev-Nef fusion protein of simian immunodeficiency virus (SIV). Three other macaques were primed with recombinant DNA vectors expressing Gag, Env, and a Pol-Tat-Nef-Vif fusion protein prior to boosting with the HSV vectors. Robust anti-Gag and anti-Env cellular responses were detected in all six macaques. Following intravenous challenge with wild-type, cloned SIV239, peak and 12-week plasma viremia levels were significantly lower in vaccinated compared to control macaques. Plasma SIV RNA in vaccinated macaques was inversely correlated with anti-Rev ELISPOT responses on the day of challenge (P value < 0.05), anti-Tat ELISPOT responses at 2 weeks post challenge (P value < 0.05) and peak neutralizing antibody titers pre-challenge (P value 0.06). These findings support continued study of recombinant herpesviruses as a vaccine approach for AIDS

  1. Mathematical modeling and analysis of combinational immune boost for tumor elimination

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    Nakada, Naoki; Nagata, Mizuho; Takeuchi, Yasuhiro; Nakaoka, Shinji

    2016-04-01

    The immune system has an ability to recognize tumor as non-self antigen, and initiates inflammatory response to eliminate tumor. A dendritic cell (DCs) population is one of immune cell subsets that specifically uptakes foreign antigen and then presents to T cells. Dendritic cell boost ex vivo is operated to enhance immune response against tumor that in general comes to fail due to several complex reasons. Although dendritic cell therapy has been operated in clinical trials by boosting tumor immune responses, less is known about dynamic behaviors generated by interactions among immune cell subsets and tumor cells. In this paper, we construct and analyze a mathematical model describing tumor killing by T cells activated by dendritic cells. A handling time representing a waiting time required for T cells to be activated during antigen presentation is incorporated in our model. Mathematical analyses imply that successful tumor elimination depends on the amount of T cells activated ex vivo when introduced. Moreover, numerical simulations imply that an immune escape basin in which tumor can escape from T cell responses increases when the handling time increases, indicating that efficient tumor elimination might result in immediate T cell inactivation due to rapid decline of antigenic stimulation.

  2. Boosting immune response with the invariant chain segments via association with non-peptide binding region of major histocompatibility complex class II molecules

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    Chen Fangfang

    2012-09-01

    Full Text Available Abstract Background Based on binding of invariant chain (Ii to major histocompatibility complex (MHC class II molecules to form complexes, Ii-segment hybrids, Ii-key structure linking an epitope, or Ii class II-associated invariant chain peptide (CLIP replaced with an epitope were used to increase immune response. It is currently unknown whether the Ii-segment cytosolic and transmembrane domains bind to the MHC non-peptide binding region (PBR and consequently influence immune response. To investigate the potential role of Ii-segments in the immune response via MHC II/peptide complexes, a few hybrids containing Ii-segments and a multiepitope (F306 from Newcastle disease virus fusion protein (F were constructed, and their binding effects on MHC II molecules and specific antibody production were compared using confocal microscopy, immunoprecipitation, western blotting and animal experiments. Results One of the Ii-segment/F306 hybrids, containing ND (Asn–Asp outside the F306 in the Ii-key structure (Ii-key/F306/ND, neither co-localized with MHC II molecules on plasma membrane nor bound to MHC II molecules to form complexes. However, stimulation of mice with the structure produced 4-fold higher antibody titers compared with F306 alone. The two other Ii-segment/F306 hybrids, in which the transmembrane and cytosolic domains of Ii were linked to this structure (Cyt/TM/Ii-key/F306/ND, partially co-localized on plasma membrane with MHC class II molecules and weakly bound MHC II molecules to form complexes. They induced mice to produce approximately 9-fold higher antibody titers compared with F306 alone. Furthermore, an Ii/F306 hybrid (F306 substituting CLIP co-localized well with MHC II molecules on the membrane to form complexes, although it increased antibody titer about 3-fold relative to F306 alone. Conclusions These results suggest that Ii-segments improve specific immune response by binding to the non-PBR on MHC class II molecules and enabling

  3. An Increase in Antimycobacterial Th1-Cell Responses by Prime-Boost Protocols of Immunization Does Not Enhance Protection against Tuberculosis

    Czech Academy of Sciences Publication Activity Database

    Majlessi, L.; Šimšová, Marcela; Jarvis, Zdeňka; Brodin, P.; Rojas, M. J.; Bauche, C.; Nouzé, C.; Ladant, D.; Cole, S. T.; Šebo, Peter; Leclerc, C.

    2006-01-01

    Roč. 74, č. 4 (2006), s. 2128-2137. ISSN 0019-9567 R&D Projects: GA AV ČR IBS5020311 Institutional research plan: CEZ:AV0Z50200510 Keywords : adenylate cyclase * mycobacterium tuberculosis * immunity Subject RIV: EE - Microbiology, Virology Impact factor: 4.004, year: 2006

  4. Activation of the reward system boosts innate and adaptive immunity.

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    Ben-Shaanan, Tamar L; Azulay-Debby, Hilla; Dubovik, Tania; Starosvetsky, Elina; Korin, Ben; Schiller, Maya; Green, Nathaniel L; Admon, Yasmin; Hakim, Fahed; Shen-Orr, Shai S; Rolls, Asya

    2016-08-01

    Positive expectations contribute to the clinical benefits of the placebo effect. Such positive expectations are mediated by the brain's reward system; however, it remains unknown whether and how reward system activation affects the body's physiology and, specifically, immunity. Here we show that activation of the ventral tegmental area (VTA), a key component of the reward system, strengthens immunological host defense. We used 'designer receptors exclusively activated by designer drugs' (DREADDs) to directly activate dopaminergic neurons in the mouse VTA and characterized the subsequent immune response after exposure to bacteria (Escherichia coli), using time-of-flight mass cytometry (CyTOF) and functional assays. We found an increase in innate and adaptive immune responses that were manifested by enhanced antibacterial activity of monocytes and macrophages, reduced in vivo bacterial load and a heightened T cell response in the mouse model of delayed-type hypersensitivity. By chemically ablating the sympathetic nervous system (SNS), we showed that the reward system's effects on immunity are, at least partly, mediated by the SNS. Thus, our findings establish a causal relationship between the activity of the VTA and the immune response to bacterial infection. PMID:27376577

  5. DNA Prime-Adenovirus Boost Immunization Induces a Vigorous and Multifunctional T-Cell Response against Hepadnaviral Proteins in the Mouse and Woodchuck Model

    OpenAIRE

    Kosinska, Anna D.; Johrden, Lena; Zhang, Ejuan; Fiedler, Melanie; Mayer, Anja; Wildner, Oliver; Lu, Mengji; Roggendorf, Michael

    2012-01-01

    Induction of hepatitis B virus (HBV)-specific cytotoxic T cells by therapeutic immunization may be a strategy to treat chronic hepatitis B. In the HBV animal model, woodchucks, the application of DNA vaccine expressing woodchuck hepatitis virus (WHV) core antigen (WHcAg) in combination with antivirals led to the prolonged control of viral replication. However, it became clear that the use of more potent vaccines is required to overcome WHV persistence. Therefore, we asked whether stronger and...

  6. A novel "priming-boosting" strategy for immune interventions in cervical cancer.

    Science.gov (United States)

    Liao, Shujie; Zhang, Weina; Hu, Xiaoji; Wang, Wei; Deng, Dongrui; Wang, Hui; Wang, Changyu; Zhou, Jianfeng; Wang, Shixuan; Zhang, Hanwang; Ma, Ding

    2015-04-01

    Despite the encouraging development of a preventive vaccine for human papillomavirus (HPV), it cannot improve ongoing infections. Therefore, a new vaccine is urgently needed that can prevent and treat cervical cancer, and cure pre-cancerous lesions. In this study, we constructed two peptide-based vaccines. The first was a short-term, long-peptide (ST-LP) vaccine that simultaneously targeted three key carcinogenic epitopes (E5-E6-E7) on HPV16. We tested this vaccine in murine TC-1 cells infected with a recombinant adeno-associated virus (rAAV) fused with HPV16E5 DNA (rTC-1 cells), which served as a cell model; we also tested it in immune-competent mice loaded with rTC-1 cells, which served as an ectopic tumor model. The ST-LP injections resulted in strong, cell-mediated immunity, capable of attacking and eliminating abnormal antigen-bearing cells. Furthermore, to prolong immunogenic capability, we designed a unique rAAV that encoded the three predicted epitopes for a second, long-term, long-peptide (LT-LP) vaccine. Moreover, we used a new immune strategy of continuous re-injections, where three ST-LP injections were performed at one-week intervals (days 0, 7, 14), then one LT-LP injection was performed on day 120. Our in vitro and in vivo studies revealed that this strategy could boost the immune response to produce longer and stronger protection against target cells, and mice were thoroughly protected from tumor growth. Our results showed that priming the immune system with the ST-LP vaccine, followed by boosting the immune system with the LT-LP vaccine could generate a rapid, robust, durable cytotoxic T-lymphocyte response to HPV16-positive tumors. PMID:25575128

  7. Sequential immune responses: The weapons of immunity

    OpenAIRE

    Mills, Charles; Ley, Klaus; Buchmann, Kurt; Canton, Jonathan

    2015-01-01

    Sequential immune responses (SIR) is a new model that describes what ‘immunity’ means in higher animals. Existing models, such as self/nonself discrimination or danger, focus on how immune responses are initiated. However, initiation is not protection. SIR describes the actual immune responses that provide protection. SIR resulted from a comprehensive analysis of the evolution of immune systems that revealed that several very different types of host innate responses occur (and at different te...

  8. Evaluation of mucosal and systemic immune responses elicited by GPI-0100- adjuvanted influenza vaccine delivered by different immunization strategies.

    Directory of Open Access Journals (Sweden)

    Heng Liu

    Full Text Available Vaccines for protection against respiratory infections should optimally induce a mucosal immune response in the respiratory tract in addition to a systemic immune response. However, current parenteral immunization modalities generally fail to induce mucosal immunity, while mucosal vaccine delivery often results in poor systemic immunity. In order to find an immunization strategy which satisfies the need for induction of both mucosal and systemic immunity, we compared local and systemic immune responses elicited by two mucosal immunizations, given either by the intranasal (IN or the intrapulmonary (IPL route, with responses elicited by a mucosal prime followed by a systemic boost immunization. The study was conducted in BALB/c mice and the vaccine formulation was an influenza subunit vaccine supplemented with GPI-0100, a saponin-derived adjuvant. While optimal mucosal antibody titers were obtained after two intrapulmonary vaccinations, optimal systemic antibody responses were achieved by intranasal prime followed by intramuscular boost. The latter strategy also resulted in the best T cell response, yet, it was ineffective in inducing nose or lung IgA. Successful induction of secretory IgA, IgG and T cell responses was only achieved with prime-boost strategies involving intrapulmonary immunization and was optimal when both immunizations were given via the intrapulmonary route. Our results underline that immunization via the lungs is particularly effective for priming as well as boosting of local and systemic immune responses.

  9. Evaluation of Mucosal and Systemic Immune Responses Elicited by GPI-0100- Adjuvanted Influenza Vaccine Delivered by Different Immunization Strategies

    Science.gov (United States)

    Liu, Heng; Patil, Harshad P.; de Vries-Idema, Jacqueline; Wilschut, Jan; Huckriede, Anke

    2013-01-01

    Vaccines for protection against respiratory infections should optimally induce a mucosal immune response in the respiratory tract in addition to a systemic immune response. However, current parenteral immunization modalities generally fail to induce mucosal immunity, while mucosal vaccine delivery often results in poor systemic immunity. In order to find an immunization strategy which satisfies the need for induction of both mucosal and systemic immunity, we compared local and systemic immune responses elicited by two mucosal immunizations, given either by the intranasal (IN) or the intrapulmonary (IPL) route, with responses elicited by a mucosal prime followed by a systemic boost immunization. The study was conducted in BALB/c mice and the vaccine formulation was an influenza subunit vaccine supplemented with GPI-0100, a saponin-derived adjuvant. While optimal mucosal antibody titers were obtained after two intrapulmonary vaccinations, optimal systemic antibody responses were achieved by intranasal prime followed by intramuscular boost. The latter strategy also resulted in the best T cell response, yet, it was ineffective in inducing nose or lung IgA. Successful induction of secretory IgA, IgG and T cell responses was only achieved with prime-boost strategies involving intrapulmonary immunization and was optimal when both immunizations were given via the intrapulmonary route. Our results underline that immunization via the lungs is particularly effective for priming as well as boosting of local and systemic immune responses. PMID:23936066

  10. Local immune response and protection in the guinea pig keratoconjunctivitis model following immunization with Shigella vaccines.

    OpenAIRE

    Hartman, A B; Van De Verg, L L; Collins, H H; Tang, D B; Bendiuk, N O; Taylor, D N; Powell, C J

    1994-01-01

    This study used the guinea pig keratoconjunctivitis model to examine the importance of route of administration (mucosal versus parenteral), frequency and timing of immunization (primary versus boosting immunization), and form of antigen given (live attenuated vaccine strain versus O-antigen-protein conjugate) on the production of protective immunity against Shigella infection. Since local immune response to the lipopolysaccharide (LPS) O-antigen of Shigella spp. is thought to be important for...

  11. The HyVac4 subunit vaccine efficiently boosts BCG-primed anti-mycobacterial protective immunity.

    Directory of Open Access Journals (Sweden)

    Rolf Billeskov

    Full Text Available BACKGROUND: The current vaccine against tuberculosis (TB, BCG, has failed to control TB worldwide and the protective efficacy is moreover limited to 10-15 years. A vaccine that could efficiently boost a BCG-induced immune response and thus prolong protective immunity would therefore have a significant impact on the global TB-burden. METHODS/FINDINGS: In the present study we show that the fusion protein HyVac4 (H4, consisting of the mycobacterial antigens Ag85B and TB10.4, given in the adjuvant IC31® or DDA/MPL effectively boosted and prolonged immunity induced by BCG, leading to improved protection against infection with virulent M. tuberculosis (M.tb. Increased protection correlated with an increased percentage of TB10.4 specific IFNγ/TNFα/IL-2 or TNFα/IL-2 producing CD4 T cells at the site of infection. Moreover, this vaccine strategy did not compromise the use of ESAT-6 as an accurate correlate of disease development/vaccine efficacy. Indeed both CD4 and CD8 ESAT-6 specific T cells showed significant correlation with bacterial levels. CONCLUSIONS/SIGNIFICANCE: H4-IC31® can efficiently boost BCG-primed immunity leading to an increased protective anti-M.tb immune response dominated by IFNγ/TNFα/IL-2 or TNFα/IL2 producing CD4 T cells. H4 in the CD4 T cell inducing adjuvant IC31® is presently in clinical trials.

  12. Subtype C gp140 Vaccine Boosts Immune Responses Primed by the South African AIDS Vaccine Initiative DNA-C2 and MVA-C HIV Vaccines after More than a 2-Year Gap.

    Science.gov (United States)

    Gray, Glenda E; Mayer, Kenneth H; Elizaga, Marnie L; Bekker, Linda-Gail; Allen, Mary; Morris, Lynn; Montefiori, David; De Rosa, Stephen C; Sato, Alicia; Gu, Niya; Tomaras, Georgia D; Tucker, Timothy; Barnett, Susan W; Mkhize, Nonhlanhla N; Shen, Xiaoying; Downing, Katrina; Williamson, Carolyn; Pensiero, Michael; Corey, Lawrence; Williamson, Anna-Lise

    2016-06-01

    A phase I safety and immunogenicity study investigated South African AIDS Vaccine Initiative (SAAVI) HIV-1 subtype C (HIV-1C) DNA vaccine encoding Gag-RT-Tat-Nef and gp150, boosted with modified vaccinia Ankara (MVA) expressing matched antigens. Following the finding of partial protective efficacy in the RV144 HIV vaccine efficacy trial, a protein boost with HIV-1 subtype C V2-deleted gp140 with MF59 was added to the regimen. A total of 48 participants (12 U.S. participants and 36 Republic of South Africa [RSA] participants) were randomized to receive 3 intramuscular (i.m.) doses of SAAVI DNA-C2 of 4 mg (months 0, 1, and 2) and 2 i.m. doses of SAAVI MVA-C of 1.45 × 10(9) PFU (months 4 and 5) (n = 40) or of a placebo (n = 8). Approximately 2 years after vaccination, 27 participants were rerandomized to receive gp140/MF59 at 100 μg or placebo, as 2 i.m. injections, 3 months apart. The vaccine regimen was safe and well tolerated. After the DNA-MVA regimen, CD4(+) T-cell and CD8(+) T-cell responses occurred in 74% and 32% of the participants, respectively. The protein boost increased CD4(+) T-cell responses to 87% of the subjects. All participants developed tier 1 HIV-1C neutralizing antibody responses as well as durable Env binding antibodies that recognized linear V3 and C5 peptides. The HIV-1 subtype C DNA-MVA vaccine regimen showed promising cellular immunogenicity. Boosting with gp140/MF59 enhanced levels of binding and neutralizing antibodies as well as CD4(+) T-cell responses to HIV-1 envelope. (This study has been registered at ClinicalTrials.gov under registration no. NCT00574600 and NCT01423825.). PMID:27098021

  13. Potent T cell Responses Induced by Single DNA Vaccine Boosted with Recombinant Vaccinia Vaccine

    Institute of Scientific and Technical Information of China (English)

    Lianxing Liu; Chao Qiu; Yang Huang; Jianqing Xu; Yiming Shao

    2013-01-01

    Plasmid DNA,an effective vaccine vector,can induce both cellular and humoral immune responses.However,plasmid DNA raises issues concerning potential genomic integration after injection.This issue should be considered in preclinical studies.Tiantan vaccinia virus (TV) has been most widely utilized in eradicating smallpox in China.This virus has also been considered as a successful vaccine vector against a few infectious diseases.Potent T cell responses through T-cell receptor (TCR) could be induced by three injections of the DNA prime vaccine followed by a single injection of recombinant vaccinia vaccine.To develop a safer immunization strategy,a single DNA prime followed by a single recombinant Tiantan vaccinia (rTV) AIDS vaccine was used to immunize mice.Our data demonstrated that one DNA prime/rTV boost regimen induced mature TCR activation with high functional avidity,preferential T cell Vβ receptor usage and high sensitivity to anti-CD3 antibody stimulation.No differences in T cell responses were observed among one,two or three DNA prime/rTV boost regimens.This study shows that one DNA prime/rTV boost regimen is sufficient to induce potent T cell responses against HIV.

  14. Intranasal Boosting with an Adenovirus-Vectored Vaccine Markedly Enhances Protection by Parenteral Mycobacterium bovis BCG Immunization against Pulmonary Tuberculosis

    OpenAIRE

    Santosuosso, Michael; McCormick, Sarah; Zhang, Xizhong; Zganiacz, Anna; Xing, Zhou

    2006-01-01

    Parenterally administered Mycobacterium bovis BCG vaccine confers only limited immune protection from pulmonary tuberculosis in humans. There is a need for developing effective boosting vaccination strategies. We examined a heterologous prime-boost regimen utilizing BCG as a prime vaccine and our recently described adenoviral vector expressing Ag85A (AdAg85A) as a boost vaccine. Since we recently demonstrated that a single intranasal but not intramuscular immunization with AdAg85A was able to...

  15. Optimisation of prime-boost immunization in mice using novel protein-based and recombinant vaccinia (Tiantan-based HBV vaccine.

    Directory of Open Access Journals (Sweden)

    Hong Chen

    Full Text Available BACKGROUND: A therapeutic vaccine for chronic hepatitis B virus (HBV infection that enhances virus-specific cellular immune responses is urgently needed. The "prime-boost" regimen is a widely used vaccine strategy against many persistence infections. However, few reports have addressed this strategy applying for HBV therapeutic vaccine development. METHODOLOGY/PRINCIPAL FINDINGS: To develop an effective HBV therapeutic vaccine, we constructed a recombinant vaccinia virus (Tiantan containing the S+PreS1 fusion antigen (RVJSS1 combined with the HBV particle-like subunit vaccine HBVSS1 to explore the most effective prime-boost regimen against HBV. The immune responses to different prime-boost regimens were assessed in C57BL/C mice by ELISA, ELISpot assay and Intracellular cytokine staining analysis. Among the combinations tested, an HBV protein particle vaccine priming and recombinant vaccinia virus boosting strategy accelerated specific seroconversion and produced high antibody (anti-PreS1, anti-S antibody titres as well as the strongest multi-antigen (PreS1, and S-specific cellular immune response. HBSS1 protein prime/RVJSS1 boost immunization was also generated more significant level of both CD4+ and CD8+ T cell responses for Th1 cytokines (TNF-α and IFN-γ. CONCLUSIONS: The HBSS1 protein-vaccine prime plus RVJSS1 vector boost elicits specific antibody as well as CD4 and CD8 cells secreting Th1-like cytokines, and these immune responses may be important parameters for the future HBV therapeutic vaccines.

  16. Evaluation of fowlpox-vaccinia virus prime-boost vaccine strategies for high-level mucosal and systemic immunity against HIV-1.

    Science.gov (United States)

    Ranasinghe, Charani; Medveczky, Jill C; Woltring, Donna; Gao, Ke; Thomson, Scott; Coupar, Barbara E H; Boyle, David B; Ramsay, Alistair J; Ramshaw, Ian A

    2006-07-26

    We have tested the efficacy of recombinant fowl pox (rFPV) and recombinant vaccinia virus (rVV) encoding antigens of AE clade HIV-1 in a prime-boost strategy, using both systemic and mucosal delivery routes. Of the various vaccine routes tested, intranasal/intramuscular (i.n./i.m.) AE FPV/AE VV prime-boosting generated the highest mucosal and systemic T cell responses. Peak mucosal T cell responses occurred as early as 3 days post-boost vaccination. In contrast only low systemic responses were observed at this time with the peak response occurring at day 7. Current data also revealed that, due to better uptake of the rFPV, intranasal viral priming was much more effective than intranasal rDNA priming tested previously. The i.m./i.m. prime-boost delivery also generated strong systemic but poor mucosal responses to Gag peptides. Interestingly, the oral administration of AE FPV followed by i.m. AE VV delivery elicited strong systemic responses to sub-dominant Pol 1 peptides that were absent in mice that received vaccine by other routes. Moreover, priming with AE FPV co-expressing cytokine IL-12 significantly enhanced the T cell responses to target antigens, whilst co-expression of IFNgamma decreased these responses. The results also indicated that the route of inoculation and the vaccine vector combination could radically influence not only the magnitude but also the antigen specificity of the immune response generated. Further, in contrast to the generally protracted HIV rDNA/rFPV multiple delivery prime-boosting, this single rFPV prime and rVV boost approach was more flexible and generated excellent mucosal and systemic immune responses to HIV vaccine antigens. PMID:16759767

  17. Fulfill Social Responsibility, Boost Western Development

    Institute of Scientific and Technical Information of China (English)

    Shi Wei

    2010-01-01

    @@ 2010 CNPC(China National Petroleum Corporation)Conference of Leading Cadres was held in Dushanzi,Xinjiang Uygur Autonomous Region on July 16.The major tasks of the Conference are to thoroughly implement the scientific concept of development,to summarize and review the achievements in promoting transformation of development mode,to analyze the situation and tasks facing the company,to effectively enhance the initiative,the sense of urgency and responsibility,to accelerate transformation of development mode,thus to promote the construction of an integrated international energy corporation and realize comprehensive,coordinated and sustainable development.

  18. Remune. Immune Response.

    Science.gov (United States)

    Lai, Derhsing; Jones, Taff

    2002-03-01

    The Immune Response Corp (IRC) is developing Remune, a potential HIV therapeutic vaccine. Remune is based on the Salk Immunogen, which is derived from an HIV isolate which has been inactivated by chemical depletion of glycoprotein 120 (gp120). Preliminary data suggested that Remune, in combination with antiviral drug therapy, results in undetectable levels of HIV. Phase III trials commenced in May 1997 and it was initially expected that registration filings would be made in 1999. However, following interim analysis of the 2500-patient, multicenter, double-blind, pivotal phase III study (study 806) in May 1999, an independent panel recommended concluding the clinical endpoint trial and IRC and licensee, Agouron, decided to pursue alternative regulatory strategies, including initiating two additional phase III surrogate marker trials. Despite this, Agouron gave IRC notice of termination of its continued development in July 2001. In August 2001, IRC informed Agouron that, due to the total number of endpoints to date falling short of that previously assumed by Agouron, it did not intend to continue Agouron's Study 202 of Remune. In July 2001, licensee Trinity Medical Group filed an NDA with the governing health authorities in Thailand for Remune. The Thai FDA certified Immune Response's Remune manufacturing facility as being in compliance with GMP standards, following an on site inspection by Thai officials in November 2001 that was performed as a requirement of Trinity's Thai NDA. As a result of this certification, Trinity expected that a "timely determination" could be made by the Thai FDA. Rhĵne-Poulenc Rorer discontinued its part in the development of Remune, with all manufacturing, marketing and distribution rights reverting to IRC. After Agouron returned rights to Remune in July 2001, IRC heldfull rights in the US, Europe and Japan, while collaborating with its partners Trinity Medical Group and Roemmers Laboratory in the Southeast Asian and Latin American

  19. Poly(I:C/alum mixed adjuvant priming enhances HBV subunit vaccine-induced immunity in mice when combined with recombinant adenoviral-based HBV vaccine boosting.

    Directory of Open Access Journals (Sweden)

    Xia Chuai

    Full Text Available BACKGROUND: Virus-specific cellular immune responses play a critical role in virus clearance during acute or chronic HBV infection. Currently, the commercially available HBV vaccine is combined with alum adjuvant, which stimulates mainly Th2 immune responses. Therefore, development of new therapeutic HBV vaccine adjuvants and immune strategies that also promote Th1 and CTL responses is urgently needed. METHODOLOGY/PRINCIPAL FINDINGS: To improve the immunity induced by the novel HBSS1 HBV vaccine, we evaluated the ability of adjuvants, including alum, CpG and polyriboinosinic polyribocytidylic acid [poly(I:C], to enhance the response when boosted with the recombinant adenoviral vector vaccine rAdSS1. The immune responses to different adjuvant combinations were assessed in C57BL/6 mice by enzyme-linked immunosorbent assay (ELISA, ELISpot and cytokine release assays. Among the combinations tested, a HBV protein particle vaccine with CpG/alum and poly(I:C/alum priming combinations accelerated specific seroconversion and produced high antibody (anti-PreS1, anti-S antibody titres with a Th1 bias. After boosting with recombinant adenoviral vector vaccine rAdSS1, both groups produced a strong multi-antigen (S and PreS1-specific cellular immune response. HBSS1 immunisation with poly(I:C/alum priming also generated high-level CD4(+ and CD8(+ T cell responses in terms of Th1 cytokines (IFN-γ and IL-2. CONCLUSIONS: The protein-vaccine HBSS1 with mixed poly(I:C/alum adjuvant priming, followed by a rAdSS1 vaccine boost, maximises specific antibody and Th1-biased cellular immune responses. This regime might prove useful in the development of HBV therapeutic vaccines. Furthermore, this promising strategy might be applied to vaccines against other persistent infections, such as human immunodeficiency virus and tuberculosis.

  20. Boosting BCG with inert spores improves immunogenicity and induces specific IL-17 responses in a murine model of bovine tuberculosis.

    Science.gov (United States)

    Garcia-Pelayo, M Carmen; Kaveh, Daryan A; Sibly, Laura; Webb, Paul R; Bull, Naomi C; Cutting, Simon M; Hogarth, Philip J

    2016-05-01

    Tuberculosis (TB) remains a global pandemic, in both animals and man, and novel vaccines are urgently required. Heterologous prime-boost of BCG represents a promising strategy for improved TB vaccines, with respiratory delivery the most efficacious to date. Such an approach may be an ideal vaccination strategy against bovine TB (bTB), but respiratory vaccination presents a technical challenge in cattle. Inert bacterial spores represent an attractive vaccine vehicle. Therefore we evaluated whether parenterally administered spores are efficacious when used as a BCG boost in a murine model of immunity against Mycobacterium bovis. Here we report the use of heat-killed, TB10.4 adsorbed, Bacillus subtilis spores delivered via subcutaneous injection to boost immunity primed by BCG. We demonstrate that this approach improves the immunogenicity of BCG. Interestingly, this associated with substantial boosting of IL-17 responses; considered to be important in protective immunity against TB. These data demonstrate that parenteral delivery of spores represents a promising vaccine vehicle for boosting BCG, and identifies potential for optimisation for use as a vaccine for bovine TB. PMID:27156624

  1. Breaking peripheral immune tolerance to CNS antigens in neurodegenerative diseases: boosting autoimmunity to fight-off chronic neuroinflammation.

    Science.gov (United States)

    Schwartz, Michal; Baruch, Kuti

    2014-11-01

    fighting off acute and chronic neurodegenerative conditions requires breaking peripheral immune tolerance to CNS self-antigens, in order to boost protective autoimmunity. Nevertheless, the optimal approach to fine tune such immune response must be individually explored for each condition. PMID:25199710

  2. Prime and boost immunization with influenza and adenovirus encoding the Toxoplasma gondii surface antigen 2 (SAG2) induces strong protective immunity.

    Science.gov (United States)

    Machado, Alexandre V; Caetano, Bráulia C; Barbosa, Rafael P; Salgado, Ana Paula C; Rabelo, Renata H; Garcia, Cristiana C; Bruna-Romero, Oscar; Escriou, Nicolas; Gazzinelli, Ricardo T

    2010-04-19

    In this work, we explored an original vaccination protocol using recombinant influenza and adenovirus. We constructed recombinant influenza viruses harboring dicistronic NA segments containing the surface antigen 2 (SAG2) from Toxoplasma gondii under control of the duplicated 3' promoter. Recombinant influenza viruses were able to drive the expression of the foreign SAG2 sequence in cell culture and to replicate efficiently both in cell culture and in lungs of infected mice. In addition, mice primed with recombinant influenza virus and boosted with a recombinant adenovirus encoding SAG2 elicited both humoral and cellular immune responses specific for SAG2. Moreover, when immunized animals were challenged with the cystogenic P-Br strain of T. gondii, they displayed up to 85% of reduction in parasite burden. These results demonstrate the potential use of recombinant influenza vectors harboring the dicistronic segments in the development of vaccines against infectious diseases. PMID:20189485

  3. Towards a human oral vaccine for anthrax: the utility of a Salmonella Typhi Ty21a-based prime-boost immunization strategy.

    Science.gov (United States)

    Baillie, Leslie W J; Rodriguez, Ana L; Moore, Stephen; Atkins, Helen S; Feng, Chiguang; Nataro, James P; Pasetti, Marcela F

    2008-11-11

    We previously demonstrated the ability of an orally administered attenuated Salmonella enterica serovar Typhimurium strain expressing the protective antigen (PA) of Bacillus anthracis to confer protection against lethal anthrax aerosol spore challenge [Stokes MG, Titball RW, Neeson BN, et al. Oral administration of a Salmonella enterica-based vaccine expressing Bacillus anthracis protective antigen confers protection against aerosolized B. anthracis. Infect Immun 2007;75(April (4)):1827-34]. To extend the utility of this approach to humans we constructed variants of S. enterica serovar Typhi Ty21a, an attenuated typhoid vaccine strain licensed for human use, which expressed and exported PA via two distinct plasmid-based transport systems: the Escherichia coli HlyA haemolysin and the S. Typhi ClyA export apparatus. Murine immunogenicity studies confirmed the ability of these constructs, especially Ty21a expressing the ClyA-PA fusion protein, to stimulate strong PA-specific immune responses following intranasal immunization. These responses were further enhanced by a subsequent boost with either parenterally delivered recombinant PA or the licensed US human alum-adsorbed anthrax vaccine (AVA). Anthrax toxin neutralizing antibody responses using this prime-boost regimen were rapid, vigorous and broad in nature. The results of this study demonstrate the feasibility of employing a mucosal prime with a licensed Salmonella Typhi vaccine strain followed by a parenteral protein boost to stimulate rapid protective immunity against anthrax. PMID:18805452

  4. Masking of antigenic epitopes by antibodies shapes the humoral immune response to influenza.

    Science.gov (United States)

    Zarnitsyna, Veronika I; Ellebedy, Ali H; Davis, Carl; Jacob, Joshy; Ahmed, Rafi; Antia, Rustom

    2015-09-01

    The immune responses to influenza, a virus that exhibits strain variation, show complex dynamics where prior immunity shapes the response to the subsequent infecting strains. Original antigenic sin (OAS) describes the observation that antibodies to the first encountered influenza strain, specifically antibodies to the epitopes on the head of influenza's main surface glycoprotein, haemagglutinin (HA), dominate following infection with new drifted strains. OAS suggests that responses to the original strain are preferentially boosted. Recent studies also show limited boosting of the antibodies to conserved epitopes on the stem of HA, which are attractive targets for a 'universal vaccine'. We develop multi-epitope models to explore how pre-existing immunity modulates the immune response to new strains following immunization. Our models suggest that the masking of antigenic epitopes by antibodies may play an important role in describing the complex dynamics of OAS and limited boosting of antibodies to the stem of HA. Analysis of recently published data confirms model predictions for how pre-existing antibodies to an epitope on HA decrease the magnitude of boosting of the antibody response to this epitope following immunization. We explore strategies for boosting of antibodies to conserved epitopes and generating broadly protective immunity to multiple strains. PMID:26194761

  5. Infection with Plasmodium berghei Boosts Antibody Responses Primed by a DNA Vaccine Encoding Gametocyte Antigen Pbs48/45

    OpenAIRE

    Haddad, Diana; Maciel, Jorge; Kumar, Nirbhay

    2006-01-01

    An important consideration in the development of a malaria vaccine for individuals living in areas of endemicity is whether vaccine-elicited immune responses can be boosted by natural infection. To investigate this question, we used Plasmodium berghei ANKA blood-stage parasites for the infection of mice that were previously immunized with a DNA vaccine encoding the P. berghei sexual-stage antigen Pbs48/45. Intramuscular immunization in mice with one or two doses of DNA-Pbs48/45 or of empty DN...

  6. Enhancement of fibroblast activation protein α-based vaccines and adenovirus boost immunity by cyclophosphamide through inhibiting IL-10 expression in 4T1 tumor bearing mice.

    Science.gov (United States)

    Xia, Qiu; Geng, Fei; Zhang, Fang-Fang; Liu, Chen-Lu; Xu, Ping; Lu, Zhen-Zhen; Zhang, Hai-Hong; Kong, Wei; Yu, Xiang-Hui

    2016-08-31

    Fibroblast activation protein α (FAPα) is expressed in cancer-associated fibroblasts (CAFs) of more than 90% of malignant epithelia carcinomas. CAFs are the main type of cells in the tumor microenvironment which offer nutrition and protection to the tumor and regulate immunosuppression. To eliminate CAFs, a vaccine targeting FAPα may be used with a heterologous prime-boost strategy to enhance the FAPα-specific cellular immunity. Here, a FAP vaccine using a recombinant adenovirus (rAd) vector was constructed as well as a DNA vaccine reported in our previous work. Although the DNA prime-rAd boost strategy enhanced FAPα-specific immune responses, improvement of anti-tumor immunity effects was not observed. Examination of immunosuppressive factors revealed that high expression of the IL-10 cytokine was considered the main cause of the failure of the prime-boost strategy. However, heterologous vaccination in combination with a low-dose of cyclophosphamide (CY), which was reported to reduce IL-10 production and promote a shift from immunosuppression to immunopotentiation, resulted in enhanced effects in terms of numbers of effector T cells and tumor growth inhibition rates, compared to the CY alone or DNA alone group. Tumor growth was inhibited markedly when the prime-boost strategy was combined with CY in both the prophylactic and therapeutic settings and the survival time of 4T1 tumor bearing mice was also prolonged significantly. With the reduction of IL-10, enhancement of the anti-tumor effect by the prime-boost strategy was observed. These results suggest that FAPα-targeted rAd boosting in combination with CY is an attractive approach to overcoming immunosuppression in cancer vaccines. PMID:27498213

  7. Immune responses to improving welfare.

    Science.gov (United States)

    Berghman, L R

    2016-09-01

    The relationship between animal welfare and the immune status of an animal has a complex nature. Indeed, the intuitive notion that "increased vigilance of the immune system is by definition better" because it is expected to better keep the animal healthy, does not hold up under scrutiny. This is mostly due to the fact that the immune system consists of 2 distinct branches, the innate and the adaptive immune system. While they are intimately intertwined and synergistic in the living organism, they are profoundly different in their costs, both in terms of performance and wellbeing. In contrast to the adaptive immune system, the action of the innate immune system has a high metabolic cost as well as undesirable behavioral consequences. When a pathogen breaches the first line of defense (often a mucosal barrier), that organism's molecular signature is recognized by resident macrophages. The macrophages respond by releasing a cocktail of pro-inflammatory cytokines (including interleukin-1 and -6) that signal the brain via multiple pathways (humoral as well as neural) of the ongoing peripheral innate immune response. The behavioral response to the release of proinflammatory cytokines, known as "sickness behavior," includes nearly all the behavioral aspects that are symptomatic for clinical depression in humans. Hence, undesired innate immune activity, such as chronic inflammation, needs to be avoided by the industry. From an immunological standpoint, one of the most pressing poultry industry needs is the refinement of our current veterinary vaccine arsenal. The response to a vaccine, especially to a live attenuated vaccine, is often a combination of innate and adaptive immune activities, and the desired immunogenicity comes at the price of high reactogenicity. The morbidity, albeit limited and transient, caused by live vaccines against respiratory diseases and coccidiosis are good examples. Thankfully, the advent of various post-genomics technologies, such as DNA

  8. Immune response to H pylori

    Institute of Scientific and Technical Information of China (English)

    Giovanni Suarez; Victor E Reyes; Ellen J Beswick

    2006-01-01

    The gastric mucosa separates the underlying tissue from the vast array of antigens that traffic through the stomach lumen. While the extreme pH of this environment is essential in aiding the activation of enzymes and food digestion, it also renders the gastric epithelium free from bacterial colonization, with the exception of one important human pathogen, H pylori. This bacterium has developed mechanisms to survive the harsh environment of the stomach, actively move through the mucosal layer,attach to the epithelium, evade immune responses, and achieve persistent colonization. While a hallmark of this infection is a marked inflammatory response with the infiltration of various immune cells into the infected gastric mucosa, the host immune response is unable to clear the infection and may actually contribute to the associated pathogenesis. Here, we review the host responses involved during infection with H pylori and how they are influenced by this bacterium.

  9. MAP Kinases in Immune Responses

    Institute of Scientific and Technical Information of China (English)

    Yongliang Zhang; Chen Dong

    2005-01-01

    MAP kinases are evolutionarily conserved signaling regulators from budding yeast to mammals and play essential roles in both innate and adaptive immune responses. There are three main families of MAPKs in mammals. Each of them has its own activators, inactivators, substrates and scaffolds, which altogether form a fine signaling network in response to different extracellular or intracellular stimulation. In this review, we summarize recent advances in understanding of the regulation of MAP kinases and the roles of MAP kinases in innate and adaptive immune responses.

  10. Immune Response After Measles Vaccination

    Directory of Open Access Journals (Sweden)

    Bhardwaj A.K

    1991-01-01

    Full Text Available Measles immunization of 192 under 5 years of age children was undertaken and the overall seroconversion was 76.0%. Seroconversion rate in the age group of 9-12 months was 70.9% and it was 100% after one year. Immune response in malnourished children was more as compared to normal children. There were negligible side reactions after measles vaccination, and this vaccine passed normal potency tests under field conditions.

  11. Immune responses in space flight

    Science.gov (United States)

    Sonnenfeld, G.

    1998-01-01

    Space flight has been shown to have profound effects on immunological parameters of humans, monkeys and rodents. These studies have been carried out by a number of different laboratories. Among the parameters affected are leukocyte blastogenesis, natural killer cell activity, leukocyte subset distribution, cytokine production - including interferons and interleukins, and macrophage maturation and activity. These changes start to occur only after a few days space flight, and some changes continue throughout long-term space flight. Antibody responses have received only very limited study, and total antibody levels have been shown to be increased after long-term space flight. Several factors could be involved in inducing these changes. These factors could include microgravity, lack of load-bearing, stress, acceleration forces, and radiation. The mechanism(s) for space flight-induced changes in immune responses remain(s) to be established. Certainly, there can be direct effects of microgravity, or other factors, on cells that play a fundamental role in immune responses. However, it is now clear that there are interactions between the immune system and other physiological systems that could play a major role. For example, changes occurring in calcium use in the musculoskeletal system induced by microgravity or lack of use could have great impact on the immune system. Most of the changes in immune responses have been observed using samples taken immediately after return from space flight. However, there have been two recent studies that have used in-flight testing. Delayed-type hypersensitivity responses to common recall antigens of astronauts and cosmonauts have been shown to be decreased when tested during space flights. Additionally, natural killer cell and blastogenic activities are inhibited in samples taken from rats during space flight. Therefore, it is now clear that events occurring during space flight itself can affect immune responses. The biological

  12. Comparison of the immunogenicity and protection against bovine tuberculosis following immunization by BCG-priming and boosting with adenovirus or protein based vaccines.

    Science.gov (United States)

    Dean, G; Whelan, A; Clifford, D; Salguero, F J; Xing, Z; Gilbert, S; McShane, H; Hewinson, R G; Vordermeier, M; Villarreal-Ramos, B

    2014-03-01

    There is a requirement for vaccines or vaccination strategies that confer better protection against TB than the current live attenuated Mycobacterium bovis Bacillus Calmette-Guerin (BCG) vaccine for use in cattle. Boosting with recombinant viral vectors expressing mycobacterial proteins, such as Ag85A, has shown a degree of promise as a strategy for improving on the protection afforded by BCG. Experiments in small animal models have indicated that broadening the immune response to include mycobacterial antigens other than Ag85A, such as Rv0288, induced by boosting with Ad5 constructs has a direct effect on the protection afforded against TB. Here, we compared the immunogenicity and protection against challenge with M. bovis afforded by boosting BCG-vaccinated cattle with a human type 5 (Ad5)-based vaccine expressing the mycobacterial antigens Ag85A (Ad5-85A); or Ag85A, Rv0251, Rv0287 and Rv0288 (Ad5-TBF); or with protein TBF emulsified in adjuvant (Adj-TBF). Boosting with TBF broaden the immune response. The kinetics of Ad5-TBF and Adj-TBF were shown to be different, with effector T cell responses from the latter developing more slowly but being more durable than those induced by Ad5-TBF. No increase in protection compared to BCG alone was afforded by Ad5-TBF or Adj-TBF by gross pathology or bacteriology. Using histopathology, as a novel parameter of protection, we show that boosting BCG vaccinated cattle with Ad5-85A induced significantly better protection than BCG alone. PMID:24269321

  13. A prime-boost immunization with Tc52 N-terminal domain DNA and the recombinant protein expressed in Pichia pastoris protects against Trypanosoma cruzi infection.

    Science.gov (United States)

    Matos, Marina N; Sánchez Alberti, Andrés; Morales, Celina; Cazorla, Silvia I; Malchiodi, Emilio L

    2016-06-14

    We have previously reported that the N-terminal domain of the antigen Tc52 (NTc52) is the section of the protein that confers the strongest protection against Trypanosoma cruzi infection. To improve vaccine efficacy, we conducted here a prime-boost strategy (NTc52PB) by inoculating two doses of pcDNA3.1 encoding the NTc52 DNA carried by attenuated Salmonella (SNTc52), followed by two doses of recombinant NTc52 expressed in Picchia pastoris plus ODN-CpG as adjuvant. This strategy was comparatively analyzed with the following protocols: (1) two doses of NTc52+ODN-CpG by intranasal route followed by two doses of NTc52+ODN-CpG by intradermal route (NTc52CpG); (2) four doses of SNTc52; and (3) a control group with four doses of Salmonella carrying the empty plasmid. All immunized groups developed a predominant Th1 cellular immune response but with important differences in antibody development and protection against infection. Thus, immunization with just SNTc52 induces a strong specific cellular response, a specific systemic antibody response that is weak yet functional (considering lysis of trypomastigotes and inhibition of cell invasion), and IgA mucosal immunity, protecting in both the acute and chronic stages of infection. The group that received only recombinant protein (NTc52CpG) developed a strong antibody immune response but weaker cellular immunity than the other groups, and the protection against infection was clear in the acute phase of infection but not in chronicity. The prime-boost strategy, which combines DNA and protein vaccine and both mucosal and systemic immunizations routes, was the best assayed protocol, inducing strong cellular and humoral responses as well as specific mucosal IgA, thus conferring better protection in the acute and chronic stages of infection. PMID:27177947

  14. Comparative evaluation of booster efficacies of BCG, Ag85B, and Ag85B peptides based vaccines to boost BCG induced immunity in BALB/c mice: a pilot study

    OpenAIRE

    Husain, Aliabbas A.; Warke, Shubhangi R.; Kalorey, Dewanand R.; Daginawala, Hatim F.; Taori, Girdhar M.; Kashyap, Rajpal S

    2015-01-01

    Purpose In the present study booster efficacies of Ag85 B, Bacillus Calmette-Guerin (BCG), and Ag85B peptides were evaluated using prime boost regimes in BALB/c mice. Materials and Methods Mice were primed with BCG vaccine and subsequently boosted with Ag85B, BCG and cocktail of Ag85B peptides. Results Based on analysis of immune response it was observed mice boosted with Ag85B peptides showed significant (p < 0.001) cytokines levels (interferon γ, interleukin 12) and BCG specific antibodies ...

  15. Apolipophorins and insects immune response

    Directory of Open Access Journals (Sweden)

    A Zdybicka-Barabas

    2013-08-01

    Full Text Available Insect lipoproteins, called lipophorins, are non-covalent assemblies of lipids and proteins serving as lipid transport vehicles. The protein moiety of lipophorin comprises two glycosylated apolipoproteins, apolipophorin I (apoLp-I and apolipophorin II (apoLp-II, constantly present in a lipophorin particle, and an exchangeable protein, apolipophorin III (apoLp-III. ApoLp-III is an abundant protein occurring in hemolymph in lipid-free and lipid-bound state and playing an important role in lipid transport and insect innate immunity. In immune response apoLp-III serves as a pattern recognition molecule. It binds and detoxifies microbial cell wall components, i.e., lipopolysaccharide, lipoteichoic acid, and β-1,3-glucan. ApoLp-III activates expression of antimicrobial peptides and proteins, stimulates their antimicrobial activity, participates in regulation of the phenoloxidase system and in hemolymph clotting. In addition, the protein is involved in cellular immune response, influencing hemocyte adhesion, phagocytosis and nodule formation, and in gut immunity. Although apoLp-III is the best studied apolipophorin in insect immunity so far, a literature review suggests that all the three apolipoproteins, apoLp-I, apoLp-II and apoLp-III, function together in a coordinated defense against pathogens

  16. Persistence of the immune response induced by BCG vaccination

    Directory of Open Access Journals (Sweden)

    Blitz Rose

    2008-01-01

    Full Text Available Abstract Background Although BCG vaccination is recommended in most countries of the world, little is known of the persistence of BCG-induced immune responses. As novel TB vaccines may be given to boost the immunity induced by neonatal BCG vaccination, evidence concerning the persistence of the BCG vaccine-induced response would help inform decisions about when such boosting would be most effective. Methods A randomised control study of UK adolescents was carried out to investigate persistence of BCG immune responses. Adolescents were tested for interferon-gamma (IFN-γ response to Mycobacterium tuberculosis purified protein derivative (M.tb PPD in a whole blood assay before, 3 months, 12 months (n = 148 and 3 years (n = 19 after receiving teenage BCG vaccination or 14 years after receiving infant BCG vaccination (n = 16. Results A gradual reduction in magnitude of response was evident from 3 months to 1 year and from 1 year to 3 years following teenage vaccination, but responses 3 years after vaccination were still on average 6 times higher than before vaccination among vaccinees. Some individuals (11/86; 13% failed to make a detectable antigen-specific response three months after vaccination, or lost the response after 1 (11/86; 13% or 3 (3/19; 16% years. IFN-γ response to Ag85 was measured in a subgroup of adolescents and appeared to be better maintained with no decline from 3 to 12 months. A smaller group of adolescents were tested 14 years after receiving infant BCG vaccination and 13/16 (81% made a detectable IFN-γ response to M.tb PPD 14 years after infant vaccination as compared to 6/16 (38% matched unvaccinated controls (p = 0.012; teenagers vaccinated in infancy were 19 times more likely to make an IFN-γ response of > 500 pg/ml than unvaccinated teenagers. Conclusion BCG vaccination in infancy and adolescence induces immunological memory to mycobacterial antigens that is still present and measurable for at least 14 years in the

  17. Metabolic engineering of Salmonella vaccine bacteria to boost human Vγ2Vδ2 T cell immunity.

    Science.gov (United States)

    Workalemahu, Grefachew; Wang, Hong; Puan, Kia-Joo; Nada, Mohanad H; Kuzuyama, Tomohisa; Jones, Bradley D; Jin, Chenggang; Morita, Craig T

    2014-07-15

    Human Vγ2Vδ2 T cells monitor isoprenoid metabolism by recognizing foreign (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP), a metabolite in the 2-C-methyl-D-erythritol-4-phosphate pathway used by most eubacteria and apicomplexan parasites, and self isopentenyl pyrophosphate, a metabolite in the mevalonate pathway used by humans. Whereas microbial infections elicit prolonged expansion of memory Vγ2Vδ2 T cells, immunization with prenyl pyrophosphates or aminobisphosphonates elicit short-term Vγ2Vδ2 expansion with rapid anergy and deletion upon subsequent immunizations. We hypothesized that a live, attenuated bacterial vaccine that overproduces HMBPP would elicit long-lasting Vγ2Vδ2 T cell immunity by mimicking a natural infection. Therefore, we metabolically engineered the avirulent aroA(-) Salmonella enterica serovar Typhimurium SL7207 strain by deleting the gene for LytB (the downstream enzyme from HMBPP) and functionally complementing for this loss with genes encoding mevalonate pathway enzymes. LytB(-) Salmonella SL7207 had high HMBPP levels, infected human cells as efficiently as did the wild-type bacteria, and stimulated large ex vivo expansions of Vγ2Vδ2 T cells from human donors. Importantly, vaccination of a rhesus monkey with live lytB(-) Salmonella SL7207 stimulated a prolonged expansion of Vγ2Vδ2 T cells without significant side effects or anergy induction. These studies provide proof-of-principle that metabolic engineering can be used to derive live bacterial vaccines that boost Vγ2Vδ2 T cell immunity. Similar engineering of metabolic pathways to produce lipid Ags or B vitamin metabolite Ags could be used to derive live bacterial vaccine for other unconventional T cells that recognize nonpeptide Ags. PMID:24943221

  18. A genetic inference on cancer immune responsiveness

    OpenAIRE

    Wang, Ena; Uccellini, Lorenzo; Marincola, Francesco M.

    2012-01-01

    A cancer immune signature implicating good prognosis and responsiveness to immunotherapy was described that is observed also in other aspects of immune-mediated, tissue-specific destruction (TSD). Its determinism remains, however, elusive. Based on limited but unique clinical observations, we propose a multifactorial genetic model of human cancer immune responsiveness.

  19. Tilapia show immunization response against Ich

    Science.gov (United States)

    This study compares the immune response of Nile tilapia and red tilapia against parasite Ichthyophthirius multifiliis (Ich) using a cohabitation challenge model. Both Nile and red tilapia showed strong immune response post immunization with live Ich theronts by IP injection or immersion. Blood serum...

  20. HIV-1 Env DNA vaccine plus protein boost delivered by EP expands B- and T-cell responses and neutralizing phenotype in vivo.

    Directory of Open Access Journals (Sweden)

    Kar Muthumani

    Full Text Available An effective HIV vaccine will most likely require the induction of strong T-cell responses, broadly neutralizing antibodies (bNAbs, and the elicitation of antibody-dependent cellular cytotoxicity (ADCC. Previously, we demonstrated the induction of strong HIV/SIV cellular immune responses in macaques and humans using synthetic consensus DNA immunogens delivered via adaptive electroporation (EP. However, the ability of this improved DNA approach to prime for relevant antibody responses has not been previously studied. Here, we investigate the immunogenicity of consensus DNA constructs encoding gp140 sequences from HIV-1 subtypes A, B, C and D in a DNA prime-protein boost vaccine regimen. Mice and guinea pigs were primed with single- and multi-clade DNA via EP and boosted with recombinant gp120 protein. Sera were analyzed for gp120 binding and induction of neutralizing antibody activity. Immunization with recombinant Env protein alone induced low-titer binding antibodies with limited neutralization breath. In contrast, the synthetic DNA prime-protein boost protocol induced significantly higher antibody binding titers. Furthermore, sera from DNA prime-protein boost groups were able to neutralize a broader range of viruses in a panel of tier 1 clade B viruses as well as multiple tier 1 clade A and clade C viruses. Further investigation of synthetic DNA prime plus adaptive EP plus protein boost appears warranted.

  1. Prophylactic administration of chicken cathelicidin-2 boosts zebrafish embryonic innate immunity.

    Science.gov (United States)

    Schneider, Viktoria A F; van Dijk, Albert; van der Sar, Astrid M; Kraaij, Marina D; Veldhuizen, Edwin J A; Haagsman, Henk P

    2016-07-01

    Chicken cathelicidin-2 (CATH-2) is a host defense peptide that exhibits immunomodulatory and antibacterial properties. Here we examined effects of CATH-2 in zebrafish embryos in the absence and presence of infection. Yolk-injection of 0.2-1.5 h post-fertilized (hpf) zebrafish embryos with 2.6 ng/kg CATH-2 increased proliferation of phagocytic cells at 48 hpf by 30%. A lethal infection model was developed to test the prophylactic protective effect of CATH-2 peptide. Embryos (0.2-1.5 hpf) were injected with 2.6 ng/kg CATH-2, challenged with a lethal dose of fluorescently labeled Salmonella enteritidis pGMDs3 at 28 hpf and monitored for survival. Prophylactic treatment with CATH-2 was found to delay infection starting at 22 h post-infection (hpi). At 18-20 hpi, significantly lower (2-fold) fluorescence intensity and decreased bacterial loads were detected in peptide-treated embryos. Thus prophylactic administration of low CATH-2 concentrations confer partial protection in zebrafish embryos by boosting the innate immune system. PMID:26920462

  2. Action of booster immunization with E2 CSFV on immune response elicited by marker DNA-vaccine against CSF

    Directory of Open Access Journals (Sweden)

    Deryabina O. G.

    2012-04-01

    Full Text Available The aim was to study the influence of booster immunization with recombinant fragment of E2 CSFV on humoral immune response, elicited by candidate marker DNA-vaccine against CSF. Methods. The fragment of E2 CSFV gene has been detected by PCR, and the expression of encoded protein – by immunohistochemical analysis. The anti-E2 antibodies in blood serum after immunization have been detected by ELISA. Results. It has been shown that candidate marker DNA-vaccine transfected myocytes of murine biceps in situ. The data of immuno-histochemical analysis revealed the expression of fragment of glycoprotein E2 CSFV from the plasmid introduced. The booster immunization with recombinant E2 led to the significant increase of the titer of antibodies specific to the antigen studied. Conclusions. The data obtained show that boosting with recombinant E2 enhances humoral immune response elicited by the candidate marker DNA-vaccine against CSF.

  3. Mathematical Modelling of Immune Response in Tissues

    OpenAIRE

    Su, B; Zhou, W; K. S. Dorman; Jones, D. E.

    2009-01-01

    We have developed a spatial–temporal mathematical model (PDE) to capture fundamental aspects of the immune response to antigen. We have considered terms that broadly describe intercellular communication, cell movement, and effector function (activation or inhibition). The PDE model is robust to variation in antigen load and it can account for (1) antigen recognition, (2) an innate immune response, (3) an adaptive immune response, (4) the elimination of antigen and subsequent resolution of the...

  4. Mosquito immune responses to arbovirus infections

    OpenAIRE

    Carol D. Blair; Olson, Ken E

    2014-01-01

    The principal mosquito innate immune response to virus infections, RNA interference (RNAi), differs substantially from the immune response to bacterial and fungal infections. The exo-siRNA pathway constitutes the major anti-arboviral RNAi response and its essential genetic components have been identified. Recent research has also implicated the Piwi-interacting RNA pathway in mosquito anti-arboviral immunity, but Piwi gene-family components involved are not well-defined. Arboviruses must evad...

  5. Immune cellular response to HPV: current concepts

    Directory of Open Access Journals (Sweden)

    Maria Alice Guimarães Gonçalves

    2004-02-01

    Full Text Available Although cellular immunity is essential for the elimination of human papillomavirus (HPV, the mechanisms involved are still poorly understood. We summarize the main mechanisms involved in cellular immune response to infections caused by HPV. Immunotherapies for HPV-related cancers require the disruption of T-cell response control mechanisms, associated with the stimulation of the Th1 cytokine response.

  6. Breastmilk-Saliva Interactions Boost Innate Immunity by Regulating the Oral Microbiome in Early Infancy.

    Directory of Open Access Journals (Sweden)

    Saad S Al-Shehri

    Full Text Available Xanthine oxidase (XO is distributed in mammals largely in the liver and small intestine, but also is highly active in milk where it generates hydrogen peroxide (H2O2. Adult human saliva is low in hypoxanthine and xanthine, the substrates of XO, and high in the lactoperoxidase substrate thiocyanate, but saliva of neonates has not been examined.Median concentrations of hypoxanthine and xanthine in neonatal saliva (27 and 19 μM respectively were ten-fold higher than in adult saliva (2.1 and 1.7 μM. Fresh breastmilk contained 27.3 ± 12.2 μM H2O2 but mixing baby saliva with breastmilk additionally generated >40 μM H2O2, sufficient to inhibit growth of the opportunistic pathogens Staphylococcus aureus and Salmonella spp. Oral peroxidase activity in neonatal saliva was variable but low (median 7 U/L, range 2-449 compared to adults (620 U/L, 48-1348, while peroxidase substrate thiocyanate in neonatal saliva was surprisingly high. Baby but not adult saliva also contained nucleosides and nucleobases that encouraged growth of the commensal bacteria Lactobacillus, but inhibited opportunistic pathogens; these nucleosides/bases may also promote growth of immature gut cells. Transition from neonatal to adult saliva pattern occurred during the weaning period. A survey of saliva from domesticated mammals revealed wide variation in nucleoside/base patterns.During breast-feeding, baby saliva reacts with breastmilk to produce reactive oxygen species, while simultaneously providing growth-promoting nucleotide precursors. Milk thus plays more than a simply nutritional role in mammals, interacting with infant saliva to produce a potent combination of stimulatory and inhibitory metabolites that regulate early oral-and hence gut-microbiota. Consequently, milk-saliva mixing appears to represent unique biochemical synergism which boosts early innate immunity.

  7. Immune responses to infectious laryngotracheitis virus.

    Science.gov (United States)

    Coppo, Mauricio J C; Hartley, Carol A; Devlin, Joanne M

    2013-11-01

    Infectious laryngotracheitis (ILT) is an upper respiratory tract disease in chickens caused by infectious laryngotracheitis virus (ILTV), an alphaherpesvirus. Despite the extensive use of attenuated, and more recently recombinant, vaccines for the control of this disease, ILT continues to affect the intensive poultry industries worldwide. Innate and cell-mediated, rather than humoral immune responses, have been identified as responsible for protection against disease. This review examines the current understandings in innate and adaptive immune responses towards ILTV, as well as the role of ILTV glycoprotein G in modulating the host immune response towards infection. Protective immunity induced by ILT vaccines is also examined. The increasing availability of tools and reagents for the characterisation of avian innate and cell-mediated immune responses are expected to further our understanding of immunity against ILTV and drive the development of new generation vaccines towards enhanced control of this disease. PMID:23567343

  8. Pre-existing immunity against Ad vectors: humoral, cellular, and innate response, what's important?.

    Science.gov (United States)

    Fausther-Bovendo, Hugues; Kobinger, Gary P

    2014-01-01

    Pre-existing immunity against human adenovirus (HAd) serotype 5 derived vector in the human population is widespread, thus hampering its clinical use. Various components of the immune system, including neutralizing antibodies (nAbs), Ad specific T cells and type I IFN activated NK cells, contribute to dampening the efficacy of Ad vectors in individuals with pre-existing Ad immunity. In order to circumvent pre-existing immunity to adenovirus, numerous strategies, such as developing alternative Ad serotypes, varying immunization routes and utilizing prime-boost regimens, are under pre-clinical or clinical phases of development. However, these strategies mainly focus on one arm of pre-existing immunity. Selection of alternative serotypes has been largely driven by the absence in the human population of nAbs against them with little attention paid to cross-reactive Ad specific T cells. Conversely, varying the route of immunization appears to mainly rely on avoiding Ad specific tissue-resident T cells. Finally, prime-boost regimens do not actually circumvent pre-existing immunity but instead generate immune responses of sufficient magnitude to confer protection despite pre-existing immunity. Combining the above strategies and thus taking into account all components regulating pre-existing Ad immunity will help further improve the development of Ad vectors for animal and human use. PMID:25483662

  9. A comparative analysis of HIV-specific mucosal/systemic T cell immunity and avidity following rDNA/rFPV and poxvirus-poxvirus prime boost immunisations.

    Science.gov (United States)

    Ranasinghe, Charani; Eyers, Fiona; Stambas, John; Boyle, David B; Ramshaw, Ian A; Ramsay, Alistair J

    2011-04-01

    In this study we have firstly compared a range of recombinant DNA poxvirus prime-boost immunisation strategies and shown that combined intramuscular (i.m.) 2× DNA-HIV/intranasal (i.n.) 2× FPV-HIV prime-boost immunisation can generate high-level of HIV-specific systemic (spleen) and mucosal (genito-rectal nodes, vaginal tissues and lung tissues) T cell responses and HIV-1 p24 Gag-specific serum IgG1, IgG2a and mucosal IgG, SIgA responses in vaginal secretions in BALB/c mice. Data indicate that following rDNA priming, two rFPV booster immunisations were necessary to generate good antibody and mucosal T cell immunity. This data also revealed that mucosal uptake of recombinant fowl pox (rFPV) was far superior to plasmid DNA. To further evaluate CD8+ T cell immunity, i.m. 2× DNA-HIV/i.n. 1× FPV-HIV immunisation strategy was directly compared with single shot poxvirus/poxvirus, i.n. FPV-HIV/i.m. VV-HIV immunisation. Results indicate that the latter strategy was able to generate strong sustained HIV-specific CD8+ T cells with higher avidity, broader cytokine/chemokine profiles and better protection following influenza-K(d)Gag(197-205) challenge compared to rDNA poxvirus prime-boost strategy. Our findings further substantiate the importance of vector selection/combination, order and route of delivery when designing effective vaccines for HIV-1. PMID:21352941

  10. Boosting BCG-primed mice with chimeric DNA vaccine HG856A induces potent multifunctional T cell responses and enhanced protection against Mycobacterium tuberculosis.

    Science.gov (United States)

    Ji, Ping; Hu, Zhi-Dong; Kang, Han; Yuan, Qin; Ma, Hui; Wen, Han-Li; Wu, Juan; Li, Zhong-Ming; Lowrie, Douglas B; Fan, Xiao-Yong

    2016-02-01

    The tuberculosis pandemic continues to rampage despite widespread use of the current Bacillus Calmette-Guerin (BCG) vaccine. Because DNA vaccines can elicit effective antigen-specific immune responses, including potent T cell-mediated immunity, they are promising vehicles for antigen delivery. In a prime-boost approach, they can supplement the inadequate anti-TB immunological memory induced by BCG. Based on this, a chimeric DNA vaccine HG856A encoding Mycobacterium tuberculosis (M. tuberculosis) immunodominant antigen Ag85A plus two copies of ESAT-6 was constructed. Potent humoral immune responses, as well as therapeutic effects induced by this DNA vaccine, were observed previously in M. tuberculosis-infected mice. In this study, we further evaluated the antigen-specific T cell immune responses and showed that repeated immunization with HG856A gave modest protection against M. tuberculosis challenge infection and significantly boosted the immune protection primed by BCG vaccination. Enhanced protection was accompanied by increased multifunctional Th1 CD4(+) T cell responses, most notably by an elevated frequency of M. tuberculosis antigen-specific IL-2-producing CD4(+) T cells post-vaccination. These data confirm the potential of chimeric DNA vaccine HG856A as an anti-TB vaccine candidate. PMID:26111521

  11. Hypothalamic neurohormones and immune responses

    Science.gov (United States)

    Quintanar, J. Luis; Guzmán-Soto, Irene

    2013-01-01

    The aim of this review is to provide a comprehensive examination of the current literature describing the neural-immune interactions, with emphasis on the most recent findings of the effects of neurohormones on immune system. Particularly, the role of hypothalamic hormones such as Thyrotropin-releasing hormone (TRH), Corticotropin-releasing hormone (CRH) and Gonadotropin-releasing hormone (GnRH). In the past few years, interest has been raised in extrapituitary actions of these neurohormones due to their receptors have been found in many non-pituitary tissues. Also, the receptors are present in immune cells, suggesting an autocrine or paracrine role within the immune system. In general, these neurohormones have been reported to exert immunomodulatory effects on cell proliferation, immune mediators release and cell function. The implications of these findings in understanding the network of hypothalamic neuropeptides and immune system are discussed. PMID:23964208

  12. Immune response to Encephalitozoon cuniculi infection

    OpenAIRE

    Khan, Imtiaz A.; Moretto, Magali; Weiss, Louis M.

    2001-01-01

    Microsporidia are obligate intracellular parasites, which can cause complications in immunocompromised individuals. Very little is known about the host immune response generated against these infectious agents. Encephalitozoon cuniculi is the best studied microsporidian and the protective immune response against this parasite is mediated by cytotoxic CD8+ T cells.

  13. Effect of praziquantel treatment of Schistosoma mansoni during pregnancy on immune responses to schistosome antigens among the offspring

    DEFF Research Database (Denmark)

    Tweyongyere, Robert; Mawa, Patrice A.; Kihembo, Macklyn; Jones, Frances M.; Webb, Emily L.; Cose, Stephen; Dunne, David W.; Vennervald, Birgitte J; Elliott, Alison M.

    2011-01-01

    Offspring of women with schistosomiasis may exhibit immune responsiveness to schistosomes due to in utero sensitisation or trans-placental transfer of antibodies. Praziquantel treatment during pregnancy boosts maternal immune responses to schistosome antigens and reduces worm burden. Effects of...... praziquantel treatment during pregnancy on responses among offspring are unknown....

  14. Micronutrients influencing the immune response in leprosy

    Directory of Open Access Journals (Sweden)

    Cecília Maria Passos Vázquez

    2014-01-01

    Full Text Available Leprosy is a chronic infectious disease caused by Mycobacterium leprae, an intracellular bacillus of airborne transmission. The disease affects the skin and peripheral nerves and can cause neurological sequelae. The bacillus multiplies slowly in the host and the disease probably occurs due to malfunctioning in host immune response. This review addresses the role of some specific micronutrients in the immune response, such as Vitamins A, D, E, C, Zinc and Selenium, detailing their mechanisms of actions in infectious diseases, and in leprosy. The immune response to pathogens releases harmful substances, which lead to tissue damage. This review discusses how a decreased level of antioxidants may contribute to an increased oxidative stress and complications of infectious diseases and leprosy. As the nutrients have a regulatory effect in the innate and adaptative immune responses, a perfect balance in their concentrations is important to improve the immune response against the pathogens.

  15. Mucosal priming of newborn mice with S. Typhi Ty21a expressing anthrax protective antigen (PA) followed by parenteral PA-boost induces B and T cell-mediated immunity that protects against infection bypassing maternal antibodies.

    Science.gov (United States)

    Ramirez, Karina; Ditamo, Yanina; Galen, James E; Baillie, Les W J; Pasetti, Marcela F

    2010-08-23

    The currently licensed anthrax vaccine has several limitations and its efficacy has been proven only in adults. Effective immunization of newborns and infants requires adequate stimulation of their immune system, which is competent but not fully activated. We explored the use of the licensed live attenuated S. Typhi vaccine strain Ty21a expressing Bacillus anthracis protective antigen [Ty21a(PA)] followed PA-alum as a strategy for immunizing the pediatric population. Newborn mice primed with a single dose of Ty21a(PA) exhibited high frequencies of mucosal IgA-secreting B cells and IFN-gamma-secreting T cells during the neonatal period, none of which was detected in newborns immunized with a single dose of PA-alum. Priming with Ty21a(PA) followed by PA-boost resulted in high levels of PA-specific IgG, toxin neutralizing and opsonophagocytic antibodies and increased frequency of bone marrow IgG plasma cells and memory B cells compared with repeated immunization with PA-alum alone. Robust B and T cell responses developed even in the presence of maternal antibodies. The prime-boost protected against systemic and respiratory infection. Mucosal priming with a safe and effective S. Typhi-based anthrax vaccine followed by PA-boost could serve as a practical and effective prophylactic approach to prevent anthrax early in life. PMID:20619377

  16. Boosting high-intensity focused ultrasound-induced anti-tumor immunity using a sparse-scan strategy that can more effectively promote dendritic cell maturation

    Directory of Open Access Journals (Sweden)

    Zhong Pei

    2010-01-01

    Full Text Available Abstract Background The conventional treatment protocol in high-intensity focused ultrasound (HIFU therapy utilizes a dense-scan strategy to produce closely packed thermal lesions aiming at eradicating as much tumor mass as possible. However, this strategy is not most effective in terms of inducing a systemic anti-tumor immunity so that it cannot provide efficient micro-metastatic control and long-term tumor resistance. We have previously provided evidence that HIFU may enhance systemic anti-tumor immunity by in situ activation of dendritic cells (DCs inside HIFU-treated tumor tissue. The present study was conducted to test the feasibility of a sparse-scan strategy to boost HIFU-induced anti-tumor immune response by more effectively promoting DC maturation. Methods An experimental HIFU system was set up to perform tumor ablation experiments in subcutaneous implanted MC-38 and B16 tumor with dense- or sparse-scan strategy to produce closely-packed or separated thermal lesions. DCs infiltration into HIFU-treated tumor tissues was detected by immunohistochemistry and flow cytometry. DCs maturation was evaluated by IL-12/IL-10 production and CD80/CD86 expression after co-culture with tumor cells treated with different HIFU. HIFU-induced anti-tumor immune response was evaluated by detecting growth-retarding effects on distant re-challenged tumor and tumor-specific IFN-γ-secreting cells in HIFU-treated mice. Results HIFU exposure raised temperature up to 80 degrees centigrade at beam focus within 4 s in experimental tumors and led to formation of a well-defined thermal lesion. The infiltrated DCs were recruited to the periphery of lesion, where the peak temperature was only 55 degrees centigrade during HIFU exposure. Tumor cells heated to 55 degrees centigrade in 4-s HIFU exposure were more effective to stimulate co-cultured DCs to mature. Sparse-scan HIFU, which can reserve 55 degrees-heated tumor cells surrounding the separated lesions, elicited an

  17. Epigenetics and the Adaptive Immune Response

    OpenAIRE

    Kondilis-Mangum, Hrisavgi D.; Wade, Paul A.

    2012-01-01

    Cells of the adaptive immune response undergo dynamic epigenetic changes as they develop and respond to immune challenge. Plasticity is a necessary prerequisite for the chromosomal dynamics of lineage specification, development, and the immune effector function of the mature cell types. The alterations in DNA methylation and histone modification that characterize activation may be integral to the generation of immunologic memory, thereby providing an advantage on secondary exposure to pathoge...

  18. The immune response to surgery and infection

    OpenAIRE

    Dąbrowska, Aleksandra M.; Słotwiński, Robert

    2014-01-01

    Surgical trauma affects both the innate and acquired immunity. The severity of immune disorders is proportional to the extent of surgical trauma and depends on a number of factors, including primarily the basic disease requiring surgical treatment (e.g. cancer), often coexisting infections and impaired nutritional status. Disorder of the immune response following surgical trauma may predispose to septic complications burdened with the highest mortality rate. Extensive surgery in cancer patien...

  19. Prime-Boost Vaccination Using Chemokine-Fused gp120 DNA and HIV Envelope Peptides Activates Both Immediate and Long-Term Memory Cellular Responses in Rhesus Macaques

    Directory of Open Access Journals (Sweden)

    Hong Qin

    2010-01-01

    Full Text Available HIV vaccine candidates with improved immunogenicity and induction of mucosal T-cell immunity are needed. A prime-boost strategy using a novel HIV glycoprotein 120 DNA vaccine was employed to immunize rhesus macaques. The DNA vaccine encoded a chimeric gp120 protein in fusion with monocyte chemoattractant protein-3, which was hypothesized to improve the ability of antigen-presenting cells to capture viral antigen through chemokine receptor-mediated endocytosis. DNA vaccination induced virus-reactive T cells in peripheral blood, detectable by T cell proliferation, INFγ ELISPOT and sustained IL-6 production, without humoral responses. With a peptide-cocktail vaccine containing a set of conserved polypeptides of HIV-1 envelope protein, given by nasogastric administration, primed T-cell immunity was significantly boosted. Surprisingly, long-term and peptide-specific mucosal memory T-cell immunity was detected in both vaccinated macaques after one year. Therefore, data from this investigation offer proof-of-principle for potential effectiveness of the prime-boost strategy with a chemokine-fused gp120 DNA and warrant further testing in the nonhuman primate models for developing as a potential HIV vaccine candidate in humans.

  20. Innate immune responses to Pseudomonas aeruginosa infection

    OpenAIRE

    Lavoie, Elise G.; Wangdi, Tamding; Kazmierczak, Barbara I.

    2011-01-01

    Innate immune responses play a critical role in controlling acute infections due to Pseudomonas aeruginosa in both mice and in humans. In this review we focus on innate immune recognition and clearance mechanisms that are important for controlling P. aeruginosa in the mammalian lung, with particular attention to those that influence the outcome of in vivo infection in murine models.

  1. Aedes mosquito salivary immune peptides: boost or block dengue viral infections

    Directory of Open Access Journals (Sweden)

    Natthanej Luplertlop

    2014-02-01

    Full Text Available Dengue virus, one of the most important arthropod-borne viruses, infected to human can severely cause dengue hemorrhagic fever and dengue shock syndrome. There are expected about 50 million dengue infections and 500 000 individuals are hospitalized with dengue hemorrhagic fever, mainly in Southeast Asia, Pacific, and in Americas reported each year. The rapid expansion of global dengue is one of a major public health challenge, together with not yet successful solutions of dengue epidemic control strategies. Thus, these dynamic dengue viral infections exhibited high demographic, societal, and public health infrastructure impacts on human. This review aimed to highlight the current understanding of dengue mosquito immune responses and role of mosquito salivary glands on dengue infection. These information may provide a valuable knowledge of disease pathogenesis, especially in mosquito vector and dengue virus interaction, which may help to control and prevent dengue distribution.

  2. Aedes mosquito salivary immune peptides:boost or block dengue viral infections

    Institute of Scientific and Technical Information of China (English)

    Natthanej Luplertlop

    2014-01-01

    Dengue virus, one of the most important arthropod-borne viruses, infected to human can severely cause dengue hemorrhagic fever and dengue shock syndrome. There are expected about 50 million dengue infections and 500 000 individuals are hospitalized with dengue hemorrhagic fever, mainly in Southeast Asia, Pacific, and in Americas reported each year. The rapid expansion of global dengue is one of a major public health challenge, together with not yet successful solutions of dengue epidemic control strategies. Thus, these dynamic dengue viral infections exhibited high demographic, societal, and public health infrastructure impacts on human. This review aimed to highlight the current understanding of dengue mosquito immune responses and role of mosquito salivary glands on dengue infection. These information may provide a valuable knowledge of disease pathogenesis, especially in mosquito vector and dengue virus interaction, which may help to control and prevent dengue distribution.

  3. Elicitation of strong immune responses by a DNA vaccine expressing a secreted form of hepatitis C virus envelope protein E2 in murine and porcine animal models

    DEFF Research Database (Denmark)

    Li, Yiping; Kang, H.N.; Babiuk, L.A.;

    2006-01-01

    . RESULTS: Intradermal injection of E2 DNA vaccine induced strong Th1-like immune responses in mice. In piglets, E2 DNA vaccine elicited moderate and more balanced immune responses. A DNA vaccine prime and protein boost vaccination, strategy induced significantly higher E2-specific antibody levels and...

  4. Characterization of the antigen-specific CD4+ T cell response induced by prime-boost strategies with CAF01 and CpG adjuvants administered by the intranasal and subcutaneous routes

    Directory of Open Access Journals (Sweden)

    Annalisa eCiabattini

    2015-08-01

    Full Text Available The design of heterologous prime-boost vaccine combinations that optimally shape the immune response is of critical importance for the development of next generation vaccines. Here we tested different prime-boost combinations using the tuberculosis vaccine antigen H56 with CAF01 or CpG ODN 1821 adjuvants, administered by the parenteral and nasal routes. By using peptide-MHC class II tetramers, antigen-specific CD4+ T cells were tracked following primary and booster immunizations. Both parenteral priming with H56 plus CAF01 and nasal priming with H56 plus CpG elicited significant expansion of CD4+ tetramer-positive T cells in the spleen, however only parenterally primed cells responded to booster immunization. Subcutaneous priming with H56 and CAF01 followed by nasal boosting with H56 and CpG showed the greater expansion of CD4+ tetramer-positive T cells in the spleen and lungs compared to all the other homologous and heterologous prime-boost combinations. Nasal boosting exerted a recruitment of primed CD4+ T cells into lungs that was stronger in subcutaneously than nasally primed mice, in accordance with different chemokine receptor expression induced by primary immunization. These data demonstrate that subcutaneous priming is fundamental for eliciting CD4+ T cells that can be efficiently boosted by the nasal route and results in the recruitment of antigen-experienced cells into the lungs. Combination of different vaccine formulations and routes of delivery for priming and boosting is a strategic approach for improving and directing vaccine-induced immune responses.

  5. Genetic control of immune responses to influenza A matrix 2 protein (M2).

    Science.gov (United States)

    Misplon, Julia A; Lo, Chia-Yun; Gabbard, Jon D; Tompkins, S Mark; Epstein, Suzanne L

    2010-08-16

    Vaccines should protect genetically diverse populations. Therefore we tested the candidate "universal" influenza A matrix protein 2 (M2) vaccine in multiple mouse strains. Mice were primed with M2 DNA and boosted with M2 recombinant adenovirus (rAd). C57BL/6 (B6) mice developed no antibody or T-cell response to M2, while BALB/c responded strongly. CBA responses were intermediate. Both MHC and background genes influenced responsiveness. To improve low responses we immunized with adjuvanted peptide-carrier conjugates, or co-immunized with nucleoprotein (NP), which can augment T-cell help. The conjugate vaccine enhanced some outcomes but not others. Co-immunizing with NP improved outcomes over either NP or M2 immunizations alone. These results have implications for vaccination of genetically diverse populations. PMID:20600476

  6. Exosomes in the Immune Response and Tolerance

    Institute of Scientific and Technical Information of China (English)

    修方明; 曹雪涛

    2004-01-01

    Exosomes, secreted by many live cells, are small non-cell vesicles with nanoparticle-grade size. In addition to the original function of discarding the uselessful membrane molecules, exosomes are involved in a range of immunoregulatory functions. Dendritic cell-derived exosomes and tumor-derived exosomes are the best characterized vesicles with potent antitumor effect by efficienfly inducing immune response. Down-regtdation of immune response or induction of immune tolerance is another interesting function of exosomes, Further functional studies of the exosomes will shed light on the application of exosomes。

  7. Immune Response to Giardia duodenalis

    OpenAIRE

    Faubert, Gaétan

    2000-01-01

    The intestinal protozoan Giardia duodenalis is a widespread opportunistic parasite of humans and animals. This parasite inhabits the upper part of the small intestine and has a direct life cycle. After ingestion of cysts, which are the infective stage, the trophozoites emerge from the cysts in the duodenum and attach to the small intestinal mucosa of the host. Since the migration of trophozoites from the lumen of the intestine into surrounding tissues is an unusual occurrence, the immune resp...

  8. Murine immune responses to oral BCG immunization in the presence or absence of prior BCG sensitization.

    Science.gov (United States)

    Cross, Martin L; Lambeth, Matthew R; Aldwell, Frank E

    2010-02-01

    Oral delivery of live Mycobacterium bovis BCG in a lipid matrix invokes cell-mediated immune (CMI) responses in mice and consequent protection against pulmonary challenge with virulent mycobacteria. To investigate the influence of prior BCG sensitization on oral vaccine efficacy, we assessed CMI responses and BCG colonization of the alimentary tract lymphatics 5 months after oral vaccination, in both previously naive mice and in mice that had been sensitized to BCG by injection 6 months previously. CMI responses did not differ significantly between mice that received subcutaneous BCG followed by oral BCG and those that received either injected or oral BCG alone. In vivo BCG colonization was predominant in the mesenteric lymph nodes after oral vaccination; this colonizing ability was not influenced by prior BCG sensitization. From this murine model study, we conclude that although prior parenteral-route BCG sensitization does not detrimentally affect BCG colonization after oral vaccination, there is no significant immune-boosting effect of the oral vaccine either. PMID:19918257

  9. Protective immune responses in lawsonia intracellularis infections

    DEFF Research Database (Denmark)

    Cordes, Henriette; Riber, Ulla; Boutrup, Torsten; Jensen, Tim Kåre; Nguyen, Lien Thi Minh; Jungersen, Gregers

    increase in acute phase response after challenge with a pathogenic isolate. Here we show results from measurements of serology as well as cell-mediated immune responses from this experiment. We found that Lawsonia-specific IgA peaked in serum around day 17-24 after a primary infection in experimentally...... exhibited a high, but short-lasting peak after re-infection. Specific IFN responses were also measured using a whole blood IFN-γ assay. These were very high in challenge infected and re-infected animals as compared to controls. These specific immune responses may contribute to the explanation of mechanisms...

  10. Modulating immune responses with probiotic bacteria.

    Science.gov (United States)

    Matsuzaki, T; Chin, J

    2000-02-01

    For many years, probiotic bacteria have been known to confer health benefits to the consumer. One possible mechanism for this may be the ability of probiotic bacteria to modulate immune responses. Oral administration of Lactobacillus casei strain Shirota (LcS) has been found to enhance innate immunity by stimulating the activity of splenic NK cells. Oral feeding with killed LcS was able to stimulate the production of Th1 cytokines, resulting in repressed production of IgE antibodies against Ovalbumin in experimental mice. The ability to switch mucosal immune responses towards Th1 with probiotic bacteria provides a strategy for treatment of allergic disorders. Growth of Meth A tumour cells in the lungs was also inhibited by intrapleural injection of LcS. Oral administration of other probiotic bacteria, such as Streptococcus thermophilus (St), Lactobacillus fermentum (Lf) and yeast (Y), elicited different immune responses. Mice that were prefed yeast or Lf followed by feeding with ovalbumin (OVA) responded better to vaccination with OVA than mice not given either probiotic or OVA or mice that had been prefed only OVA. However, antibody responses were significantly suppressed in response to vaccination with OVA in mice that had been prefed yeast followed by yeast and OVA as well as mice prefed Lf followed by Lf and OVA. Prefeeding St followed by OVA feeding enhanced cellular immune responses against ovalbumin. In contrast, mice prefed St followed by St + OVA were hyporesponsive against OVA. While antigen feeding alone appears to prime for an immune response, cofeeding antigen with probiotic bacteria can suppress both antibody and cellular immune responses and may provide an efficacious protocol to attenuate autoimmune diseases, such as experimental allergic encephalomyelitis, by jointly dosing with myelin basic protein and probiotic bacteria. PMID:10651931

  11. Plasticity of immunity in response to eating.

    Science.gov (United States)

    Luoma, Rachel L; Butler, Michael W; Stahlschmidt, Zachary R

    2016-07-01

    Following a meal, an animal can exhibit dramatic shifts in physiology and morphology, as well as a substantial increase in metabolic rate associated with the energetic costs of processing a meal (i.e. specific dynamic action, SDA). However, little is known about the effects of digestion on another important physiological and energetically costly trait: immune function. Thus, we tested two competing hypotheses. (1) Digesting animals up-regulate their immune systems (putatively in response to the increased microbial exposure associated with ingested food). (2) Digesting animals down-regulate their immune systems (presumably to allocate energy to the breakdown of food). We assayed innate immunity (lytic capacity and agglutination) in cornsnakes (Pantherophis guttatus) during and after meal digestion. Lytic capacity was higher in females, and (in support of our first hypothesis) agglutination was higher during absorption. Given its potential energetic cost, immune up-regulation may contribute to SDA. PMID:27099367

  12. Boosting of HIV-1 neutralizing antibody responses by a distally related retroviral envelope protein

    DEFF Research Database (Denmark)

    Uchtenhagen, Hannes; Schiffner, Torben; Bowles, Emma;

    2014-01-01

    Our knowledge of the binding sites for neutralizing Abs (NAb) that recognize a broad range of HIV-1 strains (bNAb) has substantially increased in recent years. However, gaps remain in our understanding of how to focus B cell responses to vulnerable conserved sites within the HIV-1 envelope glycop...... results provide a proof of concept that a distally related retroviral SIV Env protein boost can increase pre-existing NAb responses against HIV-1....

  13. Effect of cellular mobility on immune response

    Science.gov (United States)

    Pandey, R. B.; Mannion, R.; Ruskin, H. J.

    2000-08-01

    Mobility of cell types in our HIV immune response model is subject to an intrinsic mobility and an explicit directed mobility, which is governed by Pmob. We investigate how restricting the explicit mobility, while maintaining the innate mobility of a viral-infected cell, affects the model's results. We find that increasing the explicit mobility of the immune system cells leads to viral dominance for certain levels of viral mutation. We conclude that increasing immune system cellular mobility indirectly increases the virus’ inherent mobility.

  14. The immune responses of the coral

    OpenAIRE

    C Toledo-Hernández; CP Ruiz-Diaz

    2014-01-01

    Corals are among the most ancient extant animals on earth. Currently, coral viability is threatened, due in part to the increased number of diseases affecting them in recent decades. Understanding how the innate immune systems of corals function is important if we want to predict the fate of corals and their response to the environmental and biological changes they face. In this review we discuss the latest findings regarding the innate immune systems of corals. The review is organized follow...

  15. Potent and Broadly Reactive HIV-2 Neutralizing Antibodies Elicited by a Vaccinia Virus Vector Prime-C2V3C3 Polypeptide Boost Immunization Strategy▿ †

    Science.gov (United States)

    Marcelino, José Maria; Borrego, Pedro; Rocha, Cheila; Barroso, Helena; Quintas, Alexandre; Novo, Carlos; Taveira, Nuno

    2010-01-01

    Human immunodeficiency virus type 2 (HIV-2) infection affects about 1 to 2 million individuals, the majority living in West Africa, Europe, and India. As for HIV-1, new strategies for the prevention of HIV-2 infection are needed. Our aim was to produce new vaccine immunogens that elicit the production of broadly reactive HIV-2 neutralizing antibodies (NAbs). Native and truncated envelope proteins from the reference HIV-2ALI isolate were expressed in vaccinia virus or in bacteria. This source isolate was used due to its unique phenotype combining CD4 independence and CCR5 usage. NAbs were not elicited in BALB/c mice by single immunization with a truncated and fully glycosylated envelope gp125 (gp125t) or a recombinant polypeptide comprising the C2, V3, and C3 envelope regions (rpC2-C3). A strong and broad NAb response was, however, elicited in mice primed with gp125t expressed in vaccinia virus and boosted with rpC2-C3. Serum from these animals potently neutralized (median 50% neutralizing titer, 3,200) six of six highly divergent primary HIV-2 isolates. Coreceptor usage and the V3 sequence of NAb-sensitive isolates were similar to that of the vaccinating immunogen (HIV-2ALI). In contrast, NAbs were not reactive on three X4 isolates that displayed major changes in V3 loop sequence and structure. Collectively, our findings demonstrate that broadly reactive HIV-2 NAbs can be elicited by using a vaccinia virus vector-prime/rpC2-C3-boost immunization strategy and suggest a potential relationship between escape to neutralization and cell tropism. PMID:20844029

  16. Heterologous Prime-Boost Oral Immunization with GK-1 Peptide from Taenia crassiceps Cysticerci Induces Protective Immunity▿

    Science.gov (United States)

    Fragoso, Gladis; Esquivel-Guadarrama, Fernando; Santana, M. Angélica; Bobes, Raul J.; Hernández, Beatriz; Cervantes, Jacquelynne; Segura, René; Goldbaum, Fernando A.; Sciutto, Edda; Rosas, Gabriela

    2011-01-01

    Oral immunization is a goal in vaccine development, particularly for pathogens that enter the host through the mucosal system. This study was designed to explore the immunogenic properties of the Taenia crassiceps protective peptide GK-1 administered orally. Mice were orally immunized with the synthetic GK-1 peptide in its linear form with or without the Brucella lumazine synthase (BLS) protein adjuvant or as a chimera recombinantly bound to BLS (BLS-GK-1). Mice were boosted twice with GK-1 only at 15-day intervals. A significant rate of protection of 64.7% was achieved in GK-1-immunized mice, and that rate significantly increased to 91.8 and 96% when mice were primed with GK-1 coadministered with BLS as an adjuvant and BLS as a carrier, respectively. Specific antibodies and T cell activation and proliferation accompanied the protection induced, revealing the potent immunogenicity of GK-1. Through immunohistochemical studies, GK-1 was detected in T and B cell zones of the Peyer's patches (PP) and mesenteric lymph nodes. In the latter, abundant proliferating cells were detected by 5′-bromo-2′-deoxyuridine incorporation. No proliferation was detected in PP. Altogether, these results portray the potent immunogenic properties of GK-1 administered orally and reinforce the usefulness of BLS as an adjuvant and adequate vaccine delivery system for oral vaccines. PMID:21593234

  17. SUMO boosts the DNA damage response barrier against cancer

    Czech Academy of Sciences Publication Activity Database

    Bartek, Jiří; Hodný, Zdeněk

    2010-01-01

    Roč. 17, č. 1 (2010), s. 9-11. ISSN 1535-6108 R&D Projects: GA ČR GA301/08/0353 Institutional research plan: CEZ:AV0Z50520514 Keywords : DNA damage response * ubiquitylation * sumoylation Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 26.925, year: 2010

  18. The immune responses of the coral

    Directory of Open Access Journals (Sweden)

    C Toledo-Hernández

    2014-11-01

    Full Text Available Corals are among the most ancient extant animals on earth. Currently, coral viability is threatened, due in part to the increased number of diseases affecting them in recent decades. Understanding how the innate immune systems of corals function is important if we want to predict the fate of corals and their response to the environmental and biological changes they face. In this review we discuss the latest findings regarding the innate immune systems of corals. The review is organized following the chronology of steps taken by corals from the initial encounter with a potential pathogen and recognition of threats to the orchestration of a response. We begin with the literature describing the repertory of immune-related receptors involved in the recognition of threats and the subsequent pathways leading to an immune response. We then review the effector responses that eliminate the threats described for corals. Finally, we acknowledge the literature of coral microbiology to access the potential role of microbes as an essential constituent of the coral immune system.

  19. Immune Response to Ebola Virus Infection

    Directory of Open Access Journals (Sweden)

    Alain Alonso Remedios

    2016-06-01

    Full Text Available Ebola virus belongs to the family Filoviridae and causes a highly lethal hemorrhagic fever. Affected patients show an impaired immune response as a result of the evasion mechanisms employed by the virus. Cathepsin is an enzyme present in the granules of phagocytes which cleaves viral surface glycoproteins, allowing virus entry into the host cell. In addition, this virus is resistant to the antiviral effects of type I interferon, promotes the synthesis of proinflammatory cytokines and induces apoptosis of monocytes and lymphocytes. It also induces an incomplete activation of dendritic cells, thus avoiding the presentation of viral antigens. Although specific antibodies are produced after the first week, their neutralizing capacity is doubtful. The virus evades the immune response and replicates uncontrollably in the host. This paper aims to summarize the main characteristics of the immune response to Ebola virus infection.

  20. Antimicrobial peptides in innate immune responses

    DEFF Research Database (Denmark)

    Sorensen, O.E.; Borregaard, N.; Cole, A.M.

    2008-01-01

    novo synthesis or by proteolytic cleavage from antimicrobially inactive proproteins. Studies of human diseases and animal studies have given important clues to the in vivo role of AMPs. It is now evident that dysregulation of the generation of AMPs in innate immune responses plays a role in certain......Antimicrobial peptides (AMPs) are ancient effector molecules in the innate immune response of eukaryotes. These peptides are important for the antimicrobial efficacy of phagocytes and for the innate immune response mounted by epithelia of humans and other mammals. AMPs are generated either by de...... diseases like Crohn's disease and atopic dermatitis. AMPs are attractive candidates for development of novel antibiotics due to their in vivo activity profile and some peptides may serve as templates for further drug development Udgivelsesdato: 2008...

  1. Studies of Immune Responses in Candida vaginitis.

    Science.gov (United States)

    De Bernardis, Flavia; Arancia, Silvia; Sandini, Silvia; Graziani, Sofia; Norelli, Sandro

    2015-01-01

    The widespread occurrence of vaginal candidiasis and the development of resistance against anti-fungal agents has stimulated interest in understanding the pathogenesis of this disease. The aim of our work was to characterize, in an animal model of vaginal candidiasis, the mechanisms that play a role in the induction of mucosal immunity against C. albicans and the interaction between innate and adaptive immunity. Our studies evidenced the elicitation of cell-mediated immunity (CMIs) and antibody (Abs)-mediated immunity with a Th1 protective immunity. An immune response of this magnitude in the vagina was very encouraging to identify the proper targets for new strategies for vaccination or immunotherapy of vaginal candidiasis. Overall, our data provide clear evidence that it is possible to prevent C. albicans vaginal infection by active intravaginal immunization with aspartyl proteinase expressed as recombinant protein. This opens the way to a modality for anti-Candida protection at the mucosa. The recombinant protein Sap2 was assembled with virosomes, and a vaccine PEVION7 (PEV7) was obtained. The results have given evidence that the vaccine, constituted of virosomes and Secretory aspartyl proteinase 2 (Sap2) (PEV7), has an encouraging therapeutic potential for the treatment of recurrent vulvovaginal candidiasis. PMID:26473934

  2. Studies of Immune Responses in Candida vaginitis

    Directory of Open Access Journals (Sweden)

    Flavia De Bernardis

    2015-10-01

    Full Text Available The widespread occurrence of vaginal candidiasis and the development of resistance against anti-fungal agents has stimulated interest in understanding the pathogenesis of this disease. The aim of our work was to characterize, in an animal model of vaginal candidiasis, the mechanisms that play a role in the induction of mucosal immunity against C. albicans and the interaction between innate and adaptive immunity. Our studies evidenced the elicitation of cell-mediated immunity (CMIs and antibody (Abs-mediated immunity with a Th1 protective immunity. An immune response of this magnitude in the vagina was very encouraging to identify the proper targets for new strategies for vaccination or immunotherapy of vaginal candidiasis. Overall, our data provide clear evidence that it is possible to prevent C. albicans vaginal infection by active intravaginal immunization with aspartyl proteinase expressed as recombinant protein. This opens the way to a modality for anti-Candida protection at the mucosa. The recombinant protein Sap2 was assembled with virosomes, and a vaccine PEVION7 (PEV7 was obtained. The results have given evidence that the vaccine, constituted of virosomes and Secretory aspartyl proteinase 2 (Sap2 (PEV7, has an encouraging therapeutic potential for the treatment of recurrent vulvovaginal candidiasis.

  3. Studies of Immune Responses in Candida vaginitis

    Science.gov (United States)

    De Bernardis, Flavia; Arancia, Silvia; Sandini, Silvia; Graziani, Sofia; Norelli, Sandro

    2015-01-01

    The widespread occurrence of vaginal candidiasis and the development of resistance against anti-fungal agents has stimulated interest in understanding the pathogenesis of this disease. The aim of our work was to characterize, in an animal model of vaginal candidiasis, the mechanisms that play a role in the induction of mucosal immunity against C. albicans and the interaction between innate and adaptive immunity. Our studies evidenced the elicitation of cell-mediated immunity (CMIs) and antibody (Abs)-mediated immunity with a Th1 protective immunity. An immune response of this magnitude in the vagina was very encouraging to identify the proper targets for new strategies for vaccination or immunotherapy of vaginal candidiasis. Overall, our data provide clear evidence that it is possible to prevent C. albicans vaginal infection by active intravaginal immunization with aspartyl proteinase expressed as recombinant protein. This opens the way to a modality for anti-Candida protection at the mucosa. The recombinant protein Sap2 was assembled with virosomes, and a vaccine PEVION7 (PEV7) was obtained. The results have given evidence that the vaccine, constituted of virosomes and Secretory aspartyl proteinase 2 (Sap2) (PEV7), has an encouraging therapeutic potential for the treatment of recurrent vulvovaginal candidiasis. PMID:26473934

  4. Injury-induced immune responses in Hydra.

    Science.gov (United States)

    Wenger, Yvan; Buzgariu, Wanda; Reiter, Silke; Galliot, Brigitte

    2014-08-01

    The impact of injury-induced immune responses on animal regenerative processes is highly variable, positive or negative depending on the context. This likely reflects the complexity of the innate immune system that behaves as a sentinel in the transition from injury to regeneration. Early-branching invertebrates with high regenerative potential as Hydra provide a unique framework to dissect how injury-induced immune responses impact regeneration. A series of early cellular events likely require an efficient immune response after amputation, as antimicrobial defence, epithelial cell stretching for wound closure, migration of interstitial progenitors toward the wound, cell death, phagocytosis of cell debris, or reconstruction of the extracellular matrix. The analysis of the injury-induced transcriptomic modulations of 2636 genes annotated as immune genes in Hydra identified 43 genes showing an immediate/early pulse regulation in all regenerative contexts examined. These regulations point to an enhanced cytoprotection via ROS signaling (Nrf, C/EBP, p62/SQSMT1-l2), TNFR and TLR signaling (TNFR16-like, TRAF2l, TRAF5l, jun, fos-related, SIK2, ATF1/CREB, LRRC28, LRRC40, LRRK2), proteasomal activity (p62/SQSMT1-l1, Ced6/Gulf, NEDD8-conjugating enzyme Ubc12), stress proteins (CRYAB1, CRYAB2, HSP16.2, DnaJB9, HSP90a1), all potentially regulating NF-κB activity. Other genes encoding immune-annotated proteins such as NPYR4, GTPases, Swap70, the antiproliferative BTG1, enzymes involved in lipid metabolism (5-lipoxygenase, ACSF4), secreted clotting factors, secreted peptidases are also pulse regulated upon bisection. By contrast, metalloproteinases and antimicrobial peptide genes largely follow a context-dependent regulation, whereas the protease inhibitor α2macroglobulin gene exhibits a sustained up-regulation. Hence a complex immune response to injury is linked to wound healing and regeneration in Hydra. PMID:25086685

  5. Optically Triggered Immune Response through Photocaged Oligonucleotides

    Science.gov (United States)

    Govan, Jeane M.; Young, Douglas D.; Lively, Mark O.

    2015-01-01

    Bacterial and viral CpG oligonculeotides are unmethylated cytosine-phosphate-guanosine dinucleotide sequences and trigger an innate immune response through activation of the toll-like receptor 9 (TLR9). We have developed synthetic photocaged CpGs via site-specific incorporation of nitropiperonyloxymethyl (NPOM)-caged thymidine residues. These oligonucleotides enable the optical control of TLR9 function and thereby provide light-activation of an immune response. We provide a proof-of-concept model by applying a reporter assay in live cells and by quantification of endogenous production of interleukin 6. PMID:26034339

  6. Cell-mediated and humoral immune responses in pigs following primary and challenge-exposure to Lawsonia intracellularis

    DEFF Research Database (Denmark)

    Hvass, Henriette Cordes; Riber, Ulla; Jensen, Tim Kåre; Jungersen, Gregers

    2012-01-01

    To investigate immune responses upon re-infection with Lawsonia intracellularis, local and peripheral humoral and cell-mediated immune responses to primary and challenge inoculations were studied in 22 pigs. Pigs were orally inoculated with virulent L. intracellularis at the age of 5-6 weeks...... not boosted by the re-inoculation, since identical intestinal IgA responses developed in response to the inoculation in both the susceptible CC pigs and the protected RE pigs. A memory recall cell-mediated immune response developed in RE pigs which was significantly stronger compared to the primary......-mediated immune responses are likely mediators of protective immunity against L. intracellularis, with CD8+ effector cells and CD4+CD8+ double positive memory T cells as main contributors to the antigen-specific IFN-γ production....

  7. A viral vectored prime-boost immunization regime targeting the malaria Pfs25 antigen induces transmission-blocking activity.

    Directory of Open Access Journals (Sweden)

    Anna L Goodman

    Full Text Available The ookinete surface protein Pfs25 is a macrogamete-to-ookinete/ookinete stage antigen of Plasmodium falciparum, capable of exerting high-level anti-malarial transmission-blocking activity following immunization with recombinant protein-in-adjuvant formulations. Here, this antigen was expressed in recombinant chimpanzee adenovirus 63 (ChAd63, human adenovirus serotype 5 (AdHu5 and modified vaccinia virus Ankara (MVA viral vectored vaccines. Two immunizations were administered to mice in a heterologous prime-boost regime. Immunization of mice with AdHu5 Pfs25 at week 0 and MVA Pfs25 at week 10 (Ad-MVA Pfs25 resulted in high anti-Pfs25 IgG titers, consisting of predominantly isotypes IgG1 and IgG2a. A single priming immunization with ChAd63 Pfs25 was as effective as AdHu5 Pfs25 with respect to ELISA titers at 8 weeks post-immunization. Sera from Ad-MVA Pfs25 immunized mice inhibited the transmission of P. falciparum to the mosquito both ex vivo and in vivo. In a standard membrane-feeding assay using NF54 strain P. falciparum, oocyst intensity in Anopheles stephensi mosquitoes was significantly reduced in an IgG concentration-dependent manner when compared to control feeds (96% reduction of intensity, 78% reduction in prevalence at a 1 in 5 dilution of sera. In addition, an in vivo transmission-blocking effect was also demonstrated by direct feeding of immunized mice infected with Pfs25DR3, a chimeric P. berghei line expressing Pfs25 in place of endogenous Pbs25. In this assay the density of Pfs25DR3 oocysts was significantly reduced when mosquitoes were fed on vaccinated as compared to control mice (67% reduction of intensity, 28% reduction in prevalence and specific IgG titer correlated with efficacy. These data confirm the utility of the adenovirus-MVA vaccine platform for the induction of antibodies with transmission-blocking activity, and support the continued development of this alternative approach to transmission-blocking malaria subunit

  8. Immune response from a resource allocation perspective

    Directory of Open Access Journals (Sweden)

    Wendy Mercedes Rauw

    2012-12-01

    Full Text Available The immune system is a life history trait that can be expected to trade off against other life history traits. Whether or not a trait is considered to be a life history trait has consequences for the expectation on how it responds to natural selection and evolution; in addition, it may have consequences for the outcome of artificial selection when included in the breeding objective. The immune system involved in pathogen resistance comprises multiple mechanisms that define a host’s defensive capacity. Immune resistance involves employing mechanisms that either prevent pathogens from invading or eliminate the pathogens when they do invade. On the other hand, tolerance involves limiting the damage that is caused by the infection. Both tolerance and resistance traits require (reallocation of resources and carry physiological costs. Examples of trade-offs between immune function and growth, reproduction and stress response are provided in this review, in addition to consequences of selection for increased production on immune function and vice versa. Reaction norms are used to deal with questions of immune resistance versus tolerance to pathogens that relate host health to infection intensity. In essence, selection for immune tolerance in livestock is a particular case of selection for animal robustness. Since breeding goals that include robustness traits are required in the implementation of more sustainable agricultural production systems, it is of interest to investigate whether immune tolerance is a robustness trait that is positively correlated with overall animal robustness. Considerably more research is needed to estimate the shapes of the cost functions of different immune strategies, and investigate trade-offs and cross-over benefits of selection for disease resistance and/or disease tolerance in livestock production.

  9. Demonstration of brachytherapy boost dose-response relationships in glioblastoma multiforme

    International Nuclear Information System (INIS)

    Purpose: To evaluate brachytherapy dose-response relationships in adults with glioblastoma undergoing temporary 125I implant boost after external beam radiotherapy. Methods and Materials: Since June 1987, orthogonal radiographs using a fiducial marker box have been used to verify brain implant source positions and generate dose-volume histograms at the University of California, San Francisco. For adults who underwent brachytherapy boost for glioblastoma from June 1987 through December 1992, tumor volumes were reoutlined to ensure consistency and dose-volume histograms were recalculated. Univariate and multivariate analyses of various patient and treatment parameters were performed evaluating for influence of dose on freedom from local failure (FFLF) and actuarial survival. Results: Of 102 implant boosts, 5 were excluded because computer plans were unavailable. For the remaining 97 patients, analyses with adjustment for known prognostic factors (age, KPS, extent of initial surgical resection) and prognostic factors identified on univariate testing (adjuvant chemotherapy) showed that higher minimum brachytherapy tumor dose was strongly associated with improved FFLF (p = 0.001). A quadratic relationship was found between total biological effective dose and survival, with a trend toward optimal survival probability at 47 Gy minimum brachytherapy tumor dose (corresponding to about 65 Gy to 95% of the tumor volume); survival decreased with lower or higher doses. Two patients expired and one requires hospice care because of brain necrosis after brachytherapy doses > 63 Gy to 95% of the tumor volume with 60 Gy to > 18 cm3 of normal brain. Conclusion: Although higher minimum brachytherapy tumor dose was strongly associated with better local control, a brachytherapy boost dose > 50-60 Gy may result in life-threatening necrosis. We recommend careful conformation of the prescription isodose line to the contrast enhancing tumor volume, delivery of a minimum brachytherapy boost

  10. Comparison of vaccines for induction of heterosubtypic immunity to influenza A virus: cold-adapted vaccine versus DNA prime-adenovirus boost strategies.

    Science.gov (United States)

    Lo, Chia-Yun; Wu, Zhengqi; Misplon, Julia A; Price, Graeme E; Pappas, Claudia; Kong, Wing-Pui; Tumpey, Terrence M; Epstein, Suzanne L

    2008-04-16

    Influenza epidemics or pandemics can arise for which strain- or subtype-matched vaccines are unavailable. Heterosubtypic immunity (Het-I) targeting conserved influenza A antigens could reduce morbidity and mortality during preparation of matched vaccines. Various vaccines inducing Het-I in animals have been studied separately using different viruses and conditions, but effectiveness for inducing Het-I has not been directly compared. The present studies compared immunization with cold-adapted (ca) viruses to DNA prime-recombinant adenovirus (rAd) boost vaccination to conserved antigens nucleoprotein (NP), matrix-2 (M2), or A/NP+M2. Both ca and DNA-rAd vaccinations induced antibody and T cell responses, and protected against lethal H1N1 challenge. Only A/NP+M2 DNA-rAd protected against challenge with highly pathogenic A/Vietnam/1203/2004 (H5N1); ca vaccine did not. Existing ca vaccines may provide some Het-I, but experimental vaccination focusing on conserved antigens was more effective in this model for protection against a divergent, highly pathogenic virus. PMID:18378366

  11. Enhancing Immune Responses for Cancer Therapy

    Institute of Scientific and Technical Information of China (English)

    Shao-An Xue; Hans J Stauss

    2007-01-01

    Although the immune system possesses the means to respond to cancer, it often fails to control the spread of malignancy. Nonetheless, equipping endogenous immunity to release a strong antitumor response has significant advantages over conventional therapies. This review explores some of the options available to accomplish this,focusing first on vaccinations with tumor antigens to stimulate the immune system and empower stronger antitumor responses. We then compare and contrast the so-far limited clinical success of vaccination with the well-documented curative potential of adoptive therapy using T lymphocytes transfer. Finally, we highlight novel approaches using T cell receptor (TCR) gene transfer strategy to exploit allogeneic T cell repertoires in conjunction with receptors selected in vitro for defined MHC/peptide combinations, as a basis for antigen-specific gene therapy of cancers.

  12. Using Intradermal Rabies Vaccine to Boost Immunity in People with Low Rabies Antibody Levels

    OpenAIRE

    David Brown; Fooks, Anthony R.; Martin Schweiger

    2011-01-01

    Intradermal rabies vaccine is recommended by the World Health Organisation, but not all countries, including England, follow this recommendation. A group of 12 adults in England previously given pre-exposure intradermal rabies vaccine were considered to be non-immune to rabies because their rabies antibody titres were known to be less than 0.5 IU/mL. A cohort study examined the immunizing effect of increasing the participants' cumulative dose of intradermal rabies to 2.0 IU. All patients subs...

  13. Immune Response in Mussels To Environmental Pollution.

    Science.gov (United States)

    Pryor, Stephen C.; Facher, Evan

    1997-01-01

    Describes the use of mussels in measuring the extent of chemical contamination and its variation in different coastal regions. Presents an experiment to introduce students to immune response and the effects of environmental pollution on marine organisms. Contains 14 references. (JRH)

  14. Phagocytosis, a cellular immune response in insects

    Directory of Open Access Journals (Sweden)

    C Rosales

    2011-06-01

    Full Text Available Insects like many other organisms are exposed to a wide range of infectious agents. Defense against these agents is provided by innate immune systems, which include physical barriers, humoral responses, and cellular responses. The humoral responses are characterized by the production of antimicrobial peptides, while the cellular defense responses include nodulation, encapsulation, melanization and phagocytosis. The phagocytic process, whereby cells ingest large particles, is of fundamental importance for insects’ development and survival. Phagocytic cells recognize foreign particles through a series of receptors on their cell membrane for pathogen-associated molecules. These receptors in turn initiate a series of signaling pathways that instruct the cell to ingest and eventually destroy the foreign particle. This review describes insect innate humoral and cellular immune functions with emphasis on phagocytosis. Recent advances in our understanding of the phagocytic cell types in various insect species; the receptors involved and the signaling pathways activated during phagocytosis are discussed.

  15. Ovine model for studying pulmonary immune responses

    Energy Technology Data Exchange (ETDEWEB)

    Joel, D.D.; Chanana, A.D.

    1984-11-25

    Anatomical features of the sheep lung make it an excellent model for studying pulmonary immunity. Four specific lung segments were identified which drain exclusively to three separate lymph nodes. One of these segments, the dorsal basal segment of the right lung, is drained by the caudal mediastinal lymph node (CMLN). Cannulation of the efferent lymph duct of the CMLN along with highly localized intrabronchial instillation of antigen provides a functional unit with which to study factors involved in development of pulmonary immune responses. Following intrabronchial immunization there was an increased output of lymphoblasts and specific antibody-forming cells in efferent CMLN lymph. Continuous divergence of efferent lymph eliminated the serum antibody response but did not totally eliminate the appearance of specific antibody in fluid obtained by bronchoalveolar lavage. In these studies localized immunization of the right cranial lobe served as a control. Efferent lymphoblasts produced in response to intrabronchial antigen were labeled with /sup 125/I-iododeoxyuridine and their migrational patterns and tissue distribution compared to lymphoblasts obtained from the thoracic duct. The results indicated that pulmonary immunoblasts tend to relocate in lung tissue and reappear with a higher specific activity in pulmonary lymph than in thoracic duct lymph. The reverse was observed with labeled intestinal lymphoblasts. 35 references, 2 figures, 3 tables.

  16. Ovine model for studying pulmonary immune responses

    International Nuclear Information System (INIS)

    Anatomical features of the sheep lung make it an excellent model for studying pulmonary immunity. Four specific lung segments were identified which drain exclusively to three separate lymph nodes. One of these segments, the dorsal basal segment of the right lung, is drained by the caudal mediastinal lymph node (CMLN). Cannulation of the efferent lymph duct of the CMLN along with highly localized intrabronchial instillation of antigen provides a functional unit with which to study factors involved in development of pulmonary immune responses. Following intrabronchial immunization there was an increased output of lymphoblasts and specific antibody-forming cells in efferent CMLN lymph. Continuous divergence of efferent lymph eliminated the serum antibody response but did not totally eliminate the appearance of specific antibody in fluid obtained by bronchoalveolar lavage. In these studies localized immunization of the right cranial lobe served as a control. Efferent lymphoblasts produced in response to intrabronchial antigen were labeled with 125I-iododeoxyuridine and their migrational patterns and tissue distribution compared to lymphoblasts obtained from the thoracic duct. The results indicated that pulmonary immunoblasts tend to relocate in lung tissue and reappear with a higher specific activity in pulmonary lymph than in thoracic duct lymph. The reverse was observed with labeled intestinal lymphoblasts. 35 references, 2 figures, 3 tables

  17. Nutritional strategies to boost immunity and prevent infection in elderly individuals.

    Science.gov (United States)

    High, K P

    2001-12-01

    Older adults are at risk for malnutrition, which may contribute to their increased risk of infection. Nutritional supplementation strategies can reduce this risk and reverse some of the immune dysfunction associated with advanced age. This review discusses nutritional interventions that have been examined in clinical trials of older adults. The data support use of a daily multivitamin or trace-mineral supplement that includes zinc (elemental zinc, >20 mg/day) and selenium (100 microg/day), with additional vitamin E, to achieve a daily dosage of 200 mg/day. Specific syndromes may also be addressed by nutritional interventions (for example, cranberry juice consumption to reduce urinary tract infections) and may reduce antibiotic use in older adults, particularly those living in long-term care facilities. Drug-nutrient interactions are common in elderly individuals, and care providers should be aware of these interactions. Future research should evaluate important clinical end points rather than merely surrogate markers of immunity. PMID:11692301

  18. Metabolic Engineering of Salmonella Vaccine Bacteria to Boost Human Vγ2Vδ2 T Cell Immunity

    OpenAIRE

    Workalemahu, Grefachew; Wang, Hong; Puan, Kia-Joo; Nada, Mohanad H.; Kuzuyama, Tomohisa; Jones, Bradley D; Jin, Chenggang; Morita, Craig T.

    2014-01-01

    Human Vγ2Vδ2 T cells monitor isoprenoid metabolism by recognizing foreign (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP), a metabolite in the 2-C-methyl-D-erythritol-4-phosphate pathway used by most eubacteria and apicomplexan parasites, and self isopentenyl pyrophosphate, a metabolite in the mevalonate pathway used by humans. Whereas microbial infections elicit prolonged expansion of memory Vγ2Vδ2 T cells, immunization with prenyl pyrophosphates or aminobisphosphonates elicit short-...

  19. The immune system strikes back: cellular immune responses against indoleamine 2,3-dioxygenase.

    Directory of Open Access Journals (Sweden)

    Rikke Baek Sørensen

    Full Text Available BACKGROUND: The enzyme indoleamine 2,3-dioxygenase (IDO exerts an well established immunosuppressive function in cancer. IDO is expressed within the tumor itself as well as in antigen-presenting cells in tumor-draining lymph nodes, where it promotes the establishment of peripheral immune tolerance to tumor antigens. In the present study, we tested the notion whether IDO itself may be subject to immune responses. METHODS AND FINDINGS: The presence of naturally occurring IDO-specific CD8 T cells in cancer patients was determined by MHC/peptide stainings as well as ELISPOT. Antigen specific cytotoxic T lymphocytes (CTL from the peripheral blood of cancer patients were cloned and expanded. The functional capacity of the established CTL clones was examined by chrome release assays. The study unveiled spontaneous cytotoxic T-cell reactivity against IDO in peripheral blood as well as in the tumor microenvironment of different cancer patients. We demonstrate that these IDO reactive T cells are indeed peptide specific, cytotoxic effector cells. Hence, IDO reactive T cells are able to recognize and kill tumor cells including directly isolated AML blasts as well as IDO-expressing dendritic cells, i.e. one of the major immune suppressive cell populations. CONCLUSION: IDO may serve as an important and widely applicable target for anti-cancer immunotherapeutic strategies. Furthermore, as emerging evidence suggests that IDO constitutes a significant counter-regulatory mechanism induced by pro-inflammatory signals, IDO-based immunotherapy holds the promise to boost anti-cancer immunotherapy in general.

  20. Vitamin E, immune response, and disease resistance.

    Science.gov (United States)

    Tengerdy, R P

    1989-01-01

    Vitamin E as a dietary supplement or as part of an adjuvant vaccine formulation increases humoral and cell-mediated immunity and disease resistance in laboratory animals, farm animals, and humans. Adjuvant administration has far greater effect than dietary supplementation. Vitamin E as an antioxidant protects the cells of the immune response from peroxidative damage; possibly through a modulation of lipoxygenation of arachidonic acid, vitamin E alters cell membrane functions and cell-cell interactions. The most pronounced effect of vitamin E is on immune phagocytosis. Dietary supplementation is beneficial to animals, especially under stress, in decreasing susceptibility to infections. Vitamin E adjuvant vaccines have provided greater immunoprotection against enterotoxemia and epididymitis in sheep than conventional vaccines. PMID:2698109

  1. Cross-clade neutralizing antibodies against HIV-1 induced in rabbits by focusing the immune response on a neutralizing epitope

    International Nuclear Information System (INIS)

    Studies were performed to induce cross-clade neutralizing antibodies (Abs) by testing various combinations of prime and boost constructs that focus the immune response on structurally-conserved epitopes in the V3 loop of HIV-1 gp120. Rabbits were immunized with gp120 DNA containing a V3 loop characterized by the GPGR motif at its tip, and/or with gp120 DNA with a V3 loop carrying the GPGQ motif. Priming was followed by boosts with V3-fusion proteins (V3-FPs) carrying the V3 sequence from a subtype B virus (GPGR motif), and/or with V3 sequences from subtypes A and C (GPGQ motif). The broadest and most consistent neutralizing responses were generated when using a clade C gp120 DNA prime and with the V3B-FP boost. Immune sera displayed neutralizing activity in three assays against pseudoviruses and primary isolates from subtypes A, AG, B, C, and D. Polyclonal Abs in the immune rabbit sera neutralized viruses that were not neutralized by pools of human anti-V3 monoclonal Abs. Greater than 80% of the neutralizing Abs were specific for V3, showing that the immune response could be focused on a neutralizing epitope and that vaccine-induced anti-V3 Abs have cross-clade neutralizing activity.

  2. Intramuscular Priming and Intranasal Boosting Induce Strong Genital Immunity Through Secretory IgA in Minipigs Infected with Chlamydia trachomatis

    DEFF Research Database (Denmark)

    Lorenzen, Emma; Follmann, Frank; Bøje, Sarah; Erneholm, Karin; Weinreich Olsen, Anja; Agerholm, Jørgen Steen; Jungersen, Gregers; Andersen, Peter

    2015-01-01

    with a reproductive system very similar to humans. The vaccine was composed of C. trachomatis subunit antigens formulated in the Th1/Th17 promoting CAF01 adjuvant. IM priming immunizations with CAF01 induced a significant cell-mediated interferon gamma and interleukin 17A response and a significant...

  3. Regulatory T cells in cutaneous immune responses.

    OpenAIRE

    Honda, Tetsuya; MIYACHI, YOSHIKI; Kabashima, Kenji

    2011-01-01

    Regulatory T cells (Treg) are a subset of T cells with strong immunosuppressive activity. In the skin, it has recently been revealed that Treg play important roles not only in the maintenance of skin homeostasis but also in the regulation of the immune responses, such as contact hypersensitivity and atopic dermatitis. Furthermore, the skin plays important roles in the induction of Treg in the periphery. In this review, we will provide an overview of the mechanism of Treg-mediated immunosuppre...

  4. Adaptive immune responses of legumin nanoparticles.

    Science.gov (United States)

    Mirshahi, T; Irache, J M; Nicolas, C; Mirshahi, M; Faure, J P; Gueguen, J; Hecquet, C; Orecchioni, A M

    2002-12-01

    Legumin is one of the main storage proteins in the pea seeds (Pisum sativum L.) and the molecules of this protein have the capacity of binding together to form nanoparticles after aggregation and chemical cross-linkage with glutaraldehyde. The aim of this work was to study the adaptive immune response of legumin nanoparticles in rats. Following intradermal immunisation with the native protein legumin and legumin nanoparticles of about 250 nm, the humoral and cell-mediated immune responses were analysed in rats. The humoral responses against legumin and legumin nanoparticles were examined by western blot and ELISA analysis. Both techniques clearly showed that sera from rats immunised with legumin strongly expressed antibodies against this protein. On the contrary, serum samples from rats inoculated with legumin nanoparticles did not contain detectable amounts of antibodies. These results may be explained by a reduction on the antigenic epitopes of the protein induced by the glutaraldehyde used during the cross-linking step. Concerning the cell-mediated response, neither legumin nor legumin nanoparticles stimulated an immunogenic response. This absence of response of spleen lymphocytes for legumin and legumin nanoparticles may be explained by a cytostatic effect of legumin which was corroborated by the evaluation of the middle phase of cell apoptose. In fact, both legumin and legumin nanoparticles are potent inductors of a cytostatic phenomenon and showed a significant increase of the chromatin condensation (p < 0.05) as compared with control. PMID:12683667

  5. Augmented Designs to Assess Immune Response in Vaccine Trials

    OpenAIRE

    Follmann, Dean

    2006-01-01

    This article introduces methods for use in vaccine clinical trials to help determine whether the immune response to a vaccine is actually causing a reduction in the infection rate. This is not easy because immune response to the (say HIV) vaccine is only observed in the HIV vaccine arm. If we knew what the HIV-specific immune response in placebo recipients would have been, had they been vaccinated, this immune response could be treated essentially like a baseline covariate and an interaction ...

  6. Protective immune responses in lawsonia intracellularis infections

    DEFF Research Database (Denmark)

    Cordes, Henriette; Riber, Ulla; Boutrup, Torsten;

    primary L. intracellularis experimental infection in pigs protects against re-colonisation (re-infection) with a virulent L. intracellularis isolate. After re-infection the animals had reduced L. intracellularis colonisation of the intestinal mucosa compared to controls, no bacterial shedding and no...... exhibited a high, but short-lasting peak after re-infection. Specific IFN responses were also measured using a whole blood IFN-γ assay. These were very high in challenge infected and re-infected animals as compared to controls. These specific immune responses may contribute to the explanation of mechanisms...... behind the observed protection against re-infection with L. intracellularis....

  7. Regulation of immune cell responses by semaphorins and their receptors

    OpenAIRE

    Takamatsu, Hyota; Okuno, Tatsusada; Kumanogoh, Atsushi

    2010-01-01

    Semaphorins were originally identified as axon guidance factors involved in the development of the neuronal system. However, accumulating evidence indicates that several members of semaphorins, so-called ‘immune semaphorins', are crucially involved in various phases of immune responses. These semaphorins regulate both immune cell interactions and immune cell trafficking during physiological and pathological immune responses. Here, we review the following two functional aspects of semaphorins ...

  8. Pre-existing vector immunity does not prevent replication deficient adenovirus from inducing efficient CD8 T-cell memory and recall responses

    DEFF Research Database (Denmark)

    Steffensen, Maria Abildgaard; Jensen, Benjamin Anderschou Holbech; Holst, Peter Johannes;

    2012-01-01

    were generated that provided the foundation for an efficient recall response and protection upon subsequent viral challenge. Furthermore, the transgene specific response could be efficiently boosted by homologous re-immunization. Taken together, these studies indicate that adenoviral vectors can be...

  9. Flavobacterium psychrophilum - Experimental challenge and immune response

    DEFF Research Database (Denmark)

    Henriksen, Maya Maria Mihályi

    the immune system of the fry is not fully developed. Theoretically, the infection pressure could be subdued by vaccinating larger fish, but no commercial vaccine is yet available. Diagnostic methods are well described and the disease is treated with antibiotics. To prevent disease outbreaks and...... periods without disease. The main purpose and focus of the present thesis was to increase knowledge of the immune response following infection with F. psychrophilum, which may contribute to the future development of vaccines and other preventive measures. The project consisted of three main tasks: 1......The disease rainbow trout fry syndrome (RTFS) is caused by the bacterial fish pathogen Flavobacterium psychrophilum. It has been the cause of great losses of rainbow trout in aquacultures both in Denmark and around the world. It was estimated that RTFS resulted in the death of 88 million fry in...

  10. Development of CpG-oligodeoxynucleotides for effective activation of rabbit TLR9 mediated immune responses.

    Directory of Open Access Journals (Sweden)

    Tsung-Hsien Chuang

    Full Text Available CpG-oligodeoxynucleotides (CpG-ODN are potent immune stimuli being developed for use as adjuvants in different species. Toll-like receptor 9 (TLR9 is the cellular receptor for CpG-ODN in mammalian cells. The CpG-ODN with 18-24 deoxynucleotides that are in current use for human and mouse cells, however, have low activity with rabbit TLR9. Using a cell-based activation assay, we developed a type of CpG-ODN containing a GACGTT or AACGTT motif in 12 phosphorothioate-modified deoxynucleotides with potent stimulatory activity for rabbit TLR9. The developed CpG-ODN have higher activities than other developed CpG-ODN in eliciting antigen-nonspecific immune responses in rabbit splenocytes. When mixed with an NJ85 peptide derived from rabbit hemorrhagic disease virus, they had potent activities to boost an antigen-specific T cell activation and antibody production in rabbits. Compared to Freund's adjuvant, the developed CpG-ODN are capable of boosting a potent and less toxic antibody response. The results of this study suggest that both the choice of CpG-motif and its length are important factors for CpG-ODN to effectively activate rabbit TLR9 mediated immune responses.

  11. A Two-Component DNA-Prime/Protein-Boost Vaccination Strategy for Eliciting Long-Term, Protective T Cell Immunity against Trypanosoma cruzi

    OpenAIRE

    Shivali Gupta; Garg, Nisha J.

    2015-01-01

    In this study, we evaluated the long-term efficacy of a two-component subunit vaccine against Trypanosoma cruzi infection. C57BL/6 mice were immunized with TcG2/TcG4 vaccine delivered by a DNA-prime/Protein-boost (D/P) approach and challenged with T. cruzi at 120 or 180 days post-vaccination (dpv). We examined whether vaccine-primed T cell immunity was capable of rapid expansion and intercepting the infecting T. cruzi. Our data showed that D/P vaccine elicited CD4+ (30-38%) and CD8+ (22-42%) ...

  12. Lentiviral vector encoding ubiquitinated hepatitis B core antigen induces potent cellular immune responses and therapeutic immunity in HBV transgenic mice.

    Science.gov (United States)

    Dai, Shenglan; Zhuo, Meng; Song, Linlin; Chen, Xiaohua; Yu, Yongsheng; Zang, Guoqing; Tang, Zhenghao

    2016-07-01

    Predominant T helper cell type 1 (Th1) immune responses accompanied by boosted HBV-specific cytotoxic T lymphocyte (CTL) activity are essential for the clearance of hepatitis B virus (HBV) in chronic hepatitis B (CHB) patients. Ubiquitin (Ub) serves as a signal for the target protein to be recognized and degraded through the ubiquitin-proteasome system (UPS). Ubiquitinated hepatitis B core antigen (Ub-HBcAg) has been proved to be efficiently degraded into the peptides, which can be presented by major histocompatibility complex (MHC) class I resulting in stimulating cell-mediated responses. In the present study, lentiviral vectors encoding Ub-HBcAg (LV-Ub-HBcAg) were designed and constructed as a therapeutic vaccine for immunotherapy. HBcAg-specific cellular immune responses and anti-viral effects induced by LV-Ub-HBcAg were evaluated in HBV transgenic mice. We demonstrated that immunization with LV-Ub-HBcAg promoted the secretion of cytokines interleukin-2 (IL-2), interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α), generated remarkably high percentages of IFN-γ-secreting CD8(+) T cells and CD4(+) T cells, and enhanced HBcAg-specific CTL activity in HBV transgenic mice. More importantly, vaccination with LV-Ub-HBcAg could efficiently decreased the levels of serum hepatitis B surface antigen (HBsAg), HBV DNA and the expression of HBsAg and HBcAg in liver tissues of HBV transgenic mice. In addition, LV-Ub-HBcAg could upregulate the expression of T cell-specific T-box transcription factor (T-bet) and downregulate the expression of GATA-binding protein 3 (GATA-3) in spleen T lymphocytes. The therapeutic vaccine LV-Ub-HBcAg could break immune tolerance, and induce potent HBcAg specific cellular immune responses and therapeutic effects in HBV transgenic mice. PMID:26874581

  13. A comparative analysis of HIV-specific mucosal/systemic T cell immunity and avidity following rDNA/rFPV and poxvirus–poxvirus prime boost immunisations

    OpenAIRE

    Ranasinghe, Charani; Eyers, Fiona; Stambas, John; Boyle, David B.; Ramshaw, Ian A.; Ramsay, Alistair J.

    2011-01-01

    In this study we have firstly compared a range of recombinant DNA poxvirus prime-boost immunisation strategies and shown that combined intramuscular (i.m.) 2×DNA-HIV/intranasal (i.n.) 2×FPV-HIV prime-boost immunisation can generate high-level of HIV-specific systemic (spleen) and mucosal (genito-rectal nodes, vaginal tissues and lung tissues) T cell responses and HIV-1 p24 Gag-specific serum IgG1, IgG2a and mucosal IgG, SIgA responses in vaginal secretions in BALB/c mice. Data indicate that f...

  14. Immune Response of Amebiasis and Immune Evasion by Entamoeba histolytica

    Science.gov (United States)

    Nakada-Tsukui, Kumiko; Nozaki, Tomoyoshi

    2016-01-01

    Entamoeba histolytica is a protozoan parasite and the causative agent of amebiasis. It is estimated approximately 1% of humans are infected with E. histolytica, resulting in an estimate of 100,000 deaths annually. Clinical manifestations of amebic infection range widely from asymptomatic to severe symptoms, including dysentery and extra-intestinal abscesses. Like other infectious diseases, it is assumed that only ~20% of infected individuals develop symptoms, and genetic factors of both the parasite and humans as well as the environmental factors, e.g., microbiota, determine outcome of infection. There are multiple essential steps in amebic infection: degradation of and invasion into the mucosal layer, adherence to the intestinal epithelium, invasion into the tissues, and dissemination to other organs. While the mechanisms of invasion and destruction of the host tissues by the amebae during infection have been elucidated at the molecular levels, it remains largely uncharacterized how the parasite survive in the host by evading and attacking host immune system. Recently, the strategies for immune evasion by the parasite have been unraveled, including immunomodulation to suppress IFN-γ production, elimination of immune cells and soluble immune mediators, and metabolic alterations against reactive oxygen and nitrogen species to fend off the attack from immune system. In this review, we summarized the latest knowledge on immune reaction and immune evasion during amebiasis. PMID:27242782

  15. Immune Response of Amebiasis and Immune Evasion by Entamoeba histolytica.

    Science.gov (United States)

    Nakada-Tsukui, Kumiko; Nozaki, Tomoyoshi

    2016-01-01

    Entamoeba histolytica is a protozoan parasite and the causative agent of amebiasis. It is estimated approximately 1% of humans are infected with E. histolytica, resulting in an estimate of 100,000 deaths annually. Clinical manifestations of amebic infection range widely from asymptomatic to severe symptoms, including dysentery and extra-intestinal abscesses. Like other infectious diseases, it is assumed that only ~20% of infected individuals develop symptoms, and genetic factors of both the parasite and humans as well as the environmental factors, e.g., microbiota, determine outcome of infection. There are multiple essential steps in amebic infection: degradation of and invasion into the mucosal layer, adherence to the intestinal epithelium, invasion into the tissues, and dissemination to other organs. While the mechanisms of invasion and destruction of the host tissues by the amebae during infection have been elucidated at the molecular levels, it remains largely uncharacterized how the parasite survive in the host by evading and attacking host immune system. Recently, the strategies for immune evasion by the parasite have been unraveled, including immunomodulation to suppress IFN-γ production, elimination of immune cells and soluble immune mediators, and metabolic alterations against reactive oxygen and nitrogen species to fend off the attack from immune system. In this review, we summarized the latest knowledge on immune reaction and immune evasion during amebiasis. PMID:27242782

  16. The early antitumor immune response is necessary for tumor growth

    OpenAIRE

    Parmiani, Giorgio; Maccalli, Cristina

    2012-01-01

    Early events responsible of tumor growth in patients with a normal immune system are poorly understood. Here, we discuss, in the context of human melanoma, the Prehn hypothesis according to which a weak antitumor immune response may be required for tumor growth before weakly or non-immunogenic tumor cell subpopulations are selected by the immune system.

  17. Neuroendocrine and Immune System Responses with Spaceflights

    Science.gov (United States)

    Tipton, Charles M.; Greenleaf, John E.; Jackson, Catherine G. R.

    1996-01-01

    Despite the fact that the first human was in space during 1961 and individuals have existed in a microgravity environment for more than a year, there are limited spaceflight data available on the responses of the neuroendocrine and immune systems. Because of mutual interactions between these respective integrative systems, it is inappropriate to assume that the responses of one have no impact on functions of the other. Blood and plasma volume consistently decrease with spaceflight; hence, blood endocrine and immune constituents will be modified by both gravitational and measurement influences. The majority of the in-flight data relates to endocrine responses that influence fluids and electrolytes during the first month in space. Adrenocorticotropin (ACTH), aldo-sterone. and anti-diuretic hormone (ADH) appear to be elevated with little change in the atrial natriuretic peptides (ANP). Flight results longer than 60 d show increased ADH variability with elevations in angiotensin and cortisol. Although post-flight results are influenced by reentry and recovery events, ACTH and ADH appear to be consistently elevated with variable results being reported for the other hormones. Limited in-flight data on insulin and growth hormone levels suggest they are not elevated to counteract the loss in muscle mass. Post-flight results from short- and long-term flights indicate that thyroxine and insulin are increased while growth hormone exhibits minimal change. In-flight parathyroid hormone (PTH) levels are variable for several weeks after which they remain elevated. Post-flight PTH was increased on missions that lasted either 7 or 237 d, whereas calcitonin concentrations were increased after 1 wk but decreased after longer flights. Leukocytes are elevated in flights of various durations because of an increase in neutrophils. The majority of post-flight data indicates immunoglobulin concentrations are not significantly changed from pre-flight measurements. However, the numbers of T

  18. Simultaneous immunization against tuberculosis.

    Directory of Open Access Journals (Sweden)

    Elma Z Tchilian

    Full Text Available BACKGROUND: BCG, the only licensed vaccine against tuberculosis, provides some protection against disseminated disease in infants but has little effect on prevention of adult pulmonary disease. Newer parenteral immunization prime boost regimes may provide improved protection in experimental animal models but are unproven in man so that there remains a need for new and improved immunization strategies. METHODS AND FINDINGS: Mice were immunized parenterally, intranasally or simultaneously by both routes with BCG or recombinant mycobacterial antigens plus appropriate adjuvants. They were challenged with Mycobacterium tuberculosis (Mtb and the kinetics of Mtb growth in the lungs measured. We show that simultaneous immunization (SIM of mice by the intranasal and parenteral routes is highly effective in increasing protection over parenteral BCG administration alone. Intranasal immunization induces local pulmonary immunity capable of inhibiting the growth of Mtb in the early phase (the first week of infection, while parenteral immunization has a later effect on Mtb growth. Importantly, these two effects are additive and do not depend on priming and boosting the immune response. The best SIM regimes reduce lung Mtb load by up to 2 logs more than BCG given by either route alone. CONCLUSIONS: These data establish SIM as a novel and highly effective immunization strategy for Mtb that could be carried out at a single clinic visit. The efficacy of SIM does not depend on priming and boosting an immune response, but SIM is complementary to prime boost strategies and might be combined with them.

  19. Rotavirus Antagonism of the Innate Immune Response

    Directory of Open Access Journals (Sweden)

    Michelle M. Arnold

    2009-11-01

    Full Text Available Rotavirus is a primary cause of severe dehydrating gastroenteritis in infants and young children. The virus is sensitive to the antiviral effects triggered by the interferon (IFN-signaling pathway, an important component of the host cell innate immune response. To counteract these effects, rotavirus encodes a nonstructural protein (NSP1 that induces the degradation of proteins involved in regulating IFN expression, such as members of the IFN regulatory factor (IRF family. In some instances, NSP1 also subverts IFN expression by causing the degradation of a component of the E3 ubiquitin ligase complex responsible for activating NF-κB. By antagonizing multiple components of the IFN-induction pathway, NSP1 aids viral spread and contributes to rotavirus pathogenesis.

  20. Molecular immune response of channel catfish immunized with live theronts of Ichthyophthirius multifiliis.

    Science.gov (United States)

    Xu, De-Hai; Zhang, Qi-Zhong; Shoemaker, Craig A; Zhang, Dunhua; Moreira, Gabriel S A

    2016-07-01

    The parasite Ichthyophthirius multifiliis (Ich) has been reported in various freshwater fishes worldwide and results in severe losses to both food and aquarium fish production. The fish surviving natural infections or immunized with live theronts develop strong specific and non-specific immune responses. Little is known about how these immune genes are induced or how they interact and lead to specific immunity against Ichthyophthirius multifiliis in channel catfish Ictalurus punctatus. This study evaluated the differential expression of immune-related genes, including immunoglobulin, immune cell receptor, cytokine, complement factor and toll-like receptors in head kidney from channel catfish at different time points after immunization with live theronts of I. multifiliis. The immunized fish showed significantly higher anti-Ich antibody expressed as immobilization titer and ELISA titer than those of control fish. The vast majority of immunized fish (95%) survived theront challenge. Expression of IgM and IgD heavy chain genes exhibited a rapid increase from 4 hour (h4) to 2 days (d2) post immunization. Expression of immune cell receptor genes (CD4, CD8-α, MHC I, MHC II β, TcR-α, and TcR-β) showed up-regulation from h4 to d6 post immunization, indicating that different immune cells were actively involved in cellular immune response. Cytokine gene expression (IL-1βa, IL-1βb, IFN-γ and TNF-α) increased rapidly at h4 post immunization and were at an up-regulated level until d2 compared to the bovine serum albumin control. Expression of complement factor and toll-like receptor genes exhibited a rapid increase from h4 to d2 post immunization. Results of this study demonstrated differential expression of genes involved in the specific or non-specific immune response post immunization and that the vaccination against Ich resulted in protection against infection by I. multifiliis. PMID:27044331

  1. Boost Effects in the (e,e') Transverse Response of 3He

    Science.gov (United States)

    Tomusiak, Edward; Efros, Victor; Leidemann, Winfried; Orlandini, Giuseppina; Yuan, Luping

    2015-10-01

    In an earlier paper Efros et al. investigated frame dependence in calculations of the transverse (e,e') response function of 3He. These calculations were non-relativistic but did incorporate relativistic corrections in the electromagnetic operators. Those corrections, taken from the work of Ritz et al. are of order M-3 and represent kinematical effects. It was found that in the region of the quasi-elastic peak, with one proviso, frame dependence held to a good approximation up to q = 700 MeV/c. The one proviso was that we not include one of the corrections - the so-called ω-dependent term. Although this term vanishes in one of the frames (the ANB frame) the question arises as to whether or not another correction exists which might nearly restore frame independence. This work investigates the possibility that Boost effects may provide an explanation. We report on our progress in this regard.

  2. Wolbachia symbiosis and insect immune response

    Institute of Scientific and Technical Information of China (English)

    Stefanos Siozios; Panagiotis Sapountzis; Panagiotis Ioannidis; Kostas Bourtzis

    2008-01-01

    Bacterial intracellular symbiosis is very common in insects, having significant consequences in promoting the evolution of life and biodiversity. The bacterial group that has recently attracted particular attention is Wolbachia pipientis which probably represents the most ubiquitous endosymbiont on the planet. W. pipientis is a Gram-negative obligatory intracellular and maternally transmitted α-proteobacterium, that is able to establish symbiotic associations with arthropods and nematodes. In arthropods, Wolbachia pipientis infections have been described in Arachnida, in Isopoda and mainly in Insecta. They have been reported in almost all major insect orders including Diptera, Coleoptera, Hemiptera,Hymenoptera, Orthoptera and Lepidoptera. To enhance its transmission, W. pipientis can manipulate host reproduction by inducing parthenogenesis, feminization, male killing and cytoplasmic incompatibility. Several polymerase chain reaction surveys have indicated that up to 70% of all insect species may be infected with W. pipientis. How does W. pipientis manage to get established in diverse insect host species? How is this intracellular bacterial symbiont species so successful in escaping the host immune response? The present review presents recent advances and ongoing scientific efforts in the field. The current body of knowledge in the field is summarized, revelations from the available genomic information are presented and as yet unanswered questions are discussed in an attempt to present a comprehensive picture of the unique ability of W. pipientis to establish symbiosis and to manipulate reproduction while evading the host's immune system.

  3. Nanomaterial Induced Immune Responses and Cytotoxicity.

    Science.gov (United States)

    Ali, Ashraf; Suhail, Mohd; Mathew, Shilu; Shah, Muhammad Ali; Harakeh, Steve M; Ahmad, Sultan; Kazmi, Zulqarnain; Alhamdan, Mohammed Abdul Rahman; Chaudhary, Adeel; Damanhouri, Ghazi Abdullah; Qadri, Ishtiaq

    2016-01-01

    Nanomaterials are utilized in a wide array of end user products such as pharmaceuticals, electronics, clothes and cosmetic products. Due to its size (< 100 nm), nanoparticles have the propensity to enter through the airway and skin, making its path perilous with the potential to cause damages of varying severity. Once within the body, these particles have unconstrained access to different tissues and organs including the brain, liver, and kidney. As a result, nanomaterials may cause the perturbation of the immune system eliciting an inflammatory response and cytotoxicity. This potential role is dependent on many factors such as the characteristics of the nanomaterials, presence or absence of diseases, and genetic predisposition. Cobalt and nickel nanoparticles, for example, were shown to have inflammogenic properties, while silver nanoparticles were shown to reduce allergic inflammation. Just as asbestos fibers, carbon nanotubes were shown to cause lungs damage. Some nanomaterials were shown, based on animal studies, to result in cell damage, leading to the formation of pre-cancerous lesions. This review highlights the impact of nanomaterials on immune system and its effect on human health with toxicity consideration. It recommends the development of suitable animal models to study the toxicity and bio-clearance of nanomaterials and propose safety guidelines. PMID:27398432

  4. Malaria vaccines and human immune responses.

    Science.gov (United States)

    Long, Carole A; Zavala, Fidel

    2016-08-01

    Despite reductions in malaria episodes and deaths over the past decade, there is still significant need for more effective tools to combat this serious global disease. The positive results with the Phase III trial of RTS,S directed to the circumsporozoite protein of Plasmodium falciparum have established that a vaccine against malaria can provide partial protection to children in endemic areas, but its limited efficacy and relatively short window of protection mandate that new generations of more efficacious vaccines must be sought. Evidence shows that anti-parasite immune responses can control infection against other stages as well, but translating these experimental findings into vaccines for blood stages has been disappointing and clinical efforts to test a transmission blocking vaccine are just beginning. Difficulties include the biological complexity of the organism with a large array of stage-specific genes many of which in the erythrocytic stages are antigenically diverse. In addition, it appears necessary to elicit high and long-lasting antibody titers, address the redundant pathways of merozoite invasion, and still seek surrogate markers of protective immunity. Most vaccine studies have focused on a single or a few antigens with an apparent functional role, but this is likely to be too restrictive, and broad, multi-antigen, multi-stage vaccines need further investigation. Finally, novel tools and biological insights involving parasite sexual stages and the mosquito vector will provide new avenues for reducing or blocking malaria transmission. PMID:27262417

  5. Local Immune Response in Helicobacter pylori Infection.

    Science.gov (United States)

    Kivrak Salim, Derya; Sahin, Mehmet; Köksoy, Sadi; Adanir, Haydar; Süleymanlar, Inci

    2016-05-01

    There have been few studies concerning the cytokine profiles in gastric mucosa of Helicobacter pylori-infected patients with normal mucosa, chronic gastritis, and gastric carcinoma (GAC).In the present study, we aimed to elucidate the genomic expression levels and immune pathological roles of cytokines-interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-4, IL-6, IL-10, transforming growth factor (TGF)-β, IL-17A, IL-32-in H pylori-infected patients with normal gastric mucosa (NGM; control), chronic active gastritis (CAG), and GAC. Genomic expression levels of these cytokines were assayed by real-time PCR analysis in gastric biopsy specimens obtained from 93 patients.We found that the genomic expression levels of IFN-γ, TNF-α, IL-6, IL-10, IL-17A mRNA were increased in the CAG group and those of TNF-α, IL-6, IL-10, IL-17A, TGF-β mRNA were increased in the GAC group with reference to H pylori-infected NGM group.This study is on the interest of cytokine profiles in gastric mucosa among individuals with normal, gastritis, or GAC. Our findings suggest that the immune response of gastric mucosa to infection of H pylori differs from patient to patient. For individual therapy, levels of genomic expression of IL-6 or other cytokines may be tracked in patients. PMID:27196487

  6. Essential oil of clove (Eugenia caryophyllata) augments the humoral immune response but decreases cell mediated immunity.

    Science.gov (United States)

    Halder, Sumita; Mehta, Ashish K; Mediratta, Pramod K; Sharma, Krishna K

    2011-08-01

    The present study was undertaken to explore the effect of the essential oil isolated from the buds of Eugenia caryophyllata on some immunological parameters. Humoral immunity was assessed by measuring the hemagglutination titre to sheep red blood cells and delayed type hypersensitivity was assessed by measuring foot pad thickness. Clove oil administration produced a significant increase in the primary as well as secondary humoral immune response. In addition, it also produced a significant decrease in foot pad thickness compared with the control group. Thus, these results suggest that clove oil can modulate the immune response by augmenting humoral immunity and decreasing cell mediated immunity. PMID:21796701

  7. Lack of immune deficiency in sarcoidosis: compartmentalisation of the immune response.

    OpenAIRE

    Hudspith, B N; Flint, K C; Geraint-James, D; Brostoff, J; Johnson, N. M.

    1987-01-01

    The original findings of peripheral anergy in sarcoidosis led to the conclusion that sarcoidosis was a disease associated with immune deficiency, but patients with sarcoidosis do not appear to suffer from repeated infections suggestive of immune suppression. With the technique of bronchoalveolar lavage it is now possible to examine the local immune response within the lung, the most commonly affected organ in sarcoidosis. In this study three different indices of cell mediated immunity (lympho...

  8. Elicitation of strong immune responses by a DNA vaccine expressing a secreted form of hepatitis C virus envelope protein E2 in murine and porcine animal models

    Institute of Scientific and Technical Information of China (English)

    Yi-Ping Li; Hye Na Kang; Lorne A Babiuk; Qiang Liu

    2006-01-01

    AIM: To characterize the immunogenicity of a hepatitis C virus (HCV) E2 DNA vaccine alone or with a protein vaccine boost in murine and porcine animal models.METHODS: A DNA vaccine expressing a secreted form of HCV E2 protein was constructed and used to vaccinate mice and piglets with or without boosting with a recombinant E2 protein vaccine formulated with CpG ODN and 10% Emulsigen. The immunogenicity of HCV E2 vaccines was analyzed by ELISA for antibody responses, MTT assay for lymphocyte proliferation,ELISPOT for the number of interferon-γ secreting cells,and cytotoxic T lymphocyte assays.RESULTS: Intradermal injection of E2 DNA vaccine induced strong Th1-like immune responses in mice. In piglets, E2 DNA vaccine elicited moderate and more balanced immune responses. A DNA vaccine prime and protein boost vaccination strategy induced significantly higher E2-specific antibody levels and shifted the immune response towards Th2-like ones in piglets.CONCLUSION: A DNA vaccine expressing a secreted form of HCV E2 protein elicited E2-specific immune responses in mice and piglets. Recombinant E2 protein vaccination following DNA immunization significantly increased the antibody response in piglets. These HCV E2 vaccines may represent promising hepatitis C vaccine candidates for further investigations.

  9. Meeting report VLPNPV: Session 3: Immune responses.

    Science.gov (United States)

    Morrison, Trudy G

    2014-01-01

    Virus-like particles (VLPs) and nano-particles (NP) are increasingly considered for both prophylactic and therapeutic vaccines for a wide variety of human and animal diseases. Indeed, 2 VLPs have already been licensed for use in humans, the human papilloma virus vaccine and the hepatitis B virus vaccine. (1) Reflecting this increased interest, a second international conference with a specific focus on VLPs and NP was held at the Salk Institute for Biological Studies in La Jolla, California, in June 2014. Approximately 100 attendees, hailing from many nations, came from academic institutions, research institutes, and biotech companies. A wide variety of topics were discussed, ranging from development and characterization of specific VLP and NP vaccine candidates to methods of production of these particles. Session three was focused on the general question of immune responses to VLPs. PMID:25529229

  10. Population-expression models of immune response

    International Nuclear Information System (INIS)

    The immune response to a pathogen has two basic features. The first is the expansion of a few pathogen-specific cells to form a population large enough to control the pathogen. The second is the process of differentiation of cells from an initial naive phenotype to an effector phenotype which controls the pathogen, and subsequently to a memory phenotype that is maintained and responsible for long-term protection. The expansion and the differentiation have been considered largely independently. Changes in cell populations are typically described using ecologically based ordinary differential equation models. In contrast, differentiation of single cells is studied within systems biology and is frequently modeled by considering changes in gene and protein expression in individual cells. Recent advances in experimental systems biology make available for the first time data to allow the coupling of population and high dimensional expression data of immune cells during infections. Here we describe and develop population-expression models which integrate these two processes into systems biology on the multicellular level. When translated into mathematical equations, these models result in non-conservative, non-local advection-diffusion equations. We describe situations where the population-expression approach can make correct inference from data while previous modeling approaches based on common simplifying assumptions would fail. We also explore how model reduction techniques can be used to build population-expression models, minimizing the complexity of the model while keeping the essential features of the system. While we consider problems in immunology in this paper, we expect population-expression models to be more broadly applicable. (paper)

  11. Population-expression models of immune response

    Science.gov (United States)

    Stromberg, Sean P.; Antia, Rustom; Nemenman, Ilya

    2013-06-01

    The immune response to a pathogen has two basic features. The first is the expansion of a few pathogen-specific cells to form a population large enough to control the pathogen. The second is the process of differentiation of cells from an initial naive phenotype to an effector phenotype which controls the pathogen, and subsequently to a memory phenotype that is maintained and responsible for long-term protection. The expansion and the differentiation have been considered largely independently. Changes in cell populations are typically described using ecologically based ordinary differential equation models. In contrast, differentiation of single cells is studied within systems biology and is frequently modeled by considering changes in gene and protein expression in individual cells. Recent advances in experimental systems biology make available for the first time data to allow the coupling of population and high dimensional expression data of immune cells during infections. Here we describe and develop population-expression models which integrate these two processes into systems biology on the multicellular level. When translated into mathematical equations, these models result in non-conservative, non-local advection-diffusion equations. We describe situations where the population-expression approach can make correct inference from data while previous modeling approaches based on common simplifying assumptions would fail. We also explore how model reduction techniques can be used to build population-expression models, minimizing the complexity of the model while keeping the essential features of the system. While we consider problems in immunology in this paper, we expect population-expression models to be more broadly applicable.

  12. Immune Response in Thyroid Cancer: Widening the Boundaries

    OpenAIRE

    Laura Sterian Ward

    2014-01-01

    The association between thyroid cancer and thyroid inflammation has been repeatedly reported and highly debated in the literature. In fact, both molecular and epidemiological data suggest that these diseases are closely related and this association reinforces that the immune system is important for thyroid cancer progression. Innate immunity is the first line of defensive response. Unlike innate immune responses, adaptive responses are highly specific to the particular antigen that induced th...

  13. Heterologous prime-boost regimens with a recombinant chimpanzee adenoviral vector and adjuvanted F4 protein elicit polyfunctional HIV-1-specific T-Cell responses in macaques.

    Science.gov (United States)

    Lorin, Clarisse; Vanloubbeeck, Yannick; Baudart, Sébastien; Ska, Michaël; Bayat, Babak; Brauers, Geoffroy; Clarinval, Géraldine; Donner, Marie-Noëlle; Marchand, Martine; Koutsoukos, Marguerite; Mettens, Pascal; Cohen, Joe; Voss, Gerald

    2015-01-01

    HIV-1-specific CD4+ and CD8+ T lymphocytes are important for HIV-1 replication control. F4/AS01 consists of F4 recombinant fusion protein (containing clade B Gag/p24, Pol/RT, Nef and Gag/p17) formulated in AS01 Adjuvant System, and was shown to induce F4-specific polyfunctional CD4+ T-cell responses in humans. While replication-incompetent recombinant HIV-1/SIV antigen-expressing human adenoviral vectors can elicit high-frequency antigen-specific CD8+ T-cell responses, their use is hampered by widespread pre-existing immunity to human serotypes. Non-human adenovirus serotypes associated with lower prevalence may offer an alternative strategy. We evaluated the immunogenicity of AdC7-GRN ('A'), a recombinant chimpanzee adenovirus type 7 vector expressing clade B Gag, RT and Nef, and F4/AS01 ('P'), when delivered intramuscularly in homologous (PP or AA) and heterologous (AAPP or PPAA) prime-boost regimens, in macaques and mice. Vaccine-induced HIV-1-antigen-specific T cells in peripheral blood (macaques), liver, spleen, and intestinal and genital mucosa (mice) were characterized by intracellular cytokine staining. Vaccine-specific IgG antibodies (macaques) were detected using ELISA. In macaques, only the heterologous prime-boost regimens induced polyfunctional, persistent and balanced CD4+ and CD8+ T-cell responses specific to each HIV-1 vaccine antigen. AdC7-GRN priming increased the polyfunctionality of F4/AS01-induced CD4+ T cells. Approximately 50% of AdC7-GRN-induced memory CD8+ T cells exhibited an effector-memory phenotype. HIV-1-specific antibodies were detected with each regimen. In mice, antigen-specific CD4+ and CD8+ T-cell responses were detected in the mucosal and systemic anatomical compartments assessed. When administered in heterologous prime-boost regimens, AdC7-GRN and F4/AS01 candidate vaccines acted complementarily in inducing potent and persistent peripheral blood HIV-1-specific CD4+ and CD8+ T-cell responses and antibodies in macaques. Besides

  14. Immune response markers in sentinel nodes may predict melanoma progression

    OpenAIRE

    Rodolfo, Monica; Castelli, Chiara; Rivoltini, Licia

    2014-01-01

    We recently reported that variable expression of immune-response genes distinguishes tumor positive sentinel nodes in melanoma patients with malignant progression from those with non-progressing disease. Our results depict sentinel nodes as sites in which immune functions are associated with metastatic disease and identify CD30 as a host immune-related cancer prognostic marker and potential therapeutic target.

  15. Vaccines against Human Carcinomas: Strategies to Improve Antitumor Immune Responses

    Directory of Open Access Journals (Sweden)

    Claudia Palena

    2010-01-01

    Full Text Available Multiple observations in preclinical and clinical studies support a role for the immune system in controlling tumor growth and progression. Various components of the innate and adaptive immune response are able to mediate tumor cell destruction; however, certain immune cell populations can also induce a protumor environment that favors tumor growth and the development of metastasis. Moreover, tumor cells themselves are equipped with various mechanisms that allow them to evade surveillance by the immune system. The goal of cancer vaccines is to induce a tumor-specific immune response that ultimately will reduce tumor burden by tipping the balance from a protumor to an antitumor immune environment. This review discusses common mechanisms that govern immune cell activation and tumor immune escape, and some of the current strategies employed in the field of cancer vaccines aimed at enhancing activation of tumor-specific T-cells with concurrent reduction of immunosuppression.

  16. Enhancement of DNA vaccine-induced immune responses by a 72-bp element from SV40 enhancer

    Institute of Scientific and Technical Information of China (English)

    LI Hai-shan; XU Jian-qing; HONG Kun-xue; SHAO Yi-ming; LIU Yong; LI Ding-feng; ZHANG Ran-ran; TANG Hai-li; ZHANG Yu-wei; HUANG Wei; LIU Ying; PENG Hong

    2007-01-01

    Background Although DNA vaccine is considered as the next generation of vaccine, most DNA vaccine candidates are still suffering from the relatively weak immunogenicity despite the increased dosage of plasmid DNA administered. In order to enhance the immune responses elicited by a codon-optimized HIV gag DNA vaccine, a modified plasmid vector pDRVI1.0 and a booster immunization with replicating Tiantan vaccinia (RTV) strain expressing the same gene were employed.Methods Vector pDRVI1.0 was constructed through inserting the 72-bp element from the SV40 enhancer, which was reported promoting nuclear transport of plasmid DNA, to the upstream of cytomegalovirus enhancer/promoter region of the plasmid vector pVR1012. Gene expression levels from expression plasmids based on pDRVI1.0 and pVR1012 were tested. Humoral and cellular immune responses induced by DNA vaccine alone or DNA prime-RTV boost regimen were determined in mice.Results It was shown that the 72-bp element significantly enhanced the gene expression level in non-dividing cells.gag-specific humoral and cellular immune responses induced by DNA vaccination were both significantly improved, while the Th1/Th2 balance was not obviously affected by the 72-bp element. RTV boosting further significantly enhanced DNA vaccine-primed antibody and T cell responses in a Th1-biased manner.Conclusions The 72-bp SV40 enhancer element should be included in the DNA vaccine vector and RTV strain is a very efficient live vector for boosting immunization.

  17. Spaceflight and immune responses of rhesus monkeys

    Science.gov (United States)

    Sonnenfeld, Gerald; Morton, Darla S.; Swiggett, Jeanene P.; Hakenewerth, Anne M.; Fowler, Nina A.

    1995-01-01

    The effects of restraint on immunological parameters was determined in an 18 day ARRT (adult rhesus restraint test). The monkeys were restrained for 18 days in the experimental station for the orbiting primate (ESOP), the chair of choice for Space Shuttle experiments. Several immunological parameters were determined using peripheral blood, bone marrow, and lymph node specimens from the monkeys. The parameters included: response of bone marrow cells to GM-CSF (granulocyte-macrophage colony stimulating factor), leukocyte subset distribution, and production of IFN-a (interferon-alpha) and IFN-gamma (interferon-gamma). The only parameter changed after 18 days of restraint was the percentage of CD8+ T cells. No other immunological parameters showed changes due to restraint. Handling and changes in housing prior to the restraint period did apparently result in some restraint-independent immunological changes. Handling must be kept to a minimum and the animals allowed time to recover prior to flight. All experiments must be carefully controlled. Restraint does not appear to be a major issue regarding the effects of space flight on immune responses.

  18. Seasonal changes in human immune responses to malaria

    DEFF Research Database (Denmark)

    Hviid, L; Theander, T G

    1993-01-01

    Cellular as well as humorol immune responses to malaria antigens fluctuate in time in individuals living in molono-endemic areas, particularly where malaria transmission is seasonal. The most pronounced changes are seen in association with clinical attacks, but osymptomatic infection can also lead...... to apparent immune depression. However, recent data have shown that seasonal variation in cellular immune responses may occur even in the absence of detectable porositaemia. Here, Lars Hviid and Thor G. Theonder review the seasonal variation in human immune responses to malaria, and discuss its...

  19. The unfolded protein response in immunity and inflammation.

    Science.gov (United States)

    Grootjans, Joep; Kaser, Arthur; Kaufman, Randal J; Blumberg, Richard S

    2016-08-01

    The unfolded protein response (UPR) is a highly conserved pathway that allows the cell to manage endoplasmic reticulum (ER) stress that is imposed by the secretory demands associated with environmental forces. In this role, the UPR has increasingly been shown to have crucial functions in immunity and inflammation. In this Review, we discuss the importance of the UPR in the development, differentiation, function and survival of immune cells in meeting the needs of an immune response. In addition, we review current insights into how the UPR is involved in complex chronic inflammatory diseases and, through its role in immune regulation, antitumour responses. PMID:27346803

  20. Mutual boosting effects of sensitization with timothy grass pollen and latex glove extract on IgE antibody responses in a mouse model.

    Science.gov (United States)

    Mahler, V; Diepgen, T L; Kubeta, O; Leakakos, T; Truscott, W; Schuler, G; Kraft, D; Valenta, R

    2000-05-01

    Type I allergy to natural rubber latex can be an important health problem for latex-exposed individuals (e.g., health care workers, spina bifida children). Also beyond these risk groups, a high sensitization rate of varying and partly unknown clinical relevance has been reported. Atopy represents a risk factor for latex allergy and recent studies indicate that patients suffering from pollen allergies may have pollen allergen-specific IgE antibodies which cross-react with latex allergens. In order to investigate whether sensitization to pollen allergens can have priming effects on the production of IgE antibodies against latex in vivo, a mouse model was established. Groups of 10 BALB/C mice were immunized with Al(OH)3-adsorbed pollen extracts from timothy grass, ragweed, mugwort, or birch. For control purposes, one additional group received adjuvant only and another group was not immunized. Half of the mice of each group were subsequently immunized with Al(OH)3-adsorbed latex glove extract, the other half with adjuvant only. Pollen and latex-specific IgE- and IgG1-antibody responses were analyzed by enzyme-linked immunosorbent assay and statistically evaluated by analysis of variance. Antibody responses to cross-reactive antigens were investigated by immunoblotting. We found significantly increased IgE reactivities to latex after pollen sensitization and vice versa. Moreover, mice immunized with timothy grass pollen extract alone - without subsequent latex immunization - displayed IgE reactivity to latex. Cross-reactive antibodies were directed against pollen antigens of approximately 60 kDa molecular weight. Our results thus demonstrate a mutual boosting effect of pollen and latex sensitization in vivo which may be also operative in polysensitized plant allergic patients. PMID:10771489

  1. New vaccine strategies against enterotoxigenic Escherichia coli: II: Enhanced systemic and secreted antibody responses against the CFA/I fimbriae by priming with DNA and boosting with a live recombinant Salmonella vaccine

    Directory of Open Access Journals (Sweden)

    M.O. Lásaro

    1999-02-01

    Full Text Available The induction of systemic (IgG and mucosal (IgA antibody responses against the colonization factor I antigen (CFA/I of enterotoxigenic Escherichia coli (ETEC was evaluated in mice primed with an intramuscularly delivered CFA/I-encoding DNA vaccine followed by two oral immunizations with a live recombinant Salmonella typhimurium vaccine strain expressing the ETEC antigen. The booster effect induced by the oral immunization was detected two weeks and one year after the administration of the DNA vaccine. The DNA-primed/Salmonella-boosted vaccination regime showed a synergistic effect on the induced CFA/I-specific systemic and secreted antibody levels which could not be attained by either immunization strategy alone. These results suggest that the combined use of DNA vaccines and recombinant Salmonella vaccine strains can be a useful immunization strategy against enteric pathogens.

  2. Endocrine Factors Modulating Immune Responses in Pregnancy

    OpenAIRE

    Schumacher, Anne; Costa, Serban-Dan; Zenclussen, Ana Claudia

    2014-01-01

    How the semi-allogeneic fetus is tolerated by the maternal immune system remains a fascinating phenomenon. Despite extensive research activity in this field, the mechanisms underlying fetal tolerance are still not well understood. However, there are growing evidences that immune–immune interactions as well as immune–endocrine interactions build up a complex network of immune regulation that ensures fetal survival within the maternal uterus. In the present review, we aim to summarize emerging ...

  3. Immune response inhibits associative learning in insects.

    OpenAIRE

    Mallon, Eamonn B.; Brockmann, Axel; Schmid-Hempel, Paul

    2003-01-01

    In vertebrates, it is well established that there are many intricate interactions between the immune system and the nervous system, and vice versa. Regarding insects, until now little has been known about the link between these two systems. Here, we present behavioural evidence indicating a link between the immune system and the nervous system in insects. We show that otherwise non-infected honeybees whose immune systems are challenged by a non-pathogenic immunogenic elicitor lipopolysacchari...

  4. Activation and Regulation of DNA-Driven Immune Responses

    OpenAIRE

    Paludan, Søren R

    2015-01-01

    The innate immune system provides early defense against infections and also plays a key role in monitoring alterations of homeostasis in the body. DNA is highly immunostimulatory, and recent advances in this field have led to the identification of the innate immune sensors responsible for the recognition of DNA as well as the downstream pathways that are activated. Moreover, information on how cells regulate DNA-driven immune responses to avoid excessive inflammation is now emerging. Finally,...

  5. Respons imun humoral pada pulpitis (Humoral immune response on pulpitis)

    OpenAIRE

    Trijoedani Widodo

    2005-01-01

    Pulpitis is an inflammation process on dental pulp tissue, and usually as the continuous of caries. The microorganism in the caries is a potential immunogenic triggering the immune respons, both humoral and celluler immune responses. The aim of this research is to explain the humoral immune response changes in the dental pulp tissues of pulpitis. This research was done on three group samples: Irreversible pulpitis, Reversible pulpitis and sound teeth as the control group. The result showed th...

  6. Innate immune response development in nestling tree swallows

    Science.gov (United States)

    Stambaugh, T.; Houdek, B.J.; Lombardo, M.P.; Thorpe, P.A.; Caldwell, Hahn D.

    2011-01-01

    We tracked the development of innate immunity in nestling Tree Swallows (Tachycineta bicolor) and compared it to that of adults using blood drawn from nestlings during days 6, 12, and 18 of the ???20-day nestling period and from adults. Innate immunity was characterized using an in vitro assay of the ability of whole blood to kill Escherichia coli. The ability of whole blood to kill E. coli increased as nestlings matured. Neither this component of innate immunity nor right wing chord length on day18 were as developed as in adults indicating that development of the innate immune system and growth both continued after fledging. Narrow sense heritability analyses suggest that females with strong immune responses produced nestlings with strong immune responses. These data suggest nestling Tree Swallows allocated sufficient energy to support rapid growth to enable fledging by day 18, but that further development of innate immunity occurred post-fledging. ?? 2011 by the Wilson Ornithological Society.

  7. Prime-Boost Immunization Using a DNA Vaccine Delivered by Attenuated Salmonella enterica Serovar Typhimurium and a Killed Vaccine Completely Protects Chickens from H5N1 Highly Pathogenic Avian Influenza Virus▿

    OpenAIRE

    Pan, Zhiming; Zhang, Xiaoming; Geng, Shizhong; Fang, Qiang; You, Meng; Zhang, Lei; Jiao, Xinan; Liu, Xiufan

    2010-01-01

    H5N1 highly pathogenic avian influenza virus (HPAIV) has posed a great threat not only for the poultry industry but also for human health. However, an effective vaccine to provide a full spectrum of protection is lacking in the poultry field. In the current study, a novel prime-boost vaccination strategy against H5N1 HPAIV was developed: chickens were first orally immunized with a hemagglutinin (HA) DNA vaccine delivered by attenuated Salmonella enterica serovar Typhimurium, and boosting with...

  8. A New Mechanism to Curb Over-reactive Immune Responses

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ The human immune system is a truly amazing constellation of responses to attacks from the outside. It could defend you against millions of bacteria, microbes, viruses, toxins and parasites that would invade your body. However, there are cases where the immune response to innocuous substances is inappropriate and over-reactive, leading to diseases such as allergies and arthritis.

  9. Murine major histocompatibility complex and immune response to Eimeria falciformis.

    OpenAIRE

    Mahrt, J L; Shi, Y F

    1988-01-01

    The genetics of the immune response to Eimeria falciformis were investigated in three inbred and six congenic strains of mice. There were significant differences among strains in oocyst production and age-related mortality from parasitic infection. Genes within the H-2 complex and also non-H-2 genes share in the immune response to eimerian infection.

  10. Salicylic acid regulates Plasmodesmata closure during innate immune responses in Arabidopsis.

    Science.gov (United States)

    Wang, Xu; Sager, Ross; Cui, Weier; Zhang, Chong; Lu, Hua; Lee, Jung-Youn

    2013-06-01

    In plants, mounting an effective innate immune strategy against microbial pathogens involves triggering local cell death within infected cells as well as boosting the immunity of the uninfected neighboring and systemically located cells. Although not much is known about this, it is evident that well-coordinated cell-cell signaling is critical in this process to confine infection to local tissue while allowing for the spread of systemic immune signals throughout the whole plant. In support of this notion, direct cell-to-cell communication was recently found to play a crucial role in plant defense. Here, we provide experimental evidence that salicylic acid (SA) is a critical hormonal signal that regulates cell-to-cell permeability during innate immune responses elicited by virulent bacterial infection in Arabidopsis thaliana. We show that direct exogenous application of SA or bacterial infection suppresses cell-cell coupling and that SA pathway mutants are impaired in this response. The SA- or infection-induced suppression of cell-cell coupling requires an enhanced desease resistance1- and nonexpressor of pathogenesis-related genes1-dependent SA pathway in conjunction with the regulator of plasmodesmal gating Plasmodesmata-located protein5. We discuss a model wherein the SA signaling pathway and plasmodesmata-mediated cell-to-cell communication converge under an intricate regulatory loop. PMID:23749844

  11. Immunization with Immune Complexes Modulates the Fine Specificity of Antibody Responses to a Flavivirus Antigen

    OpenAIRE

    Tsouchnikas, Georgios; Zlatkovic, Juergen; Jarmer, Johanna; Strauß, Judith; Vratskikh, Oksana; Kundi, Michael; Stiasny, Karin; Heinz, Franz X.

    2015-01-01

    The antibody response to proteins may be modulated by the presence of preexisting antigen-specific antibodies and the formation of immune complexes (ICs). Effects such as a general increase or decrease of the response as well as epitope-specific phenomena have been described. In this study, we investigated influences of IC immunization on the fine specificity of antibody responses in a structurally well-defined system, using the envelope (E) protein of tick-borne encephalitis (TBE) virus as a...

  12. Self-adjuvanted mRNA vaccines induce local innate immune responses that lead to a potent and boostable adaptive immunity.

    Science.gov (United States)

    Kowalczyk, Aleksandra; Doener, Fatma; Zanzinger, Kai; Noth, Janine; Baumhof, Patrick; Fotin-Mleczek, Mariola; Heidenreich, Regina

    2016-07-19

    mRNA represents a new platform for the development of therapeutic and prophylactic vaccines with high flexibility with respect to production and application. We have previously shown that our two component self-adjuvanted mRNA-based vaccines (termed RNActive® vaccines) induce balanced immune responses comprising both humoral and cellular effector as well as memory responses. Here, we evaluated the early events upon intradermal application to gain more detailed insights into the underlying mode of action of our mRNA-based vaccine. We showed that the vaccine is taken up in the skin by both non-leukocytic and leukocytic cells, the latter being mostly represented by antigen presenting cells (APCs). mRNA was then transported to the draining lymph nodes (dLNs) by migratory dendritic cells. Moreover, the encoded protein was expressed and efficiently presented by APCs within the dLNs as shown by T cell proliferation and immune cell activation, followed by the induction of the adaptive immunity. Importantly, the immunostimulation was limited to the injection site and lymphoid organs as no proinflammatory cytokines were detected in the sera of the immunized mice indicating a favorable safety profile of the mRNA-based vaccines. Notably, a substantial boostability of the immune responses was observed, indicating that mRNA can be used effectively in repetitive immunization schedules. The evaluation of the immunostimulation following prime and boost vaccination revealed no signs of exhaustion as demonstrated by comparable levels of cytokine production at the injection site and immune cell activation within dLNs. In summary, our data provide mechanistic insight into the mode of action and a rational for the use of mRNA-based vaccines as a promising immunization platform. PMID:27269061

  13. Early cellular immune response to a new candidate mycobacterial vaccine antigen in childhood tuberculosis.

    Science.gov (United States)

    Schepers, K; Dirix, V; Mouchet, F; Verscheure, V; Lecher, S; Locht, C; Mascart, F

    2015-02-18

    The search for novel vaccines against tuberculosis (TB) would benefit from in-depths knowledge of the human immune responses to Mycobacterium tuberculosis (Mtb) infection. Here, we characterised in a low TB incidence country, the immune responses to a new candidate vaccine antigen against TB, the heparin-binding haemagglutinin (HBHA), in young children in contact with an active TB case (aTB). Children with no history of BCG vaccination were compared to those vaccinated at birth to compare the initial immune responses to HBHA with secondary immune responses. Fifty-eight children with aTB and 76 with latent TB infection (LTBI) were included and they were compared to 90 non-infected children. Whereas Mtb-infected children globally secreted more interferon-gamma (IFN-γ) in response to HBHA compared to the non-infected children, these IFN-γ concentrations were higher in previously BCG-vaccinated compared to non-vaccinated children. The IFN-γ concentrations were similar in LTBI and aTB children, but appeared to differ qualitatively. Whereas the IFN-γ secretion induced by native methylated and recombinant non-methylated HBHA were well correlated for aTB, this was not the case for LTBI children. Thus, Mtb-infected young children develop IFN-γ responses to HBHA that are enhanced by prior BCG vaccination, indicating BCG-induced priming, thereby supporting a prime-boost strategy for HBHA-based vaccines. The qualitative differences between aTB and LTBI in their HBHA-induced IFN-γ responses may perhaps be exploited for diagnostic purposes. PMID:25583385

  14. Intranasal vaccination with a helper-dependent adenoviral vector enhances transgene-specific immune responses in BALB/c mice.

    Science.gov (United States)

    Fu, Yuan-hui; He, Jin-sheng; Zheng, Xian-xian; Wang, Xiao-bo; Xie, Can; Shi, Chang-xin; Zhang, Mei; Tang, Qian; Wei, Wei; Qu, Jian-guo; Hong, Tao

    2010-01-01

    Helper-dependent adenoviral (HDAd) vectors were developed primarily for genetic disease therapy by deleting all coding regions for attenuating the host cellular immune response to adenovirus (Ad) and long-lasting gene expression. Recently Harui et al. reported that HDAd vaccine could stimulate superior transgene-specific cytotoxic T lymphocyte (CTL) and antibody responses via the intraperitoneal route, compared to first-generation adenoviral (FGAd) vaccine. This prompted us to explore the potential of HDAd as a vaccine vector administrated intranasally. In this study, we prepared HDAd and FGAd vectors expressing enhanced green fluorescent protein (EGFP), respectively, and compared their efficacy in mice. Mice were immunized intranasally with 5x10(9) vp HDAd or FGAd vector particles. Despite stimulating similar anti-Ad antibody responses with FGAd vaccine in the prime/boost strategy, HDAd vector expressing EGFP displayed superior transgene-specific serum IgG, mucosal IgA and cellular immune response, with the characterization of balanced or mixed Th1/Th2 CD4+ T-cell responses. Meanwhile, a single dose of intranasal (i.n.) vaccine of HDAd-EGFP induced a serum IgG response with more efficacy than FGAd-EGFP. In addition, i.n. boost immunization enhanced transgene-specific humoral and cellular responses, compared to single i.n. HDAd-EGFP immunization. Our results suggest that HDAd has potential for a mucosal vaccine vector via i.n. route, which will be useful for the development of vaccines against respiratory viruses, such as respiratory syncytial virus and influenza virus. PMID:19945423

  15. Characteristics of immune response to protozoan infections

    OpenAIRE

    Arsić-Arsenijević Valentina S.; Džamić Aleksandar M.; Mitrović Sanja M.; Radonjić Ivana V.; Kranjčić-Zec Ivana F.

    2003-01-01

    Introduction When protozoa enter the blood stream or tissues they can often survive and replicate because they adapt to the resisting natural host defenses. The interaction of immune system with infectious organisms is a dynamic interplay of host mechanisms aimed at eliminating infections and microbial strategies designed to permit survival in the face of powerful effectors mechanisms. Protozoa cause chronic and persistent infections, because natural immunity against them is weak and because ...

  16. Endocrine factors modulating immune responses in pregnancy.

    Science.gov (United States)

    Schumacher, Anne; Costa, Serban-Dan; Zenclussen, Ana Claudia

    2014-01-01

    How the semi-allogeneic fetus is tolerated by the maternal immune system remains a fascinating phenomenon. Despite extensive research activity in this field, the mechanisms underlying fetal tolerance are still not well understood. However, there are growing evidences that immune-immune interactions as well as immune-endocrine interactions build up a complex network of immune regulation that ensures fetal survival within the maternal uterus. In the present review, we aim to summarize emerging research data from our and other laboratories on immune modulating properties of pregnancy hormones with a special focus on progesterone, estradiol, and human chorionic gonadotropin. These pregnancy hormones are critically involved in the successful establishment, maintenance, and termination of pregnancy. They suppress detrimental maternal alloresponses while promoting tolerance pathways. This includes the reduction of the antigen-presenting capacity of dendritic cells (DCs), monocytes, and macrophages as well as the blockage of natural killer cells, T and B cells. Pregnancy hormones also support the proliferation of pregnancy supporting uterine killer cells, retain tolerogenic DCs, and efficiently induce regulatory T (Treg) cells. Furthermore, they are involved in the recruitment of mast cells and Treg cells into the fetal-maternal interface contributing to a local accumulation of pregnancy-protective cells. These findings highlight the importance of endocrine factors for the tolerance induction during pregnancy and encourage further research in the field. PMID:24847324

  17. Endocrine factors modulating immune responses in pregnancy

    Directory of Open Access Journals (Sweden)

    Anne eSchumacher

    2014-05-01

    Full Text Available How the semi-allogeneic fetus is tolerated by the maternal immune system remains a fascinating phenomenon. Despite extensive research activity in this field the mechanisms underlying fetal tolerance are still not well understood. However, there are growing evidences that immune-immune interactions as well as immune-endocrine interactions build up a complex network of immune regulation that ensures fetal survival within the maternal uterus. In the present review, we aim to summarize emerging research data from our and other laboratories on immune modulating properties of pregnancy hormones with a special focus on progesterone, estradiol and human Chorionic Gonadotropin. These pregnancy hormones are critically involved in the successful establishment, maintenance and termination of pregnancy. They suppress detrimental maternal alloresponses while promoting tolerance pathways. This includes the reduction of the antigen-presenting capacity of dendritic cells, monocytes and macrophages as well as the blockage of natural killer cells, T and B cells. Pregnancy hormones also support the proliferation of pregnancy supporting uterine killer cells, retain tolerogenic dendritic cells and efficiently induce regulatory T cells. Furthermore, they are involved in the recruitment of mast cells and regulatory T cells into the fetal-maternal interface contributing to a local accumulation of pregnancy-protective cells. These findings highlight the importance of endocrine factors for the tolerance induction during pregnancy and encourage further research in the field.

  18. The effect of 5-amino-3-methyl-4-isoxazolecarboxylic acid hydrazide on lymphocyte subsets and humoral immune response in SRBC-immunized mice.

    Science.gov (United States)

    Drynda, Angelika; Obmińska-Mrukowicz, Bożena; Mączyński, Marcin; Ryng, Stanisław

    2015-04-01

    5-Amino-3-methyl-4-isoxazolecarboxylic acid hydrazide is a non-cytotoxic synthetic isoxazole derivative with considerable immunomodulatory properties demonstrated in in vitro experiments. The aim of this study was to investigate the influence of this compound, depending on the dosage and schedule of treatment, on lymphocyte subsets in non-immunized mice and humoral immune response in SRBC (sheep red blood cells)-immunized mice. An analysis of lymphocyte subsets was carried out by flow cytometry, using specific monoclonal antibodies stained with fluorescein isothiocyanate (FITC) or phycoerythrin (PE). In the SRBC-immunized mice, the influence of the compound on the humoral response was determined, depending on the time of administration relative to the antigen. The number of plaque forming cells (PFC) was determined by a local hemolysis technique in an agar gel. Total and 2-mercaptoethanol resistant serum agglutination titers were defined by active hemagglutination test carried out on microplates. The investigated hydrazide was able to modulate the percentage and absolute number of T lymphocyte subsets in the thymus, and T and B lymphocytes in the peripheral lymphatic organs. It also enhanced humoral immune response in SRBC-immunized mice by increasing the number of cells producing hemolytic anti-SRBC antibodies (PFC) and by augmenting the level of total and 2-mercaptoethanol resistant hemagglutinin. The present study showed modulatory effects of 5-amino-3-methyl-4-isoxazolecarboxylic acid hydrazide on lymphocyte subsets and humoral immune response in mice. This compound could be potentially useful for the treatment of autoimmune diseases, infections or as an adjuvant for boosting the efficacy of vaccines. PMID:25572572

  19. Enhancing antibody: a novel component of the immune response.

    OpenAIRE

    Nemazee, D A; Sato, V L

    1982-01-01

    Current descriptions of the immune response identify two classes of antigenic stimuli that result in the production of specific antibody: (i) exogenous antigens and (ii) endogenous variable-region determinants of the immune system. We expand this scheme to include a third class of antigenic stimulus--new determinants created by the binding of antibody to antigen. This paper describes a set of monoclonal antibodies which arose after repeated immunization with antigen alone but which bound anti...

  20. The innate immune response during urinary tract infection and pyelonephritis

    OpenAIRE

    Spencer, John David; Schwaderer, Andrew L.; Becknell, Brian; Watson, Joshua; Hains, David S.

    2013-01-01

    Despite its proximity to the fecal flora, the urinary tract is considered sterile. The precise mechanisms by which the urinary tract maintains sterility are not well understood. Host immune responses are critically important in the antimicrobial defense of the urinary tract. During recent years, considerable advances have been made in our understanding of the mechanisms underlying immune homeostasis of the kidney and urinary tract. Dysfunctions in these immune mechanisms may result in acute d...

  1. Innate immune responses of Drosophila melanogaster are altered by spaceflight.

    Directory of Open Access Journals (Sweden)

    Oana Marcu

    Full Text Available Alterations and impairment of immune responses in humans present a health risk for space exploration missions. The molecular mechanisms underpinning innate immune defense can be confounded by the complexity of the acquired immune system of humans. Drosophila (fruit fly innate immunity is simpler, and shares many similarities with human innate immunity at the level of molecular and genetic pathways. The goals of this study were to elucidate fundamental immune processes in Drosophila affected by spaceflight and to measure host-pathogen responses post-flight. Five containers, each containing ten female and five male fruit flies, were housed and bred on the space shuttle (average orbit altitude of 330.35 km for 12 days and 18.5 hours. A new generation of flies was reared in microgravity. In larvae, the immune system was examined by analyzing plasmatocyte number and activity in culture. In adults, the induced immune responses were analyzed by bacterial clearance and quantitative real-time polymerase chain reaction (qPCR of selected genes following infection with E. coli. The RNA levels of relevant immune pathway genes were determined in both larvae and adults by microarray analysis. The ability of larval plasmatocytes to phagocytose E. coli in culture was attenuated following spaceflight, and in parallel, the expression of genes involved in cell maturation was downregulated. In addition, the level of constitutive expression of pattern recognition receptors and opsonins that specifically recognize bacteria, and of lysozymes, antimicrobial peptide (AMP pathway and immune stress genes, hallmarks of humoral immunity, were also reduced in larvae. In adults, the efficiency of bacterial clearance measured in vivo following a systemic infection with E. coli post-flight, remained robust. We show that spaceflight altered both cellular and humoral immune responses in Drosophila and that the disruption occurs at multiple interacting pathways.

  2. Immune responses to cancer: are they potential biomarkers of prognosis?

    Directory of Open Access Journals (Sweden)

    Theresa L Whiteside

    2013-05-01

    Full Text Available Recent technical improvements in evaluations of immune cells in situ and immune monitoring of patients with cancer have provided a wealth of new data confirming that immune cells play a key role in human cancer progression. This, in turn, has revived the expectation that immune endpoints might serve as reliable biomarkers of outcome or response to therapy in cancer. The recent successes in linking the T-cell signature in human colorectal carcinoma (CRC with prognosis have provided a strong motive for searching for additional immune biomarkers that could serve as intermediate endpoints of response to therapy and outcome in human cancers. A number of potentially promising immune biomarkers have emerged, but most remain to be validated. Among them, the B-cell signature, as exemplified by expression of the immunoglobulin G kappa chain (IGKC in tumor-infiltrating lymphocytes (TIL, has been validated as a biomarker of response to adjuvant therapy and better survival in patients with breast carcinoma and several other types of human solid tumors. Additional immune endpoints are being currently tested as potentially promising biomarkers in cancer. In view of currently growing use of immune cancer therapies, the search for immune biomarkers of prognosis are critically important for identifying patients who would benefit the most from adjuvant immunotherapy.

  3. Proteasome function shapes innate and adaptive immune responses.

    Science.gov (United States)

    Kammerl, Ilona E; Meiners, Silke

    2016-08-01

    The proteasome system degrades more than 80% of intracellular proteins into small peptides. Accordingly, the proteasome is involved in many essential cellular functions, such as protein quality control, transcription, immune responses, cell signaling, and apoptosis. Moreover, degradation products are loaded onto major histocompatibility class I molecules to communicate the intracellular protein composition to the immune system. The standard 20S proteasome core complex contains three distinct catalytic active sites that are exchanged upon stimulation with inflammatory cytokines to form the so-called immunoproteasome. Immunoproteasomes are constitutively expressed in immune cells and have different proteolytic activities compared with standard proteasomes. They are rapidly induced in parenchymal cells upon intracellular pathogen infection and are crucial for priming effective CD8(+) T-cell-mediated immune responses against infected cells. Beyond shaping these adaptive immune reactions, immunoproteasomes also regulate the function of immune cells by degradation of inflammatory and immune mediators. Accordingly, they emerge as novel regulators of innate immune responses. The recently unraveled impairment of immunoproteasome function by environmental challenges and by genetic variations of immunoproteasome genes might represent a currently underestimated risk factor for the development and progression of lung diseases. In particular, immunoproteasome dysfunction will dampen resolution of infections, thereby promoting exacerbations, may foster autoimmunity in chronic lung diseases, and possibly contributes to immune evasion of tumor cells. Novel pharmacological tools, such as site-specific inhibitors of the immunoproteasome, as well as activity-based probes, however, hold promises as innovative therapeutic drugs for respiratory diseases and biomarker profiling, respectively. PMID:27343191

  4. Chemical Tools To Monitor and Manipulate Adaptive Immune Responses.

    Science.gov (United States)

    Doran, Todd M; Sarkar, Mohosin; Kodadek, Thomas

    2016-05-18

    Methods to monitor and manipulate the immune system are of enormous clinical interest. For example, the development of vaccines represents one of the earliest and greatest accomplishments of the biomedical research enterprise. More recently, drugs capable of "reawakening" the immune system to cancer have generated enormous excitement. But, much remains to be done. All drugs available today that manipulate the immune system cannot distinguish between "good" and "bad" immune responses and thus drive general and systemic immune suppression or activation. Indeed, with the notable exception of vaccines, our ability to monitor and manipulate antigen-specific immune responses is in its infancy. Achieving this finer level of control would be highly desirable. For example, it might allow the pharmacological editing of pathogenic immune responses without restricting the ability of the immune system to defend against infection. On the diagnostic side, a method to comprehensively monitor the circulating, antigen-specific antibody population could provide a treasure trove of clinically useful biomarkers, since many diseases expose the immune system to characteristic molecules that are deemed foreign and elicit the production of antibodies against them. This Perspective will discuss the state-of-the-art of this area with a focus on what we consider seminal opportunities for the chemistry community to contribute to this important field. PMID:27115249

  5. The Role of the Immune Response in Merkel Cell Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Triozzi, Pierre L., E-mail: triozzp@ccf.org [Taussig Cancer Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195 (United States); Fernandez, Anthony P. [Departments of Dermatology and Anatomic Pathology, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195 (United States)

    2013-02-28

    Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer. The Merkel cell polyomavirus (MCPyV) is implicated in its pathogenesis. Immune mechanisms are also implicated. Patients who are immunosuppressed have an increased risk. There is evidence that high intratumoral T-cell counts and immune transcripts are associated with favorable survival. Spontaneous regressions implicate immune effector mechanisms. Immunogenicity is also supported by observation of autoimmune paraneoplastic syndromes. Case reports suggest that immune modulation, including reduction of immune suppression, can result in tumor regression. The relationships between MCPyV infection, the immune response, and clinical outcome, however, remain poorly understood. Circulating antibodies against MCPyV antigens are present in most individuals. MCPyV-reactive T cells have been detected in both MCC patients and control subjects. High intratumoral T-cell counts are also associated with favorable survival in MCPyV-negative MCC. That the immune system plays a central role in preventing and controlling MCC is supported by several observations. MCCs often develop, however, despite the presence of humoral and cellular immune responses. A better understanding on how MCPyV and MCC evade the immune response will be necessary to develop effective immunotherapies.

  6. The Role of the Immune Response in Merkel Cell Carcinoma

    International Nuclear Information System (INIS)

    Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer. The Merkel cell polyomavirus (MCPyV) is implicated in its pathogenesis. Immune mechanisms are also implicated. Patients who are immunosuppressed have an increased risk. There is evidence that high intratumoral T-cell counts and immune transcripts are associated with favorable survival. Spontaneous regressions implicate immune effector mechanisms. Immunogenicity is also supported by observation of autoimmune paraneoplastic syndromes. Case reports suggest that immune modulation, including reduction of immune suppression, can result in tumor regression. The relationships between MCPyV infection, the immune response, and clinical outcome, however, remain poorly understood. Circulating antibodies against MCPyV antigens are present in most individuals. MCPyV-reactive T cells have been detected in both MCC patients and control subjects. High intratumoral T-cell counts are also associated with favorable survival in MCPyV-negative MCC. That the immune system plays a central role in preventing and controlling MCC is supported by several observations. MCCs often develop, however, despite the presence of humoral and cellular immune responses. A better understanding on how MCPyV and MCC evade the immune response will be necessary to develop effective immunotherapies

  7. Heavy metal pollution disturbs immune response in wild ant populations

    Energy Technology Data Exchange (ETDEWEB)

    Sorvari, Jouni [Section of Ecology, Department of Biology, University of Turku, FIN-20014 Turku (Finland)]. E-mail: jouni.sorvari@utu.fi; Rantala, Liisa M. [Department of Biological and Environmental Science, University of Jyvaeskylae, P.O. Box 35, FIN-40351 Jyvaeskylae (Finland); Rantala, Markus J. [Section of Ecology, Department of Biology, University of Turku, FIN-20014 Turku (Finland); Department of Biology, University of California, Riverside, CA 92521 USA (United States); Hakkarainen, Harri [Section of Ecology, Department of Biology, University of Turku, FIN-20014 Turku (Finland); Eeva, Tapio [Section of Ecology, Department of Biology, University of Turku, FIN-20014 Turku (Finland)

    2007-01-15

    Concern about the effects of environmental contaminants on immune function in both humans and wildlife is growing and practically nothing is known about this impact on terrestrial invertebrates, even though they are known to easily accumulate pollutants. We studied the effect of industrial heavy metal contamination on immune defense of a free-living wood ant (Formica aquilonia). To find out whether ants show an adapted immune function in a polluted environment, we compared encapsulation responses between local and translocated colonies. Local colonies showed higher heavy metal levels than the translocated ones but the encapsulation response was similar between the two groups, indicating that the immune system of local ants has not adapted to high contamination level. The encapsulation response was elevated in moderate whereas suppressed in high heavy metal levels suggesting higher risk for infections in heavily polluted areas. - Heavy metal pollution affects immune function in ants.

  8. Immune response induction in the central nervous system

    DEFF Research Database (Denmark)

    Owens, Trevor; Babcock, Alicia

    2002-01-01

    The primary function of the immune response is protection of the host against infection with pathogens, including viruses. Since viruses can infect any tissue of the body, including the central nervous system (CNS), it is logical that cells of the immune system should equally have access to all...... tissues. Nevertheless, the brain and spinal cord are noted for their lack of immune presence. Relative to other organ systems, the CNS appears immunologically privileged. Furthermore, when immune responses do occur in the CNS, they are frequently associated with deleterious effects such as inflammatory...... and/or demyelinating pathology. This article will review the molecular and cellular dynamics of immune responses in the CNS, with particular emphasis on autoimmune inflammation, as has been studied in the authors' laboratory....

  9. Heavy metal pollution disturbs immune response in wild ant populations

    International Nuclear Information System (INIS)

    Concern about the effects of environmental contaminants on immune function in both humans and wildlife is growing and practically nothing is known about this impact on terrestrial invertebrates, even though they are known to easily accumulate pollutants. We studied the effect of industrial heavy metal contamination on immune defense of a free-living wood ant (Formica aquilonia). To find out whether ants show an adapted immune function in a polluted environment, we compared encapsulation responses between local and translocated colonies. Local colonies showed higher heavy metal levels than the translocated ones but the encapsulation response was similar between the two groups, indicating that the immune system of local ants has not adapted to high contamination level. The encapsulation response was elevated in moderate whereas suppressed in high heavy metal levels suggesting higher risk for infections in heavily polluted areas. - Heavy metal pollution affects immune function in ants

  10. Paradoxical acclimation responses in the thermal performance of insect immunity.

    Science.gov (United States)

    Ferguson, Laura V; Heinrichs, David E; Sinclair, Brent J

    2016-05-01

    Winter is accompanied by multiple stressors, and the interactions between cold and pathogen stress potentially determine the overwintering success of insects. Thus, it is necessary to explore the thermal performance of the insect immune system. We cold-acclimated spring field crickets, Gryllus veletis, to 6 °C for 7 days and measured the thermal performance of potential (lysozyme and phenoloxidase activity) and realised (bacterial clearance and melanisation) immune responses. Cold acclimation decreased the critical thermal minimum from -0.5 ± 0.25 to -2.1 ± 0.18 °C, and chill coma recovery time after 72 h at -2 °C from 16.8 ± 4.9 to 5.2 ± 2.0 min. Measures of both potential and realised immunity followed a typical thermal performance curve, decreasing with decreasing temperature. However, cold acclimation further decreased realised immunity at low, but not high, temperatures; effectively, immune activity became paradoxically specialised to higher temperatures. Thus, cold acclimation induced mismatched thermal responses between locomotor and immune systems, as well as within the immune system itself. We conclude that cold acclimation in insects appears to preferentially improve cold tolerance over whole-animal immune performance at low temperatures, and that the differential thermal performance of physiological responses to multiple pressures must be considered when predicting ectotherms' response to climate change. PMID:26846428

  11. Altered Allogeneic Immune Responses in Middle-Aged Mice

    Institute of Scientific and Technical Information of China (English)

    YiminSun; HanhanLi; AlanN.Langnas

    2004-01-01

    It is well known that leukocyte composition, T cell phenotypes and immune function change in aged mice and humans. However, limited and conflicting results on the age-related immune changes in middle-aged mice were reported. Identification of the characteristics of allogeneic immune responses in aging mice may offer important information for transplantation immunology. The major age-related changes in the immune cell phenotypes and function of 12 months old mice include: 1) the significantly decreased CD4+ cell population in the peripheral blood, the major peripheral CD4+ cells is CD45RBlowCD62Llow memory phenotype; 2) the in vitro responses to alloantigens and Con A of splenocytes markedly reduced; 3) the in vivo secondary humoral immune responses to alloantigens significantly declined; 4) the age-related alteration in the thymus mainly occurred in CD4/CD8 double positive (DP) stage; and 5) increased CD80+ and MHC class II+ cell population in spleens. Thus, the major age-related immune changes in 12 months old mice occurred in CD4+ T cells in the periphery and DP stage in the thymus, which may subsequently lead to the decreased allogeneic immune responses and the different sensitivity to immunosuppressive drugs and treatments. Further studies on the characteristics of allogeneic immunity in aging individuals may help to determine the appropriated treatment for transplant aging individuals. Cellular & Molecular Immunology. 2004;1(6):440-446.

  12. Altered Allogeneic Immune Responses in Middle-Aged Mice

    Institute of Scientific and Technical Information of China (English)

    Yimin Sun; Hanhan Li; Alan N. Langnas; Yong Zhao

    2004-01-01

    It is well known that leukocyte composition, T cell phenotypes and immune function change in aged mice and humans. However, limited and conflicting results on the age-related immune changes in middle-aged mice were reported. Identification of the characteristics of allogeneic immune responses in aging mice may offer important information for transplantation immunology. The major age-related changes in the immune cell phenotypes and function of 12 months old mice include: 1) the significantly decreased CD4+ cell population in the peripheral blood, the major peripheral CD4+ cells is CD45RBlowCD62Llow memory phenotype; 2) the in vitro responses to alloantigens and Con A of splenocytes markedly reduced; 3) the in vivo secondary humoral immune responses to alloantigens significantly declined; 4) the age-related alteration in the thymus mainly occurred in CD4/CD8 double positive (DP) stage; and 5) increased CD80+ and MHC class Ⅱ+ cell population in spleens. Thus, the major age-related immune changes in 12 months old mice occurred in CD4+ T cells in the periphery and DP stage in the thymus, which may subsequently lead to the decreased allogeneic immune responses and the different sensitivity to immunosuppressive drugs and treatments. Further studies on the characteristics of allogeneic immunity in aging individuals may help to determine the appropriated treatment for transplant aging individuals. Cellular & Molecular Immunology. 2004; 1(6) :440-446.

  13. Measuring antigen-specific immune responses: 2008 Update

    NARCIS (Netherlands)

    J.W. Gratama (Jan-Willem); F. Kern (Florian); F. Manca (Fabrizio); M. Roederer (Mario)

    2008-01-01

    textabstractOverall, the last 10 years have seen an explosion in the field of antigen-specific immune response monitoring. As summarized in this issue of Cytometry and at the MASIR conferences, these technologies have provided new insights into the basic biology of the immune system and are beginnin

  14. A Mycobacterium bovis BCG-naked DNA prime-boost vaccination strategy induced CD4⁺ and CD8⁺ T-cell response against Mycobacterium tuberculosis immunogens.

    Science.gov (United States)

    Lu, Miao; Xia, Zhi Yang; Bao, Lang

    2014-01-01

    Mycobacterium tuberculosis infection is still a major global public health problem. Presently the only tuberculosis (TB) vaccine available is Bacille Calmette-Guérin (BCG), although it fails to adequately protect against pulmonary TB in adults. To solve this problem, the development of a new effective vaccine is urgently desired. BCG-prime DNA-booster vaccinations strategy has been shown to induce greater protection against tuberculosis (TB) than BCG alone. Some studies have demonstrated that the two genes (Rv1769 and Rv1772) are excellent T-cell antigens and could induce T-cell immune responses. In this research, we built BCG-C or BCG-P prime-recombination plasmid PcDNA3.1-Rv1769 or PcDNA3.1-Rv1772 boost vaccinations strategy to immunize BALB/c mice and evaluated its immunogenicity. The data suggests that the BCG-C+3.1-72 strategy could elicit the most long-lasting and strongest Th1-type cellular immune responses and the BCG-C+3.1-69 strategy could induce the high level CD8+ T-cell response at certain time points. These findings support the ideas that the prime-boost strategy as a combination of vaccines may be better than a single vaccine for protection against tuberculosis. PMID:24741595

  15. Sublingual nucleotides and immune response to exercise

    Directory of Open Access Journals (Sweden)

    Ostojic Sergej M

    2012-07-01

    Full Text Available Abstract Evidence exists regarding the potential role of exogenous nucleotides as regulators of the immune function in physically active humans, yet the potential use of nucleotides has been hindered by their low bioavailability after oral administration. We conducted a double-blind, placebo-controlled, randomized trial to assess the effect of sublingual nucleotides (50 mg/day on salivary and serum immunity indicators as compared to placebo, both administered to healthy males aged 20 to 25 years for 14 days. Sublingual administration of nucleotides for 14 days increased serum immunoglobulin A, natural killer cells count and cytotoxic activity, and offset the post-exercise drop of salivary immunoglobulins and lactoferrin (P  0.05. It seems that sublingual administration of nucleotides for two weeks considerably affected immune function in healthy males.

  16. Host Immune Response to Histophilus somni.

    Science.gov (United States)

    Corbeil, Lynette B

    2016-01-01

    Histophilus somni is known to cause several overlapping syndromes or to be found in genital or upper respiratory carrier states in ruminants. Vaccines have been used for decades, yet efficacy is controversial and mechanisms of protective immunity are not well understood. Since H. somni survives phagocytosis, it has sometimes been considered to be a facultative intercellular parasite, implying that cell-mediated immunity would be critical in protection. However, H. somni not only inhibits phagocyte function, but also is cytotoxic for macrophages. Therefore, it does not live for long periods in healthy phagocytes. Protection of calves against H. somni pneumonia by passive immunization is also evidence that H. somni is more like an extracellular pathogen than an intracellular pathogen. Several studies showed that bovine IgG2 antibodies are more protective than IgG1 antibodies. Even the IgG2 allotypes tend to vary in protection. Of course, antigenic specificity also determines protection. So far, there is most evidence for protection by a 40 K outer membrane protein and by Immunoglobulin binding protein A fibrils. Serology and immunohistochemistry have both been used for immunodiagnosis. Many evasive mechanisms by H. somni have been defined, including decreased phagocyte function, antibodies bound by shed antigens, decreased immune stimulation, and antigenic variation. Interaction of H. somni with other bovine respiratory disease organisms is another layer of pathogenesis. Studies of bovine respiratory syncytial virus (BRSV) and H. somni in calfhood pneumonia revealed an increase in IgE antibodies to H. somni, which were associated with more severe disease of longer duration than with either agent alone. Innate immune mechanisms at the epithelial cell level are also affected by dual infection by BRSV and H. somni as compared to either pathogen alone. Although much more work needs to be done, the complex mechanisms of H. somni immunity are becoming clearer. PMID

  17. Carbohydrate Mimetic Peptides Augment Carbohydrate-Reactive Immune Responses in the Absence of Immune Pathology

    Energy Technology Data Exchange (ETDEWEB)

    Hennings, Leah; Artaud, Cecile; Jousheghany, Fariba; Monzavi-Karbassi, Behjatolah; Pashov, Anastas; Kieber-Emmons, Thomas, E-mail: tke@uams.edu [Winthrop P. Rockefeller Cancer Institute and Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205 (United States)

    2011-11-11

    Among the most challenging of clinical targets for cancer immunotherapy are Tumor Associated Carbohydrate Antigens (TACAs). To augment immune responses to TACA we are developing carbohydrate mimetic peptides (CMPs) that are sufficiently potent to activate broad-spectrum anti-tumor reactivity. However, the activation of immune responses against terminal mono- and disaccharide constituents of TACA raises concerns regarding the balance between “tumor destruction” and “tissue damage”, as mono- and disaccharides are also expressed on normal tissue. To support the development of CMPs for clinical trial testing, we demonstrate in preclinical safety assessment studies in mice that vaccination with CMPs can enhance responses to TACAs without mediating tissue damage to normal cells expressing TACA. BALB/c mice were immunized with CMPs that mimic TACAs reactive with Griffonia simplicifolia lectin 1 (GS-I), and tissue reactivity of serum antibodies were compared with the tissue staining profile of GS-I. Tissues from CMP immunized mice were analyzed using hematoxylin and eosin stain, and Luxol-fast blue staining for myelination. Western blots of membranes from murine mammary 4T1 cells, syngeneic with BALB/c mice, were also compared using GS-I, immunized serum antibodies, and naive serum antibodies. CMP immunization enhanced glycan reactivities with no evidence of pathological autoimmunity in any immunized mice demonstrating that tissue damage is not an inevitable consequence of TACA reactive responses.

  18. Carbohydrate Mimetic Peptides Augment Carbohydrate-Reactive Immune Responses in the Absence of Immune Pathology

    International Nuclear Information System (INIS)

    Among the most challenging of clinical targets for cancer immunotherapy are Tumor Associated Carbohydrate Antigens (TACAs). To augment immune responses to TACA we are developing carbohydrate mimetic peptides (CMPs) that are sufficiently potent to activate broad-spectrum anti-tumor reactivity. However, the activation of immune responses against terminal mono- and disaccharide constituents of TACA raises concerns regarding the balance between “tumor destruction” and “tissue damage”, as mono- and disaccharides are also expressed on normal tissue. To support the development of CMPs for clinical trial testing, we demonstrate in preclinical safety assessment studies in mice that vaccination with CMPs can enhance responses to TACAs without mediating tissue damage to normal cells expressing TACA. BALB/c mice were immunized with CMPs that mimic TACAs reactive with Griffonia simplicifolia lectin 1 (GS-I), and tissue reactivity of serum antibodies were compared with the tissue staining profile of GS-I. Tissues from CMP immunized mice were analyzed using hematoxylin and eosin stain, and Luxol-fast blue staining for myelination. Western blots of membranes from murine mammary 4T1 cells, syngeneic with BALB/c mice, were also compared using GS-I, immunized serum antibodies, and naive serum antibodies. CMP immunization enhanced glycan reactivities with no evidence of pathological autoimmunity in any immunized mice demonstrating that tissue damage is not an inevitable consequence of TACA reactive responses

  19. Virus-like nanostructures for tuning immune response

    Science.gov (United States)

    Mammadov, Rashad; Cinar, Goksu; Gunduz, Nuray; Goktas, Melis; Kayhan, Handan; Tohumeken, Sehmus; Topal, Ahmet E.; Orujalipoor, Ilghar; Delibasi, Tuncay; Dana, Aykutlu; Ide, Semra; Tekinay, Ayse B.; Guler, Mustafa O.

    2015-11-01

    Synthetic vaccines utilize viral signatures to trigger immune responses. Although the immune responses raised against the biochemical signatures of viruses are well characterized, the mechanism of how they affect immune response in the context of physical signatures is not well studied. In this work, we investigated the ability of zero- and one-dimensional self-assembled peptide nanostructures carrying unmethylated CpG motifs (signature of viral DNA) for tuning immune response. These nanostructures represent the two most common viral shapes, spheres and rods. The nanofibrous structures were found to direct immune response towards Th1 phenotype, which is responsible for acting against intracellular pathogens such as viruses, to a greater extent than nanospheres and CpG ODN alone. In addition, nanofibers exhibited enhanced uptake into dendritic cells compared to nanospheres or the ODN itself. The chemical stability of the ODN against nuclease-mediated degradation was also observed to be enhanced when complexed with the peptide nanostructures. In vivo studies showed that nanofibers promoted antigen-specific IgG production over 10-fold better than CpG ODN alone. To the best of our knowledge, this is the first report showing the modulation of the nature of an immune response through the shape of the carrier system.

  20. Nanoparticles for nasal delivery of vaccines : monitoring adaptive immune responses

    NARCIS (Netherlands)

    Keijzer, C.

    2013-01-01

    The continuous emergence of new pathogens and growing drug resistance of microorganisms asks for innovative vaccination strategies. An alternative to conventional multiple injection vaccines is the nasal route of vaccine delivery. The immune response induced following nasal antigen delivery depends

  1. Role of nutrients in the development of neonatal immune response.

    Science.gov (United States)

    Cunningham-Rundles, Susanna; Lin, Hong; Ho-Lin, Deborah; Dnistrian, Ann; Cassileth, Barrie R; Perlman, Jeffrey M

    2009-11-01

    Nutrients exert unique regulatory effects in the perinatal period that mold the developing immune system. The interactions of micronutrients and microbial and environmental antigens condition the post-birth maturation of the immune system, influencing reactions to allergens, fostering tolerance towards the emerging gastrointestinal flora and ingested antigens, and defining patterns of host defense against potential pathogens. The shared molecular structures that are present on microbes or certain plants, but not expressed by human cells, are recognized by neonatal innate immune receptors. Exposure to these activators in the environment through dietary intake in early life can modify the immune response to allergens and prime the adaptive immune response towards pathogens that express the corresponding molecular structures. PMID:19906219

  2. Effect of mycotoxins on swine in immune responses

    OpenAIRE

    Fornalés Pallàs, Clara

    2014-01-01

    Póster Mycotoxins are secondary metabolites of fungi, hazardous to human and animal health. Their effect has been mostly studied in medium or half doses. It has been stated that, at lower, subclinical doses, mycotoxins may alter immune response, thus predisposing the appearance of diseases. Swine are a good model for studying the effect of mycotoxins to extrapolate to humans. This review is focused on the effect of most common mycotoxins on Swine immune response.

  3. Immune response to measles vaccine in Peruvian children.

    OpenAIRE

    Bautista-López Norma L.; Vaisberg Abraham; Kanashiro Rosa; Hernández Herminio; Ward Brian J.

    2001-01-01

    OBJECTIVE: To evaluate the immune response in Peruvian children following measles vaccination. METHODS: Fifty-five Peruvian children received Schwarz measles vaccine (about 10(3) plaque forming units) at about 9 months of age. Blood samples were taken before vaccination, then twice after vaccination: one sample at between 1 and 4 weeks after vaccination and the final sample 3 months post vaccination for evaluation of immune cell phenotype and lymphoproliferative responses to measles and non-m...

  4. A preliminary study to evaluate the immune responses induced by immunization of dogs with inactivated Ehrlichia canis organisms

    Directory of Open Access Journals (Sweden)

    Sunita Mahan

    2005-09-01

    Full Text Available Ehrlichia canis is an intracellular pathogen that causes canine monocytic ehrlichiosis. Although the role of antibody responses cannot be discounted, control of this intracellular pathogen is expected to be by cell mediated immune responses. The immune responses in dogs immunized with inactivated E. canis organisms in combination with Quil A were evaluated. Immunization provoked strong humoral and cellular immune responses, which were demonstrable by Western blotting and lymphocyte proliferation assays. By Western blotting antibodies to several immunodominant E. canis proteins were detected in serum from immunized dogs and antibody titres increased after each immunization. The complement of immunogenic proteins recognized by the antisera were similar to those recognized in serum from infected dogs. Upon challenge with live E. canis, rapid anamnestic humoral responses were detected in the serum of immunized dogs and primary antibody responses were detected in the serum from control dogs. Following immunization, a lymphocyte proliferative response (cellular immunity was detected in peripheral blood mononuclear cells (PBMNs of immunized dogs upon stimulation with E. canis antigens. These responses were absent from non-immunized control dogs until after infection with live E. canis, when antigen specific-lymphocyte proliferation responses were also detected in the PBMNs of the control dogs. It can be thus concluded that immunization against canine monocytic ehrlichiosis may be feasible. However, the immunization regimen needs to be optimized and a detailed investigation needs to be done to determine if this regimen can prevent development of acute and chronic disease.

  5. A Viral Vectored Prime-Boost Immunization Regime Targeting the Malaria Pfs25 Antigen Induces Transmission-Blocking Activity

    OpenAIRE

    Goodman, Anna L.; Blagborough, Andrew M.; Sumi Biswas; Yimin Wu; Hill, Adrian V.; Sinden, Robert E.; Draper, Simon J

    2011-01-01

    The ookinete surface protein Pfs25 is a macrogamete-to-ookinete/ookinete stage antigen of Plasmodium falciparum, capable of exerting high-level anti-malarial transmission-blocking activity following immunization with recombinant protein-in-adjuvant formulations. Here, this antigen was expressed in recombinant chimpanzee adenovirus 63 (ChAd63), human adenovirus serotype 5 (AdHu5) and modified vaccinia virus Ankara (MVA) viral vectored vaccines. Two immunizations were administered to mice in a ...

  6. Respons imun humoral pada pulpitis (Humoral immune response on pulpitis

    Directory of Open Access Journals (Sweden)

    Trijoedani Widodo

    2005-06-01

    Full Text Available Pulpitis is an inflammation process on dental pulp tissue, and usually as the continuous of caries. The microorganism in the caries is a potential immunogenic triggering the immune respons, both humoral and celluler immune responses. The aim of this research is to explain the humoral immune response changes in the dental pulp tissues of pulpitis. This research was done on three group samples: Irreversible pulpitis, Reversible pulpitis and sound teeth as the control group. The result showed that there were three pulpitis immunopathologic patterns: the sound teeth immunopathologic pattern showing a low humoral immune response, in a low level of IgG, IgA and IgM, the reversible pulpitis pattern showing that in a higher humoral immune response, IgG and IgA decreased but IgM increased, the irreversible pulpitis pattern showing that IgG and IgM increased, but it couldn't be repaired although it has highly immunity, and it showed an unusually low level of IgA. This low level of IgA meant that irreversible pulpitis had a low mucosal immunity.

  7. Modeling the interactions between pathogenic bacteria, bacteriophage and immune response

    Science.gov (United States)

    Leung, Chung Yin (Joey); Weitz, Joshua S.

    The prevalence of antibiotic-resistant strains of pathogenic bacteria has led to renewed interest in the use of bacteriophage (phage), or virus that infects bacteria, as a therapeutic agent against bacterial infections. However, little is known about the theoretical mechanism by which phage therapy may work. In particular, interactions between the bacteria, the phage and the host immune response crucially influences the outcome of the therapy. Few models of phage therapy have incorporated all these three components, and existing models suffer from unrealistic assumptions such as unbounded growth of the immune response. We propose a model of phage therapy with an emphasis on nonlinear feedback arising from interactions with bacteria and the immune response. Our model shows a synergistic effect between the phage and the immune response which underlies a possible mechanism for phage to catalyze the elimination of bacteria even when neither the immune response nor phage could do so alone. We study the significance of this effect for different parameters of infection and immune response, and discuss its implications for phage therapy.

  8. Chemical agents and the immune response.

    OpenAIRE

    Luster, M I; Rosenthal, G J

    1993-01-01

    Our desire to understand the potential adverse human health effects of environmental chemical exposure has coincided with an increased understanding of the immune system and an appreciation of its complex regulatory network. This has spawned a broad interest in the area of immunotoxicology within the scientific community as well as certain concerns in the public sector regarding chemical-induced hypersensitivity and immunosuppression. The incidence of alleged human sensitization to chemicals ...

  9. Legionella secreted effectors and innate immune responses

    OpenAIRE

    Luo, Zhao-Qing

    2011-01-01

    Legionella pneumophila is a facultative intracellular pathogen capable of replicating in a wide spectrum of cells. Successful infection by Legionella requires the Dot/Icm type IV secretion system, which translocates a large number of effector proteins into infected cells. By co-opting numerous host cellular processes, these proteins function to establish a specialized organelle that allows bacterial survival and proliferation. Even within the vacuole, L. pneumophila triggers robust immune res...

  10. Humoral immune response of dairy cattle immunized with rBm95 (KU-VAC1) derived from Thai Rhipicephalus microplus.

    Science.gov (United States)

    Jittapalapong, S; Kaewhom, P; Kengradomkij, C; Saratapan, N; Canales, M; de la Fuente, J; Stich, R W

    2010-04-01

    Rhipicephalus (Boophilus) microplus is an important cause of economic losses in Thailand through direct effects of feeding on cattle and pathogen transmission. Current tick control methods rely on expensive chemical acaricides that result in environmental contamination, residues in food animal products and acaricide-resistant ticks. Anti-tick vaccines based on concealed antigens have shown promising results in the control of cattle tick. Thus, recombinant Bm95 (rBm95) from Thai R. microplus (KU-VAC1) was cloned and expressed to test as an anti-tick vaccine in Thailand. The objective of this study was to compare antibody responses induced by KU-VAC1 to that obtained after vaccination with Gavac that is based on the Bm86 homologue. Four groups of six cattle each were immunized with KU-VAC1, Gavac, adjuvant or phosphate-buffered saline, and boosted three times at 21-day intervals. Enzyme-linked-immunosorbent serologic assay were used to measure the humoral antibody responses specific to Thai rBm95. Cattle immunized with either KU-VAC1 or Gavac showed significantly greater antibody production than the controls. Antibody titres were detected after the first immunization and peaked after the seventh week. These results indicated that KU-VAC1 and Gavac are similarly immunogenic, and that further studies are warranted to compare performance parameters of ticks fed on immunized cattle. PMID:20537117

  11. The role of lysosomal cysteine proteases in crustacean immune response

    Directory of Open Access Journals (Sweden)

    FL Garcia-Carreño

    2014-04-01

    Full Text Available Over the long course of evolution and under the selective pressure exerted by pathogens and parasites, animals have selectively fixed a number of defense mechanisms against the constant attack of intruders. The immune response represents a key component to optimize the biological fitness of individuals. Two decades ago, prevention and control of diseases in crustacean aquaculture systems were considered priorities in most shrimp-producing countries, but knowledge was scarce and various pathogens have severely affected aquaculture development around the world. Scientific contributions have improved our understanding of the crustacean immune response. Several studies confirm the central role played by proteases in the immune response of animals, and the cooperative interaction of these enzymes in a wide variety of organisms is well known. This review summarizes the current information regarding the role of cysteine proteases in the immune system of Crustacea and points to aspects that are needed to provide a better integration of our knowledge.

  12. Modulation of systemic immune responses through commensal gastrointestinal microbiota.

    Directory of Open Access Journals (Sweden)

    Kyle M Schachtschneider

    Full Text Available Colonization of the gastrointestinal (GI tract is initiated during birth and continually seeded from the individual's environment. Gastrointestinal microorganisms play a central role in developing and modulating host immune responses and have been the subject of investigation over the last decades. Animal studies have demonstrated the impact of GI tract microbiota on local gastrointestinal immune responses; however, the full spectrum of action of early gastrointestinal tract stimulation and subsequent modulation of systemic immune responses is poorly understood. This study explored the utility of an oral microbial inoculum as a therapeutic tool to affect porcine systemic immune responses. For this study a litter of 12 pigs was split into two groups. One group of pigs was inoculated with a non-pathogenic oral inoculum (modulated, while another group (control was not. DNA extracted from nasal swabs and fecal samples collected throughout the study was sequenced to determine the effects of the oral inoculation on GI and respiratory microbial communities. The effects of GI microbial modulation on systemic immune responses were evaluated by experimentally infecting with the pathogen Mycoplasma hyopneumoniae. Coughing levels, pathology, toll-like receptors 2 and 6, and cytokine production were measured throughout the study. Sequencing results show a successful modulation of the GI and respiratory microbiomes through oral inoculation. Delayed type hypersensitivity responses were stronger (p = 0.07, and the average coughing levels and respiratory TNF-α variance were significantly lower in the modulated group (p<0.0001 and p = 0.0153, respectively. The M. hyopneumoniae infection study showed beneficial effects of the oral inoculum on systemic immune responses including antibody production, severity of infection and cytokine levels. These results suggest that an oral microbial inoculation can be used to modulate microbial communities, as well as

  13. Detailing profiles of Lawsonia intracellularis specific lymphocytes in the immune response to a challenge inoculation after oral vaccination or primary inoculation with virulent bacteria

    DEFF Research Database (Denmark)

    Riber, Ulla; Hvass, Henriette Cordes; Heegaard, Peter M. H.; Ståhl, Marie; Jensen, Tim Kåre; Jungersen, Gregers

    2012-01-01

    not induce measurable primary humoral or cell-mediated immune responses, nor was it able to reduce faecal shedding of bacteria from eight vaccinated pigs compared to seven age-matched naïve challenge-control pigs. Vaccinated pigs did, however, respond to vaccination with an acute phase protein...... IFN-γ producing cells in the vaccinated pigs showed profiles primarily of CD8+(CD4neg) and CD4+CD8+ double positive lymphocytes. Similar profiles of IFN-γ producing cells were found in re-inoculated immune pigs, which experienced a boost in CMI responses. Cellular proliferation was identified in...

  14. [Effect of anabolic steroid on immune response].

    Science.gov (United States)

    Yamagishi, H; Kobayashi, M; Konosu, H; Kurioka, H; Naito, K; Sonoyama, T; Nishimoto, T; Hashimoto, I

    1984-03-01

    Using lymphocyte, monocyte and eosinophil counts of the peripheral blood, PHA-blastoid transformation, immunoglobulin and beta 2-microglobulin, the influence of anabolic steroid on the immune reactivity of the host was dissected by administration of Deca-Durabolin ( nandrolone decanoate) to both tumor-bearing host and tumor-free host after operation for alimentary tract. The number of peripheral lymphocytes and monocytes, the PHA-blastoid transformation of peripheral lymphocytes and the IgG level were increased, and the beta 2-microglobulin level showed the tendency of decrease after the administration of Deca-Durabolin. PMID:6367663

  15. Genetic immunization in the lung induces potent local and systemic immune responses.

    Science.gov (United States)

    Song, Kaimei; Bolton, Diane L; Wei, Chih-Jen; Wilson, Robert L; Camp, Jeremy V; Bao, Saran; Mattapallil, Joseph J; Herzenberg, Leonore A; Herzenberg, Leonard A; Andrews, Charla A; Sadoff, Jerald C; Goudsmit, Jaap; Pau, Maria Grazia; Seder, Robert A; Kozlowski, Pamela A; Nabel, Gary J; Roederer, Mario; Rao, Srinivas S

    2010-12-21

    Successful vaccination against respiratory infections requires elicitation of high levels of potent and durable humoral and cellular responses in the lower airways. To accomplish this goal, we used a fine aerosol that targets the entire lung surface through normal respiration to deliver replication-incompetent recombinant adenoviral vectors expressing gene products from several infectious pathogens. We show that this regimen induced remarkably high and stable lung T-cell responses in nonhuman primates and that it also generated systemic and respiratory tract humoral responses of both IgA and IgG isotypes. Moreover, strong immunogenicity was achieved even in animals with preexisting antiadenoviral immunity, overcoming a critical hurdle to the use of these vectors in humans, who commonly are immune to adenoviruses. The immunogenicity profile elicited with this regimen, which is distinct from either intramuscular or intranasal delivery, has highly desirable properties for protection against respiratory pathogens. We show that it can be used repeatedly to generate mucosal humoral, CD4, and CD8 T-cell responses and as such may be applicable to other mucosally transmitted pathogens such as HIV. Indeed, in a lethal challenge model, we show that aerosolized recombinant adenoviral immunization completely protects ferrets against H5N1 highly pathogenic avian influenza virus. Thus, genetic immunization in the lung offers a powerful platform approach to generating protective immune responses against respiratory pathogens. PMID:21135247

  16. Immunomodulator-based enhancement of anti smallpox immune responses.

    Directory of Open Access Journals (Sweden)

    Osmarie Martínez

    Full Text Available The current live vaccinia virus vaccine used in the prevention of smallpox is contraindicated for millions of immune-compromised individuals. Although vaccination with the current smallpox vaccine produces protective immunity, it might result in mild to serious health complications for some vaccinees. Thus, there is a critical need for the production of a safe virus-free vaccine against smallpox that is available to everyone. For that reason, we investigated the impact of imiquimod and resiquimod (Toll-like receptors agonists, and the codon-usage optimization of the vaccinia virus A27L gene in the enhancement of the immune response, with intent of producing a safe, virus-free DNA vaccine coding for the A27 vaccinia virus protein.We analyzed the cellular-immune response by measuring the IFN-γ production of splenocytes by ELISPOT, the humoral-immune responses measuring total IgG and IgG2a/IgG1 ratios by ELISA, and the TH1 and TH2 cytokine profiles by ELISA, in mice immunized with our vaccine formulation.The proposed vaccine formulation enhanced the A27L vaccine-mediated production of IFN-γ on mouse spleens, and increased the humoral immunity with a TH1-biased response. Also, our vaccine induced a TH1 cytokine milieu, which is important against viral infections.These results support the efforts to find a new mechanism to enhance an immune response against smallpox, through the implementation of a safe, virus-free DNA vaccination platform.

  17. Signaling molecules involved in immune responses in mussels

    Directory of Open Access Journals (Sweden)

    S Koutsogiannaki

    2010-01-01

    Full Text Available Immune system of molluscs is constituted by hemocytes and humoral factors that cooperate for the protection of the organism, triggering a wide range of immune responses. In molluscs, immune responses include phagocytosis, encapsulation, respiratory burst leading to reactive oxygen species (ROS production and nitric oxide (NO synthesis, release of antimicrobial molecules and the activation of phenoloxidase system. These responses are mediated firstly by a variety of hemocyte receptors binding to ligands that results to a cascade of signaling events. The processes of hemocytes adhesion to and migration through extracellular matrix (ECM proteins play a crucial role in cell immunity. Results suggest that cadmium and oxidants induce adhesion to and migration through ECM proteins in Mytilus gallorovincialis hemocytes with the involvement of Na+/H+ exchanger (NHE, phosphatidylinositol-3 kinase (PI-3K, protein kinase C (PKC, NADPH oxidase, ROS and NO as well as with α2 integrin subunit. Furthermore, the data so far suggests the involvement of additional signaling molecules such as mitogen-activated protein kinases (MAPKs, signal transducers and activators of transcription (STATs, c-Jun N-terminal kinase (JNK, extracellular signal-regulated kinase (ERK, cyclic adenosine monophosphate (cAMP, responsive element binding protein (CREB and nuclear factor kappa B (NF-kB in molluscs immunity. Further research in mollusc immune system may lead to a more sufficient protection and to a better control of these economically important organisms.

  18. Balancing immune protection and immune pathology by CD8+ T cell responses to influenza infection

    Directory of Open Access Journals (Sweden)

    Susu eDuan

    2016-02-01

    Full Text Available Influenza A virus (IAV is a significant human pathogen causing annual epidemics and periodic pandemics. CD8+ cytotoxic T lymphocyte (CTL-mediated immunity contributes to clearance of virus-infected cells; CTL immunity targeting the conserved internal proteins of IAVs is a key protection mechanism when neutralizing antibodies are absent during heterosubtypic IAV infection. However, CTL infiltration into the airways, their cytotoxicity, and the effects of produced pro-inflammatory cytokines can cause severe lung tissue injury, thereby contributing to immunopathology. Studies have discovered complicated and exquisite stimulatory and inhibitory mechanisms that regulate CTL magnitude and effector activities during IAV infection. Here, we review the state of knowledge on the roles of IAV-specific CTLs in immune protection and immunopathology during IAV infection in animal models, highlighting the key findings of various requirements and constraints regulating the balance of immune protection and pathology involved in CTL immunity. We also discuss the evidence of cross-reactive CTL immunity as a positive correlate of cross-subtype protection during secondary IAV infection in both animal and human studies. We argue that the effects of CTL immunity on protection and immunopathology depend on multiple layers of host and viral factors, including complex host mechanisms to regulate CTL magnitude and effector activity, the pathogenic nature of the IAV, the innate response milieu, and the host historical immune context of influenza infection. Future efforts are needed to further understand these key host and viral factors, especially to differentiate those that constrain optimally effective CTL anti-viral immunity from those necessary to restrain CTL-mediated nonspecific immunopathology in the various contexts of IAV infection, in order to develop better vaccination and therapeutic strategies for modifying protective CTL immunity.

  19. Immune responses and protection in bovine anaplasmosis and babesiosis

    International Nuclear Information System (INIS)

    For many decades there was a consensus of opinion that an induction of effective protective immunity against bovine anaplasmosis and babesiosis requires prior exposure of the host to live, preferably replicating, causative agents of these diseases. A procedure for inducing protective immunity by infection and treatment, known as premunization, is the oldest one. Since then, safer immunization procedures have been developed by altering the virulence of the immunizing organism by fast serial passages in splenectomized calves (B. bovis), exposure of the infective blood to irradiation (B. bigemina), and selection of a mutant (A. marginale) by adapting the organism to growth in an atypical host (sheep). The immune response to live immunogens includes both humoral and cell-mediated components (CMI). Some antibodies appear to be protective; however, the exact mechanism of humoral protection and that of parasite killing by the CMI system are not known. Use of live immunogens under field conditions (whole blood) has met with serious obstacles. Apart from difficulties of maintenance and field dispensation of blood-derived vaccines, there were reports of reversion to virulence of the immunizing agent, and actual broadening of the source of infectious agent for the disease vector. In addition, immunization by infection frequently sets forth a series of host-parasite interacting processes that exert an excessive demand on the host's immune system, leading to immunosuppression and interference with selective anti-parasitic action. (author)

  20. [Bone marrow stromal damage mediated by immune response activity].

    Science.gov (United States)

    Vojinović, J; Kamenov, B; Najman, S; Branković, Lj; Dimitrijević, H

    1994-01-01

    The aim of this work was to estimate influence of activated immune response on hematopoiesis in vitro, using the experimental model of BCG immunized BALB/c mice and in patients with chronic immunoactivation: long-lasting infections, autoimmunity or malignancy. We correlated changes in long term bone marrow cultures (Dexter) and NBT reduction with appearance of anemia in patients and experimental model of immunization by BCG. Increased spontaneous NBT reduction pointed out role of macrophage activation in bone marrow stroma damage. Long-term bone marrow cultures showed reduced number of hematopoietic cells, with predomination of fibroblasts and loss of fat cells. This results correlated with anemia and leucocytosis with stimulated myelopoiesis in peripheral blood. Activation of immune response, or acting of any agent that directly changes extracellular matrix and cellularity of bone marrow, may result in microenviroment bone marrow damage that modify hematopoiesis. PMID:18173180

  1. The Impact of Ultraviolet Radiation on Immune Responses (invited paper)

    International Nuclear Information System (INIS)

    In addition to its genotoxic and mutagenic effects, UV has the capacity to suppress immune responses. The mechanism involved is complex, beginning with chromophores located in the skin which absorb UV, this leading in turn to changes in the production of a range of immune mediators locally and systemically which then induce phenotypic and functional alterations in antigen presentation. The cascade ends with the promotion of a subset of T-cells downregulating cell-mediated immunity. The possible consequences of this immunomodulation for the control of tumours and infectious diseases require careful evaluation from laboratory and human studies. (author)

  2. Modulation of Immune Response Using Engineered Nanoparticle Surfaces.

    Science.gov (United States)

    Moyano, Daniel F; Liu, Yuanchang; Peer, Dan; Rotello, Vincent M

    2016-01-01

    Nanoparticles (NPs) coated with a monolayer of ligands can be recognized by different components of the immune system, opening new doors for the modulation of immunological responses. By the use of different physical or chemical properties at the NP surface (such as charge, functional groups, and ligand density), NPs can be designed to have distinct cellular uptake, cytokine secretion, and immunogenicity, factors that influence the distribution and clearance of these particles. Understanding these immunological responses is critical for the development of new NP-based carriers for the delivery of therapeutic molecules, and as such several studies have been performed to understand the relationships between immune responses and NP surface functionality. In this review, we will discuss recent reports of these structure-activity relationships, and explore how these motifs can be controlled to elicit therapeutically useful immune responses. PMID:26618755

  3. The Immune Response and Its Therapeutic Modulation in Bronchiectasis

    OpenAIRE

    Massoud Daheshia; Prahl, James D.; Carmichael, Jacob J.; Parrish, John S.; Gilbert Seda

    2012-01-01

    Bronchiectasis (BC) is a chronic pulmonary disease with tremendous morbidity and significant mortality. As pathogen infection has been advocated as a triggering insult in the development of BC, a central role for the immune response in this process seems obvious. Inflammatory cells are present in both the airways as well as the lung parenchyma, and multiple mediators of immune cells including proteases and cytokines or their humoral products are increased locally or in the periphery. Interest...

  4. Interactions between dietary chicory, gut microbiota and immune responses

    OpenAIRE

    Liu, Haoyu

    2013-01-01

    This thesis provides a better understanding of interactions between diet, gut microbiota, and immune responses to a specific dietary fiber source, chicory (Cichorium intybus L). This was achieved by examining the impact of chicory fiber on animal performance, digestibility, gut development, commensal bacteria community structure in small and large intestine, and follow-up reactions with specific immune components, cytoprotective heat shock protein (HSP) 27 and 72, in vivo and in vitro. T...

  5. Extracellular Adenosine Mediates a Systemic Metabolic Switch during Immune Response

    OpenAIRE

    Lazzaro, Brian P.

    2015-01-01

    Life history theory predicts that trait evolution should be constrained by competing physiological demands on an organism. Immune defense provides a classic example in which immune responses are presumed to be costly and therefore come at the expense of other traits related to fitness. One strategy for mitigating the costs of expensive traits is to render them inducible, such that the cost is paid only when the trait is utilized. In the current issue of PLOS Biology, Bajgar and colleagues ele...

  6. A Humoral Immune Response Confers Protection against Haemophilus ducreyi Infection

    OpenAIRE

    Cole, Leah E.; Toffer, Kristen L.; Fulcher, Robert A.; San Mateo, Lani R; Orndorff, Paul E.; Kawula, Thomas H.

    2003-01-01

    Haemophilus ducreyi is the etiologic agent of the sexually transmitted genital ulcer disease chancroid. Neither naturally occurring chancroid nor experimental infection with H. ducreyi results in protective immunity. Likewise, a single inoculation of H. ducreyi does not protect pigs against subsequent infection. Accordingly, we used the swine model of chancroid infection to examine the impact of multiple inoculations on a host's immune response. After three successive inoculations with H. duc...

  7. Bovine anaplasmosis with emphasis on immune responses and protection

    International Nuclear Information System (INIS)

    Anaplasmosis is an infectious and transmissible disease manifested by progressive anaemia and the appearance of other characteristic disease symptoms. It is a world-wide tick-borne disease of cattle and some wild ruminants caused by the rickettsia Anaplasma marginale. By drawing on information obtained from studies of plasmodial cell cultures, a method has recently been developed for short-term in vitro cultivation of A. marginale. An attenuated Anaplasma organism capable of growth in both ovine and bovine erythrocytes was used to demonstrate that the in vitro system provided the necessary requirements for active transfer of the organism from cell to cell. Organismal antigens are found in the erythrocytes of infected animals, whereas soluble antigens are derived from their erythrocytes and serum. Serums from convalescing animals interact with these antigens in agglutination, complement fixation, fluorescent antibody and precipitation tests. Passive transfer of sera from immune to susceptible cattle, however, does not seem to confer protection against the infection and development of the disease. Studies that employed various tests for measuring cell-mediated immune (CMI) responses (leukocyte migration inhibition, blast transformation and cytotoxicity), in association with information collected simultaneously on antibody activity, have shown that both humoral and cellular immune responses are needed for the development of protective immunity in anaplasmosis. It was further shown that an active replication of Anaplasma is essential for induction of these two types of immune responses. Consequently, live virulent and attenuated immunogens fulfil requirements for induction of protective immunity. With the virulent agent, however, development of protective immunity is preceded by induction of auto-immune responses apparently associated with pathogenesis of anaemia in anaplasmosis. Inactivated immunogens derived from blood of infected cattle and used in combination with

  8. Scaling of immune responses against intracellular bacterial infection

    OpenAIRE

    Abdullah, Zeinab; Knolle, Percy A.

    2014-01-01

    Macrophages detect bacterial infection through pattern recognition receptors (PRRs) localized at the cell surface, in intracellular vesicles or in the cytosol. Discrimination of viable and virulent bacteria from non-virulent bacteria (dead or viable) is necessary to appropriately scale the anti-bacterial immune response. Such scaling of anti-bacterial immunity is necessary to control the infection, but also to avoid immunopathology or bacterial persistence. PRR-mediated detection of bacterial...

  9. ENDOCANNABINOIDS AND EICOSAMOIDS: BIOSYNTHESIS AND INTERACTIONS WITH IMMUNE RESPONSE

    Directory of Open Access Journals (Sweden)

    Yu. K. Karaman

    2014-07-01

    Full Text Available The review is dedicated to modern concepts of arachidonic acid metabolites, i.e., endocannabinoids and eicosanoids, their biosynthetic pathways, cross-talk mechanisms and participation in immune response. New information from literature and own results include data concerning overlapping enzymatic pathways controlling biosynthesis of endocannabinoids and eicosanoids. Impact of synthetic cannabinoid receptor ligands upon production rates of proinflammatory cytokines and eicosanoids is discussed, as like as relationships among immune system reactivity and expression levels of cannabinoid receptors.

  10. Ageing and the humoral immune response in mice

    International Nuclear Information System (INIS)

    The study presented in this thesis is concerned with changes in the humoral immune system as a function of age in different inbred mouse strains. Their capacity to develop humoral immune responses to experimentally given thymus-dependent and thymus-independent antigens under various conditions is compared. Furthermore, experiments employing thymus transplantation and thymic humoral factors which are directed at the restoration of the diminished T cell functions in old age are reported. (Auth.)

  11. The immune response to sand fly salivary proteins and its influence on Leishmania immunity

    Directory of Open Access Journals (Sweden)

    Regis eGomes

    2012-05-01

    Full Text Available Leishmaniasis is a vector-borne disease transmitted by bites of phlebotomine sand flies. During Leishmania transmission, sand fly saliva is co-inoculated with parasites into the skin of the mammalian host. Sand fly saliva consists of roughly thirty different salivary proteins, many with known roles linked to blood feeding facilitation. Apart from the anti-hemostatic capacity of saliva, several sand fly salivary proteins have been shown to be immunogenic upon multiple contacts with a mammalian host. Immunization with single immunogenic salivary proteins or exposure to uninfected bites can produce protective immune responses against leishmaniasis. These sand fly salivary proteins induce cellular immune responses and/or antibodies. Antibodies to saliva are not required for protection in a mouse model against leishmaniasis. A strong body of evidence points to the role for saliva-specific T cells producing IFN-γ in the form of a delayed-type hypersensitivity reaction at the bite site as the main protective response. Herein, we review immunity to sand fly salivary proteins in the context of its vector-parasite-host combinations and vaccine potential, as well as some recent advances to shed light on the mechanism of how an immune response to sand fly saliva protects against leishmaniasis.

  12. Innate Immune Response to Intramammary Mycoplasma bovis Infection

    Science.gov (United States)

    Mastitis caused by Mycoplasma bovis is a growing concern for the dairy industry. M. bovis intramammary infection commonly results in an untreatable case of chronic mastitis. The innate immune system is responsible for initial recognition of, and immediate host responses to, infectious pathogens. ...

  13. Flavobacterium psychrophilum, prevention and immune response

    DEFF Research Database (Denmark)

    Henriksen, Maya Maria Mihályi; Dalsgaard, Inger

    The fish pathogen Flavobacterium psychrophilum is one of the main causes of mortality in farmed rainbow trout and other salmonid fish. The disease following infection is often called bacterial coldwater disease (BCWD) in USA or rainbow trout fry syndrome (RTFS) in Europe. An infected farm can...... expect mortality rates around 50-60% in fry and 2-10% in juvenile fish within few weeks, which causes significant economical losses worldwide. Presently no commercial vaccine exists, and fish farmers control the disease with antibiotics. The project is currently in its preliminary phase but the overall...... goal is to examine gene expression and location of transcription products in rainbow trout fry, in order to optimize vaccination or immune-stimulation. The presentation will focus on the future plans for the project, since no data have yet been obtained....

  14. Modulation of immune responses in stress by Yoga

    Directory of Open Access Journals (Sweden)

    Arora Sarika

    2008-01-01

    Full Text Available Stress is a constant factor in today′s fastpaced life that can jeopardize our health if left unchecked. It is only in the last half century that the role of stress in every ailment from the common cold to AIDS has been emphasized, and the mechanisms involved in this process have been studied. Stress influences the immune response presumably through the activation of the hypothalamic-pituitary adrenal axis, hypothalamic pituitary-gonadal axis, and the sympathetic-adrenal-medullary system. Various neurotransmitters, neuropeptides, hormones, and cytokines mediate these complex bidirectional interactions between the central nervous system (CNS and the immune system. The effects of stress on the immune responses result in alterations in the number of immune cells and cytokine dysregulation. Various stress management strategies such as meditation, yoga, hypnosis, and muscle relaxation have been shown to reduce the psychological and physiological effects of stress in cancers and HIV infection. This review aims to discuss the effect of stress on the immune system and examine how relaxation techniques such as Yoga and meditation could regulate the cytokine levels and hence, the immune responses during stress.

  15. Characterization of the immune response of domestic fowl following immunization with proteins extracted from Dermanyssus gallinae.

    Science.gov (United States)

    Harrington, David; Din, Hatem Mohi El; Guy, Jonathan; Robinson, Karen; Sparagano, Olivier

    2009-03-23

    Dermanyssus gallinae is the most significant ectoparasite of European poultry egg laying production systems due to high costs of control and associated production losses as well as adverse effects on bird welfare. In this study, soluble proteins were extracted from unfed D. gallinae (DGE) using a urea-based detergent and ultra-filtration, passed through a 0.22 microm filter and blended aseptically with adjuvant. One group of laying hens was immunized with DGE and adjuvant (Montanide ISA 50 V) whilst another group (Control) received physiological saline and adjuvant. All birds were immunized on two occasions, 21 days apart. Antibody response to immunization was determined by ELISA and western blotting using immunoglobulins (Igs) extracted from egg yolk. DGE immunization of hens resulted in a significant (P<0.05) IgY response compared to controls, although there was no significant difference in IgM response between treatments. A number of proteins were identified by western blotting using IgY antibodies from DGE immunized birds, most prominently at 40 and 230kDa. Analysis of proteins from approximately corresponding bands on SDS-PAGE confirmed the identity of tropomyosin, whilst other proteins showed high sequence homology with myosin and actin from other arachnid and insect species. Immunization of hens with DGE resulted in a 50.6% increase in mite mortality (P<0.001) 17h after feeding when tested by an in vitro mite feeding model. Data in this study demonstrate that somatic antigens from D. gallinae can be used to stimulate a protective immune response in laying hens. Further work is needed to identify other proteins of interest that could confer higher protection against D. gallinae, as well as optimization of the vaccination and in vitro testing protocol. PMID:19091480

  16. Immune responses in multiple myeloma: role of the natural immune surveillance and potential of immunotherapies.

    Science.gov (United States)

    Guillerey, Camille; Nakamura, Kyohei; Vuckovic, Slavica; Hill, Geoffrey R; Smyth, Mark J

    2016-04-01

    Multiple myeloma (MM) is a tumor of terminally differentiated B cells that arises in the bone marrow. Immune interactions appear as key determinants of MM progression. While myeloid cells foster myeloma-promoting inflammation, Natural Killer cells and T lymphocytes mediate protective anti-myeloma responses. The profound immune deregulation occurring in MM patients may be involved in the transition from a premalignant to a malignant stage of the disease. In the last decades, the advent of stem cell transplantation and new therapeutic agents including proteasome inhibitors and immunoregulatory drugs has dramatically improved patient outcomes, suggesting potentially key roles for innate and adaptive immunity in disease control. Nevertheless, MM remains largely incurable for the vast majority of patients. A better understanding of the complex interplay between myeloma cells and their immune environment should pave the way for designing better immunotherapies with the potential of very long term disease control. Here, we review the immunological microenvironment in myeloma. We discuss the role of naturally arising anti-myeloma immune responses and their potential corruption in MM patients. Finally, we detail the numerous promising immune-targeting strategies approved or in clinical trials for the treatment of MM. PMID:26801219

  17. LIGHT May Improve Immune Checkpoint Blockade Response.

    Science.gov (United States)

    2016-06-01

    A new study suggests that insufficient T-cell infiltration may explain why a majority of patients do not respond to immunotherapy. Combining PD-L1 inhibitors with antibody-guided LIGHT, a protein that recruits tumor-infiltrating lymphocytes, increased antitumor response in mice, and may have the potential to improve patient response rates to immunotherapy. PMID:27080334

  18. Coexpressed RIG-I agonist enhances humoral immune response to influenza virus DNA vaccine.

    Science.gov (United States)

    Luke, Jeremy M; Simon, Gregory G; Söderholm, Jonas; Errett, John S; August, J Thomas; Gale, Michael; Hodgson, Clague P; Williams, James A

    2011-02-01

    Increasing levels of plasmid vector-mediated activation of innate immune signaling pathways is an approach to improve DNA vaccine-induced adaptive immunity for infectious disease and cancer applications. Retinoic acid-inducible gene I (RIG-I) is a critical cytoplasmic double-stranded RNA (dsRNA) pattern receptor required for innate immune activation in response to viral infection. Activation of RIG-I leads to type I interferon (IFN) and inflammatory cytokine production through interferon promoter stimulator 1 (IPS-1)-mediated activation of interferon regulatory factor 3 (IRF3) and NF-κB signaling. DNA vaccines coexpressing antigen and an expressed RNA (eRNA) RIG-I agonist were made, and the effect of RIG-I activation on antigen-specific immune responses to the encoded antigen was determined. Plasmid vector backbones expressing various RIG-I ligands from RNA polymerase III promoters were screened in a cell culture assay for RIG-I agonist activity, and optimized, potent RIG-I ligands were developed. One of these, eRNA41H, combines (i) eRNA11a, an immunostimulatory dsRNA expressed by convergent transcription, with (ii) adenovirus VA RNAI. eRNA41H was integrated into the backbone of DNA vaccine vectors expressing H5N1 influenza virus hemagglutinin (HA). The resultant eRNA vectors potently induced type 1 IFN production in cell culture through RIG-I activation and combined high-level HA antigen expression with RNA-mediated type I IFN activation in a single plasmid vector. The eRNA vectors induced increased HA-specific serum antibody binding avidity after naked DNA intramuscular prime and boost delivery in mice. This demonstrates that DNA vaccine potency may be augmented by the incorporation of RIG-I-activating immunostimulatory RNA into the vector backbone. PMID:21106745

  19. Effects of inhalation of 239PuO2 on immune responses following lung immunization

    International Nuclear Information System (INIS)

    Results of this study indicated that the number of antibody-forming cells in lung-associated lymph nodes after intratracheal immunization was significantly lower in animals exposed to 239PuO2. Only a few antibody-forming cells were found in spleen and cervical lymph nodes. Thus, 239PuO2 exposure suppressed immune responses in lung-associated lymph nodes, although their filtering capacity was unaffected and antigen did not translocate to the spleen. Changes in immunologic responses were observed as the animals aged and the number of antibody-forming cells gradually decreased in the lung-associated lymph nodes and increased in the spleen

  20. The genetic regulation of infant immune responses to vaccination

    Directory of Open Access Journals (Sweden)

    Melanie eNewport

    2015-02-01

    Full Text Available A number of factors are recognised to influence immune responses to vaccinations including age, gender, the dose and quality of the antigen used, the number of doses given, the route of administration and the nutritional status of the recipient. Additionally, several immunogenetic studies have identified associations between polymorphisms in genes encoding immune response proteins, both innate and adaptive, and variation in responses to vaccines. Variants in the genes encoding Toll-like receptors, HLA molecules, cytokines, cytokine receptors have associated with heterogeneity of responses to a wide range of vaccines including measles, hepatitis B, influenza A, BCG, Haemophilus influenzae type b and certain Neisseria meningitidis serotypes, amongst others. However, the vast majority of these studies have been conducted in older children and adults and there are very few data available from studies conducted in infants. This paper reviews the evidence to date that host genes influencing vaccines responses in these older population and identifies a large gap in our understanding of the genetic regulation of responses in early life. . Given the high mortality from infection in early life and the challenges of developing vaccines that generate effective immune responses in the context of the developing immune system further research on infant populations is required.

  1. Bacterial Outer Membrane Vesicles Induce Plant Immune Responses.

    Science.gov (United States)

    Bahar, Ofir; Mordukhovich, Gideon; Luu, Dee Dee; Schwessinger, Benjamin; Daudi, Arsalan; Jehle, Anna Kristina; Felix, Georg; Ronald, Pamela C

    2016-05-01

    Gram-negative bacteria continuously pinch off portions of their outer membrane, releasing membrane vesicles. These outer membrane vesicles (OMVs) are involved in multiple processes including cell-to-cell communication, biofilm formation, stress tolerance, horizontal gene transfer, and virulence. OMVs are also known modulators of the mammalian immune response. Despite the well-documented role of OMVs in mammalian-bacterial communication, their interaction with plants is not well studied. To examine whether OMVs of plant pathogens modulate the plant immune response, we purified OMVs from four different plant pathogens and used them to treat Arabidopsis thaliana. OMVs rapidly induced a reactive oxygen species burst, medium alkalinization, and defense gene expression in A. thaliana leaf discs, cell cultures, and seedlings, respectively. Western blot analysis revealed that EF-Tu is present in OMVs and that it serves as an elicitor of the plant immune response in this form. Our results further show that the immune coreceptors BAK1 and SOBIR1 mediate OMV perception and response. Taken together, our results demonstrate that plants can detect and respond to OMV-associated molecules by activation of their immune system, revealing a new facet of plant-bacterial interactions. PMID:26926999

  2. Acute psychological stress induces short-term variable immune response.

    Science.gov (United States)

    Breen, Michael S; Beliakova-Bethell, Nadejda; Mujica-Parodi, Lilianne R; Carlson, Joshua M; Ensign, Wayne Y; Woelk, Christopher H; Rana, Brinda K

    2016-03-01

    In spite of advances in understanding the cross-talk between the peripheral immune system and the brain, the molecular mechanisms underlying the rapid adaptation of the immune system to an acute psychological stressor remain largely unknown. Conventional approaches to classify molecular factors mediating these responses have targeted relatively few biological measurements or explored cross-sectional study designs, and therefore have restricted characterization of stress-immune interactions. This exploratory study analyzed transcriptional profiles and flow cytometric data of peripheral blood leukocytes with physiological (endocrine, autonomic) measurements collected throughout the sequence of events leading up to, during, and after short-term exposure to physical danger in humans. Immediate immunomodulation to acute psychological stress was defined as a short-term selective up-regulation of natural killer (NK) cell-associated cytotoxic and IL-12 mediated signaling genes that correlated with increased cortisol, catecholamines and NK cells into the periphery. In parallel, we observed down-regulation of innate immune toll-like receptor genes and genes of the MyD88-dependent signaling pathway. Correcting gene expression for an influx of NK cells revealed a molecular signature specific to the adrenal cortex. Subsequently, focusing analyses on discrete groups of coordinately expressed genes (modules) throughout the time-series revealed immune stress responses in modules associated to immune/defense response, response to wounding, cytokine production, TCR signaling and NK cell cytotoxicity which differed between males and females. These results offer a spring-board for future research towards improved treatment of stress-related disease including the impact of stress on cardiovascular and autoimmune disorders, and identifies an immune mechanism by which vulnerabilities to these diseases may be gender-specific. PMID:26476140

  3. Escaping Deleterious Immune Response in Their Hosts: Lessons from Trypanosomatids

    Science.gov (United States)

    Geiger, Anne; Bossard, Géraldine; Sereno, Denis; Pissarra, Joana; Lemesre, Jean-Loup; Vincendeau, Philippe; Holzmuller, Philippe

    2016-01-01

    The Trypanosomatidae family includes the genera Trypanosoma and Leishmania, protozoan parasites displaying complex digenetic life cycles requiring a vertebrate host and an insect vector. Trypanosoma brucei gambiense, Trypanosoma cruzi, and Leishmania spp. are important human pathogens causing human African trypanosomiasis (HAT or sleeping sickness), Chagas’ disease, and various clinical forms of Leishmaniasis, respectively. They are transmitted to humans by tsetse flies, triatomine bugs, or sandflies, and affect millions of people worldwide. In humans, extracellular African trypanosomes (T. brucei) evade the hosts’ immune defenses, allowing their transmission to the next host, via the tsetse vector. By contrast, T. cruzi and Leishmania sp. have developed a complex intracellular lifestyle, also preventing several mechanisms to circumvent the host’s immune response. This review seeks to set out the immune evasion strategies developed by the different trypanosomatids resulting from parasite–host interactions and will focus on: clinical and epidemiological importance of diseases; life cycles: parasites–hosts–vectors; innate immunity: key steps for trypanosomatids in invading hosts; deregulation of antigen-presenting cells; disruption of efficient specific immunity; and the immune responses used for parasite proliferation. PMID:27303406

  4. Role of DNA repair in host immune response and inflammation.

    Science.gov (United States)

    Fontes, Fabrícia Lima; Pinheiro, Daniele Maria Lopes; Oliveira, Ana Helena Sales de; Oliveira, Rayssa Karla de Medeiros; Lajus, Tirzah Braz Petta; Agnez-Lima, Lucymara Fassarella

    2015-01-01

    In recent years, the understanding of how DNA repair contributes to the development of innate and acquired immunity has emerged. The DNA damage incurred during the inflammatory response triggers the activation of DNA repair pathways, which are required for host-cell survival. Here, we reviewed current understanding of the mechanism by which DNA repair contributes to protection against the oxidized DNA damage generated during infectious and inflammatory diseases and its involvement in innate and adaptive immunity. We discussed the functional role of DNA repair enzymes in the immune activation and the relevance of these processes to: transcriptional regulation of cytokines and other genes involved in the inflammatory response; V(D)J recombination; class-switch recombination (CSR); and somatic hypermutation (SHM). These three last processes of DNA damage repair are required for effective humoral adaptive immunity, creating genetic diversity in developing T and B cells. Furthermore, viral replication is also dependent on host DNA repair mechanisms. Therefore, the elucidation of the pathways of DNA damage and its repair that activate innate and adaptive immunity will be important for a better understanding of the immune and inflammatory disorders and developing new therapeutic interventions for treatment of these diseases and for improving their outcome. PMID:25795123

  5. Mitochondrial DNA in the regulation of innate immune responses.

    Science.gov (United States)

    Fang, Chunju; Wei, Xiawei; Wei, Yuquan

    2016-01-01

    Mitochondrion is known as the energy factory of the cell, which is also a unique mammalian organelle and considered to be evolved from aerobic prokaryotes more than a billion years ago. Mitochondrial DNA, similar to that of its bacterial ancestor’s, consists of a circular loop and contains significant number of unmethylated DNA as CpG islands. The innate immune system plays an important role in the mammalian immune response. Recent research has demonstrated that mitochondrial DNA (mtDNA) activates several innate immune pathways involving TLR9, NLRP3 and STING signaling, which contributes to the signaling platforms and results in effector responses. In addition to facilitating antibacterial immunity and regulating antiviral signaling, mounting evidence suggests that mtDNA contributes to inflammatory diseases following cellular damage and stress. Therefore, in addition to its well-appreciated roles in cellular metabolism and energy production,mtDNA appears to function as a key member in the innate immune system. Here, we highlight the emerging roles of mtDNA in innate immunity. PMID:26498951

  6. Control of the adaptive immune response by tumor vasculature

    Directory of Open Access Journals (Sweden)

    Laetitia eMauge

    2014-03-01

    Full Text Available The endothelium is nowadays described as an entire organ that regulates various processes: vascular tone, coagulation, inflammation, and immune cell trafficking, depending on the vascular site and its specific microenvironment as well as on endothelial cell-intrinsic mechanisms like epigenetic changes. In this review, we will focus on the control of the adaptive immune response by the tumor vasculature. In physiological conditions, the endothelium acts as a barrier regulating cell trafficking by specific expression of adhesion molecules enabling adhesion of immune cells on the vessel, and subsequent extravasation. This process is also dependent on chemokine and integrin expression, and on the type of junctions defining the permeability of the endothelium. Endothelial cells can also regulate immune cell activation. In fact, the endothelial layer can constitute immunological synapses due to its close interactions with immune cells, and the delivery of co-stimulatory or co-inhibitory signals. In tumor conditions, the vasculature is characterized by abnormal vessel structure and permeability, and by specific phenotype of endothelial cells. All these abnormalities lead to a modulation of intratumoral immune responses and contribute to the development of intratumoral immunosuppression, which is a major mechanism for promoting the development, progression and treatment resistance of tumors. The in-depth analysis of these various abnormalities will help defining novel targets for the development of antitumoral treatments. Furthermore, eventual changes of the endothelial cell phenotype identified by plasma biomarkers could secondarily be selected to monitor treatment efficacy.

  7. Danger signals activating the immune response after trauma

    OpenAIRE

    Stefanie Hirsiger; Hans-Peter Simmen; Werner, Clément M. L.; Wanner, Guido A; Daniel Rittirsch

    2012-01-01

    Sterile injury can cause a systemic inflammatory response syndrome (SIRS) that resembles the host response during sepsis. The inflammatory response following trauma comprises various systems of the human body which are cross-linked with each other within a highly complex network of inflammation. Endogenous danger signals (danger-associated molecular patterns; DAMPs; alarmins) as well as exogenous pathogen-associated molecular patterns (PAMPs) play a crucial role in the initiation of the immun...

  8. Nanotechnology, neuromodulation & the immune response: discourse, materiality & ethics.

    Science.gov (United States)

    Fins, Joseph J

    2015-04-01

    Drawing upon the American Pragmatic tradition in philosophy and the more recent work of philosopher Karen Barad, this paper examines how scientific problems are both obscured, and resolved by our use of language describing the natural world. Using the example of the immune response engendered by neural implants inserted in the brain, the author explains how this discourse has been altered by the advent of nanotechnology methods and devices which offer putative remedies that might temper the immune response in the central nervous system. This emergent nanotechnology has altered this problem space and catalyzed one scientific community to acknowledge a material reality that was always present, if not fully acknowledged. PMID:25681046

  9. Complement Activation Pathways: A Bridge between Innate and Adaptive Immune Responses in Asthma

    OpenAIRE

    Wills-Karp, Marsha

    2007-01-01

    Although it is widely accepted that allergic asthma is driven by T helper type 2 (Th2)-polarized immune responses to innocuous environmental allergens, the mechanisms driving these aberrant immune responses remain elusive. Recent recognition of the importance of innate immune pathways in regulating adaptive immune responses have fueled investigation into the role of innate immune pathways in the pathogenesis of asthma. The phylogenetically ancient innate immune system, the complement system, ...

  10. [Stimulation of the antiviral innate immune response by pyrimidine biosynthesis inhibitors: a surprise of phenotypic screening].

    Science.gov (United States)

    Vidalain, Pierre-Olivier; Lucas-Hourani, Marianne; Helynck, Olivier; Tangy, Frédéric; Munier-Lehmann, Hélène

    2015-01-01

    RNA viruses are responsible for major human diseases such as flu, bronchitis, dengue, hepatitis C or measles. They also represent an emerging threat because of increased worldwide exchanges and human populations penetrating more and more natural ecosystems. Recent progresses in our understanding of cellular pathways controlling viral replication suggest that compounds targeting host cell functions, rather than the virus itself, could inhibit a large panel of RNA viruses. In particular, several academic laboratories and private companies are now seeking molecules that stimulate the host innate antiviral response. One appealing strategy is to identify molecules that induce the large cluster of antiviral genes known as Interferon-Stimulated Genes (ISGs). To reach this goal, we have developed a phenotypic assay based on human cells transfected with a luciferase reporter gene under control of an interferon-stimulated response element (ISRE). This system was used in a high-throughput screening of chemical libraries comprising around 54,000 compounds. Among validated hits, compound DD264 was shown to boost the innate immune response in cell cultures, and displayed a broad-spectrum antiviral activity. While deciphering its mode of action, DD264 was found to target the fourth enzyme of de novo pyrimidine biosynthesis, namely the dihydroorotate dehydrogenase (DHODH). Thus, our data unraveled a yet unsuspected link between pyrimidine biosynthesis and the innate antiviral response. PMID:25658737

  11. Photodynamic therapy for cancer and activation of immune response

    Science.gov (United States)

    Mroz, Pawel; Huang, Ying-Ying; Hamblin, Michael R.

    2010-02-01

    Anti-tumor immunity is stimulated after PDT for cancer due to the acute inflammatory response, exposure and presentation of tumor-specific antigens, and induction of heat-shock proteins and other danger signals. Nevertheless effective, powerful tumor-specific immune response in both animal models and also in patients treated with PDT for cancer, is the exception rather than the rule. Research in our laboratory and also in others is geared towards identifying reasons for this sub-optimal immune response and discovering ways of maximizing it. Reasons why the immune response after PDT is less than optimal include the fact that tumor-antigens are considered to be self-like and poorly immunogenic, the tumor-mediated induction of CD4+CD25+foxP3+ regulatory T-cells (T-regs), that are able to inhibit both the priming and the effector phases of the cytotoxic CD8 T-cell anti-tumor response and the defects in dendritic cell maturation, activation and antigen-presentation that may also occur. Alternatively-activated macrophages (M2) have also been implicated. Strategies to overcome these immune escape mechanisms employed by different tumors include combination regimens using PDT and immunostimulating treatments such as products obtained from pathogenic microorganisms against which mammals have evolved recognition systems such as PAMPs and toll-like receptors (TLR). This paper will cover the use of CpG oligonucleotides (a TLR9 agonist found in bacterial DNA) to reverse dendritic cell dysfunction and methods to remove the immune suppressor effects of T-regs that are under active study.

  12. Immune responses in DNA vaccine formulated with PMMA following immunization and after challenge with Leishmania major.

    Science.gov (United States)

    Zarrati, Somayeh; Mahdavi, Mehdi; Tabatabaie, Fatemeh

    2016-06-01

    Leishmaniasis is a major infectious disease caused by protozoan parasites of the genus Leishmania. Despite of many efforts toward vaccine against Leishmania no effective vaccine has been approved yet. DNA vaccines can generate more powerful and broad immune responses than conventional vaccines. In order to increase immunity, the DNA vaccine has been supplemented with adjuvant. In this study a new nano-vaccine containing TSA recombinant plasmid and poly(methylmethacrylate) nanoparticles (act as adjuvant) was designed and its immunogenicity tested on BALB/c mouse. After three intramuscular injection of nano-vaccine (100 μg), the recombinant TSA protein (20 μg) was injected subcutaneously. Finally as a challenge animals were infected by Leishmania major. After the last injection of nano-vaccine, after protein booster injection, and also after challenge, cellular immune and antibody responses were evaluated by ELISA method. The findings of this study showed the new nano-vaccine was capable of induction both cytokines secretion and specific antibody responses, but predominant Th1 immune response characterized by IFN-γ production compared to control groups. Moreover, results revealed that nano-vaccine was effective in reducing parasite burden in the spleen of Leishmania major-infected BALB/c mice. Base on results, current candidate vaccine has potency for further studies. PMID:27413316

  13. The host immune response to gastrointestinal nematode infection in sheep.

    Science.gov (United States)

    McRae, K M; Stear, M J; Good, B; Keane, O M

    2015-12-01

    Gastrointestinal nematode infection represents a major threat to the health, welfare and productivity of sheep populations worldwide. Infected lambs have a reduced ability to absorb nutrients from the gastrointestinal tract, resulting in morbidity and occasional mortality. The current chemo-dominant approach to nematode control is considered unsustainable due to the increasing incidence of anthelmintic resistance. In addition, there is growing consumer demand for food products from animals not subjected to chemical treatment. Future mechanisms of nematode control must rely on alternative, sustainable strategies such as vaccination or selective breeding of resistant animals. Such strategies take advantage of the host's natural immune response to nematodes. The ability to resist gastrointestinal nematode infection is considered to be dependent on the development of a protective acquired immune response, although the precise immune mechanisms involved in initiating this process remain to be fully elucidated. In this study, current knowledge on the innate and acquired host immune response to gastrointestinal nematode infection in sheep and the development of immunity is reviewed. PMID:26480845

  14. Effect of produced water on cod (Gadus morhua) immune responses

    Energy Technology Data Exchange (ETDEWEB)

    Hamoutene, D.; Mabrouk, G.; Samuelson, S.; Mansour, A.; Lee, K. [Fisheries and Oceans Canada, Dartmouth, NS (Canada). Maritimes Region, Ocean Sciences Division; Volkoff, H.; Parrish, C. [Memorial Univ. of Newfoundland, St. John' s, NL (Canada); Mathieu, A. [Oceans Ltd., St. John' s, NL (Canada)

    2007-07-01

    Studies have shown that produced water (PW) discharged from North Sea offshore platforms affects the biota at greater distances from operational platforms than originally presumed. According to PW dispersion simulations, dilution by at least 240 times occurs within 50-100 m, and up to 9000 times by 20 km from the discharge. In this study, the effect of PW on cod immunity was investigated by exposing fish to 0, 100 ppm (x 10,000 dilution) or 200 ppm (x 500) of PW for 76 days. Immune responses were evaluated at the end of the exposure. Fish from the 3 groups were injected with Aeromonas salmonicida lipopolysaccharides (LPS). Blood cell observation and flow cytometry were used to investigate the serum cortisol levels and gill histology along with ratios and respiratory burst (RB) responses of both circulating and head-kidney white blood cells (WBCs). The study revealed that baseline immunity and stress response were not affected by PW, other than an irritant-induced change in gill cells found in treated cod. In all groups, LPS injection resulted in a pronounced decrease in RB of head-kidney cells and an increase in serum cortisol and protein levels. However, the group exposed to 200 ppm of PW exhibited the most significant changes. LPS injection was also shown to influence WBC ratios, but further studies are needed to determine if this impact is stronger in fish exposed to PW. This study suggested an effect of PW on cod immunity after immune challenge with LPS.

  15. Effect of produced water on cod (Gadus morhua) immune responses

    International Nuclear Information System (INIS)

    Studies have shown that produced water (PW) discharged from North Sea offshore platforms affects the biota at greater distances from operational platforms than originally presumed. According to PW dispersion simulations, dilution by at least 240 times occurs within 50-100 m, and up to 9000 times by 20 km from the discharge. In this study, the effect of PW on cod immunity was investigated by exposing fish to 0, 100 ppm (x 10,000 dilution) or 200 ppm (x 500) of PW for 76 days. Immune responses were evaluated at the end of the exposure. Fish from the 3 groups were injected with Aeromonas salmonicida lipopolysaccharides (LPS). Blood cell observation and flow cytometry were used to investigate the serum cortisol levels and gill histology along with ratios and respiratory burst (RB) responses of both circulating and head-kidney white blood cells (WBCs). The study revealed that baseline immunity and stress response were not affected by PW, other than an irritant-induced change in gill cells found in treated cod. In all groups, LPS injection resulted in a pronounced decrease in RB of head-kidney cells and an increase in serum cortisol and protein levels. However, the group exposed to 200 ppm of PW exhibited the most significant changes. LPS injection was also shown to influence WBC ratios, but further studies are needed to determine if this impact is stronger in fish exposed to PW. This study suggested an effect of PW on cod immunity after immune challenge with LPS

  16. A human type 5 adenovirus-based Trypanosoma cruzi therapeutic vaccine re-programs immune response and reverses chronic cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Isabela Resende Pereira

    2015-01-01

    Full Text Available Chagas disease (CD, caused by the protozoan Trypanosoma cruzi, is a prototypical neglected tropical disease. Specific immunity promotes acute phase survival. Nevertheless, one-third of CD patients develop chronic chagasic cardiomyopathy (CCC associated with parasite persistence and immunological unbalance. Currently, the therapeutic management of patients only mitigates CCC symptoms. Therefore, a vaccine arises as an alternative to stimulate protective immunity and thereby prevent, delay progression and even reverse CCC. We examined this hypothesis by vaccinating mice with replication-defective human Type 5 recombinant adenoviruses (rAd carrying sequences of amastigote surface protein-2 (rAdASP2 and trans-sialidase (rAdTS T. cruzi antigens. For prophylactic vaccination, naïve C57BL/6 mice were immunized with rAdASP2+rAdTS (rAdVax using a homologous prime/boost protocol before challenge with the Colombian strain. For therapeutic vaccination, rAdVax administration was initiated at 120 days post-infection (dpi, when mice were afflicted by CCC. Mice were analyzed for electrical abnormalities, immune response and cardiac parasitism and tissue damage. Prophylactic immunization with rAdVax induced antibodies and H-2Kb-restricted cytotoxic and interferon (IFNγ-producing CD8+ T-cells, reduced acute heart parasitism and electrical abnormalities in the chronic phase. Therapeutic vaccination increased survival and reduced electrical abnormalities after the prime (analysis at 160 dpi and the boost (analysis at 180 and 230 dpi. Post-therapy mice exhibited less heart injury and electrical abnormalities compared with pre-therapy mice. rAdVax therapeutic vaccination preserved specific IFNγ-mediated immunity but reduced the response to polyclonal stimuli (anti-CD3 plus anti-CD28, CD107a+ CD8+ T-cell frequency and plasma nitric oxide (NO levels. Moreover, therapeutic rAdVax reshaped immunity in the heart tissue as reduced the number of perforin+ cells

  17. Verification of immune response optimality through cybernetic modeling.

    Science.gov (United States)

    Batt, B C; Kompala, D S

    1990-02-01

    An immune response cascade that is T cell independent begins with the stimulation of virgin lymphocytes by antigen to differentiate into large lymphocytes. These immune cells can either replicate themselves or differentiate into plasma cells or memory cells. Plasma cells produce antibody at a specific rate up to two orders of magnitude greater than large lymphocytes. However, plasma cells have short life-spans and cannot replicate. Memory cells produce only surface antibody, but in the event of a subsequent infection by the same antigen, memory cells revert rapidly to large lymphocytes. Immunologic memory is maintained throughout the organism's lifetime. Many immunologists believe that the optimal response strategy calls for large lymphocytes to replicate first, then differentiate into plasma cells and when the antigen has been nearly eliminated, they form memory cells. A mathematical model incorporating the concept of cybernetics has been developed to study the optimality of the immune response. Derived from the matching law of microeconomics, cybernetic variables control the allocation of large lymphocytes to maximize the instantaneous antibody production rate at any time during the response in order to most efficiently inactivate the antigen. A mouse is selected as the model organism and bacteria as the replicating antigen. In addition to verifying the optimal switching strategy, results showing how the immune response is affected by antigen growth rate, initial antigen concentration, and the number of antibodies required to eliminate an antigen are included. PMID:2338827

  18. Effects of yeast subcomponent diet supplements on growth, stress resistance and immune response in Nile tilapia

    Science.gov (United States)

    Yeast cells contain glucan and mannan subcomponents which have been reported to boost immunity in several fish species. We prepared diets using a commercial feed supplemented with 4 different yeast or yeast subcomponents obtained from commercial sources. These were added at rates recommended by supp...

  19. Elevated EBNA1 Immune Responses Predict Conversion to Multiple Sclerosis

    Science.gov (United States)

    Lünemann, Jan D.; Tintoré, Mar; Messmer, Brady; Strowig, Till; Rovira, Álex; Perkal, Héctor; Caballero, Estrella; Münz, Christian; Montalban, Xavier; Comabella, Manuel

    2009-01-01

    Objective The aims of the study were to determine the immune responses to candidate viral triggers of multiple sclerosis (MS) in patients with clinically isolated syndromes (CIS), and to evaluate their potential value in predicting conversion to MS. Methods Immune responses to Epstein-Barr virus (EBV), human herpesvirus 6, cytomegalovirus (HCMV), and measles were determined in a cohort of 147 CIS patients with a mean follow-up of 7 years and compared with 50 demographically matched controls. Results Compared to controls, CIS patients showed increased humoral (p<0.0001) and cellular (p=0.007) immune responses to the EBV-encoded nuclear antigen-1 (EBNA1), but not to other EBV-derived proteins. IgG responses to other virus antigens and frequencies of T cells specific for HCMV and influenza virus gene products were unchanged in CIS patients. EBNA1 was the only viral antigen towards which immune responses correlated with number of T2 lesions (p=0.006) and number of Barkhof criteria (p=0.001) at baseline, and with number of T2 lesions (p=0.012 both at 1 and 5 years), presence of new T2 lesions (p=0.003 and p=0.028 at 1 and 5 years), and EDSS (p=0.015 and p=0.010 at 1 and 5 years) during follow-up. In a univariate Cox regression model, increased EBNA1-specific IgG responses predicted conversion to MS based on McDonald criteria [hazard ratio (95% confidence interval), 2.2 (1.2–4.3); p=0.003]. Interpretation Our results indicate that elevated immune responses towards EBNA1 are selectively increased in CIS patients and suggest that EBNA1-specific IgG titers could be used as a prognostic marker for disease conversion and disability progression. PMID:20225269

  20. C-reactive protein collaborates with plasma lectins to boost immune response against bacteria

    DEFF Research Database (Denmark)

    Ng, PM; Le Saux, A; Lee, CM; Tan, NS; Lu, J; Thiel, Steffen; Ho, B; Ding, JL

    2007-01-01

    Although human C-reactive protein (CRP) becomes upregulated during septicemia, its role remains unclear, since purified CRP showed no binding to many common pathogens. Contrary to previous findings, we show that purified human CRP (hCRP) binds to Salmonella enterica, and that binding is enhanced in...... the presence of plasma factors. In the horseshoe crab, Carcinoscorpius rotundicauda, CRP is a major hemolymph protein. Incubation of hemolymph with a range of bacteria resulted in CRP binding to all the bacteria tested. Lipopolysaccharide-affinity chromatography of the hemolymph co-purified CRP......, galactose-binding protein (GBP) and carcinolectin-5 (CL5). Yeast two-hybrid and pull-down assays suggested that these pattern recognition receptors (PRRs) form pathogen recognition complexes. We show the conservation of PRR crosstalk in humans, whereby hCRP interacts with ficolin (CL5 homologue). This...

  1. The role of complement in the acquired immune response

    DEFF Research Database (Denmark)

    Nielsen, C H; Fischer, E M; Leslie, R G

    2000-01-01

    specific T cells; the activation of a CD21/CD19 complex-mediated signalling pathway in B cells, which provides a stimulus synergistic to that induced by antigen interaction with the B-cell receptor (BCR); and promotion of the interaction between B cells and FDC, where C3d-bearing immune complexes......Studies over the past three decades have clearly established a central role for complement in the promotion of a humoral immune response. The primary function of complement, in this regard, is to opsonize antigen or immune complexes for uptake by complement receptor type 2 (CR2, CD21) expressed on...... B cells, follicular dendritic cells (FDC) and some T cells. A variety of mechanisms appear to be involved in complement-mediated promotion of the humoral response. These include: enhancement of antigen (Ag) uptake and processing by both Ag-specific and non-specific B cells for presentation to...

  2. Review: Adjuvant effects of saponins on animal immune responses

    Institute of Scientific and Technical Information of China (English)

    RAJPUT Zahid Iqbal; HU Song-hua; XIAO Chen-wen; ARIJO Abdullah G.

    2007-01-01

    Vaccines require optimal adjuvants including immunopotentiator and delivery systems to offer long term protection from infectious diseases in animals and man. Initially it was believed that adjuvants are responsible for promoting strong and sustainable antibody responses. Now it has been shown that adjuvants influence the isotype and avidity of antibody and also affect the properties of cell-mediated immunity. Mostly oil emulsions, lipopolysaccharides, polymers, saponins, liposomes, cytokines,ISCOMs (immunostimulating complexes), Freund's complete adjuvant, Freund's incomplete adjuvant, alums, bacterial toxins etc.,are common adjuvants under investigation. Saponin based adjuvants have the ability to stimulate the cell mediated immune system as well as to enhance antibody production and have the advantage that only a low dose is needed for adjuvant activity. In the present study the importance of adjuvants, their role and the effect of saponin in immune system is reviewed.

  3. Durable and sustained immune tolerance to ERT in Pompe disease with entrenched immune responses

    Science.gov (United States)

    Kazi, Zoheb B.; Prater, Sean N.; Kobori, Joyce A.; Viskochil, David; Bailey, Carrie; Gera, Renuka; Stockton, David W.; McIntosh, Paul; Rosenberg, Amy S.; Kishnani, Priya S.

    2016-01-01

    BACKGROUND Enzyme replacement therapy (ERT) has prolonged survival and improved clinical outcomes in patients with infantile Pompe disease (IPD), a rapidly progressive neuromuscular disorder. Yet marked interindividual variability in response to ERT, primarily attributable to the development of antibodies to ERT, remains an ongoing challenge. Immune tolerance to ongoing ERT has yet to be described in the setting of an entrenched immune response. METHODS Three infantile Pompe patients who developed high and sustained rhGAA IgG antibody titers (HSAT) and received a bortezomib-based immune tolerance induction (ITI) regimen were included in the study and were followed longitudinally to monitor the long-term safety and efficacy. A trial to taper the ITI protocol was attempted to monitor if true immune tolerance was achieved. RESULTS Bortezomib-based ITI protocol was safely tolerated and led to a significant decline in rhGAA antibody titers with concomitant sustained clinical improvement. Two of the 3 IPD patients were successfully weaned off all ITI protocol medications and continue to maintain low/no antibody titers. ITI protocol was significantly tapered in the third IPD patient. B cell recovery was observed in all 3 IPD patients. CONCLUSION This is the first report to our knowledge on successful induction of long-term immune tolerance in patients with IPD and HSAT refractory to agents such as cyclophosphamide, rituximab, and methotrexate, based on an approach using the proteasome inhibitor bortezomib. As immune responses limit the efficacy and cost-effectiveness of therapy for many conditions, proteasome inhibitors may have new therapeutic applications. FUNDING This research was supported by a grant from the Genzyme Corporation, a Sanofi Company (Cambridge, Massachusetts, USA), and in part by the Lysosomal Disease Network, a part of NIH Rare Diseases Clinical Research Network (RDCRN).

  4. A Drosophila immune response against Ras-induced overgrowth

    Directory of Open Access Journals (Sweden)

    Thomas Hauling

    2014-03-01

    Full Text Available Our goal is to characterize the innate immune response against the early stage of tumor development. For this, animal models where genetic changes in specific cells and tissues can be performed in a controlled way have become increasingly important, including the fruitfly Drosophila melanogaster. Many tumor mutants in Drosophila affect the germline and, as a consequence, also the immune system itself, making it difficult to ascribe their phenotype to a specific tissue. Only during the past decade, mutations have been induced systematically in somatic cells to study the control of tumorous growth by neighboring cells and by immune cells. Here we show that upon ectopic expression of a dominant-active form of the Ras oncogene (RasV12, both imaginal discs and salivary glands are affected. Particularly, the glands increase in size, express metalloproteinases and display apoptotic markers. This leads to a strong cellular response, which has many hallmarks of the granuloma-like encapsulation reaction, usually mounted by the insect against larger foreign objects. RNA sequencing of the fat body reveals a characteristic humoral immune response. In addition we also identify genes that are specifically induced upon expression of RasV12. As a proof-of-principle, we show that one of the induced genes (santa-maria, which encodes a scavenger receptor, modulates damage to the salivary glands. The list of genes we have identified provides a rich source for further functional characterization. Our hope is that this will lead to a better understanding of the earliest stage of innate immune responses against tumors with implications for mammalian immunity.

  5. Platelets in Pulmonary Immune Responses and Inflammatory Lung Diseases.

    Science.gov (United States)

    Middleton, Elizabeth A; Weyrich, Andrew S; Zimmerman, Guy A

    2016-10-01

    Platelets are essential for physiological hemostasis and are central in pathological thrombosis. These are their traditional and best known activities in health and disease. In addition, however, platelets have specializations that broaden their functional repertoire considerably. These functional capabilities, some of which are recently discovered, include the ability to sense and respond to infectious and immune signals and to act as inflammatory effector cells. Human platelets and platelets from mice and other experimental animals can link the innate and adaptive limbs of the immune system and act across the immune continuum, often also linking immune and hemostatic functions. Traditional and newly recognized facets of the biology of platelets are relevant to defensive, physiological immune responses of the lungs and to inflammatory lung diseases. The emerging view of platelets as blood cells that are much more diverse and versatile than previously thought further predicts that additional features of the biology of platelets and of megakaryocytes, the precursors of platelets, will be discovered and that some of these will also influence pulmonary immune defenses and inflammatory injury. PMID:27489307

  6. Induction of cross-protection against influenza A virus by DNA prime-intranasal protein boost strategy based on nucleoprotein

    Directory of Open Access Journals (Sweden)

    Luo Jian

    2012-11-01

    Full Text Available Abstract Background The highly conserved nucleoprotein (NP is an internal protein of influenza virus and is capable of inducing cross-protective immunity against different influenza A viruses, making it a main target of universal influenza vaccine. In current study, we characterized the immune response induced by DNA prime-intranasal protein boost strategy based on NP (A/PR/8/34, H1N1 in mouse model, and evaluated its protection ability against a lethal dose challenge of influenza virus. Results The intranasal boost with recombinant NP (rNP protein could effectively enhance the pre-immune response induced by the NP DNA vaccine in mice. Compared to the vaccination with NP DNA or rNP protein alone, the prime-boost strategy increased the level of NP specific serum antibody, enhanced the T cell immune response, and relatively induced more mucosal IgA antibody. The overall immune response induced by this heterologous prime-boost regimen was Th-1-biased. Furthermore, the immune response in mice induced by this strategy provided not only protection against the homologous virus but also cross-protection against a heterosubtypic H9N2 strain. Conclusions The NP DNA prime-intranasal protein boost strategy may provide an effective strategy for universal influenza vaccine development.

  7. Systems biology of neutrophil differentiation and immune response

    DEFF Research Database (Denmark)

    Theilgaard-Mönch, Kim; Porse, Bo T; Borregaard, Niels

    2005-01-01

    Systems biology has emerged as a new scientific field, which aims at investigating biological processes at the genomic and proteomic levels. Recent studies have unravelled aspects of neutrophil differentiation and immune responses at the systems level using high-throughput technologies. These...

  8. Polysaccharides isolated from Acai fruit induce innate immune responses.

    Directory of Open Access Journals (Sweden)

    Jeff Holderness

    Full Text Available The Açaí (Acai fruit is a popular nutritional supplement that purportedly enhances immune system function. These anecdotal claims are supported by limited studies describing immune responses to the Acai polyphenol fraction. Previously, we characterized γδ T cell responses to both polyphenol and polysaccharide fractions from several plant-derived nutritional supplements. Similar polyphenol and polysaccharide fractions are found in Acai fruit. Thus, we hypothesized that one or both of these fractions could activate γδ T cells. Contrary to previous reports, we did not identify agonist activity in the polyphenol fraction; however, the Acai polysaccharide fraction induced robust γδ T cell stimulatory activity in human, mouse, and bovine PBMC cultures. To characterize the immune response to Acai polysaccharides, we fractionated the crude polysaccharide preparation and tested these fractions for activity in human PBMC cultures. The largest Acai polysaccharides were the most active in vitro as indicated by activation of myeloid and γδ T cells. When delivered in vivo, Acai polysaccharide induced myeloid cell recruitment and IL-12 production. These results define innate immune responses induced by the polysaccharide component of Acai and have implications for the treatment of asthma and infectious disease.

  9. Primary immune response to blood group antigens in burned children.

    Science.gov (United States)

    Bacon, N; Patten, E; Vincent, J

    1991-01-01

    Delayed hemolytic transfusion reactions (DHTRs) are generally attributed to an anamnestic immune response. Case reports of DHTRs due to a primary immune response are rare. Transfusion reactions occurring in patients on the pediatric burn unit from 1981 to September 1988 were reviewed, and additional information was obtained for patients for whom a DHTR was documented. Of 62 transfusion reactions, 11 were classified as a primary immune response (DHTR), with either a positive antibody screen, a positive direct antiglobulin test (DAT), or both. None of the 11 patients included in the study had been previously tranfused or pregnant. The average number of units transfused prior to antibody identification was 19. The average time elapsed between the first transfusion and antibody identification was 3.6 weeks. Anti-K and anti-E were the most frequently identified. Three patients had a decrease in hemoglobin (average 1.5 g/dL) and hematocrit at the time that a positive DAT was detected. Such changes could not be demonstrated for the remaining eight patients. The conclusion was that a DHTR may he caused by a primary immune response in burned children more often than expected, but DHTR signs and symptoms are often not apparent due to the complications of burn trauma. PMID:15946011

  10. HTLV-1, Immune Response and Autoimmunity.

    Science.gov (United States)

    Quaresma, Juarez A S; Yoshikawa, Gilberto T; Koyama, Roberta V L; Dias, George A S; Fujihara, Satomi; Fuzii, Hellen T

    2016-01-01

    Human T-lymphotropic virus type-1 (HTLV-1) infection is associated with adult T-cell leukemia/lymphoma (ATL). Tropical spastic paraparesis/HTLV-1-associated myelopathy (PET/HAM) is involved in the development of autoimmune diseases including Rheumatoid Arthritis (RA), Systemic Lupus Erythematosus (SLE), and Sjögren's Syndrome (SS). The development of HTLV-1-driven autoimmunity is hypothesized to rely on molecular mimicry, because virus-like particles can trigger an inflammatory response. However, HTLV-1 modifies the behavior of CD4⁺ T cells on infection and alters their cytokine production. A previous study showed that in patients infected with HTLV-1, the activity of regulatory CD4⁺ T cells and their consequent expression of inflammatory and anti-inflammatory cytokines are altered. In this review, we discuss the mechanisms underlying changes in cytokine release leading to the loss of tolerance and development of autoimmunity. PMID:26712781

  11. Glassy Dynamics in the Adaptive Immune Response Prevents Autoimmune Disease

    Science.gov (United States)

    Sun, Jun; Deem, Michael

    2006-03-01

    The immune system normally protects the human host against death by infection. However, when an immune response is mistakenly directed at self antigens, autoimmune disease can occur. We describe a model of protein evolution to simulate the dynamics of the adaptive immune response to antigens. Computer simulations of the dynamics of antibody evolution show that different evolutionary mechanisms, namely gene segment swapping and point mutation, lead to different evolved antibody binding affinities. Although a combination of gene segment swapping and point mutation can yield a greater affinity to a specific antigen than point mutation alone, the antibodies so evolved are highly cross-reactive and would cause autoimmune disease, and this is not the chosen dynamics of the immune system. We suggest that in the immune system a balance has evolved between binding affinity and specificity in the mechanism for searching the amino acid sequence space of antibodies. Our model predicts that chronic infection may lead to autoimmune disease as well due to cross-reactivity and suggests a broad distribution for the time of onset of autoimmune disease due to chronic exposure. The slow search of antibody sequence space by point mutation leads to the broad of distribution times.

  12. Effect of traditional Chinese medicine for treating human immunodeficiency virus infections and acquired immune deficiency syndrome: Boosting immune and alleviating symptoms.

    Science.gov (United States)

    Zou, Wen; Wang, Jian; Liu, Ying

    2016-01-01

    To respond to the human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) epidemic in China, the integration of antiretroviral therapy (ART) and traditional Chinese medicine (TCM) has important implications in health outcomes, especially in China where the use of TCM is widespread. The National Free TCM Pilot Program for HIV Infected People began in 5 provinces (Henan, Hebei, Anhui, Hubei, and Guangdong) in 2004, and quickly scaled up to 19 provinces, autonomous regions, and municipalities in China including some places with high prevalence, 26,276 adults have been treated thus far. Usually, people with HIV infection seek TCM for four main reasons: to enhance immune function, to treat symptoms, to improve quality of life, and to reduce side effects related to medications. Evidences from randomized controlled clinical trials suggested some beneficial effects of use of traditional Chinese herbal medicine for HIV infections and AIDS. More proofs from large, well-designed, rigorous trials is needed to give firm support. Challenges include interaction between herbs and antiretroviral drugs, stigma and discrimination. The Free TCM Program has made considerable progress in providing the necessary alternative care and treatment for HIV-infected people in China, and has strong government support for continued improvement and expansion, establishing and improving a work mechanism integrating Chinese and Western medicines. PMID:26577109

  13. Antibody response in silver catfish (Rhamdia quelen) immunized with a model antigen associated with different adjuvants.

    Science.gov (United States)

    Pavan, T R; Di Domenico, J; Kirsten, K S; Nied, C O; Frandoloso, R; Kreutz, L C

    2016-07-25

    Adjuvants are essential to boost the immune response to inoculated antigen and play a central role in vaccine development. In this study, we investigated the efficacy of several adjuvants in the production of anti-bovine serum albumin (BSA) antibodies in silver catfish. Two hundred and seventy juvenile silver catfish (60-80 g) of both sexes were intraperitoneally vaccinated with BSA (200 µg/fish) alone or mixed to the following adjuvants: Freund's complete adjuvant (FCA), Freund's incomplete adjuvant (FIA), aluminum hydroxide (AlOH), Montanide, four types of cytosine-phosphate-guanine (CpG) oligodeoxynucleotides (ODNs) and three concentrations of β-glucan, and the immune enhancing property was evaluated by measuring anti-BSA antibodies in blood samples at biweekly intervals. Our results demonstrated that CpGs ODNs and β-glucan were as effective as classical adjuvants (FCA, FIA, AlOH and Montanide) in promoting anti-BSA antibodies and that the kinetics of antibody production induced by all adjuvants used in our study had a similar trend to that observed in other fish species, with a peak at 28 days post-vaccination. These results may be useful for the selection of adjuvants for vaccine formulation intended for silver catfish and for the development of vaccine and vaccination strategies to other fish species. PMID:27464022

  14. Role of Echinacea Purpurea in Oxidative Stress and Immune Responses in Gamma Irradiated Rats

    International Nuclear Information System (INIS)

    Interest in Echinacea purpurea is growing rapidly since it was discovered to boost the immune system and to possess antioxidant properties. The objective of this study was to evaluate the modulator role of E. purpurea in radiation-induced oxidative stress in spleen tissues and alterations in some immune responses. Rats were whole body gamma irradiated with 3 Gy/week up to a total dose of 6 Gy. E. purpurea (30 mg/kg/day) was given to rats via gavages during 14 days before irradiation and 7 days after each radiation dose. Animals were sacrificed on the 7th day after the last radiation dose. Significant increase in xanthine oxidase (XO) and significant decrease in xanthine dehydrogenase (XDH) were recorded in the spleen of irradiated rats. In addition, the levels of oxidative bio markers; thiobarbituric acid reactive substances (TBARS), protein carbonyl and advanced oxidation protein products (AOPP), showed significant increases. The antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) showed significant increases, while glutathione peroxidase (GSHPx) showed significant decrease and glutathione showed normal value in the spleen of irradiated rats. Irradiation results showed non-significant decrease in total counts of white blood cells (WBCs), lymphocytes, monocytes, neutrophils, eosinophils and basophils. Significant increase in the level of C-reactive protein (CRP) was recorded in the serum of irradiated rats. E. purpurea supplementation has significantly improved oxidative stress in the spleen of irradiated rats. Total and differential count of white blood cells (WBCs) showed an increase as compared to their corresponding values in irradiated rats while serum CRP showed decreased value. It could be concluded that E. purpurea may afford protection against radiation-induced oxidative stress in spleen tissue and might be involved in the modulation of immune responses

  15. The influence of quartz and surfactant on immune responses

    OpenAIRE

    Zetterberg, Göran

    1998-01-01

    Pulmonary surfactant is a mixture of lipids and proteins that embeds the alveolar cells, has surface tension reducing properties but also influences the immune response. To further investigate this, quartz was used to initiate an inflammatory response in two different models. Firstly, in vitro exposures of resting and activated human leukocytes to combinations of quartz and surfactant were done, and secondly in vivo exposures of rats to instilled quartz were performed. W...

  16. Immune Response to Electromagnetic Fields through Cybernetic Modeling

    Science.gov (United States)

    Godina-Nava, J. J.; Segura, M. A. Rodríguez; Cadena, S. Reyes; Sierra, L. C. Gaitán

    2008-08-01

    We study the optimality of the humoral immune response through a mathematical model, which involves the effect of electromagnetic fields over the large lymphocytes proliferation. Are used the so called cybernetic variables in the context of the matching law of microeconomics or mathematical psychology, to measure the large lymphocytes population and to maximize the instantaneous antibody production rate in time during the immunologic response in order to most efficiently inactivate the antigen.

  17. Immune Response to Electromagnetic Fields through Cybernetic Modeling

    International Nuclear Information System (INIS)

    We study the optimality of the humoral immune response through a mathematical model, which involves the effect of electromagnetic fields over the large lymphocytes proliferation. Are used the so called cybernetic variables in the context of the matching law of microeconomics or mathematical psychology, to measure the large lymphocytes population and to maximize the instantaneous antibody production rate in time during the immunologic response in order to most efficiently inactivate the antigen

  18. Reprogramming immune responses via microRNA modulation

    Science.gov (United States)

    Cubillos-Ruiz, Juan R.; Rutkowski, Melanie R; Tchou, Julia; Conejo-Garcia, Jose R.

    2013-01-01

    It is becoming increasingly clear that there are unique sets of miRNAs that have distinct governing roles in several aspects of both innate and adaptive immune responses. In addition, new tools allow selective modulation of the expression of individual miRNAs, both in vitro and in vivo. Here, we summarize recent advances in our understanding of how miRNAs drive the activity of immune cells, and how their modulation in vivo opens new avenues for diagnostic and therapeutic interventions in multiple diseases, from immunodeficiency to cancer. PMID:25285232

  19. Effect of doxycycline on immune response in mice.

    OpenAIRE

    Bellahsene, A; Forsgren, A

    1985-01-01

    The effect of doxycycline on immune response has been studied in mice, cell-mediated immunity being evaluated with the split heart allograft technique. Survival duration of heart transplants in animals treated with 2.5 mg of doxycycline per kg per day from the day of transplantation until rejection was slightly but significantly longer than in untreated animals, 18.8 days (P less than 0.05) as compared with 14.5 days. In doxycycline-treated animals, both agglutinating and hemolytic antibody r...

  20. Mechanisms of immune response regulation in lung cancer

    OpenAIRE

    Domagala-Kulawik, Joanna; Osinska, Iwona; Hoser, Grazyna

    2014-01-01

    Lung cancer is a leading cause of cancer deaths. As a solid tumor with low antigenicity and heterogenic phenotype lung cancer evades host immune defense. The cytotoxic anticancer effect is suppressed by a complex mechanism in tumor microenvironment. The population of regulatory T cells (Tregs) plays a crucial role in this inhibition of immune response. Tregs are defined by presence of forkhead box P3 (Foxp3) molecule. The high expression of Foxp3 was found in lung cancer cells and in tumor in...

  1. Ginsenoside Re as an adjuvant to enhance the immune response to the inactivated rabies virus vaccine in mice.

    Science.gov (United States)

    Su, Xiaoyan; Pei, Zengyang; Hu, Songhua

    2014-06-01

    The inactivated rabies virus vaccine (RV) is a relatively expensive vaccine, prone to failure in some cases. Ginsenoside Re (Re) is a saponin isolated from Panax ginseng, and has an adjuvant property. Here the adjuvant effect of Re to improve the immune response to the RV is evaluated in mice. ICR mice were immunized with saline, 2.50mg/kg Re, 20μl RV, 100μl RV, or 20μl of RV adjuvanted with Re (1.25, 2.50 or 5.00mg/kg). Different time points after boosting, we measured serum antibodies in blood samples and separated splenocytes to detect lymphocyte proliferation and the production of IL-4, IL-10, IL-12, and IFN-γ in vitro. We also compared immunizations containing 20μl RV and 20μl RV adjuvanted with Re (5.00mg/kg) for the expression of CD4(+) and CD8(+) T-cell subsets at different time points. Results indicated that co-administration of Re significantly enhanced serum antibody titers, increased the CD4(+):CD8(+) ratio, and enhanced both proliferation responses and IL-4, IL-10, IL-12 and IFN-γ secretions. Both Th1 and Th2 immune responses were activated. The supplementation of the Re (5.00mg/kg) to 20μl of RV significantly amplified serum antibody responses and Th1/Th2 responses inducing similar protection as did 100μl of RV. This suggests that Re could be used to reduce the dose, and therefore the cost, of the RV to achieve the same effective protection. Re merits further studies for use with vaccines of mixed Th1/Th2 immune responses. PMID:24680943

  2. Immunization with Brucella VirB proteins reduces organ colonization in mice through a Th1-type immune response and elicits a similar immune response in dogs.

    Science.gov (United States)

    Pollak, Cora N; Wanke, María Magdalena; Estein, Silvia M; Delpino, M Victoria; Monachesi, Norma E; Comercio, Elida A; Fossati, Carlos A; Baldi, Pablo C

    2015-03-01

    VirB proteins from Brucella spp. constitute the type IV secretion system, a key virulence factor mediating the intracellular survival of these bacteria. Here, we assessed whether a Th1-type immune response against VirB proteins may protect mice from Brucella infection and whether this response can be induced in the dog, a natural host for Brucella. Splenocytes from mice immunized with VirB7 or VirB9 responded to their respective antigens with significant and specific production of gamma interferon (IFN-γ), whereas interleukin-4 (IL-4) was not detected. Thirty days after an intraperitoneal challenge with live Brucella abortus, the spleen load of bacteria was almost 1 log lower in mice immunized with VirB proteins than in unvaccinated animals. As colonization reduction seemed to correlate with a Th1-type immune response against VirB proteins, we decided to assess whether such a response could be elicited in the dog. Peripheral blood mononuclear cells (PBMCs) from dogs immunized with VirB proteins (three subcutaneous doses in QuilA adjuvant) produced significantly higher levels of IFN-γ than cells from control animals upon in vitro stimulation with VirB proteins. A skin test to assess specific delayed-type hypersensitivity was positive in 4 out of 5 dogs immunized with either VirB7 or VirB9. As both proteins are predicted to locate in the outer membrane of Brucella organisms, the ability of anti-VirB antibodies to mediate complement-dependent bacteriolysis of B. canis was assessed in vitro. Sera from dogs immunized with either VirB7 or VirB9, but not from those receiving phosphate-buffered saline (PBS), produced significant bacteriolysis. These results suggest that VirB-specific responses that reduce organ colonization by Brucella in mice can be also elicited in dogs. PMID:25540276

  3. Inflammation and Immune Response in COPD: Where Do We Stand?

    Directory of Open Access Journals (Sweden)

    Nikoletta Rovina

    2013-01-01

    Full Text Available Increasing evidence indicates that chronic inflammatory and immune responses play key roles in the development and progression of COPD. Recent data provide evidence for a role in the NLRP3 inflammasome in the airway inflammation observed in COPD. Cigarette smoke activates innate immune cells by triggering pattern recognition receptors (PRRs to release “danger signal”. These signals act as ligands to Toll-like receptors (TLRs, triggering the production of cytokines and inducing innate inflammation. In smokers who develop COPD there appears to be a specific pattern of inflammation in the airways and parenchyma as a result of both innate and adaptive immune responses, with the predominance of CD8+ and CD4+ cells, and in the more severe disease, with the presence of lymphoid follicles containing B lymphocytes and T cells. Furthermore, viral and bacterial infections interfere with the chronic inflammation seen in stable COPD and exacerbations via pathogen-associated molecular patterns (PAMPs. Finally, autoimmunity is another novel aspect that may play a critical role in the pathogenesis of COPD. This review is un update of the currently discussed roles of inflammatory and immune responses in the pathogenesis of COPD.

  4. Cell signalling in the immune response of mussel hemocytes

    Directory of Open Access Journals (Sweden)

    L Canesi

    2006-05-01

    Full Text Available In this work data on immune cell signallling in the circulating hemocytes of the edible bivalve, themussel Mytilus spp, are summarized. Studies with different bacterial species and strains, heterologouscytokines and natural hormones, as well as with organic environmental chemicals, led to theidentification of the role of conserved components of kinase-mediated transduction pathways,including cytosolic kinases (such as MAPKs and PKC and kinase-activated transcription factors (suchas STATs, CREB, NF-kB, in the immune response. From these data a general scenario emergedindicating that close similarities exist in the signalling pathways involved in cell mediated immunity inbivalve and mammalian immunocytes. In particular, the results indicate that both the extent andduration of activation of components of kinase-mediated cascades are crucial in determining thehemocyte response to extracellular stimuli. The identification of the basic mechanisms of immunityand its modulation in mussels can give important information for the possible utilization of thesespecies as an invertebrate model for studies on innate immunity. Moreover, the application of thisknowledge to the understanding of the actual adaptive responses of bivalves when exposed to microorganismsin their natural environment can represent significant ecological, economical and publichealth-related interest.

  5. The Effect of Radiation on the Immune Response to Cancers

    Directory of Open Access Journals (Sweden)

    Bonggoo Park

    2014-01-01

    Full Text Available In cancer patients undergoing radiation therapy, the beneficial effects of radiation can extend beyond direct cytotoxicity to tumor cells. Delivery of localized radiation to tumors often leads to systemic responses at distant sites, a phenomenon known as the abscopal effect which has been attributed to the induction and enhancement of the endogenous anti-tumor innate and adaptive immune response. The mechanisms surrounding the abscopal effect are diverse and include trafficking of lymphocytes into the tumor microenvironment, enhanced tumor recognition and killing via up-regulation of tumor antigens and antigen presenting machinery and, induction of positive immunomodulatory pathways. Here, we discuss potential mechanisms of radiation-induced enhancement of the anti-tumor response through its effect on the host immune system and explore potential combinational immune-based strategies such as adoptive cellular therapy using ex vivo expanded NK and T cells as a means of delivering a potent effector population in the context of radiation-enhanced anti-tumor immune environment.

  6. Immunization with avian metapneumovirus harboring chicken Fc induces higher immune responses.

    Science.gov (United States)

    Paudel, Sarita; Easwaran, Maheswaran; Jang, Hyun; Jung, Ho-Kyoung; Kim, Joo-Hun; Shin, Hyun-Jin

    2016-07-15

    In this study, we evaluated the immune responses of avian metapneumovirus harboring chicken Fc molecule. Stable Vero cells expressing chicken Fc chimera on its surface (Vero-cFc) were established, and we confirmed that aMPV grown in Vero-cFc incorporated host derived chimera Fc into the aMPV virions. Immunization of chicken with aMPV-cFc induced higher level of antibodies and inflammatory cytokines; (Interferon (IFN)-γ and Interleukin (IL)-1β) compared to those of aMPV. The increased levels of antibodies and inflammatory cytokines in chicken immunized with aMPV-cFc were statistically significantly (p<0.05) to that of aMPV and control. The aMPV-cFc group also generated the highest neutralizing antibody response. After challenges, chickens immunized with aMPV-cFc showed much less pathological signs in nasal turbinates and trachea so that we could confirm aMPV-cFc induced higher protection than that of aMPV. The greater ability of aMPV harboring chicken Fc to that of aMPV presented it as a possible vaccine candidate. PMID:27130629

  7. Cell mediated immune response in human antirabies revaccination

    Directory of Open Access Journals (Sweden)

    Débora Regina Veiga

    1987-04-01

    Full Text Available The occurrence of secondary cell mediated immune response (CMI in human antirabies immunization was studied. The Puenzalida & Palácios vaccine was used because it is routinely used in Brazil. CMI was evaluated by lymphoblastic transformation indices obtained in whole blood culture in the presence of rabies and control (nervous tissue antigens. Eleven volunteers submitted to revaccination constituted the group under study, while three other volunteers submitted primo vaccination were utilized as control group. A clear secondary CMI to rabies antigen was detected in all the revaccinated volunteers who showed earlier and more intense response than the control group. Response to the control antigen, however, present in all the components of the first group was not detectable in two out of the three primovaccinated and very low in the third one.

  8. Functional characterization of Foxp3-specific spontaneous immune responses

    DEFF Research Database (Denmark)

    Larsen, Susanne Købke; Munir, S; Andersen, Anders Woetmann;

    2013-01-01

    Tumor-infiltrating CD4+CD25+ regulatory T cells (Tregs) are associated with an impaired prognosis in several cancers. The transcription factor forkhead box P3 (Foxp3) is generally expressed in Tregs. Here, we identify and characterize spontaneous cytotoxic immune responses to Foxp3-expressing cells...... Foxp3 protein indicating that this protein was indeed internalized, processed and cross-presented in the context of HLA-A2. More importantly, however, Foxp3-specific T cells were able to specifically recognize Tregs. Similarly, Foxp3+ malignant T cells established from a Cutaneous T-cell lymphomas...... (CTCL) patient were readily killed by the Foxp3-specific cytotoxic T lymphocytes. The spontaneous presence of Foxp3-specific cytotoxic T-cell responses suggest a general role of such T cells in the complex network of immune regulation as such responses may eliminate Tregs, that is, suppression of the...

  9. Enhanced immune response to foot-and-mouth disease vaccine by oral administration of ginseng stem-leaf saponins.

    Science.gov (United States)

    Li, Renjun; Ma, Yanfen; Zhai, Lijuan; Lu, Yisong; Chi, Xiaoqing; Wu, Jiusheng; Hu, Songhua

    2016-08-01

    Vaccination is an important approach to the control of foot-and-mouth disease (FMD). This study evaluated the effect of oral administration of ginseng stem-leaf saponins (GSLS) on the immune response to FMD vaccine and the gut mucosal immunity in mice. In experiment 1, mice were orally administered GSLS or not treated as a control. The animals were then immunized twice with FMD vaccine. Blood was sampled weekly within five weeks after the boost immunization for measurement of serum IgG and the isotypes. In experiment 2, mice were orally administrated GSLS or not treated as a control. After that, splenocytes were prepared from sacrificed mice for lymphocyte proliferation assay and intestinal tissues were sampled for immunohistochemistry and histological examination. The results showed that oral administration of GSLS significantly enhanced serum IgG and the isotype responses to FMD vaccine as well as the number of intestinal intraepithelial lymphocytes (IELs) and immunoglobulin A (IgA)+ cells. Therefore, GSLS may be a potent oral adjuvant and deserve further study to improve vaccination in susceptible animals. PMID:27216768

  10. Immune responses to Mycoplasma bovis proteins formulated with different adjuvants.

    Science.gov (United States)

    Prysliak, Tracy; Perez-Casal, Jose

    2016-06-01

    Most vaccines for protection against Mycoplasma bovis disease are made of bacterins, and they offer varying degrees of protection. Our focus is on the development of a subunit-based protective vaccine, and to that end, we have identified 10 novel vaccine candidates. After formulation of these candidates with TriAdj, an experimental tri-component novel vaccine adjuvant developed at VIDO-InterVac, we measured humoral and cell-mediated immune responses in vaccinated animals. In addition, we compared the immune responses after formulation with TriAdj with the responses measured in animals vaccinated with a mix of a commercial adjuvant (Emulsigen™) and 2 of the components of the TriAdj, namely polyinosinic:polycytidylic acid (poly I:C) and the cationic innate defense regulator (IDR) peptide 1002 (VQRWLIVWRIRK). In this latter trial, we detected significant IgG1 humoral immune responses to 8 out of 10 M. bovis proteins, and IgG2 responses to 7 out of 10 proteins. Thus, we concluded that the commercial adjuvant formulated with poly I:C and the IDR peptide 1002 is the best formulation for the experimental vaccine. PMID:27105454

  11. Plasmodium Riboprotein PfP0 Induces a Deviant Humoral Immune Response in Balb/c Mice

    Directory of Open Access Journals (Sweden)

    Sulabha Pathak

    2012-01-01

    Full Text Available Passive immunization with antibodies to recombinant Plasmodium falciparum P0 riboprotein (rPfP0, 61–316 amino acids provides protection against malaria. Carboxy-terminal 16 amino acids of the protein (PfP0C0 are conserved and show 69% identity to human and mouse P0. Antibodies to this domain are found in 10–15% of systemic lupus erythematosus patients. We probed the nature of humoral response to PfP0C0 by repeatedly immunizing mice with rPfP0. We failed to raise stable anti-PfP0C0 hybridomas from any of the 21 mice. The average serum anti-PfP0C0 titer remained low (5.1±1.3×104. Pathological changes were observed in the mice after seven boosts. Adsorption with dinitrophenyl hapten revealed that the anti-PfP0C0 response was largely polyreactive. This polyreactivity was distributed across all isotypes. Similar polyreactive responses to PfP0 and PfP0C0 were observed in sera from malaria patients. Our data suggests that PfP0 induces a deviant humoral response, and this may contribute to immune evasion mechanisms of the parasite.

  12. No apparent cost of evolved immune response in Drosophila melanogaster.

    Science.gov (United States)

    Gupta, Vanika; Venkatesan, Saudamini; Chatterjee, Martik; Syed, Zeeshan A; Nivsarkar, Vaishnavi; Prasad, Nagaraj G

    2016-04-01

    Maintenance and deployment of the immune system are costly and are hence predicted to trade-off with other resource-demanding traits, such as reproduction. We subjected this longstanding idea to test using laboratory experimental evolution approach. In the present study, replicate populations of Drosophila melanogaster were subjected to three selection regimes-I (Infection with Pseudomonas entomophila), S (Sham-infection with MgSO4 ), and U (Unhandled Control). After 30 generations of selection flies from the I regime had evolved better survivorship upon infection with P. entomophila compared to flies from U and S regimes. However, contrary to expectations and previous reports, we did not find any evidence of trade-offs between immunity and other life history related traits, such as longevity, fecundity, egg hatchability, or development time. After 45 generations of selection, the selection was relaxed for a set of populations. Even after 15 generations, the postinfection survivorship of populations under relaxed selection regime did not decline. We speculate that either there is a negligible cost to the evolved immune response or that trade-offs occur on traits such as reproductive behavior or other immune mechanisms that we have not investigated in this study. Our research suggests that at least under certain conditions, life-history trade-offs might play little role in maintaining variation in immunity. PMID:26932243

  13. Immune markers and correlates of protection for vaccine induced immune responses

    DEFF Research Database (Denmark)

    Thakur, Aneesh; Pedersen, Lasse Eggers; Jungersen, Gregers

    2012-01-01

    Vaccines have been a major innovation in the history of mankind and still have the potential to address the challenges posed by chronic intracellular infections including tuberculosis, HIV and malaria which are leading causes of high morbidity and mortality across the world. Markers of an...... appropriate humoral response currently remain the best validated correlates of protective immunity after vaccination. Despite advancements in the field of immunology over the past few decades currently there are, however, no sufficiently validated immune correlates of vaccine induced protection against...... chronic infections in neither human nor veterinary medicine. Technological and conceptual advancements within cell-mediated immunology have led to a number of new immunological read-outs with the potential to emerge as correlates of vaccine induced protection. For TH1 type responses, antigen...

  14. [Immune response in experimental animals immunized with Burkholderia pseudomallei surface antigens].

    Science.gov (United States)

    Avrorova, I V; Piven', N N; Zhukova, S I; Viktorov, D V; Khrapova, N P; Popov, S F

    2004-01-01

    The influence of the chromatographic fractions of B. pseudomallei surface antigenic complex (C, C1, D, H) on immune response in white rats and white mice was under study. These antigenic complexes were noted to produce perceptible stimulating effect on the immune system of white rats, in contrast to that of white mice. The immunization of the mice the above-mentioned fractions suppressed the phagocytic activity of peritoneal macrophages (PM) and slightly enhanced cell-mediated immunity. In experiments on white rats, fraction C induced the growth of specific antibody titers and stimulated the phagocytic activity of PM, as well as the indices of delayed hypersensitivity (DH). Fraction D showed a lower level of the induction of the phagocytic activity of PM and was inactive in the manifestation of cell-mediated immunity, but induced a high level of humoral immunity. Antigenic complexes C1 and H increased the phagocytic activity of PM and DH characteristics with a low level of antibody production. The studied fractions of the causative agent of melioidosis decreased the content of bactericidal cationic proteins (BCP) in rat blood neutrophils, and in mice a decreased content of BCP in phagocytes was registered. The fractions increased the activity of myeloperoxidase in blood neutrophils in mice and rats. As revealed with the use of immunoelectrophoresis, SDS PAAG electrophoresis and immunoblotting, the surface antigenic complex contained proteins of 18, 22, 39 kD and glycoproteins 42, 55, 90 kD. The latter glycoprotein was found in all the fractions under study, having protective properties. PMID:15554321

  15. DMPD: Innate immune responses during infection. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 15576198 Innate immune responses during infection. Ulevitch RJ, Mathison JC, da Sil...va Correia J. Vaccine. 2004 Dec 6;22 Suppl 1:S25-30. (.png) (.svg) (.html) (.csml) Show Innate immune response...s during infection. PubmedID 15576198 Title Innate immune responses during infection. Authors Ulevitch RJ,

  16. Myeloid IKKβ promotes antitumor immunity by modulating CCL11 and the innate immune response.

    Science.gov (United States)

    Yang, Jinming; Hawkins, Oriana E; Barham, Whitney; Gilchuk, Pavlo; Boothby, Mark; Ayers, Gregory D; Joyce, Sebastian; Karin, Michael; Yull, Fiona E; Richmond, Ann

    2014-12-15

    Myeloid cells are capable of promoting or eradicating tumor cells and the nodal functions that contribute to their different roles are still obscure. Here, we show that mice with myeloid-specific genetic loss of the NF-κB pathway regulatory kinase IKKβ exhibit more rapid growth of cutaneous and lung melanoma tumors. In a BRAF(V600E/PTEN(-/-)) allograft model, IKKβ loss in macrophages reduced recruitment of myeloid cells into the tumor, lowered expression of MHC class II molecules, and enhanced production of the chemokine CCL11, thereby negatively regulating dendritic-cell maturation. Elevated serum and tissue levels of CCL11 mediated suppression of dendritic-cell differentiation/maturation within the tumor microenvironment, skewing it toward a Th2 immune response and impairing CD8(+) T cell-mediated tumor cell lysis. Depleting macrophages or CD8(+) T cells in mice with wild-type IKKβ myeloid cells enhanced tumor growth, where the myeloid cell response was used to mediate antitumor immunity against melanoma tumors (with less dependency on a CD8(+) T-cell response). In contrast, myeloid cells deficient in IKKβ were compromised in tumor cell lysis, based on their reduced ability to phagocytize and digest tumor cells. Thus, mice with continuous IKKβ signaling in myeloid-lineage cells (IKKβ(CA)) exhibited enhanced antitumor immunity and reduced melanoma outgrowth. Collectively, our results illuminate new mechanisms through which NF-κB signaling in myeloid cells promotes innate tumor surveillance. PMID:25336190

  17. Inhibition of the immune response to experimental fresh osteoarticular allografts

    International Nuclear Information System (INIS)

    The immune response to osteoarticular allografts is capable of destroying the cartilage--a tissue that has antigens on its cells identical to those on the bone and marrow cells. Osteoarticular allografts of the distal femur were performed in rats using various methods to attempt to temporarily inhibit the antibody response. The temporary systemic immunosuppressant regimens investigated were cyclophosphamide, azathioprine and prednisolone, cyclosporine A, and total lymphoid irradiation. The most successful appeared to be cyclosporine A, but significant side effects were observed. To specifically inhibit the immune response in the allograft antigens without systemically inhibiting the entire immune system, passive enhancement and preadministration of donor blood were tried. Neither was as effective as coating the donor bone with biodegradable cements, a method previously found to be successful. Cyclosporine A was investigated in dogs in a preliminary study of medial compartmental knee allografts and was found to be successful in inhibiting the antibody response and in producing a more successful graft; however, some significant side effects were similarly observed

  18. Inhibition of the immune response to experimental fresh osteoarticular allografts

    Energy Technology Data Exchange (ETDEWEB)

    Rodrigo, J.J.; Schnaser, A.M.; Reynolds, H.M. Jr.; Biggart, J.M. 3d.; Leathers, M.W.; Chism, S.E.; Thorson, E.; Grotz, T.; Yang, Q.M. (Univ. of California, Davis, Sacramento (USA))

    1989-06-01

    The immune response to osteoarticular allografts is capable of destroying the cartilage--a tissue that has antigens on its cells identical to those on the bone and marrow cells. Osteoarticular allografts of the distal femur were performed in rats using various methods to attempt to temporarily inhibit the antibody response. The temporary systemic immunosuppressant regimens investigated were cyclophosphamide, azathioprine and prednisolone, cyclosporine A, and total lymphoid irradiation. The most successful appeared to be cyclosporine A, but significant side effects were observed. To specifically inhibit the immune response in the allograft antigens without systemically inhibiting the entire immune system, passive enhancement and preadministration of donor blood were tried. Neither was as effective as coating the donor bone with biodegradable cements, a method previously found to be successful. Cyclosporine A was investigated in dogs in a preliminary study of medial compartmental knee allografts and was found to be successful in inhibiting the antibody response and in producing a more successful graft; however, some significant side effects were similarly observed.

  19. Immune responses of Helicoverpa armigera to different kinds of pathogens

    Directory of Open Access Journals (Sweden)

    Zhao Xiao-Fan

    2010-03-01

    Full Text Available Abstract Background Insects react against pathogens through innate immunity. The cotton bollworm Helicoverpa armigera (H. armigera is an important defoliator and an extremely destructive pest insect of many crops. The elucidation of the mechanism of the immune response of H. armigera to various pathogens can provide a theoretical basis for new approaches to biologically control this pest. Results Four kinds of pathogens Bacillus thuringiensis, Klebsiella pneumoniae, Candida albicans, and Autographa californica multiple nucleocapsid nucleopolyhedrovirus harbored green fluorescence protein and polyhedron (AcMNPV-GFP were used to challenge the insect. The cellular and humoral immune responses to the pathogens were analyzed in the challenged H. armigera. The results show that in the five kinds of haemocytes, only granulocytes phagocytized the Gram-negative and Gram-positive bacteria and fungi. All haemocytes can be infected by AcMNPV. Fourteen immune-related genes including pattern recognition receptors (PRRs such as peptidoglycan recognition proteins (HaPGRP and HaPGRP C and Gram-Negative Bacteria-Binding Protein (HaGNBP, and antimicrobial peptides (AMPs such as cecropin-1, 2 and 3 (HaCec-1, 2 and 3, lysozyme (HaLys, attacin (HaAtt, gallerimycin-like (HaGall, gloverin-like (HaGlo, moricin-like (HaMor, cobatoxin-like (HaCob, galiomicin-like (HaGali, and immune inducible protein (HaIip appeared in different expression profiles to different pathogen infections. The transcripts of 13 immune related genes (except HaPGRPC are obviously up-regulated by Gram-positive bacteria. HaCec-1 and 3, HaMor, HaAtt, HaLys, HaIip, HaPGRP and HaGNBP are greatly up-regulated after fungal infection. HaGNBP, HaCec-2, HaGall, HaGlo, HaMor, HaCob, HaGali obviously increased in Gram-negative bacterial infection. Only five genes, HaGNBP, HaCec-1, HaGali, HaGlo, and HaLys, are weakly up-regulated after viral infection. The AMP transcripts had higher expression levels than the

  20. FEATURES OF THE IMMUNE RESPONSE DURING VIRAL INFECTION

    Directory of Open Access Journals (Sweden)

    G. A. Borisov

    2015-06-01

    Full Text Available The aim of the investigation was to select using cluster analysis and comparatively characterize immune disorders types in acute and chronic viral infections. Patients with acute and chronic viral infections (n = 896 were examined: 77 patients with acute viral hepatitis B, 94 — chronic viral hepatitis B, 119 — chronic hepatitis C, 531 — recurrent herpes, 75 — human papillomavirus infection. Healthy persons (n = 466 were examined as control. The research of blood lymphocyte phenotype was performed by flow cytometry. Four-color immunophenotyping were used in the following panels: Т-lymphocytes (CD3+CD19–CD16/56–CD45+, Т-helpers (CD3+CD4+CD45+, cytotoxic Т-cells (CD3+CD8+CD45+, NKcells (CD3–CD16/56+CD45+, B-lymphocytes (CD3–CD19+CD16/56+CD45+. Absolute values were obtained on a dualplatform technology using the results of haematological analysis. The immunoglobulin concentrations were determined by ELISA. The clustering was performed by a single linkage method. The number of clusters was determined on the basis of calculating the values of the Euclidean distance between the mean group values. It was found that the parameters, characterizing the functional state of the various parts of the immune system in acute and chronic viral infections, considerable diversity values. Custer analysis allows to allocate 6 immunotypes defined different states of innate and adaptive immunity: characterized by activation of the innate (increasing the number of neutrophils and NK-cells and adaptive immunity humoral response (increasing the concentration of IgG, characterized by hyperreaction of adaptive immunity (a significant increase in the concentration of IgG, discoordinated (multidirectional changes in the values of immunological parameters, immunodeficiency and unresponsiveness (did not differ from the control parameters immunotypes. It is proved that in patients with viral infections most often determined by the

  1. Recombinant BCG prime and PPE protein boost provides potent protection against acute Mycobacterium tuberculosis infection in mice.

    Science.gov (United States)

    Yang, Enzhuo; Gu, Jin; Wang, Feifei; Wang, Honghai; Shen, Hongbo; Chen, Zheng W

    2016-04-01

    Since BCG, the only vaccine widely used against tuberculosis (TB) in the world, provides varied protective efficacy and may not be effective for inducing long-term cellular immunity, it is in an urgent need to develop more effective vaccines and more potent immune strategies against TB. Prime-boost is proven to be a good strategy by inducing long-term protection. In this study, we tested the protective effect against Mycobacterium tuberculosis (Mtb) challenge of prime-boost strategy by recombinant BCG (rBCG) expressing PPE protein Rv3425 fused with Ag85B and Rv3425. Results showed that the prime-boost strategy could significantly increase the protective efficiency against Mtb infection, characterized by reduction of bacterial load in lung and spleen, attenuation of tuberculosis lesions in lung tissues. Importantly, we found that Rv3425 boost, superior to Ag85B boost, provided better protection against Mtb infection. Further research proved that rBCG prime-Rv3425 boost could obviously increase the expansion of lymphocytes, significantly induce IL-2 production by lymphocytes upon PPD stimulation, and inhibit IL-6 production at an early stage. It implied that rBCG prime-Rv3425 boost opted to induce Th1 immune response and provided a long-term protection against TB. These results implicated that rBCG prime-Rv3425 boost is a potent and promising strategy to prevent acute Mtb infection. PMID:26792673

  2. Anti-tumor immune response after photodynamic therapy

    Science.gov (United States)

    Mroz, Pawel; Castano, Ana P.; Wu, Mei X.; Kung, Andrew L.; Hamblin, Michael R.

    2009-06-01

    Anti-tumor immunity is stimulated after PDT due a number of factors including: the acute inflammatory response caused by PDT, release of antigens from PDT-damaged tumor cells, priming of the adaptive immune system to recognize tumor-associated antigens (TAA), and induction of heat-shock proteins. The induction of specific CD8+ T-lymphocyte cells that recognize major histocompatibility complex class I (MHC-I) restricted epitopes of TAAs is a highly desirable goal in cancer therapy as it would allow the treatment of tumors that may have already metastasized. The PDT killed tumor cells may be phagocytosed by dendritic cells (DC) that then migrate to draining lymph nodes and prime naÃve T-cells that recognize TAA epitopes. We have carried out in vivo PDT with a BPD-mediated vascular regimen using a pair of BALB/c mouse colon carcinomas: CT26 wild type expressing the naturally occurring retroviral antigen gp70 and CT26.CL25 additionally expressing beta-galactosidase (b-gal) as a model tumor rejection antigen. PDT of CT26.CL25 cured 100% of tumors but none of the CT26WT tumors (all recurred). Cured CT26.CL25 mice were resistant to rechallenge. Moreover mice with two bilateral CT26.CL25 tumors that had only one treated with PDT demonstrated spontaneous regression of 70% of untreated contralateral tumors. T-lymphocytes were isolated from lymph nodes of PDT cured mice that recognized a particular peptide specific to b-gal antigen. T-lymphocytes from LN were able to kill CT26.CL25 target cells in vitro but not CT26WT cells as shown by a chromium release assay. CT26.CL25 tumors treated with PDT and removed five days later had higher levels of Th1 cytokines than CT26 WT tumors showing a higher level of immune response. When mice bearing CT26WT tumors were treated with a regimen of low dose cyclophosphamide (CY) 2 days before, PDT led to 100% of cures (versus 0% without CY) and resistance to rechallenge. Low dose CY is thought to deplete regulatory T-cells (Treg, CD4+CD25+foxp

  3. Changes in macrophage phenotype as the immune response evolves

    Science.gov (United States)

    Lichtnekert, Julia; Kawakami, Takahisa; Parks, William C.; Duffield, Jeremy S.

    2013-01-01

    Mononuclear phagocytic cells, including macrophages and dendritic cells, are widely distributed throughout our organs where they perform important homeostatic, surveillance and regenerative tasks. In response to infection or injury, the composition and number of mononuclear phagocytic cells changes remarkably, in part due to the recruitment of inflammatory monocytes from bone marrow. In infection or injury, macrophages and dendritic cells perform important innate and adaptive immune roles from the initial insult through repair and regeneration of the tissue and resolution of inflammation. Evidence from mouse models of disease has shown increasing complexity and subtlety to the mononuclear phagocytic system, which will be reviewed here. New studies show that in addition to monocytes, the resident populations of mononuclear phagocytes expand in disease states and play distinct but important roles in the immune response. Finally, new insights into these functionally diverse cells are now translating into therapeutics to treat human disease. PMID:23747023

  4. An overview of HCV molecular biology, replication and immune responses

    Directory of Open Access Journals (Sweden)

    Nawaz Zafar

    2011-04-01

    Full Text Available Abstract Hepatitis C virus (HCV causes acute and chronic hepatitis which can eventually lead to permanent liver damage, hepatocellular carcinoma and death. Currently, there is no vaccine available for prevention of HCV infection due to high degree of strain variation. The current treatment of care, Pegylated interferon α in combination with ribavirin is costly, has significant side effects and fails to cure about half of all infections. In this review, we summarize molecular virology, replication and immune responses against HCV and discussed how HCV escape from adaptive and humoral immune responses. This advance knowledge will be helpful for development of vaccine against HCV and discovery of new medicines both from synthetic chemistry and natural sources.

  5. Responsive immunization and intervention for infectious diseases in social networks

    Science.gov (United States)

    Wu, Qingchu; Zhang, Haifeng; Zeng, Guanghong

    2014-06-01

    By using the microscopic Markov-chain approximation approach, we investigate the epidemic spreading and the responsive immunization in social networks. It is assumed that individual vaccination behavior depends on the local information of an epidemic. Our results suggest that the responsive immunization has negligible impact on the epidemic threshold and the critical value of initial epidemic outbreak, but it can effectively inhibit the outbreak of epidemic. We also analyze the influence of the intervention on the disease dynamics, where the vaccination is available only to those individuals whose number of neighbors is greater than a certain value. Simulation analysis implies that the intervention strategy can effectively reduce the vaccine use under the epidemic control.

  6. Curcumin prevents human dendritic cell response to immune stimulants

    Science.gov (United States)

    Shirley, Shawna A.; Montpetit, Alison J.; Lockey, R.F.; Mohapatra, Shyam S.

    2012-01-01

    Curcumin, a compound found in the Indian spice turmeric, has anti-inflammatory and immunomodulatory properties, though the mechanism remains unclear. Dendritic cells (DCs) are important to generating an immune response and the effect of curcumin on human DCs has not been explored. The role curcumin in the DC response to bacterial and viral infection was investigated in vitro using LPS and Poly I:C as models of infection. CD14+ monocytes, isolated from human peripheral blood, were cultured in GM-CSF- and IL-4-supplemented medium to generate immature DCs. Cultures were incubated with curcumin, stimulated with LPS or Poly I:C and functional assays were performed. Curcumin prevents DCs from responding to immunostimulants and inducing naïve CD4+ T cell proliferation by blocking maturation marker, cytokine and chemokine expression and reducing both migration and endocytosis. These data suggest a therapeutic role for curcumin as an immune suppressant. PMID:18639521

  7. Curcumin prevents human dendritic cell response to immune stimulants

    International Nuclear Information System (INIS)

    Curcumin, a compound found in the Indian spice turmeric, has anti-inflammatory and immunomodulatory properties, though the mechanism remains unclear. Dendritic cells (DCs) are important to generating an immune response and the effect of curcumin on human DCs has not been explored. The role curcumin in the DC response to bacterial and viral infection was investigated in vitro using LPS and Poly I:C as models of infection. CD14+ monocytes, isolated from human peripheral blood, were cultured in GM-CSF- and IL-4-supplemented medium to generate immature DCs. Cultures were incubated with curcumin, stimulated with LPS or Poly I:C and functional assays were performed. Curcumin prevents DCs from responding to immunostimulants and inducing CD4+ T cell proliferation by blocking maturation marker, cytokine and chemokine expression and reducing both migration and endocytosis. These data suggest a therapeutic role for curcumin as an immune suppressant

  8. Modulation of immune responses in stress by Yoga

    OpenAIRE

    Arora Sarika; Bhattacharjee Jayashree

    2008-01-01

    Stress is a constant factor in today′s fastpaced life that can jeopardize our health if left unchecked. It is only in the last half century that the role of stress in every ailment from the common cold to AIDS has been emphasized, and the mechanisms involved in this process have been studied. Stress influences the immune response presumably through the activation of the hypothalamic-pituitary adrenal axis, hypothalamic pituitary-gonadal axis, and the sympathetic-adrenal-medullary syste...

  9. Changes in macrophage phenotype as the immune response evolves

    OpenAIRE

    Lichtnekert, Julia; Kawakami, Takahisa; Parks, William C.; Duffield, Jeremy S.

    2013-01-01

    Mononuclear phagocytic cells, including macrophages and dendritic cells, are widely distributed throughout our organs where they perform important homeostatic, surveillance and regenerative tasks. In response to infection or injury, the composition and number of mononuclear phagocytic cells changes remarkably, in part due to the recruitment of inflammatory monocytes from bone marrow. In infection or injury, macrophages and dendritic cells perform important innate and adaptive immune roles fro...

  10. Immune response to racotumomab in a child with relapsed neuroblastoma

    Directory of Open Access Journals (Sweden)

    CLAUDIAVANESASAMPOR

    2012-12-01

    Full Text Available Immunotherapy targeting ganglioside antigens is a powerful tool for the treatment of high risk neuroblastoma. However, only treatment with anti-GD2 antibodies has been used in clinical practice and other options may be pursued. We report the use of racotumomab, an anti-idiotype vaccine against N-glycolyl neuraminic acid (NeuGc- containing gangliosides, eliciting an immune response in a child with relapsed neuroblastoma expressing the NeuGcGM3 ganglioside.

  11. Regional tissue immune responses after sciatic nerve injury in rats

    OpenAIRE

    Chen, Yu-ming; Shen, Ruo-Wu; Zhang, Bei; Zhang, Wei-Ning

    2015-01-01

    Inflammatory cells play a critical role during nerve regeneration following peripheral nerve injury. In this study, we investigated immune responses in rat sciatic nerve after injury. Wistar rats were randomly divided into the sciatic nerve injury (model) group and control group. The right sciatic nerve of rats in the model group was transected and sutured end-to-end. Our results showed that rats in the model group functionally recovered following sciatic nerve injury. We detected inflammator...

  12. Healthcare Worker Occupation and Immune Response to Pneumocystis jirovecii

    OpenAIRE

    Tipirneni, Renuka; Daly, Kieran R.; Leah G Jarlsberg; Koch, Judy V.; Swartzman, Alexandra; Roth, Brenna M.; Walzer, Peter D.; Huang, Laurence

    2009-01-01

    The reservoir and mode of transmission of Pneumocystis jirovecii remain uncertain. We conducted a cross-sectional study of 126 San Francisco General Hospital staff in clinical (n = 103) and nonclinical (n = 23) occupations to assess whether occupational exposure was associated with immune responses to P. jirovecii. We examined antibody levels by ELISA for 3 overlapping fragments that span the P. jirovecii major surface glycoprotein (Msg): MsgA, MsgB, and MsgC1. Clinical occupation participant...

  13. Dynamics of immune response and drug resistance in malaria infection

    OpenAIRE

    Gurarie David; McKenzie F Ellis

    2006-01-01

    Abstract Background Malaria parasites that concurrently infect a host compete on the basis of their intrinsic growth rates and by stimulating cross-reactive immune responses that inhibit each others' growth. If the phenotypes also show different drug sensitivities ('sensitive' vs. 'resistant' strains), drug treatment can change their joint dynamics and the long-term outcome of the infection: most obviously, persistent drug pressure can permit the more resistant, but otherwise competitively-in...

  14. Suppression of Hyperactive Immune Responses Protects against Nitrogen Mustard Injury

    OpenAIRE

    Au, Liemin; Meisch, Jeffrey P.; Das, Lopa M; Binko, Amy M; Boxer, Rebecca S.; Wen, Amy M.; Steinmetz, Nicole F.; Lu, Kurt Q.

    2015-01-01

    DNA alkylating agents like nitrogen mustard (NM) are easily absorbed through the skin and exposure to such agents manifest not only in direct cellular death but also in triggering inflammation. We show that toxicity resulting from topical mustard exposure is mediated in part by initiating exaggerated host innate immune responses. Using an experimental model of skin exposure to NM we observe activation of inflammatory dermal macrophages that exacerbate local tissue damage in an inducible nitri...

  15. Mutants of rabies viruses in skunks: immune response and pathogenicity.

    OpenAIRE

    Tolson, N D; Charlton, K M; Stewart, R B; Casey, G A; Webster, W A; Mackenzie, K.; Campbell, J. B.; Lawson, K. F.

    1990-01-01

    In studies to develop an oral rabies vaccine for wildlife, the immune response to and pathogenicity of two types of mutants of rabies viruses were examined. Forty-five small plaque mutants were selected from cultures of ERA rabies virus treated with 8-azaguanine or 5-fluorouracil and tested for pathogenicity in mice. Two of these mutants AZA 1 and AZA 2 (low pathogenicity in mice) were given to skunks by oral (bait), intestinal (endoscope) and intramuscular routes. Additionally, challenge vir...

  16. Assessing humoral and cell-mediated immune response in Hawaiian green turtles, Chelonia mydas

    Science.gov (United States)

    Work, T.M.; Balazs, G.H.; Rameyer, R.A.; Chang, S.P.; Berestecky, J.

    2000-01-01

    Seven immature green turtles, Chelonia mydas, captured from Kaneohe Bay on the island of Oahu were used to evaluate methods for assessing their immune response. Two turtles each were immunized intramuscularly with egg white lysozyme (EWL) in Freunda??s complete adjuvant, Gerbu, or ISA-70; a seventh turtle was immunized with saline only and served as a control. Humoral immune response was measured with an indirect enzyme linked immunosorbent assay (ELISA). Cell-mediated immune response was measured using in vitro cell proliferation assays (CPA) using whole blood or peripheral blood mononuclear cells (PBM) cultured with concanavalin A (ConA), phytohaemagglutinin (PHA), or soluble egg EWL antigen. All turtles, except for one immunized with Gerbu and the control, produced a detectable humoral immune response by 6 weeks which persisted for at least 14 weeks after a single immunization. All turtles produced an anamnestic humoral immune response after secondary immunization. Antigen specific cell-mediated immune response in PBM was seen in all turtles either after primary or secondary immunization, but it was not as consistent as humoral immune response; antigen specific cell-mediated immune response in whole blood was rarely seen. Mononuclear cells had significantly higher stimulation indices than whole blood regardless of adjuvant, however, results with whole blood had lower variability. Both Gerbu and ISA-70 appeared to potentiate the cell-mediated immune response when PBM or whole blood were cultured with PHA. This is the first time cell proliferation assays have been compared between whole blood and PBM for reptiles. This is also the first demonstration of antigen specific cell-mediated response in reptiles. Cell proliferation assays allowed us to evaluate the cell-mediated immune response of green turtles. However, CPA may be less reliable than ELISA for detecting antigen specific immune response. Either of the three adjuvants appears suitable to safely elicit a

  17. Protective and pathologic immune responses in human tegumentary leishmaniasis.

    Science.gov (United States)

    Carvalho, Lucas P; Passos, Sara; Schriefer, Albert; Carvalho, Edgar M

    2012-01-01

    Studies in the recent years have advanced the knowledge of how host and parasite factors contribute to the pathogenesis of human tegumentary leishmaniasis. Polymorphism within populations of Leishmania from the same species has been documented; indicating that infection with different strains may lead to distinct clinical pictures and can also interfere in the response to treatment. Moreover, detection of parasite genetic tags for the precise identification of strains will improve diagnostics and therapy against leishmaniasis. On the host side, while a predominant Th1 type immune response is important to control parasite growth, it does not eradicate Leishmania and, in some cases, does not prevent parasite dissemination. Evidence has accumulated showing the participation of CD4(+) and CD8(+) T cells, as well as macrophages, in the pathology associated with L. braziliensis, L. guayanensis, and L. major infection. The discovery that a large percentage of individuals that are infected with Leishmania do not develop disease will help to understand how the host controls Leishmania infection. As these individuals have a weaker type 1 immune response than patients with cutaneous leishmaniasis, it is possible that control of parasite replication in these individuals is dependent, predominantly, on innate immunity, and studies addressing the ability of neutrophils, macrophages, and NK cells to kill Leishmania should be emphasized. PMID:23060880

  18. Evolutionary immune response to conserved domains in parasites and aeroallergens.

    Science.gov (United States)

    Bielory, Brett Phillip; Mainardi, Timothy; Rottem, Menachem

    2013-01-01

    The immune response based on immunoglobulin E (IgE) evolved as a defense against specific parasitic infections. In the absence of active helminthic infections, the immune system has redirected its IgE epitopes toward innocuous environmental antigens. Helminths and aeroallergens have a similar stereotypical IgE response to unique antigens that can not be explained by chance alone. This study was designed to evaluate potential homology between conserved protein domains embedded in parasitic organisms and aeroallergens. Search and retrieval systems for nucleotide and protein sequences (Entrez, BLAST, and National Center for Biotechnology Information) were searched to identify conserved domains between allergens and certain parasites. A total score was developed that correlated positively with homology between compared sequences. Over 2000 domains were examined. We found matches with a high total score (>100) that signified a strong positive correlation between sequences in allergens (n = 30) and parasites (n = 13). Multiple shared conserved domains were identified between parasites and allergens. Parasite-allergen combinations with the most significant homology (greatest total score) were Plasmodium falciparum enolase and Hev b9 (total score, 612), Schistosoma mansoni albumin and Fel d 2 (total score, 991), Ascaris lumbricoides tropomyosin and Ani s3 (total score, 531), and Wuchereria bancrofti trypsin and Blo t3 (138). Homologous conserved domains exist in specific parasites and allergens, consistent with the theory that the human IgE-eosinophil immune response to common allergens is a direct consequence of stimulation by parasitic organisms. PMID:23406942

  19. Modulation of the Post-Ischemic Immune Response to Improve Stroke Outcome

    OpenAIRE

    Becker, Kyra J.

    2010-01-01

    Recent advances in understanding how the post-stroke immune response may contribute to ischemic brain injury are discussed. In particular, the potential of modulating the post-ischemic immune response to improve stroke outcome is explored.

  20. Immune Response to Hepatitis B Vaccine among Dental Students

    Directory of Open Access Journals (Sweden)

    HR Abdolsamadi

    2009-06-01

    Full Text Available "nBackground: Hepatitis B infection is a major public health problem worldwide. Dental students who are frequently in contact with body fluids like blood and saliva are still at high risk for HBV exposure. The aim of this study was to evaluate the effectiveness of HBV vaccine and personal factors associated with serologic evidence of the immune response."nMethods: A descriptive-cross sectional study was carried out using data from Hamadan dental school students that received just three doses of HBV vaccine. The serum sample of 86 dental clinical students were examined in order to determine hepatitis B surface antigen and the level of anti-HBs using IEMA method. Logistic regression models were used to assess the relationship of vaccine response to the variables Sex, age weight, smoking status and the time lasting from the third dose of vaccine injection."nResults: Ninety-three percent had positive anti-HBs response and 7% were non-responders. No one showed HBsAg. Vaccine response was most strongly associated with age, smoking status, sex and weight. The time lasting from the third dose was unrelated to vaccine response."nConclusion: Clinical dental students had desirable immune response to the HBV vaccine nevertheless recommended num­ber of doses, standard protocol and early vaccination are critical to adequate protection against hepatitis infection among all health care workers, in particular dental students and dentists who are often exposed to blood and other body fluids.

  1. New concepts in immunity to Neisseria gonorrhoeae: innate responses and suppression of adaptive immunity favor the pathogen, not the host

    Directory of Open Access Journals (Sweden)

    Yingru eLiu

    2011-03-01

    Full Text Available It is well known that gonorrhea can be acquired repeatedly with no apparent development of protective immunity arising from previous episodes of infection. Symptomatic infection is characterized by a purulent exudate, but the host response mechanisms are poorly understood. While the remarkable antigenic variability displayed by Neisseria gonorrhoeae and its capacity to inhibit complement activation allow it to evade destruction by the host’s immune defenses, we propose that it also has the capacity to avoid inducing specific immune responses. In a mouse model of vaginal gonococcal infection, N. gonorrhoeae elicits Th17-driven inflammatory- immune responses, which recruit innate defense mechanisms including an influx of neutrophils. Concomitantly, N. gonorrhoeae suppresses Th1- and Th2-dependent adaptive immunity, including specific antibody responses, through a mechanism involving TGF-β and regulatory T cells. Blockade of TGF-β alleviates the suppression of specific anti-gonococcal responses and allows Th1 and Th2 responses to emerge with the generation of immune memory and protective immunity. Genital tract tissues are naturally rich in TGF-β, which fosters an immunosuppressive environment that is important in reproduction. In exploiting this niche, N. gonorrhoeae exemplifies a well-adapted pathogen that proactively elicits from its host innate responses that it can survive and concomitantly suppresses adaptive immunity. Comprehension of these mechanisms of gonococcal pathogenesis should allow the development of novel approaches to therapy and facilitate the development of an effective vaccine.

  2. New concepts in immunity to Neisseria gonorrhoeae: innate responses and suppression of adaptive immunity favor the pathogen, not the host.

    Science.gov (United States)

    Liu, Yingru; Feinen, Brandon; Russell, Michael W

    2011-01-01

    It is well-known that gonorrhea can be acquired repeatedly with no apparent development of protective immunity arising from previous episodes of infection. Symptomatic infection is characterized by a purulent exudate, but the host response mechanisms are poorly understood. While the remarkable antigenic variability displayed by Neisseria gonorrhoeae and its capacity to inhibit complement activation allow it to evade destruction by the host's immune defenses, we propose that it also has the capacity to avoid inducing specific immune responses. In a mouse model of vaginal gonococcal infection, N. gonorrhoeae elicits Th17-driven inflammatory-immune responses, which recruit innate defense mechanisms including an influx of neutrophils. Concomitantly, N. gonorrhoeae suppresses Th1- and Th2-dependent adaptive immunity, including specific antibody responses, through a mechanism involving TGF-β and regulatory T cells. Blockade of TGF-β alleviates the suppression of specific anti-gonococcal responses and allows Th1 and Th2 responses to emerge with the generation of immune memory and protective immunity. Genital tract tissues are naturally rich in TGF-β, which fosters an immunosuppressive environment that is important in reproduction. In exploiting this niche, N. gonorrhoeae exemplifies a well-adapted pathogen that proactively elicits from its host innate responses that it can survive and concomitantly suppresses adaptive immunity. Comprehension of these mechanisms of gonococcal pathogenesis should allow the development of novel approaches to therapy and facilitate the development of an effective vaccine. PMID:21833308

  3. A novel naturally occurring tandem promoter in modified vaccinia virus ankara drives very early gene expression and potent immune responses.

    Science.gov (United States)

    Wennier, Sonia T; Brinkmann, Kay; Steinhäußer, Charlotte; Mayländer, Nicole; Mnich, Claudia; Wielert, Ursula; Dirmeier, Ulrike; Hausmann, Jürgen; Chaplin, Paul; Steigerwald, Robin

    2013-01-01

    Modified vaccinia virus Ankara (MVA) has been shown to be suitable for the generation of experimental vaccines against cancer and infectious diseases, eliciting strong humoral and cellular immune responses. In viral vectored vaccines, strong recombinant antigen expression and timing of expression influence the quantity and quality of the immune response. Screening of synthetic and native poxvirus promoters for strong protein expression in vitro and potent immune responses in vivo led to the identification of the MVA13.5L promoter, a unique and novel naturally occurring tandem promoter in MVA composed of two 44 nucleotide long repeated motifs, each containing an early promoter element. The MVA13.5L gene is highly conserved across orthopoxviruses, yet its function is unknown. The unique structure of its promoter is not found for any other gene in the MVA genome and is also conserved in other orthopoxviruses. Comparison of the MVA13.5L promoter activity with synthetic poxviral promoters revealed that the MVA13.5L promoter produced higher levels of protein early during infection in HeLa cells and particularly in MDBK cells, a cell line in which MVA replication stops at an early stage before the expression of late genes. Finally, a recombinant antigen expressed under the control of this novel promoter induced high antibody titers and increased CD8 T cell responses in homologous prime-boost immunization compared to commonly used promoters. In particular, the recombinant antigen specific CD8 T cell responses dominated over the immunodominant B8R vector-specific responses after three vaccinations and even more during the memory phase. These results have identified the native MVA13.5L promoter as a new potent promoter for use in MVA vectored preventive and therapeutic vaccines. PMID:23951355

  4. Control of the immune response by proangiogenic factors

    Directory of Open Access Journals (Sweden)

    MagaliTERME

    2014-04-01

    Full Text Available The progressive conversion of normal cells into cancer cells is characterized by the acquisition of eight hallmarks. Among these criteria, the capability of the cancer cell to avoid the immune destruction is found. Thus, tumors develop mechanisms to become invisible to the immune system, such as the induction of immunosuppressive cells which are able to inhibit the development of an efficient immune response. Molecules produced in the tumor microenvironment are involved in the occurrence of an immunosuppressive microenvironment. Recently, it has been shown that Vascular Endothelial Growth Factor -A (VEGF-A exhibits immunosuppressive properties in addition to its proangiogenic activities. VEGF-A can induce the accumulation of immature dendritic cells, myeloid derived suppressor cells, regulatory T cells and inhibit the migration of T lymphocytes to the tumor. Other proangiogenic factors such as Placental Growth Factor (PlGF could also participate in tumor-induced immunosuppression, but only few works have been performed on this point. Here, we review the impact of proangiogenic factors (especially VEGF-A on immune cells. Anti-angiogenic molecules, which target VEGF-A/VEGFR axis, have been developed in the last decades and are commonly used to treat cancer patients. These drugs have anti-angiogenic properties but can also counteract the tumor-induced immunosuppression. Based on these immunomodulatory properties, anti-angiogenic molecules could be efficiently associated with immunotherapeutic strategies in preclinical models. These combinations are currently under investigation in cancer patients.

  5. Effect of host nutrition on immunity and local immune response of rabbits to Obeliscoides cuniculi

    International Nuclear Information System (INIS)

    In a series of experiments carried out on young and adult rabbits the effect of isocaloric low protein diets containing 4% or 8% protein compared with a diet containing 21% protein on Obeliscoides cuniculi infection was studied. The pathogenesis, resistance and local immunity were assessed after single infections with 10,000 larvae or reinfection with 5000 larvae. Live weight gain was reduced in young and adult rabbits fed the low protein diets, but the establishment of parasites was not substantially influenced by protein deprivation. However, development of worms in the histotrophic phase and parasite fecundity were impaired in association with the low protein diet. Moreover, mild anaemia as well as changes in the mucosal immune response as a result of infection were related to the level of dietary protein. (author). 30 refs, 6 figs, 5 tabs

  6. Alterations in immune responses in prenatally irradiated dogs

    International Nuclear Information System (INIS)

    Immunologic responses were studied in beagle dogs following prenatal (35 days gestation) irradiation to evaluate the effects of ionizing radiation on the developing immune system. Each dog received 1.5 Gy 60Co gamma irradiation or sham irradiation. Prenatally irradiated dogs exhibited a significant reduction in primary humoral antibody responses to inoculated sheep red blood cells, a T-dependent antigen, and a concurrent decrease in T-helper lymphocyte subpopulations in the peripheral blood at 3 to 4 months of age. Similarly, irradiated fetuses have been shown to have defects in epitheliostromal development of the thymus. It is suggested that the postnatal immunologic deficits may relate to the prenatal thymic injury

  7. Impact on allergic immune response after treatment with vitamin A

    DEFF Research Database (Denmark)

    Matheu, Victor; Berggård, Karin; Barrios, Yvelise;

    2009-01-01

    ABSTRACT: BACKGROUND: Vitamin A may have some influence on the immune system, but the role in allergy modulation is still unclear. OBJECTIVE: To clarify whether high levels of retinoic acid (RA) affects allergic response in vivo, we used a murine experimental model of airway allergic disease...... in the group treated with 2,500 ug compared to the other 2 groups (50 and 500 ug). Finally, total lung resistance was decreased in group treated with 2,500 ug compared to non-treated mice. CONCLUSION: Our results suggest that retinoic acid directly enhances allergic response in vivo, but in higher...

  8. Immunity to rhabdoviruses in rainbow trout: the antibody response

    DEFF Research Database (Denmark)

    Lorenzen, Niels; Lapatra, S.E.

    1999-01-01

    occasional detrimental effect on rainbow trout farming. Research efforts have been focused on understanding the mechanisms involved in protective immunity. Several specific and nonspecific cellular and humoral parameters are believed to be involved, but only the antibody response has been characterised in......, have demonstrated that rainbow trout can produce specific and highly functional antibodies that are able to neutralise virus pathogenicity in vitro as well as in vivo. The apparently more restricted antibody response to IHNV and VHSV antigens in fish compared to mammals could possibly be explained by...

  9. SEX DIFFERENCES AND ESTROGEN MODULATION OF THE CELLULAR IMMUNE RESPONSE AFTER INJURY

    OpenAIRE

    Bird, Melanie D.; Karavitis, John; Kovacs, Elizabeth J

    2008-01-01

    Cell-mediated immunity is extremely important for resolution of infection and for proper healing from injury. However, the cellular immune response is dysregulated following injuries such as burn and hemorrhage. Sex hormones are known to regulate immunity, and a well-documented dichotomy exists in the immune response to injury between the sexes. This disparity is caused by differences in immune cell activation, infiltration, and cytokine production during and after injury. Estrogen and testos...

  10. Transition between immune and disease states in a cellular automaton model of clonal immune response

    CERN Document Server

    Bezzi, M; Ruffo, S; Seiden, P E; Bezzi, Michele; Celada, Franco; Ruffo, Stefano; Seiden, Philip E.

    1997-01-01

    In this paper we extend the Celada-Seiden (CS) model of the humoral immune response to include infectious virus and cytotoxic T lymphocytes (cellular response). The response of the system to virus involves a competition between the ability of the virus to kill the host cells and the host's ability to eliminate the virus. We find two basins of attraction in the dynamics of this system, one is identified with disease and the other with the immune state. There is also an oscillating state that exists on the border of these two stable states. Fluctuations in the population of virus or antibody can end the oscillation and drive the system into one of the stable states. The introduction of mechanisms of cross-regulation between the two responses can bias the system towards one of them. We also study a mean field model, based on coupled maps, to investigate virus-like infections. This simple model reproduces the attractors for average populations observed in the cellular automaton. All the dynamical behavior connect...

  11. DMPD: Innate immune responses: crosstalk of signaling and regulation of genetranscription. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 16753195 Innate immune responses: crosstalk of signaling and regulation of genetran...l) (.csml) Show Innate immune responses: crosstalk of signaling and regulation of genetranscription. PubmedI...D 16753195 Title Innate immune responses: crosstalk of signaling and regulation o

  12. DMPD: Innate immune response to viral infection. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18694646 Innate immune response to viral infection. Koyama S, Ishii KJ, Coban C, Ak...ira S. Cytokine. 2008 Sep;43(3):336-41. Epub 2008 Aug 9. (.png) (.svg) (.html) (.csml) Show Innate immune response... to viral infection. PubmedID 18694646 Title Innate immune response to viral infection. Authors Koyama

  13. DMPD: Cytosolic DNA recognition for triggering innate immune responses. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18280611 Cytosolic DNA recognition for triggering innate immune responses. Takaoka ...) Show Cytosolic DNA recognition for triggering innate immune responses. PubmedID 18280611 Title Cytosolic D...NA recognition for triggering innate immune responses. Authors Takaoka A, Taniguc

  14. Multi-scale modeling of the CD8 immune response

    Science.gov (United States)

    Barbarroux, Loic; Michel, Philippe; Adimy, Mostafa; Crauste, Fabien

    2016-06-01

    During the primary CD8 T-Cell immune response to an intracellular pathogen, CD8 T-Cells undergo exponential proliferation and continuous differentiation, acquiring cytotoxic capabilities to address the infection and memorize the corresponding antigen. After cleaning the organism, the only CD8 T-Cells left are antigen-specific memory cells whose role is to respond stronger and faster in case they are presented this very same antigen again. That is how vaccines work: a small quantity of a weakened pathogen is introduced in the organism to trigger the primary response, generating corresponding memory cells in the process, giving the organism a way to defend himself in case it encounters the same pathogen again. To investigate this process, we propose a non linear, multi-scale mathematical model of the CD8 T-Cells immune response due to vaccination using a maturity structured partial differential equation. At the intracellular scale, the level of expression of key proteins is modeled by a delay differential equation system, which gives the speeds of maturation for each cell. The population of cells is modeled by a maturity structured equation whose speeds are given by the intracellular model. We focus here on building the model, as well as its asymptotic study. Finally, we display numerical simulations showing the model can reproduce the biological dynamics of the cell population for both the primary response and the secondary responses.

  15. Host recognition of Clostridium difficile and the innate immune response.

    Science.gov (United States)

    Cowardin, Carrie A; Petri, William A

    2014-12-01

    Clostridium difficile is a Gram-positive, spore forming bacillus and the most common cause of antibiotic-associated diarrhea in the United States. Clinical outcomes of C. difficile infection (CDI) range from asymptomatic colonization to pseudomembranous colitis, sepsis and death. Disease is primarily mediated by the action of the Rho-glucosylating toxins A and B, which induce potent pro-inflammatory signaling within the host. The role of this inflammatory response during infection is just beginning to be appreciated, with recent data suggesting inflammatory markers correlate closely with disease severity. In addition to the toxins, multiple innate immune signaling pathways have been implicated in establishing an inflammatory response during infection. In intoxication-based models of disease, inflammation typically enhances pathogenesis, while protection from infection seems to require some level of inflammatory response. Thus, the host immune response plays a key role in shaping the course of infection and a balanced inflammatory response which eradicates infection without damaging host tissues is likely required for successful resolution of disease. PMID:25223264

  16. Effects of anti-schistosomal chemotherapy on immune responses, protection and immunity. II. Concomitant immunity and immunization with irradiated cercariae

    Energy Technology Data Exchange (ETDEWEB)

    Tawfik, A.F.; Colley, D.G.

    1986-01-01

    Resistance of mice to challenge infections of Schistosoma mansoni was evaluated before and after elimination of their primary, established S. mansoni infections with the chemotherapeutic drug praziquantel. Mice treated after either 10 or 20 weeks of primary infection were challenged 6 or 10 weeks after treatment. Mice infected for for 10 weeks prior to treatment expressed progressively less resistance 6 and 10 weeks after treatment. By 10 weeks after treatment significant levels of protection were no longer observed. Resistance waned more slowly if mice were treated 20 weeks after infection, and there was still significant expression of resistance to challenge 10 weeks after treatment. A separate set of experiments evaluated the use of highly irradiated cercariae as a vaccine in mice that had been previously infected with S. mansoni and cured with praziquantel. It was observed that effective immunizations were possible in previously infected mice. These studies demonstrate that established resistance waned after treatment and the rate of loss of protection was dependent upon the duration of infection prior to treatment. Furthermore, the irradiated cercarial vaccine studies indicate that in the murine model induction of immunological resistance was feasible following chemotherapeutic treatment of infected populations.

  17. Effects of anti-schistosomal chemotherapy on immune responses, protection and immunity. II. Concomitant immunity and immunization with irradiated cercariae

    International Nuclear Information System (INIS)

    Resistance of mice to challenge infections of Schistosoma mansoni was evaluated before and after elimination of their primary, established S. mansoni infections with the chemotherapeutic drug praziquantel. Mice treated after either 10 or 20 weeks of primary infection were challenged 6 or 10 weeks after treatment. Mice infected for for 10 weeks prior to treatment expressed progressively less resistance 6 and 10 weeks after treatment. By 10 weeks after treatment significant levels of protection were no longer observed. Resistance waned more slowly if mice were treated 20 weeks after infection, and there was still significant expression of resistance to challenge 10 weeks after treatment. A separate set of experiments evaluated the use of highly irradiated cercariae as a vaccine in mice that had been previously infected with S. mansoni and cured with praziquantel. It was observed that effective immunizations were possible in previously infected mice. These studies demonstrate that established resistance waned after treatment and the rate of loss of protection was dependent upon the duration of infection prior to treatment. Furthermore, the irradiated cercarial vaccine studies indicate that in the murine model induction of immunological resistance was feasible following chemotherapeutic treatment of infected populations

  18. Dynamics of immune response and drug resistance in malaria infection

    Directory of Open Access Journals (Sweden)

    Gurarie David

    2006-10-01

    Full Text Available Abstract Background Malaria parasites that concurrently infect a host compete on the basis of their intrinsic growth rates and by stimulating cross-reactive immune responses that inhibit each others' growth. If the phenotypes also show different drug sensitivities ('sensitive' vs. 'resistant' strains, drug treatment can change their joint dynamics and the long-term outcome of the infection: most obviously, persistent drug pressure can permit the more resistant, but otherwise competitively-inferior, strains to dominate. Methods Here a mathematical model is developed to analyse how these and more subtle effects of antimalarial drug use are modulated by immune response, repeated re-inoculation of parasites, drug pharmacokinetic parameters, dose and treatment frequency. Results The model quantifies possible effects of single and multiple (periodic treatment on the outcome of parasite competition. In the absence of further inoculation, the dosage and/or treatment frequency required for complete clearance can be estimated. With persistent superinfection, time-average parasite densities can be derived in terms of the basic immune-regulating parameters, the drug efficacy and treatment regimen. Conclusion The functional relations in the model are applicable to a wide range of conditions and transmission environments, allowing predictions to be made on both the individual and the community levels, and, in particular, transitions from drug-sensitive to drug-resistant parasite dominance to be projected on both levels.

  19. Danger Signals Activating the Immune Response after Trauma

    Directory of Open Access Journals (Sweden)

    Stefanie Hirsiger

    2012-01-01

    Full Text Available Sterile injury can cause a systemic inflammatory response syndrome (SIRS that resembles the host response during sepsis. The inflammatory response following trauma comprises various systems of the human body which are cross-linked with each other within a highly complex network of inflammation. Endogenous danger signals (danger-associated molecular patterns; DAMPs; alarmins as well as exogenous pathogen-associated molecular patterns (PAMPs play a crucial role in the initiation of the immune response. With popularization of the “danger theory,” numerous DAMPs and PAMPs and their corresponding pathogen-recognition receptors have been identified. In this paper, we highlight the role of the DAMPs high-mobility group box protein 1 (HMGB1, interleukin-1α (IL-1α, and interleukin-33 (IL-33 as unique dual-function mediators as well as mitochondrial danger signals released upon cellular trauma and necrosis.

  20. The reconstitution of the thymus in immunosuppressed individuals restores CD4-specific cellular and humoral immune responses.

    Science.gov (United States)

    Plana, Montserrat; Garcia, Felipe; Darwich, Laila; Romeu, Joan; López, Anna; Cabrera, Cecilia; Massanella, Marta; Canto, Esther; Ruiz-Hernandez, Raul; Blanco, Julià; Sánchez, Marcelo; Gatell, Josep M; Clotet, Bonaventura; Ruiz, Lidia; Bofill, Margarita

    2011-07-01

    Infection with HIV-1 frequently results in the loss of specific cellular immune responses and an associated lack of antibodies. Recombinant growth hormone (rGH) administration reconstitutes thymic tissue and boosts the levels of peripheral T cells, so rGH therapy may be an effective adjuvant through promoting the recovery of lost cellular and T-cell-dependent humoral immune responses in immunosuppressed individuals. To test this concept, we administered rGH to a clinically defined group of HIV-1-infected subjects with defective cellular and serological immune responses to at least one of three commonly employed vaccines (hepatitis A, hepatitis B or tetanus toxoid). Of the original 278 HIV-1-infected patients entering the trial, only 20 conformed to these immunological criteria and were randomized into three groups: Group A (n = 8) receiving rGH and challenged with the same vaccine to which they were unresponsive and Groups B (n = 5) and C (n = 7) who received either rGH or vaccination alone, respectively. Of the eight subjects in Group A, five recovered CD4 cellular responses to vaccine antigen and four of these produced the corresponding antibodies. In the controls, three of the five in group B recovered cellular responses with two producing antibodies, whereas three of the seven in Group C recovered CD4 responses, with only two producing antibodies. Significantly, whereas seven of ten patients receiving rGH treatment in Group A (six patients) and B (one patient) recovered T-cell responses to HIVp24, only two of six in Group C responded similarly. In conclusion, reconstitution of the thymus in immunosuppressed adults through rGH hormone treatment restored both specific antibody and CD4 T-cell responses. PMID:21501161

  1. Lymphocytes and the Adventitial Immune Response in Atherosclerosis

    Science.gov (United States)

    Campbell, Kirsti A.; Lipinski, Michael J.; Doran, Amanda C.; Skaflen, Marcus D.; Fuster, Valentin; McNamara, Coleen A.

    2012-01-01

    Though much of the research on atherosclerosis has focused on the intimal accumulation of lipids and inflammatory cells, there is an increasing amount of interest in the role of the adventitia in coordinating the immune response in atherosclerosis. In this review of the contributions of the adventitia and adventitial lymphocytes to the development of atherosclerosis, we discuss recent research on the formation and structural nature of adventitial immune aggregates, potential mechanisms of crosstalk between the intima, media, and adventitia, specific contributions of B lymphocytes and T lymphocytes, and the role of the vasa vasorum and surrounding perivascular adipose tissue (PVAT). Furthermore, we highlight techniques for the imaging of lymphocytes in the vasculature. PMID:22427326

  2. Immunity

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008254 Prokaryotic expression and immunogenicity of Fba,a novel fibronectin-binding protein of group A streptococcus.MA Cuiqing(马翠柳),et al.Dept Immunol,Basic Med Coll,Hebei Med Univ,Shijiazhuang 050017.Chin J Infect Dis 2008;26(3):146-150.Objective To express the novel fibronectin-binding protein Fba ofgroupAstreptococcus(GAS)and analyze its immunogenicity,so to evaluate the immune responses to GAS infection.Methods fbagene was amplified by

  3. ANTI-ERGOTYPIC RESPONSE: ROLE IN NORMAL IMMUNE RESPONSE AND AUTOIMMUNE PATHOLOGY IN EXPERIMENTAL MODEL

    Directory of Open Access Journals (Sweden)

    N. A. Ilyina

    2014-07-01

    Full Text Available Abstract. Anti-ergotypic cells are a part of peripheral regulatory network, and they are thought to control autoreactive T cells by recognition of certain clonotypic and ergotypic determinants on the surface of activated T cells. The aim of our study was to investigate ability of anti-CD3 activated syngeneic splenocytes to induce anti-ergotypic  response  and  to  assess  immune  response  in  delayed-type hypersensitivity (DTH reaction.DTH response in experimental group was significantly greater than in control and intact groups. Upon crossadministration, DTH response was minimal and there were no significant differences between the groups. No changes in cellular and humoral immune response were observed under such conditions. These results suggest a development of immune response to activated antigen-nonspecific cells. In a model of chronic GvHD, donor immunization was shown to exert a protective effect, with regard of proteinuria dynamics in recipients, whereas immunization of recipients did not alter the GvHD dynamics. (Med. Immunol., 2011, vol. 13, N 1, pp 29-34

  4. Innate Cellular Immune Responses in Aedes caspius (Diptera: Culicidae) Mosquitoes.

    Science.gov (United States)

    Soliman, D E; Farid, H A; Hammad, R E; Gad, A M; Bartholomay, L C

    2016-03-01

    Mosquitoes transmit a variety of pathogens that have devastating consequences for global public and veterinary health. Despite their capacity to serve as vectors, these insects have a robust capacity to respond to invading organisms with strong cellular and humoral immune responses. In Egypt, Aedes caspius (Pallas, 1771) has been suspected to act as a bridge vector of Rift Valley Fever virus between animals and humans. Microscopic analysis of Ae. caspius hemolymph revealed the presence of phagocytic cells called granulocytes. We further evaluated cellular immune responses produced by Ae. caspius as a result of exposure to a Gram-negative, and Gram-positive bacterium, and to latex beads. After challenge, a rapid and strong phagocytic response against either a natural or synthetic invader was evident. Hemocyte integrity in bacteria-inoculated mosquitoes was not morphologically affected. The number of circulating granulocytes decreased with age, reducing the overall phagocytic capacity of mosquitoes over time. The magnitude and speed of the phagocytic response suggested that granulocytes act as an important force in the battle against foreign invaders, as has been characterized in other important mosquito vector species. PMID:26792848

  5. PEB1-LTB DNA vaccine primer-protein boost enhances the immunization against Campylobacter ;jejuni in mice%抗空肠弯曲菌 PEB1-LTB 疫苗联合应用增强免疫应答的研究

    Institute of Scientific and Technical Information of China (English)

    刘琳琳

    2014-01-01

    Objective To develop novel and effective Campylobacter jejuni vaccine, we constructed Campylobacter jejuni gene PEB1 fused LTB. In present study, we determined if the pcDNA3.1(-)-PEB1-LTB DNA vaccines boosting with PEB1-LTB protein vaccines could enhance immunization in mice. Methods We immunized mice by intramuscular injection. The mice were inoculated with DNA vaccines and DNA boosting with protein at 0, 3, 6 week. The specific humoral and cellular immune responses were detected at 5,8 week. Results In the DNA vaccine prime-boost group after 3 times, the levels of IgG in serum, (14.392±0.579)μg/ml were higher than the others. The DNA vaccine boosting protein vaccine could enhance the humoral response. But the levels of IFN-γ, (1472.34±73.99)pg/ml in PEB1-LTB DNA vaccine were the highest. Conclusions DNA vaccines can induce different immunization, specially the better cellular immune responses, compared with DNA vaccines boosting with protein vaccines. The results provide a basis for ration design and application of the Campylobacter jejuni vaccine.%目的:为研制有效的空肠弯曲菌疫苗,构建 PEB1与 LTB 融合基因的空肠弯曲菌疫苗,并初步探讨pcDNA3.1(-)-PEB1-LTB核酸疫苗与蛋白疫苗联合免疫BALB/c小鼠的免疫应答水平。方法通过腿部肌肉注射免疫小鼠的方式,在第0、3、6周采用核酸单独免疫与核酸蛋白联合免疫小鼠的免疫程序,于第5、8周末,测量小鼠体液免疫应答和细胞免疫应答水平。结果3次免疫后,核酸蛋白免疫组诱导的IgG抗体含量[(14.392±0.579)μg/ml]是核酸疫苗单独免疫的2.43倍(P<0.05),说明核酸蛋白联合免疫诱导了更高的体液免疫应答水平;3次免疫后,核酸疫苗单独免疫组诱导的IFN-γ水平[(1472.34±73.99)pg/ml]是联合免疫组[(290.323±15.46)pg/ml]的5.07倍,说明PEB1-LTB核酸疫苗单独免疫诱导较高的细胞免疫应答。结论核酸疫苗能诱导较

  6. [Local Immune response in rabbits following enteral immunization with live attenuated bacterial Enterobacteriaceae vaccines].

    Science.gov (United States)

    Dentschev, W; Marinova, S; Sumerska, T; Nenkov, P; Koitschev, T; Trifonowa, A

    1980-01-01

    Streptomycin-dependent and inactivated Shigella flexneri 2a and Shigella sonnei strains were intra-intestinally applied to rabbits for immunisation. Rosette and plaque tests and well as indirect haemagglutination gave short-time secretion of low titres of specific copro-antibody, following monovaccines and bivaccines. High titres of secretory antibody were induced, depending on doses, by re-immunisation. No antigen competition was established. The localised immune response caused by Shigella live vaccines was found to be much stronger than that induced by inactivated vaccines PMID:6998404

  7. Immune Response to Sipuleucel-T in Prostate Cancer

    Directory of Open Access Journals (Sweden)

    David I. Quinn

    2012-04-01

    Full Text Available Historically, chemotherapy has remained the most commonly utilized therapy in patients with metastatic cancers. In prostate cancer, chemotherapy has been reserved for patients whose metastatic disease becomes resistant to first line castration or androgen deprivation. While chemotherapy palliates, decreases serum prostate specific antigen and improves survival, it is associated with significant side effects and is only suitable for approximately 60% of patients with castrate-resistant prostate cancer. On that basis, exploration of other therapeutic options such as active secondary hormone therapy, bone targeted treatments and immunotherapy are important. Until recently, immunotherapy has had no role in the treatment of solid malignancies aside from renal cancer and melanoma. The FDA-approved autologous cellular immunotherapy sipuleucel-T has demonstrated efficacy in improving overall survival in patients with metastatic castrate-resistant prostate cancer in randomized clinical trials. The proposed mechanism of action is reliant on activating the patients’ own antigen presenting cells (APCs to prostatic acid phosphatase (PAP fused with granulocyte-macrophage colony stimulating factor (GM-CSF and subsequent triggered T-cell response to PAP on the surface of prostate cancer cells in the patients body. Despite significant prolongation of survival in Phase III trials, the challenge to health care providers remains the dissociation between objective changes in serum PSA or on imaging studies after sipleucel-T and survival benefit. On that basis there is an unmet need for markers of outcome and a quest to identify immunologic or clinical surrogates to fill this role. This review focuses on the impact of sipuleucel-T on the immune system, the T and B cells, and their responses to relevant antigens and prostate cancer. Other therapeutic modalities such as chemotherapy, corticosteroids and GM-CSF and host factors can also affect immune response. The

  8. Pilot Study on the Use of DNA Priming Immunization to Enhance Y. pestis LcrV-Specific B Cell Responses Elicited by a Recombinant LcrV Protein Vaccine

    Directory of Open Access Journals (Sweden)

    Wei Li

    2013-12-01

    Full Text Available Recent studies indicate that DNA immunization is powerful in eliciting antigen-specific antibody responses in both animal and human studies. However, there is limited information on the mechanism of this effect. In particular, it is not known whether DNA immunization can also enhance the development of antigen-specific B cell development. In this report, a pilot study was conducted using plague LcrV immunogen as a model system to determine whether DNA immunization is able to enhance LcrV-specific B cell development in mice. Plague is an acute and often fatal infectious disease caused by Yersinia pestis (Y. pestis. Humoral immune responses provide critical protective immunity against plague. Previously, we demonstrated that a DNA vaccine expressing LcrV antigen can protect mice from lethal mucosal challenge. In the current study, we further evaluated whether the use of a DNA priming immunization is able to enhance the immunogenicity of a recombinant LcrV protein vaccine, and in particular, the development of LcrV-specific B cells. Our data indicate that DNA immunization was able to elicit high-level LcrV antibody responses when used alone or as part of a prime-boost immunization approach. Most significantly, DNA immunization was also able to increase the levels of LcrV-specific B cell development. The finding that DNA immunization can enhance antigen-specific B cell responses is highly significant and will help guide similar studies in other model antigen systems.

  9. Analysis of immune responses against H pylori in rabbits

    Institute of Scientific and Technical Information of China (English)

    Khademul Islam; Ibrahim Khalil; Chowdhury Rafiqul Ahsan; Mahmuda Yasmin; Jamalun Nessa

    2007-01-01

    AIM: To investigate the immunogenicity of H pylori proteins, to evaluate the production rate of anti H pylori IgG antibodies in relation to time and to demonstrate the fidelity of newly optimized in-house enzymelinked immunosorbent assay (ELISA) technique as an alternative for H pylori infection assay.METHODS: In the present study, 100 μg of formalinfixed H pylori whole cell antigens was injected into an experimental animal (New Zealand white female rabbit) intramuscularly on d 0, 16, 27 and 36. The first two doses were injected with adjuvants. On d 0,a serum sample was collected from the rabbit before immunization and this pre-immunized serum was used as a negative control for the whole study. To evaluate the immunogenic responses of the injected antigen,serum samples were collected from the rabbit at regular intervals up to d 42. The sera were analyzed using inhouse ELISA and Western blot techniques.RESULTS: The production of anti H pylori IgG antibodies in the rabbit in response to the injected antigen increased almost exponentially up to d 14 and after that it was maintained at the same level until the last day (d 42). By analyzing the immune profiles of immunized sera, 11 proteins were identified to be immunogenic,among them 2 (approximately 100 kDa and 85 kDa)were most prominent.CONCLUSION: Analysis of the immune responses against pathogenic microorganisms like H pylori is necessary for the development of various diagnostic and preventive approaches. The results of this experiment reveal that the formalin-fixed H pylori whole cell antigens injected into the rabbit are highly immunogenic. These prominent proteins (approximately 100 kDa and 85 kDa)might have higher immunogenic effects among humans infected with H pylori and some of these immunogenic proteins can be included in diagnostic approaches based on serology and also for vaccine formulation. The inhouse ELISA is a promising alternative compared to invasive techniques.

  10. Innate immune response to pulmonary contusion: Identification of cell-type specific inflammatory responses

    OpenAIRE

    Hoth, J. Jason; Wells, Jonathan D.; Yoza, Barbara K.; McCall, Charles E.

    2012-01-01

    Lung injury from pulmonary contusion is a common traumatic injury, predominantly seen after blunt chest trauma such as in vehicular accidents. The local and systemic inflammatory response to injury includes activation of innate immune receptors, elaboration of a variety inflammatory mediators, and recruitment of inflammatory cells to the injured lung. Using a mouse model of pulmonary contusion, we had previously shown that innate immune Toll like receptors 2 and 4 (TLR2 and TLR4) mediate the ...

  11. The immune response during the luteal phase of the ovarian cycle : a Th2-type response?

    NARCIS (Netherlands)

    Faas, Marijke; Bouman, Annechien; Moes, H; Heineman, Maas Jan; de Leij, Loe; Schuiling, Gerard

    2000-01-01

    Objective: To test the hypothesis that during the luteal phase of the ovarian cycle, as compared with the follicular phase, the peripheral immune response is shifted toward a type-2 response. Design: Prospective study. Setting: Academic research setting. Patient(s): Women with regular menstrual cycl

  12. Humoral and cell-mediated immune responses in DNA immunized mink challenged with wild-type canine distemper virus

    DEFF Research Database (Denmark)

    Nielsen, Line; Søgaard, Mette; Karlskov-Mortensen, Peter;

    2009-01-01

    The aim of the study was to investigate the different phases of the immune response after DNA immunization with the hemagglutinin and nucleoprotein genes from canine distemper virus (CDV). Although attenuated live CDV vaccines have effectively reduced the incidence of disease, canine distemper is...

  13. Yersinia type III effectors perturb host innate immune responses.

    Science.gov (United States)

    Pha, Khavong; Navarro, Lorena

    2016-02-26

    The innate immune system is the first line of defense against invading pathogens. Innate immune cells recognize molecular patterns from the pathogen and mount a response to resolve the infection. The production of proinflammatory cytokines and reactive oxygen species, phagocytosis, and induced programmed cell death are processes initiated by innate immune cells in order to combat invading pathogens. However, pathogens have evolved various virulence mechanisms to subvert these responses. One strategy utilized by Gram-negative bacterial pathogens is the deployment of a complex machine termed the type III secretion system (T3SS). The T3SS is composed of a syringe-like needle structure and the effector proteins that are injected directly into a target host cell to disrupt a cellular response. The three human pathogenic Yersinia spp. (Y. pestis, Y. enterocolitica, and Y. pseudotuberculosis) are Gram-negative bacteria that share in common a 70 kb virulence plasmid which encodes the T3SS. Translocation of the Yersinia effector proteins (YopE, YopH, YopT, YopM, YpkA/YopO, and YopP/J) into the target host cell results in disruption of the actin cytoskeleton to inhibit phagocytosis, downregulation of proinflammatory cytokine/chemokine production, and induction of cellular apoptosis of the target cell. Over the past 25 years, studies on the Yersinia effector proteins have unveiled tremendous knowledge of how the effectors enhance Yersinia virulence. Recently, the long awaited crystal structure of YpkA has been solved providing further insights into the activation of the YpkA kinase domain. Multisite autophosphorylation by YpkA to activate its kinase domain was also shown and postulated to serve as a mechanism to bypass regulation by host phosphatases. In addition, novel Yersinia effector protein targets, such as caspase-1, and signaling pathways including activation of the inflammasome were identified. In this review, we summarize the recent discoveries made on Yersinia

  14. Gelam Honey Scavenges Peroxynitrite During the Immune Response

    Directory of Open Access Journals (Sweden)

    Kamaruddin Mohd Yusoff

    2012-09-01

    Full Text Available Monocytes and macrophages are part of the first-line defense against bacterial, fungal, and viral infections during host immune responses; they express high levels of proinflammatory cytokines and cytotoxic molecules, including nitric oxide, reactive oxygen species, and their reaction product peroxynitrite. Peroxynitrite is a short-lived oxidant and a potent inducer of cell death. Honey, in addition to its well-known sweetening properties, is a natural antioxidant that has been used since ancient times in traditional medicine. We examined the ability of Gelam honey, derived from the Gelam tree (Melaleuca spp., to scavenge peroxynitrite during immune responses mounted in the murine macrophage cell line RAW 264.7 when stimulated with lipopolysaccharide/interferon-γ (LPS/IFN-γ and in LPS-treated rats. Gelam honey significantly improved the viability of LPS/IFN-γ-treated RAW 264.7 cells and inhibited nitric oxide production—similar to the effects observed with an inhibitor of inducible nitric oxide synthase (1400W. Furthermore, honey, but not 1400W, inhibited peroxynitrite production from the synthetic substrate 3-morpholinosydnonimine (SIN-1 and prevented the peroxynitrite-mediated conversion of dihydrorhodamine 123 to its fluorescent oxidation product rhodamine 123. Honey inhibited peroxynitrite synthesis in LPS-treated rats. Thus, honey may attenuate inflammatory responses that lead to cell damage and death, suggesting its therapeutic uses for several inflammatory disorders.

  15. The changing shape of vaccination: improving immune responses through geometrical variations of a microdevice for immunization.

    Science.gov (United States)

    Crichton, Michael Lawrence; Muller, David Alexander; Depelsenaire, Alexandra Christina Isobel; Pearson, Frances Elizabeth; Wei, Jonathan; Coffey, Jacob; Zhang, Jin; Fernando, Germain J P; Kendall, Mark Anthony Fernance

    2016-01-01

    Micro-device use for vaccination has grown in the past decade, with the promise of ease-of-use, painless application, stable solid formulations and greater immune response generation. However, the designs of the highly immunogenic devices (e.g. the gene gun, Nanopatch or laser adjuvantation) require significant energy to enter the skin (30-90 mJ). Within this study, we explore a way to more effectively use energy for skin penetration and vaccination. These modifications change the Nanopatch projections from cylindrical/conical shapes with a density of 20,000 per cm(2) to flat-shaped protrusions at 8,000 per cm(2), whilst maintaining the surface area and volume that is placed within the skin. We show that this design results in more efficient surface crack initiations, allowing the energy to be more efficiently be deployed through the projections into the skin, with a significant overall increase in penetration depth (50%). Furthermore, we measured a significant increase in localized skin cell death (>2 fold), and resultant infiltrate of cells (monocytes and neutrophils). Using a commercial seasonal trivalent human influenza vaccine (Fluvax 2014), our new patch design resulted in an immune response equivalent to intramuscular injection with approximately 1000 fold less dose, while also being a practical device conceptually suited to widespread vaccination. PMID:27251567

  16. The changing shape of vaccination: improving immune responses through geometrical variations of a microdevice for immunization

    Science.gov (United States)

    Crichton, Michael Lawrence; Muller, David Alexander; Depelsenaire, Alexandra Christina Isobel; Pearson, Frances Elizabeth; Wei, Jonathan; Coffey, Jacob; Zhang, Jin; Fernando, Germain J. P.; Kendall, Mark Anthony Fernance

    2016-06-01

    Micro-device use for vaccination has grown in the past decade, with the promise of ease-of-use, painless application, stable solid formulations and greater immune response generation. However, the designs of the highly immunogenic devices (e.g. the gene gun, Nanopatch or laser adjuvantation) require significant energy to enter the skin (30–90 mJ). Within this study, we explore a way to more effectively use energy for skin penetration and vaccination. These modifications change the Nanopatch projections from cylindrical/conical shapes with a density of 20,000 per cm2 to flat-shaped protrusions at 8,000 per cm2, whilst maintaining the surface area and volume that is placed within the skin. We show that this design results in more efficient surface crack initiations, allowing the energy to be more efficiently be deployed through the projections into the skin, with a significant overall increase in penetration depth (50%). Furthermore, we measured a significant increase in localized skin cell death (>2 fold), and resultant infiltrate of cells (monocytes and neutrophils). Using a commercial seasonal trivalent human influenza vaccine (Fluvax 2014), our new patch design resulted in an immune response equivalent to intramuscular injection with approximately 1000 fold less dose, while also being a practical device conceptually suited to widespread vaccination.

  17. ELISpot for measuring human immune responses to vaccines

    OpenAIRE

    Slota, Meredith; Lim, Jong-Baeck; Dang, Yushe; Disis, Mary L

    2011-01-01

    The enzyme-linked immunosorbent spot (ELISpot) assay is one of the most commonly used methods to measure antigen-specific T cells in both mice and humans. Some of the primary reasons for the popularity of the method are that ELISpot is highly quantitative, can measure a broad range of magnitudes of response and is capable of assessing critical cellular immune-related activities such as IFN-γ secretion and granzyme B release. Furthermore, ELISpot is adaptable not only to the evaluation of a va...

  18. COMPARATIVE IMMUNE RESPONSE OF BROILER CHICKS TO NEWCASTLE

    Directory of Open Access Journals (Sweden)

    M. Shuaib, M. Ashfaque, Sajjad-ur-Rahman, M.K. Mansoor and I. Yousaf1

    2003-04-01

    Full Text Available An experimental study was designed to asses the humoral and cell mediated immune response in the broiler chicks double vaccinated against Newcastle disease (ND using Lasota strain of ND virus vaccine. Double vaccination 7 days following Ist vaccination gave haemagglutination inhibition (HI titers ranging from 1:16 to 1:128, that was significantly higher than the HI antibody titer recorded after single vaccination. Similarly, macrophage migration inhibition (MMI activity ranged from 28.57 to 40.86%, with mean activity of 36.07%. No correlation was found between HI titer and MMI test.

  19. Immune response to 60-day head-down bed rest

    Science.gov (United States)

    Song, Jinping; Guo, Aihua; Zhong, Ping; Zhang, Hongyu; Wu, Feng; Wan, Yumin; Bai, Yanqiang; Chen, Shanguang; Li, Yinghui

    Introduction: Exposure of humans to spaceflight has resulted in disregulation of the immune system. Head-down bed rest (HDBR) has been extensively used as an earth-bound analog to study physiologic effects mimicking those occurring in weightlessness during spaceflight. It is uncertain how a prolonged period of bed rest affect human immune responses. The objective of this study was to investigate the effects of 60-day HDBR on immune function and EB virus reactivation in seven male volunteers. Methods: There were seven healthy male volunteers who were subjected to HDBR for 60d. Immunological parameters including leukocyte subset distribution, lymphocyte proliferation to mitogens, secreted cytokine profiles and EB virus reactivation were monitored. Results: Total WBC conunts increased significantly 10d post-HDBR as compared with pre-HDBR. At the same time, the relative percentage of neutrophils was also higher than pre-HDBR but not significant. MFI of CD11b in neutrophils was reduced obviously at thd end of HDBR. T Lymphocyte proliferations to PHA reduced at HDBR 30, HDBR 60 and 10d post-HDBR while IL-2 production decreased significantly at the same time. IFN-and IL-4 production trended to decrease at HDBR 30 and HDBR 60. The relative percentage of T lymphocyte subset, B lymphocyte and NK cells were not altered. EBV EA (early antigen) were negative and EBV VCA titers had no changes through HDBR. Conclusion: The results indicate that several immunological parameters (mainly cellular immunity) are altered significantly by prolonged HDBR, and these changes were similar to those happened in spaceflight.

  20. The effect of environmental temperature on immune response and metabolism of the young chicken

    NARCIS (Netherlands)

    Henken, A.M.

    1982-01-01

    The effect of environmental temperature on immune response and metabolism was studied in young chickens. Immunization was performed by injecting intramuscularly 0.5 ml packed SRBC (sheep red blood cells) in both thighs of 32 days old pullets ( WarrenSSL ). The ensueing immune response

  1. The Immune Response to Acute Focal Cerebral Ischemia and Associated Post-stroke Immunodepression: A Focused Review

    OpenAIRE

    Famakin, Bolanle M.

    2014-01-01

    It is currently well established that the immune system is activated in response to transient or focal cerebral ischemia. This acute immune activation occurs in response to damage, and injury, to components of the neurovascular unit and is mediated by the innate and adaptive arms of the immune response. The initial immune activation is rapid, occurs via the innate immune response and leads to inflammation. The inflammatory mediators produced during the innate immune response in turn lead to r...

  2. Corporate Social Responsibility Boosts Value Creation at the Base of the Pyramid

    OpenAIRE

    André, Thomas

    2014-01-01

    Multinational enterprises (MNEs) have embraced the possibility to find growth or strategic opportunities by targeting the Base of the Pyramid (BoP) segment, while contributing to alleviate poverty. Taking stock of the notorious early BoP initiatives shows that the bet made upon this responsible commitment is not yet won. Indeed, some were relegated to philanthropic programmes or simply dismantled, highlighting a tension to combine both societal and financial sustainability. The paper question...

  3. Modified cellular immune responses in dogs infected with Echinococcus multilocularis.

    Science.gov (United States)

    Kato, Naoko; Nonaka, Nariaki; Oku, Yuzaburo; Kamiya, Masao

    2005-03-01

    Parasite-specific antigen responses and lymphocyte blastogenesis in dogs orally inoculated with Echinococcus multilocuralis metacestodes were examined. Serum IgG1 (Th2-oriented) and IgG2 (Th 1-oriented) levels against somatic and excretory-secretory (ES) antigens of protoscoleces and adult worms increased from 7 days post-infection (DPI), with the highest responses against protoscolex excretory-secretory antigen (PES). Specific blastogenesis of peripheral blood mononuclear cells (PBMC) against the parasite antigens was not observed during the 21-day infection period, but Peyer's patches cells from one out of two dogs at 21 DPI showed blastogenesis against PES (stimulation index: 4.65). Interestingly, only at 7 DPI were concanavalin A (ConA)-induce proliferative responses of PBMC reduced. Moreover, ConA-induced proliferative responses of lymphocytes from various origins were suppressed by the addition of parasite antigens, especially with PES. These data suggest that although both Th1- and Th2-oriented humoral immune responses were observed in E. multilocularis infected dogs, the parasite antigens, especially PES, may have incompletely suppressed lymphocyte responses in these dogs. PMID:15719262

  4. Autoimmune disease-associated variants of extracellular endoplasmic reticulum aminopeptidase 1 induce altered innate immune responses by human immune cells

    OpenAIRE

    Aldhamen, Yasser A; Pepelyayeva, Yuliya; Rastall, David P. W.; Seregin, Sergey S.; Zervoudi, Efthalia; Koumantou, Despoina; Charles F Aylsworth; Quiroga, Dionisia; Godbehere, Sarah; Georgiadis, Dimitris; Stratikos, Efstratios; Amalfitano, Andrea

    2015-01-01

    ERAP1 gene polymorphisms have been linked to several autoimmune diseases; however, the molecular mechanisms underlying these associations are not well understood. Recently, we have demonstrated that ERAP1 regulates key aspects of the innate immune response. Moreover, previous studies show ERAP1 to be ER-localized and secreted during inflammation. Herein, we investigate the possible roles that ERAP1 polymorphic variants may have in modulating innate immune responses of human PBMCs using two ex...

  5. Gamma-irradiated influenza A virus can prime for a cross-reactive and cross-protective immune response against influenza A viruses

    International Nuclear Information System (INIS)

    A-strain influenza virus A/JAP (H2N2) was tested for its ability to induce cytotoxic T cells (Tc) after being rendered non-infectious by either UV or gamma irradiation. Gamma-irradiated virus proved to be more efficient than UV-inactivated virus in priming for a memory Tc cell response or in boosting memory spleen cells in vitro. Most importantly, γ-inactivated, but not UV-inactivated, A/JAP immunized animals survived lethal challenge with heterologous (A/PC(H3N2), A/WSN(H1N1)) virus as effectively as mice primed with infectious virus

  6. Paraquat and temperature affect nonspecific immune response of Colossoma macropomum.

    Science.gov (United States)

    Salazar-Lugo, Raquel; Estrella, América; Oliveros, Aridays; Rojas-Villarroel, Evelyn; Villalobos de B, Luz; Lemus, Mairin

    2009-05-01

    This study evaluated the effect of paraquat (PQ) and temperature on hematological parameters and nonspecific immune system of fish Colossoma macropomum (Cachama). Juveniles were used for all experiments. Fish were exposed to three temperatures (18, 28, 35°C) and 10mg/L PQ during 21 days (PQ LC(50) 96h was of 48.05mg/L). Hematological (Hb, Ht, VCM, HCM and CHCM and RBC) and immunological parameters (WBC, differential count of white cells, phagocytes, and bacterial killing by phagocytes) were analyzed for 7, 14 and 21 days. Fishes PQ exposed at 18°C decreased Hb, MCH and MCHC; we observed sickle erythrocytes in control group at 18°C, and in PQ-exposed groups at 18 and 35°C. Immunological parameters were not affected by temperature. Neutrophils decreased significantly in all PQ-exposed groups. Bacterial killing by phagocytes decreased in 18 and 35°C PQ-groups; a synergistic interaction was shown between PQ and temperature on WBC and lymphocytes. These results indicate that PQ affected neutrophils counts independently of temperature exposure; the temperature exerted a synergistic effect on PQ toxicity in lymphocyte counts and phagocytic response and besides nonspecific immune response, PQ and temperature affects hematological parameters such as Hb, MCH, MCHC and erythrocytes morphology. PMID:21783960

  7. Cinobufagin Modulates Human Innate Immune Responses and Triggers Antibacterial Activity.

    Science.gov (United States)

    Xie, Shanshan; Spelmink, Laura; Codemo, Mario; Subramanian, Karthik; Pütsep, Katrin; Henriques-Normark, Birgitta; Olliver, Marie

    2016-01-01

    The traditional Chinese medicine Chan-Su is widely used for treatment of cancer and cardiovascular diseases, but also as a remedy for infections such as furunculosis, tonsillitis and acute pharyngitis. The clinical use of Chan-Su suggests that it has anti-infective effects, however, the mechanism of action is incompletely understood. In particular, the effect on the human immune system is poorly defined. Here, we describe previously unrecognized immunomodulatory activities of cinobufagin (CBG), a major bioactive component of Chan-Su. Using human monocyte-derived dendritic cells (DCs), we show that LPS-induced maturation and production of a number of cytokines was potently inhibited by CBG, which also had a pro-apoptotic effect, associated with activation of caspase-3. Interestingly, CBG triggered caspase-1 activation and significantly enhanced IL-1β production in LPS-stimulated cells. Finally, we demonstrate that CBG upregulates gene expression of the antimicrobial peptides (AMPs) hBD-2 and hBD-3 in DCs, and induces secretion of HNP1-3 and hCAP-18/LL-37 from neutrophils, potentiating neutrophil antibacterial activity. Taken together, our data indicate that CBG modulates the inflammatory phenotype of DCs in response to LPS, and triggers an antibacterial innate immune response, thus proposing possible mechanisms for the clinical effects of Chan-Su in anti-infective therapy. PMID:27529866

  8. The immune response in cattle infected with Tritrichomonas foetus.

    Science.gov (United States)

    Soto, P; Parma, A E

    1989-10-01

    Holando-Argentina calves (males and females) were experimentally infected with Tritrichomonas foetus var. Belfast (T. foetus) by introducing 10(7) protozoa into the preputial and vaginal cavities, in order to analyse the course of the immune response to infection. Samples of serum, vaginal mucus and preputial secretion were taken periodically and assayed by means of microagglutination of living protozoa. The serum antibody titre, which averaged 32 before infection and was equivalent to titres in a non-infected group, increased to 512 in the heifers 11 weeks later and to 128 in the bulls 4 months post-infection. Agglutinating antibodies were not detected in the preputial cavity, but heifers showed antibodies in the vaginal mucus and became trichomoniasis free after 4 months. Conversely, genital secretions from the bulls gave rise to positive cultures during the whole period of experimentation. The intradermal sensitivity was checked using a soluble antigen from T. foetus. The diameter of the papula increased up to three times in heifers, while in bulls the results were no different than those from the non-infected group. Serum antibodies were of the IgG2 subclass, while those isolated from vaginal mucus were characterized as IgG1, an opsonizing antibody. Heifers were refractory to challenge infection after 1 year. The poor immune response in bulls is consistent with their role as carriers of T. foetus. PMID:2683348

  9. Immunity to rhabdoviruses in rainbow trout: the antibody response

    DEFF Research Database (Denmark)

    Lorenzen, Niels; Lapatra, S.E.

    1999-01-01

    detail so far. Analysis of the specificity of anti-virus trout antibodies has been complicated by a generally insufficient ability of the antibodies to bind the viral proteins in assays such as immunoblotting. However, other assays, specifically designed for detection of fish anti IHNV/VHSV antibodies...... occasional detrimental effect on rainbow trout farming. Research efforts have been focused on understanding the mechanisms involved in protective immunity. Several specific and nonspecific cellular and humoral parameters are believed to be involved, but only the antibody response has been characterised in......, have demonstrated that rainbow trout can produce specific and highly functional antibodies that are able to neutralise virus pathogenicity in vitro as well as in vivo. The apparently more restricted antibody response to IHNV and VHSV antigens in fish compared to mammals could possibly be explained by...

  10. Monitoring Immune Responses in Organ Recipients by Flow Cytometry

    Directory of Open Access Journals (Sweden)

    Al-Mukhalafi Zuha

    2001-01-01

    Full Text Available Allograft rejection remains a major barrier to successful organ transplan-tation. Cellular and humoral immune responses play a critical role in mediating graft rejection. During the last few years, monoclonal antibodies have been used as a new specific therapeutic approach in the prevention of allograft rejection. Recently, the technology of flow cytometry has become a useful tool for monitoring immunological responses in transplant recipients. The application of this valuable tool in clinical transplantation at the present time is aimed at, i determining the extent of immuno-suppressive therapy through T-cell receptor analysis of cellular components, ii monitoring levels of alloreactive antibodies to identify high-risk recipients (sensitized patients in the pre-operative period and iii to predict rejection by monitoring their development post-operatively. In future, further development of this technology may demonstrate greater benefit to the field of organ transplantation.

  11. Neonate intestinal immune response to CpG oligodeoxynucleotide stimulation.

    Directory of Open Access Journals (Sweden)

    Sonia Lacroix-Lamandé

    Full Text Available BACKGROUND: The development of mucosal vaccines is crucial to efficiently control infectious agents for which mucosae are the primary site of entry. Major drawbacks of these protective strategies are the lack of effective mucosal adjuvant. Synthetic oligodeoxynucleotides that contain several unmethylated cytosine-guanine dinucleotide (CpG-ODN motifs are now recognized as promising adjuvants displaying mucosal adjuvant activity through direct activation of TLR9-expressing cells. However, little is known about the efficacy of these molecules in stimulating the intestinal immune system in neonates. METHODOLOGY/PRINCIPAL FINDINGS: First, newborn mice received CpG-ODN orally, and the intestinal cytokine and chemokine response was measured. We observed that oral administration of CpG-ODN induces CXC and CC chemokine responses and a cellular infiltration in the intestine of neonates as detected by immunohistochemistry. We next compared the efficiency of the oral route to intraperitoneal administration in stimulating the intestinal immune responses of both adults and neonates. Neonates were more responsive to TLR9-stimulation than adults whatever the CpG-ODN administration route. Their intestinal epithelial cells (IECs indirectly responded to TLR9 stimulation and contributed to the CXC chemokine response, whereas other TLR9-bearing cells of the lamina-propria produced CC chemokines and Th1-type cytokines. Moreover, we showed that the intestine of adult exhibited a significantly higher level of IL10 at homeostasis than neonates, which might be responsible for the unresponsiveness to TLR9-stimulation, as confirmed by our findings in IL10-deficient mice. CONCLUSIONS/SIGNIFICANCE: This is the first report that deciphers the role played by CpG-ODN in the intestine of neonates. This work clearly demonstrates that an intraperitoneal administration of CpG-ODN is more efficient in neonates than in adults to stimulate an intestinal chemokine response due to their

  12. ANAMNESTIC IMMUNE RESPONSE EIGHT YEARS AFTER IMMUNIZATION OF PRIMATES WITH A MULTIVALENT HIV-1 GP120 VARIABLE PEPTIDE VACCINE

    Directory of Open Access Journals (Sweden)

    Rebecca Rivera

    2013-01-01

    Full Text Available Successful development of an effective HIV vaccine hasn’t occurred yet partly as a consequence of the antigenic variation deployed by HIV-1 to escape the immune system. Our laboratory is dedicated to develop a single peptide synthesis approach to create multivalent peptides representing hypervariable epitopes of the gp120 envelope glycoprotein of HIV-1. Our previous study showed that our HIV HECs are potent immunogens that activate both humoral and cellular arms of the acquired immune response and that these responses are broadly reactive, recognizing epitopes from divergent strains of HIV-1. To detect the long term duration of memory response induced by HIV HECs, two rhesus macaques were immunized at weeks 0 and 8 and euthanized two weeks after a third immunization at week 393 (more than 8 years later. Antibody response to individual components of HIV HEC immunogens and HIV HEC-induced cross-reactive antibody response were determined by an Enzyme-Linked Immunosorbent Assay (ELISA. The antibody titer to individual HIV HEC components and a mixture of the five peptides was greater than 1:5000 dilution. Antibodies from HIV HEC-immunized macaques recognized HIV HEC analogs representing the monovalent epitopes of five variable regions of gp120 from subtype B HIV-1 MN, HIV-1 RF and HIV-1 SF2 isolates with an antibody titer greater than 1: 500 dilution. Moreover, lymphocytes from lymph nodes of HIV HEC-immunized macaques showed T cell proliferative responses specific to HIV HEC individual components and to the five HIV HEC peptides combined. Our results clearly show that in these two macaques, HIV HECs induced strong, long-lasting anamnestic immune responses 8 years after immunization.

  13. Immune response in mice and cattle after immunization with a Boophilus microplus DNA vaccine containing bm86 gene.

    Science.gov (United States)

    Ruiz, Lina María; Orduz, Sergio; López, Elkin D; Guzmán, Fanny; Patarroyo, Manuel E; Armengol, Gemma

    2007-03-15

    Plasmid pBMC2 encoding antigen Bm86 from a Colombian strain of cattle tick Boophilus microplus, was used for DNA-mediated immunization of BALB/c mice, employing doses of 10 and 50microg, delivered by intradermic and intramuscular routes. Anti-Bm86 antibody levels were significantly higher compared to control mice treated with PBS. In the evaluation of immunoglobulin isotypes, significant levels of IgG2a and IgG2b were observed in mice immunized with 50microg of pBMC2. Measurement of interleukine (IL) levels (IL-4, IL-5, IL-12(p40)) and interferon-gamma (IFN-gamma) in the sera of mice immunized with pBMC2 indicated high levels of IL-4 and IL-5, although there were also significant levels of IFN-gamma. Mice immunized with pBMC2 showed antigen-specific stimulation of splenocytes according to the incorporation of bromodeoxyuridine and IFN-gamma secretion. In all trials, mice injected intramuscularly with 50microg of pBMC2 presented the highest immune response. Moreover, cattle immunized with this DNA vaccine showed antibody production significantly different to the negative control. In conclusion, these results suggest the potential of DNA immunization with pBMC2 to induce humoral and cellular immune responses against B. microplus. PMID:17055651

  14. Granulocyte-macrophage colony-stimulating factor DNA prime-protein boost strategy to enhance efficacy of a recombinant pertussis DNA vaccine

    Institute of Scientific and Technical Information of China (English)

    Qing-tian LI; Yong-zhang ZHU; Jia-you CHU; Ke DONG; Ping HE; Chun-yan FENG; Bao-yu HU; Shu-min ZHANG; Xiao-kui GUO

    2006-01-01

    Aim: To investigate a new strategy to enhance the efficacy of a recombinant pertussis DNA vaccine. The strategy is co-injection with cytokine plasmids as prime, and boosted with purified homologous proteins. Method: A recombinant pertussis DNA vaccine containing the pertussis toxin subunit 1 (PTS1), fragments of the filamentous hemagglutinin (FHA) gene and pertactin (PRN) gene encoding filamentous hemagglutinin and pertactin were constructed. Balb/c mice were immunized with several DNA vaccines and antigen-specific antibodies anti-PTSl, anti-PRN, anti-FHA, cytokines interleukin (IL)-10, IL-4, IFN-γ, TNF-oc, and spleno-cyte-proliferation assay were used to describe immune responses. Results: The recombinant DNA vaccine could elicit similar immune responses in mice as that of separate plasmids encoding the 3 fragments, respectively. Mice immunized with DNA and boosted with the corresponding protein elicited more antibodies than those that received DNA as boost. In particular, when the mice were co-immunized with murine granulocyte-macrophage colony-stimulating factor plasmids and boosted with proteins, all 4 cytokines and the 3 antigen-specific antibodies were significantly increased compared to the pVAXl group. Anti-PTSl, anti-FHA, IL-4 and TNF-α elicited in the colony stimulating factor (CSF) prime-protein boost group showed significant increase compared to all the other groups. Conclusion: This prime and boost strategy has proven to be very useful in improving the immunogenicity of DNA vaccines against pertussis.

  15. Evaluation of an intranasal virosomal vaccine against respiratory syncytial virus in mice: effect of TLR2 and NOD2 ligands on induction of systemic and mucosal immune responses.

    Directory of Open Access Journals (Sweden)

    Muhammad Shafique

    Full Text Available INTRODUCTION: RSV infection remains a serious threat to newborns and the elderly. Currently, there is no vaccine available to prevent RSV infection. A mucosal RSV vaccine would be attractive as it could induce mucosal as well as systemic antibodies, capable of protecting both the upper and lower respiratory tract. Previously, we reported on a virosomal RSV vaccine for intramuscular injection with intrinsic adjuvant properties mediated by an incorporated lipophilic Toll-like receptor 2 (TLR2 ligand. However, it has not been investigated whether this virosomal RSV vaccine candidate would be suitable for use in mucosal immunization strategies and if additional incorporation of other innate receptor ligands, like NOD2-ligand, could further enhance the immunogenicity and protective efficacy of the vaccine. OBJECTIVE: To explore if intranasal (IN immunization with a virosomal RSV vaccine, supplemented with TLR2 and/or NOD2-ligands, is an effective strategy to induce RSV-specific immunity. METHODS: We produced RSV-virosomes carrying TLR2 (Pam3CSK4 and/or NOD2 (L18-MDP ligands. We tested the immunopotentiating properties of these virosomes in vitro, using TLR2- and/or NOD2-ligand-responsive murine and human cell lines, and in vivo by assessing induction of protective antibody and cellular responses upon IN immunization of BALB/c mice. RESULTS: Incorporation of Pam3CSK4 and/or L18-MDP potentiates the capacity of virosomes to activate (antigen-presenting cells in vitro, as demonstrated by NF-κB induction. In vivo, incorporation of Pam3CSK4 in virosomes boosted serum IgG antibody responses and mucosal antibody responses after IN immunization. While L18-MDP alone was ineffective, incorporation of L18-MDP in Pam3CSK4-carrying virosomes further boosted mucosal antibody responses. Finally, IN immunization with adjuvanted virosomes, particularly Pam3CSK4/L18-MDP-adjuvanted-virosomes, protected mice against infection with RSV, without priming for enhanced

  16. Mosquito immune responses and malaria transmission: lessons from insect model systems and implications for vertebrate innate immunity and vaccine development.

    Science.gov (United States)

    Barillas-Mury, C; Wizel, B; Han, Y S

    2000-06-01

    The introduction of novel biochemical, genetic, molecular and cell biology tools to the study of insect immunity has generated an information explosion in recent years. Due to the biodiversity of insects, complementary model systems have been developed. The conceptual framework built based on these systems is used to discuss our current understanding of mosquito immune responses and their implications for malaria transmission. The areas of insect and vertebrate innate immunity are merging as new information confirms the remarkable extent of the evolutionary conservation, at a molecular level, in the signaling pathways mediating these responses in such distant species. Our current understanding of the molecular language that allows the vertebrate innate immune system to identify parasites, such as malaria, and direct the acquired immune system to mount a protective immune response is very limited. Insect vectors of parasitic diseases, such as mosquitoes, could represent excellent models to understand the molecular responses of epithelial cells to parasite invasion. This information could broaden our understanding of vertebrate responses to parasitic infection and could have extensive implications for anti-malarial vaccine development. PMID:10802234

  17. Immune response modulation by curcumin in a latex allergy model

    Directory of Open Access Journals (Sweden)

    Raju Raghavan

    2007-01-01

    Full Text Available Abstract Background There has been a worldwide increase in allergy and asthma over the last few decades, particularly in industrially developed nations. This resulted in a renewed interest to understand the pathogenesis of allergy in recent years. The progress made in the pathogenesis of allergic disease has led to the exploration of novel alternative therapies, which include herbal medicines as well. Curcumin, present in turmeric, a frequently used spice in Asia has been shown to have anti-allergic and inflammatory potential. Methods We used a murine model of latex allergy to investigate the role of curcumin as an immunomodulator. BALB/c mice were exposed to latex allergens and developed latex allergy with a Th2 type of immune response. These animals were treated with curcumin and the immunological and inflammatory responses were evaluated. Results Animals exposed to latex showed enhanced serum IgE, latex specific IgG1, IL-4, IL-5, IL-13, eosinophils and inflammation in the lungs. Intragastric treatment of latex-sensitized mice with curcumin demonstrated a diminished Th2 response with a concurrent reduction in lung inflammation. Eosinophilia in curcumin-treated mice was markedly reduced, co-stimulatory molecule expression (CD80, CD86, and OX40L on antigen-presenting cells was decreased, and expression of MMP-9, OAT, and TSLP genes was also attenuated. Conclusion These results suggest that curcumin has potential therapeutic value for controlling allergic responses resulting from exposure to allergens.

  18. Anaphylatoxins coordinate innate and adaptive immune responses in allergic asthma.

    Science.gov (United States)

    Schmudde, Inken; Laumonnier, Yves; Köhl, Jörg

    2013-02-01

    Allergic asthma is a chronic disease of the airways in which maladaptive Th2 and Th17 immune responses drive airway hyperresponsiveness (AHR), eosinophilic and neutrophilic airway inflammation and mucus overproduction. Airway epithelial and pulmonary vascular endothelial cells in concert with different resident and monocyte-derived dendritic cells (DC) play critical roles in allergen sensing and consecutive activation of TH cells and their differentiation toward TH2 and TH17 effector or regulatory T cells (Treg). Further, myeloid-derived regulatory cells (MDRC) act on TH cells and either suppress or enhance their activation. The complement-derived anaphylatoxins (AT) C3a and C5a are generated during initial antigen encounter and regulate the development of maladaptive immunity at allergen sensitization. Here, we will review the complex role of ATs in activation and modulation of different DC populations, MDRCs and CD4⁺ TH cells. We will also discuss the potential impact of ATs on the regulation of the pulmonary stromal compartment as an important means to regulate DC functions. PMID:23694705

  19. Steroid-sensitive mechanism of soluble immune response suppressor production in steroid-responsive nephrotic syndrome.

    OpenAIRE

    Schnaper, H W; Aune, T M

    1987-01-01

    Soluble immune response suppressor (SIRS), a lymphokine that suppresses antibody production and delayed type hypersensitivity in vivo, has been detected in urine and serum from certain patients with nephrotic syndrome. In the present paper, the relationship between SIRS production and nephrotic syndrome is further characterized. A striking correlation was found between detection of SIRS and the presence of steroid-responsive nephrotic syndrome (SRNS). A potential mechanism of SIRS production ...

  20. Mechanisms Underlying the Immune Response Generated by an Oral Vibrio cholerae Vaccine.

    Science.gov (United States)

    Sirskyj, Danylo; Kumar, Ashok; Azizi, Ali

    2016-01-01

    Mechanistic details underlying the resulting protective immune response generated by mucosal vaccines remain largely unknown. We investigated the involvement of Toll-like receptor signaling in the induction of humoral immune responses following oral immunization with Dukoral, comparing wild type mice with TLR-2-, TLR-4-, MyD88- and Trif-deficient mice. Although all groups generated similar levels of IgG antibodies, the proliferation of CD4+ T-cells in response to V. cholerae was shown to be mediated via MyD88/TLR signaling, and independently of Trif signaling. The results demonstrate differential requirements for generation of immune responses. These results also suggest that TLR pathways may be modulators of the quality of immune response elicited by the Dukoral vaccine. Determining the critical signaling pathways involved in the induction of immune response to this vaccine would be beneficial, and could contribute to more precisely-designed versions of other oral vaccines in the future. PMID:27384558

  1. Immune response to HHV-6 and implications for immunotherapy.

    Science.gov (United States)

    Becerra, Aniuska; Gibson, Laura; Stern, Lawrence J; Calvo-Calle, J Mauricio

    2014-12-01

    Most adults remain chronically infected with HHV-6 after resolution of a primary infection in childhood, with the latent virus held in check by the immune system. Iatrogenic immunosuppression following solid organ transplantation (SOT) or hematopoetic stem cell transplantation (HSCT) can allow latent viruses to reactivate. HHV-6 reactivation has been associated with increased morbidity, graft rejection, and neurological complications post-transplantation. Recent work has identified HHV-6 antigens that are targeted by the CD4+ and CD8+ T cell response in chronically infected adults. T cell populations recognizing these targets can be expanded in vitro and are being developed for use in autologous immunotherapy to control post-transplantation HHV-6 reaction. PMID:25462448

  2. Effect of radiation dose on patients' immune response

    International Nuclear Information System (INIS)

    This paper studies the relations between dose delivered and changes in T-cell subsets as an expression of the effect of radiation therapy on patients' immune response. One hundred twenty-eight patients were studied before and 6 weeks after irradiation. Blood samples were analyzed by flow cytometry. A dose effect was noted wherein the OKT4 helper/OKT8 suppressor cell ratio was reduced by more than 10% in 79% of patients receiving a dose greater than 6,000 cGy as compared with 54% of patients given a lower dose (P = .01). Several variables, including sex, age, tumor site, and cancer burden, were analyzed. Male subjects showed a greater reduction of OKT4 helper cells at doses greater than 6,000 cGy-73%, versus 47% in female subjects (P = .05)

  3. Tissue specific heterogeneity in effector immune cell response

    Directory of Open Access Journals (Sweden)

    Saba eTufail

    2013-08-01

    Full Text Available Post pathogen invasion, migration of effector T-cell subsets to specific tissue locations is of prime importance for generation of robust immune response. Effector T cells are imprinted with distinct ‘homing codes’ (adhesion molecules and chemokine receptors during activation which regulate their targeted trafficking to specific tissues. Internal cues in the lymph node microenvironment along with external stimuli from food (vitamin A and sunlight (vitamin D3 prime dendritic cells, imprinting them to play centrestage in the induction of tissue tropism in effector T cells. B cells as well, in a manner similar to effector T cells, exhibit tissue tropic migration. In this review, we have focused on the factors regulating the generation and migration of effector T cells to various tissues alongwith giving an overview of tissue tropism in B cells.

  4. Mucosal immune response in common carp (Cyprinus carpio L.)

    DEFF Research Database (Denmark)

    Przybylska, Dominika Alicja

    of the biological impact of two commercially available ß-glucan enriched products on the wound healing process in common carp (Cyprinus carpio L.) in sterile, controlled conditions; 2. investigation of potential impact of intravenously injected ß-glucan on mucosal immune response and immunoglobulin......-glucans. Further work showed that bath in two commercially available ß-glucan enriched products, specifically MacroGard and 6.3 kDa oat fiber, had a direct positive effects on the wound closure in common carp and promoted faster wound healing compared to non-treated fish. We showed the immunological and......Control of fish diseases is a great concern in aquaculture because of losses in the production. Drug choices for the treatment of common infectious diseases are becoming increasingly limited and expensive and, in some cases, unavailable due to the emergence of drug resistance in bacteria and fungi...

  5. TRAF-mediated regulation of immune and inflammatory responses

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    The tumor necrosis factor (TNF) receptor-associated factor (TRAF) family consists of six mammalian members,and is shown to participate in signal transduction of a large number of receptor families including TNF receptor family (TNFR) and Toll-like receptors-interleukin-1 receptors (TLR-IL-1R) family.Upon receptor activation,TRAFs are directly or indirectly recruited to the intracellular domains of these receptors.They subsequently engage other signaling proteins to activate inhibitor of κB kinase (IKK) complex,TRAF family member-associated NF-κB activator (TANK)-binding kinase 1 (TBK1) and inducible I κB kinase (IKK-i) (also known as IKKε),ultimately leading to activation of transcription factors such as NF-κB and interferon-regulatory factor (IRF) to induce immune and inflammatory responses.

  6. Modulation of humoral immune response through probiotic intake.

    Science.gov (United States)

    Fang, H; Elina, T; Heikki, A; Seppo, S

    2000-09-01

    Thirty healthy volunteers were randomised into three different treatment groups and consumed Lactobacillus GG, Lactococcus lactis or placebo (ethyl cellulose) for 7 days. On days 1, 3 and 5, an attenuated Salmonella typhi Ty21a oral vaccine was given to all subjects to mimic an enteropathogenic infection. All subjects responded well to the vaccine, but no significant differences were observed in numbers of IgA-, IgG- and IgM-secreting cells among the different groups. There was a trend towards a greater increase in specific IgA among the subjects receiving the vaccine in combination with Lactobacillus GG. Those receiving L. lactis with their vaccine evinced significantly higher CR3 receptor expression on neutrophils than those receiving either the placebo or Lactobacillus GG. These results indicate that probiotics may influence differently the immune response to oral S. typhi vaccine and that the immunomodulatory effect of probiotics is strain-dependent. PMID:10967260

  7. GITR Activation Positively Regulates Immune Responses against Toxoplasma gondii

    Science.gov (United States)

    Costa, Frederico R. C.; Mota, Caroline M.; Santiago, Fernanda M.; Silva, Murilo V.; Ferreira, Marcela D.; Fonseca, Denise M.; Silva, João S.; Mineo, José R.; Mineo, Tiago W. P.

    2016-01-01

    Toxoplasma gondii is a widespread parasite responsible for causing clinical diseases especially in pregnant and immunosuppressed individuals. Glucocorticoid-induced TNF receptor (GITR), which is also known as TNFRS18 and belongs to the TNF receptor superfamily, is found to be expressed in various cell types of the immune system and provides an important costimulatory signal for T cells and myeloid cells. However, the precise role of this receptor in the context of T. gondii infection remains elusive. Therefore, the current study investigated the role of GITR activation in the immunoregulation mechanisms induced during the experimental infection of mice with T. gondii. Our data show that T. gondii infection slightly upregulates GITR expression in Treg cells and B cells, but the most robust increment in expression was observed in macrophages and dendritic cells. Interestingly, mice infected and treated with an agonistic antibody anti-GITR (DTA-1) presented a robust increase in pro-inflammatory cytokine production at preferential sites of parasite replication, which was associated with the decrease in latent brain parasitism of mice under treatment with DTA-1. Several in vivo and in vitro analysis were performed to identify the cellular mechanisms involved in GITR activation upon infection, however no clear alterations were detected in the phenotype/function of macrophages, Tregs and B cells under treatment with DTA-1. Therefore, GITR appears as a potential target for intervention during infection by the parasite Toxoplasma gondii, even though further studies are still necessary to better characterize the immune response triggered by GITR activation during T. gondii infection. PMID:27027302

  8. Immune Response in Microgravity: Genetic Basis and Countermeasure Development Implications

    Science.gov (United States)

    Risin, Diana; Ward, Nancy E.; Risin, Semyon A.; Pellis, Neal R.

    2006-01-01

    Impairment of the immunity in astronauts and cosmonauts even in shortterm flights is a recognized risk. Longterm orbital space missions and anticipated interplanetary flights increase the concern for more pronounced effects on the immune system with potential clinical consequences. Studies in true and modeled microgravity (MG) have demonstrated that MG directly affects numerous lymphocyte functions. The purpose of this study was to screen for genes involved in lymphocytes response to modeled microgravity (MMG) that could explain the functional and structural changes observed earlier. The microgravity-induced changes in gene expression were analyzed by microarray DNA chip technology. CD3and IL2activated Tcells were cultured in 1g (static) and modeled microgravity (NASA Rotating Wall Vessel bioreactor) conditions for 24 hours. Total RNA was extracted using the RNeasy isolation kit (Qiagen, Valencia, CA). Microarray experiments were performed utilizing Affymetrix Gene Chips (U133A), allowing testing for 18,400 human genes. To decrease the biological variation and aid in detecting microgravity-associated changes, experiments were performed in triplicate using cells obtained from three different donors. Exposure to modeled microgravity resulted in alteration of 89 genes, 10 of which were upregulated and 79 down-regulated. Altered genes were categorized by their function, structural role and by association with metabolic and regulatory pathways. A large proportion was found to be involved in fundamental cellular processes: signal transduction, DNA repair, apoptosis, and multiple metabolic pathways. There was a group of genes directly related to immune and inflammatory responses (IL7R, granulysin, proteasome activator subunit 2, peroxiredoxin 4, HLADRA, lymphocyte antigen 75, IL18R and DOCK2 genes). Among these genes only one (IL7R) was upregulated, the rest were downregulated. The upregulation of the IL7 receptor gene was confirmed by RT PCR. Three genes with altered

  9. The role of metalloproteinase ADAM17 in regulating ICOS ligand-mediated humoral immune responses

    DEFF Research Database (Denmark)

    Marczynska, Joanna; Ozga, Aleksandra; Wlodarczyk, Agnieszka;

    2014-01-01

    Immune cells regulate cell surface receptor expression during their maturation, activation, and motility. Although many of these receptors are regulated largely at the level of expression, protease-mediated ectodomain shedding represents an alternative means of refashioning the surface of immune ...... suggest a functional link between ADAM17 and ICOSL in controlling adaptive immune responses....

  10. Effects of mild stress on the immune response against pseudorabies virus in mice

    NARCIS (Netherlands)

    de Groot, J; Moonen-Leusen, HWM; Thomas, G; Bianchi, ATJ; Koolhaas, JM; van Milligen, FJ

    1999-01-01

    Stress is a recognised problem in intensive pig husbandry, which might lead to changes in immune reactivity. To study the effect of stress on the development of an anti-viral immune response, we used a murine model in which mice were immunized with an attenuated strain of pseudorabies virus (PRV). T

  11. Pleomorphic forms of Borrelia burgdorferi induce distinct immune responses.

    Science.gov (United States)

    Meriläinen, Leena; Brander, Heini; Herranen, Anni; Schwarzbach, Armin; Gilbert, Leona

    2016-01-01

    Borrelia burgdorferi is the causative agent of tick-borne Lyme disease. As a response to environmental stress B. burgdorferi can change its morphology to a round body form. The role of B. burgdorferi pleomorphic forms in Lyme disease pathogenesis has long been debated and unclear. Here, we demonstrated that round bodies were processed differently in differentiated macrophages, consequently inducing distinct immune responses compared to spirochetes in vitro. Colocalization analysis indicated that the F-actin participates in internalization of both forms. However, round bodies end up less in macrophage lysosomes than spirochetes suggesting that there are differences in processing of these forms in phagocytic cells. Furthermore, round bodies stimulated distinct cytokine and chemokine production in these cells. We confirmed that spirochetes and round bodies present different protein profiles and antigenicity. In a Western blot analysis Lyme disease patients had more intense responses to round bodies when compared to spirochetes. These results suggest that round bodies have a role in Lyme disease pathogenesis. PMID:27139815

  12. Regulation of the immune response to bacterial lipopolysaccharide by adherent cells.

    OpenAIRE

    Citron, M O; Michael, J G

    1981-01-01

    Immune response to bacterial lipopolysaccharide is usually short lived, but it often reappears without additional stimulus in a cyclic fashion. Activated adherent cells, presumably macrophages, were found to have a role in the reduction of the immune response to Escherichia coli O127 lipopolysaccharide. The suppressive activity of the adherent cells was abrogated before renewal of the responsiveness.

  13. Enhancement of anamnestic immunospecific antibody response in orally immunized chickens

    DEFF Research Database (Denmark)

    Mayo, Susan; Carlsson, Hans-Erik; Zagon, Andrea; Royo, Felix; Hau, Jann

    one oral dose with BSA+RV. The eggs of the chickens in this group had a significantly higher immunospecific anti BSA IgY-concentration than did any of the eggs from the orally immunized chickens. One of the immunization regimes (immunizations in weeks 1, 7 and 18) clearly included a booster effect of...

  14. The Relationship Between Morphological Symmetry and Immune Response in Wild-Caught Adult Bush-Crickets

    Directory of Open Access Journals (Sweden)

    Åsa Berggren

    2009-09-01

    Full Text Available Despite interest in the relationship between fluctuating asymmetry (FA, immune response and ecological factors in insects, little data are available from wild populations. In this study we measured FA and immune response in 370 wild-caught male bush-crickets, Metrioptera roeseli, from 20 experimentally introduced populations in southern-central Sweden. Individuals with more-symmetric wings had a higher immune response as measured by the cellular encapsulation of a surgically-implanted nylon monofilament. However, we found no relationship between measures of FA in other organs (i.e. tibia and maxillary palp and immune response, suggesting that this pattern may reflect differing selection pressures.

  15. Immune responses to Fasciola hepatica infection, and Fasciola hepatica derived antigens

    OpenAIRE

    Walshe, Alan

    2003-01-01

    The aim of this study was to investigate immune responses as a result of infection with the parasitic helminth, Fasciola hepatica. Analysis of IL-4 and Interferon-y cytokines described a predominant type 2 immune response in BALB/c mice infected with metacercana of F hepatica Levels of IL-4 mRNA assessed by reverse transcnption-polymerase chain reaction (RT-PCR) provide the first evidence that the immune response becomes polarised 1 day post infection. We also investigated immune responses to...

  16. Autoimmune disease-associated variants of extracellular endoplasmic reticulum aminopeptidase 1 induce altered innate immune responses by human immune cells.

    Science.gov (United States)

    Aldhamen, Yasser A; Pepelyayeva, Yuliya; Rastall, David P W; Seregin, Sergey S; Zervoudi, Efthalia; Koumantou, Despoina; Aylsworth, Charles F; Quiroga, Dionisia; Godbehere, Sarah; Georgiadis, Dimitris; Stratikos, Efstratios; Amalfitano, Andrea

    2015-01-01

    Endoplasmic reticulum aminopeptidase 1 (ERAP1) gene polymorphisms have been linked to several autoimmune diseases; however, the molecular mechanisms underlying these associations are not well understood. Recently, we demonstrated that ERAP1 regulates key aspects of the innate immune response. Previous studies show ERAP1 to be endoplasmic reticulum-localized and secreted during inflammation. Herein, we investigate the possible roles that ERAP1 polymorphic variants may have in modulating the innate immune responses of human peripheral blood mononuclear cells (hPBMCs) using two experimental methods: extracellular exposure of hPBMCs to ERAP1 variants and adenovirus (Ad)-based ERAP1 expression. We found that exposure of hPBMCs to ERAP1 variant proteins as well as ERAP1 overexpression by Ad5 vectors increased inflammatory cytokine and chemokine production, and enhanced immune cell activation. Investigating the molecular mechanisms behind these responses revealed that ERAP1 is able to activate innate immunity via multiple pathways, including the NLRP3 (NOD-like receptor, pyrin domain-containing 3) inflammasome. Importantly, these responses varied if autoimmune disease-associated variants of ERAP1 were examined in the assay systems. Unexpectedly, blocking ERAP1 cellular internalization augmented IL-1β production. To our knowledge, this is the first report identifying ERAP1 as being involved in modulating innate responses of human immune cells, a finding that may explain why ERAP1 has been genetically associated with several autoimmune diseases. PMID:25591727

  17. Immune responses in cattle vaccinated with gamma-irradiated Anaplasma marginale

    International Nuclear Information System (INIS)

    The infectivity and immunogenecity of gamma-irradiated Anaplasma marginale organisms were studied in bovine calves. The severity of Anaplasma infection based on per cent infected red blood cells, haematological values and mortality was more in animals immunized with blood exposed to 60 kR in comparison to those inoculated with blood irradiated at 70, 80 and 90 kR. The immunizing controls demonstrated a significantly high parasitaemia, marked anaemia and more deaths. Marked and prolonged cell-mediated and humoral immune responses detectable in the first 3 weeks of post-immunization may be responsible for conferring of protective immunity. (author)

  18. Accelerated immune senescence and reduced response to vaccination in ovariectomized female rhesus macaques

    OpenAIRE

    Engelmann, Flora; Barron, Alex; Urbanski, Henryk; Neuringer, Martha; Kohama, Steven G.; Park, Byung; Messaoudi, Ilhem

    2010-01-01

    Aging is associated with a general dysregulation in immune function, commonly referred to as “immune senescence”. Several studies have shown that female sex steroids can modulate the immune response. However, the impact of menopause-associated loss of estrogen and progestins on immune senescence remains poorly understood. To help answer this question, we examined the effect of ovariectomy on T-cell homeostasis and function in adult and aged female rhesus macaques. Our data show that in adult ...

  19. Immune response in spirlins (Alburnoides bipunctatus, Bloch 1782) infested by Ligula intestinalis parasite

    OpenAIRE

    Mostafa Halimi; Abasalt Hosseinzadeh Colagar; Mohammad Reza Youssefi

    2014-01-01

    Ligula intestinalis parasite is a cestode that can cause remarkable damages to fishes. SDS-PAGE is one of the methods that can be used to determine the immune serum band polymorphism and immune responses in fishes infested by Ligula intestinalis. This study reports the results of an investigation conducted using SDS-PAGE focusing on immune serum band polymorphism and on the reaction of the immune system in spirlins (Alburnoides bipunctatus) infested by pleurocercoids of Ligula intestinalis pa...

  20. The ability of four genotypic interpretation systems to predict virological response to ritonavir-boosted protease inhibitors

    DEFF Research Database (Denmark)

    Fox, Zoe V; Geretti, Anna Maria; Kjaer, Jesper;

    2007-01-01

    : Limited information exists on the prognostic value of genotypic interpretation systems (GISs) for ritonavir-boosted protease inhibitors (PI/rs). We compared PI/r resistance levels ascribed by four GIS and examined their abilities to predict HIV-RNA reductions after starting a PI/r-based regimen...

  1. Pre-existing vector immunity does not prevent replication deficient adenovirus from inducing efficient CD8 T-cell memory and recall responses.

    Directory of Open Access Journals (Sweden)

    Maria Abildgaard Steffensen

    Full Text Available Adenoviral vectors have shown a great potential for vaccine development due to their inherent ability to induce potent and protective CD8 T-cell responses. However, a critical issue regarding the use of these vectors is the existence of inhibitory immunity against the most commonly used Ad5 vector in a large part of the human population. We have recently developed an improved adenoviral vaccine vector system in which the vector expresses the transgene tethered to the MHC class II associated invariant chain (Ii. To further evaluate the potential of this system, the concept of pre-existing inhibitory immunity to adenoviral vectors was revisited to investigate whether the inhibition previously seen with the Ad5 vector also applied to the optimized vector system. We found this to be the case, and antibodies dominated as the mechanism underlying inhibitory vector immunity. However, presence of CD8 T cells directed against epitopes in the adenoviral vector seemed to correlate with repression of the induced response in re-vaccinated B-cell deficient mice. More importantly, despite a repressed primary effector CD8 T-cell response in Ad5-immune animals subjected to vaccination, memory T cells were generated that provided the foundation for an efficient recall response and protection upon subsequent viral challenge. Furthermore, the transgene specific response could be efficiently boosted by homologous re-immunization. Taken together, these studies indicate that adenoviral vectors can be used to induce efficient CD8 T-cell memory even in individuals with pre-existing vector immunity.

  2. Bystander T cells in human immune responses to dengue antigens

    Directory of Open Access Journals (Sweden)

    Suwannasaen Duangchan

    2010-09-01

    Full Text Available Abstract Background Previous studies of T cell activation in dengue infection have focused on restriction of specific T cell receptors (TCRs and classical MHC molecules. However, bystander T cell activation, which is TCR independent, occurs via cytokines in other viral infections, both in vitro and in vivo, and enables T cells to bypass certain control checkpoints. Moreover, clinical and pathological evidence has pointed to cytokines as the mediators of dengue disease severity. Therefore, we investigated bystander T cell induction by dengue viral antigen. Results Whole blood samples from 55 Thai schoolchildren aged 13-14 years were assayed for in vitro interferon-gamma (IFN-γ induction in response to inactivated dengue serotype 2 antigen (Den2. The contribution of TCR-dependent and independent pathways was tested by treatment with cyclosporin A (CsA, which inhibits TCR-dependent activation of T cells. ELISA results revealed that approximately 72% of IFN-γ production occurred via the TCR-dependent pathway. The major IFN-γ sources were natural killer (NK (mean ± SE = 55.2 ± 3.3, CD4+T (24.5 ± 3.3 and CD8+T cells (17.9 ± 1.5, respectively, as demonstrated by four-color flow cytometry. Interestingly, in addition to these cells, we found CsA-resistant IFN-γ producing T cells (CD4+T = 26.9 ± 3.6% and CD8+T = 20.3 ± 2.1% implying the existence of activated bystander T cells in response to dengue antigen in vitro. These bystander CD4+ and CD8+T cells had similar kinetics to NK cells, appeared after 12 h and were inhibited by anti-IL-12 neutralization indicating cytokine involvement. Conclusions This study described immune cell profiles and highlighted bystander T cell activation in response to dengue viral antigens of healthy people in an endemic area. Further studies on bystander T cell activation in dengue viral infection may reveal the immune mechanisms that protect or enhance pathogenesis of secondary dengue infection.

  3. Polar lipids of Burkholderia pseudomallei induce different host immune responses.

    Directory of Open Access Journals (Sweden)

    Mercedes Gonzalez-Juarrero

    Full Text Available Melioidosis is a disease in tropical and subtropical regions of the world that is caused by Burkholderia pseudomallei. In endemic regions the disease occurs primarily in humans and goats. In the present study, we used the goat as a model to dissect the polar lipids of B. pseudomallei to identify lipid molecules that could be used for adjuvants/vaccines or as diagnostic tools. We showed that the lipidome of B. pseudomallei and its fractions contain several polar lipids with the capacity to elicit different immune responses in goats, namely rhamnolipids and ornithine lipids which induced IFN-γ, whereas phospholipids and an undefined polar lipid induced strong IL-10 secretion in CD4(+ T cells. Autologous T cells co-cultured with caprine dendritic cells (cDCs and polar lipids of B. pseudomallei proliferated and up-regulated the expression of CD25 (IL-2 receptor molecules. Furthermore, we demonstrated that polar lipids were able to up-regulate CD1w2 antigen expression in cDCs derived from peripheral blood monocytes. Interestingly, the same polar lipids had only little effect on the expression of MHC class II DR antigens in the same caprine dendritic cells. Finally, antibody blocking of the CD1w2 molecules on cDCs resulted in decreased expression for IFN-γ by CD4(+ T cells. Altogether, these results showed that polar lipids of B. pseudomallei are recognized by the caprine immune system and that their recognition is primarily mediated by the CD1 antigen cluster.

  4. Invitro immune responses in children following BCG vaccination

    Directory of Open Access Journals (Sweden)

    Vijayalakshmi V

    2006-01-01

    Full Text Available Introduction: There is still no consensus on the efficacy of BCG vaccine in the prevention of tuberculosis. This study therefore addressed the question of the magnitude of immunity afforded by BCG, by studying the effector mechanisms of protection in children. The main objectives were to assess the degree of immunity conferred by BCG vaccine in children and to identify the most immunogenic antigen(s of BCG by conducting in-vitro studies. Materials and methods: Children in the age-group of 1 to 10 years, were categorized: (A normal, and vaccinated with BCG during the first year, n=45, (B normal, without scar and with no evident history of vaccination, n=31: and (C children admitted in the hospital with a confirmed diagnosis of tuberculosis, n=31. Fractions of BCG were obtained by lysis, sonication, separation by gel chromatography, HPLC and confirmed by SDS-PAGE. In lymphoproliferative assays PBMC were cultured and stimulated with either Concanavalin-A or Tuberculin or the fractions of BCG. Stimulation indices (SI in lymphoproliferation, CD4/CD8 cells, levels of Interferon-γ (IFN- γ in the culture supernatants were measured by ELISA. Results: The vaccinated children displayed significantly high (P< 0.05 mean values of SI in LTT, CD4/CD8 cell ratio against the unfractionated, 67kDa fraction and BCG-CF Ags. While 100% of the vaccinated children had positive lymphoproliferation indices to BCG-CF, only 8.3% of the unvaccinated children were positive. Conclusion: Some of the components of BCG induced a strong Thl cell response in children. These immunogenic antigens were present in the whole cell lysate. The use of BCG vaccine for tuberculosis is worthwhile till a new vaccine is developed.

  5. Contribution of C3d-P28 repeats to enhancement of immune responses against HBV-preS2/S induced by gene immunization

    Institute of Scientific and Technical Information of China (English)

    Li-Xin Wang; Wei Xu; Qing-Dong Guan; Yi-Wei Chu; Ying Wang; Si-Dong Xiong

    2004-01-01

    AIM: To investigate whether P28 derived from C3d can enhance the immune response to HBV-preS2/S induced by directly injection of naked plasmids containing variable repeats of P28 and HBV-preS2/S in fusion form.METHODS: One to four copies of C3d-P28 coding gene,amplified by PCR and modified by restriction endonucleases digestion, were subcloned into a eukaryotic expression vector pVAON33 to construct pVAON33-P28, pVAON33-P28.2, pVAON33-P28.3 and pVAON33-P28.4 (pVAON33-P28.[1-4]). HBV-preS2/S coding sequence was then introduced into the pVAON33-P28.[1-4] and identified by both PCR and DNA sequencing. BALB/c mice were primed by intramuscular gene immunization with 100 μg different recombinant plasmids on day 0 and were boosted by subcutaneous inoculation with HBsAg protein (1 μg) 12wk post-priming. The levels and avidity of specific IgG in sera collected at the indicated times from each group were determined by ELISA and NaSCN-displacement ELISA,respectively.RESULTS: HBsAg specific antibody response was elicited in groups primed with plasmids pVAON33-S2/S-P28.[1-4]and pVAON33-S2/S. However, the response against HBsAg in the groups primed with pVAON33-S2/S-P28.[1-4] was significantly higher than that in pVAON33-S2/S group, the highest level of the specific antibody response was observed in the groups primed with pVAON33-S2/S-P28.4 (P<0.01).After secondary immunization with specific antigen, the acceleration of antibody levels was significantly higher and faster in the mice primed with DNA expressing preS2/S-P28 fusions than that with DNA expressing preS2/S only (P<0.05).Interestingly, mice primed with DNA expressing preS2/SP28.4 fusions maintained the highest levels of anti-HBs antibodies in all animals. The avidity assay showed that the avidity index (AI) collected at 18 wk from mice primed with pVAON33-S2/S-P28.3 and pVAON33-S2/S-P28.4 were significantly higher than that from preS2/S-DNA vaccinated mice (P<0.01).CONCLUSION: Different repeats of C3d-P28 can

  6. Movement Limitation and Immune Responses of Rhesus Monkeys

    Science.gov (United States)

    Sonnenfeld, Gerald; Morton, Darla S.; Swiggett, Jeanene P.; Hakenewerth, Anne M.; Fowler, Nina A.

    1993-01-01

    The effects of restraint on immunological parameters was determined in an 18 day ARRT (adult rhesus restraint test). The monkeys were restrained for 18 days in the experimental station for the orbiting primate (ESOP), the chair of choice for Space Shuttle experiments. Several immunological parameters were determined using peripheral blood, bone marrow, and lymph node specimens from the monkeys. The parameters included: response of bone marrow cells to GM-CSF (granulocyte-macrophage colony stimulating factor), leukocyte subset distribution, and production of IFN-alpha (interferon-alpha) and IFN-gamma (interferon-gamma). The only parameter changed after 18 days of restraint was the percentage of CDB+ T cells. No other immunological parameters showed changes due to restraint. Handling and changes in housing prior to the restraint period did apparently result in some restraint-independent immunological changes. Handling must be kept to a minimum and the animals allowed time to recover prior to flight. All experiments must be carefully controlled. Restraint does not appear to be a major issue regarding the effects of space flight on immune responses.

  7. Control of the innate immune response by the mevalonate pathway.

    Science.gov (United States)

    Akula, Murali K; Shi, Man; Jiang, Zhaozhao; Foster, Celia E; Miao, David; Li, Annie S; Zhang, Xiaoman; Gavin, Ruth M; Forde, Sorcha D; Germain, Gail; Carpenter, Susan; Rosadini, Charles V; Gritsman, Kira; Chae, Jae Jin; Hampton, Randolph; Silverman, Neal; Gravallese, Ellen M; Kagan, Jonathan C; Fitzgerald, Katherine A; Kastner, Daniel L; Golenbock, Douglas T; Bergo, Martin O; Wang, Donghai

    2016-08-01

    Deficiency in mevalonate kinase (MVK) causes systemic inflammation. However, the molecular mechanisms linking the mevalonate pathway to inflammation remain obscure. Geranylgeranyl pyrophosphate, a non-sterol intermediate of the mevalonate pathway, is the substrate for protein geranylgeranylation, a protein post-translational modification that is catalyzed by protein geranylgeranyl transferase I (GGTase I). Pyrin is an innate immune sensor that forms an active inflammasome in response to bacterial toxins. Mutations in MEFV (encoding human PYRIN) result in autoinflammatory familial Mediterranean fever syndrome. We found that protein geranylgeranylation enabled Toll-like receptor (TLR)-induced activation of phosphatidylinositol-3-OH kinase (PI(3)K) by promoting the interaction between the small GTPase Kras and the PI(3)K catalytic subunit p110δ. Macrophages that were deficient in GGTase I or p110δ exhibited constitutive release of interleukin 1β that was dependent on MEFV but independent of the NLRP3, AIM2 and NLRC4 inflammasomes. In the absence of protein geranylgeranylation, compromised PI(3)K activity allows an unchecked TLR-induced inflammatory responses and constitutive activation of the Pyrin inflammasome. PMID:27270400

  8. Effect of tetanus-diphtheria (Td) vaccine on immune response to hepatitis B vaccine in healthy individuals with insufficient immune response

    OpenAIRE

    Maryam Salehi; Abbas Haghighat; Hassan Salehi; Roya Taleban; Marzieh Salehi; Nader Kalbasi; Mohammad Moafi; Mohammad Mahdi Salehi

    2015-01-01

    Background: Hepatitis B virus (HBV) fails to produce appropriate immune responses in some healthy individuals; thus, different strategies have been adopted to promote immune responses. The current study aimed at evaluating the efficacy of HBV vaccine coadministered with tetanus-diphtheria (Td) vaccine compared with HBV vaccine in healthy individuals through measuring hepatitis B surface antibody (HBsAb) levels. Materials and Methods: This was a randomized controlled clinical trial, which was ...

  9. Immune responses of pigs immunized with a recombinant porcine reproductive and respiratory syndrome virus expressing porcine GM-CSF.

    Science.gov (United States)

    Li, Zhijun; Wang, Gang; Wang, Yan; Zhang, Chong; Huang, Baicheng; Li, Qiongyi; Li, Liangliang; Xue, Biyun; Ding, Peiyang; Cai, Xuehui; Wang, Chengbao; Zhou, En-Min

    2015-11-15

    Porcine reproductive and respiratory syndrome virus (PRRSV) has spread worldwide, causing huge economic losses to the swine industry. The current PRRSV vaccines have failed to provide broad protection against various strains. Granulocyte macrophage colony-stimulating factor (GM-CSF), an efficacious adjuvant, has been shown to enhance the immunogenicity of various vaccines. The purpose of this study was to construct a recombinant live attenuated PRRSV that expresses porcine GM-CSF (pGM-CSF) and evaluate the immune responses of pigs immunized with the recombinant virus. The results showed that the recombinant PRRSV was successfully rescued and had similar growth properties to parental virus grown in Marc-145 cells. The recombinant virus was stable for 10 passages in cell culture. Pigs intramuscularly immunized with the recombinant virus produced a similar humoral response to that elicited using parental virus. With regard to cell-mediated immunity assessed in peripheral blood, the recombinant virus induced higher proportion of CD4(+)CD8(+) double-positive T cells (DPT), higher IFN-γ level at 0 and 7 days post-challenge (DPC), and lower viremia at 21 DPC than pigs immunized with parental virus. These results indicate that recombinant PRRSV expressing pGM-CSF can induce a significant higher cellular immune response and reduce the persistent infection compared pigs vaccinated with the parental virus. This is first report of evaluation of immune response in pigs elicited by a recombinant live attenuated PRRSV expressing porcine GM-CSF. It may represent a novel strategy for future development of genetic engineered vaccines against PRRSV infection. PMID:26300317

  10. Differences in immune responses against Leishmania induced by infection and by immunization with killed parasite antigen: implications for vaccine discovery.

    Science.gov (United States)

    Mendonça, Sergio C F

    2016-01-01

    The leishmaniases are a group of diseases caused by different species of the protozoan genus Leishmania and transmitted by sand fly vectors. They are a major public health problem in almost all continents. There is no effective control of leishmaniasis and its geographical distribution is expanding in many countries. Great effort has been made by many scientists to develop a vaccine against leishmaniasis, but, so far, there is still no effective vaccine against the disease. The only way to generate protective immunity against leishmaniasis in humans is leishmanization, consisting of the inoculation of live virulent Leishmania as a means to acquire long-lasting immunity against subsequent infections. At present, all that we know about human immune responses to Leishmania induced by immunization with killed parasite antigens came from studies with first generation candidate vaccines (killed promastigote extracts). In the few occasions that the T cell-mediated immune responses to Leishmania induced by infection and immunization with killed parasite antigens were compared, important differences were found both in humans and in animals. This review discusses these differences and their relevance to the development of a vaccine against leishmaniasis, the major problems involved in this task, the recent prospects for the selection of candidate antigens and the use of attenuated Leishmania as live vaccines. PMID:27600664

  11. The serological response to heartwater immunization in cattle is an indicator of protective immunity

    DEFF Research Database (Denmark)

    Lawrence, J A; Tjørnehøj, Kirsten; Whiteland, A P;

    1995-01-01

    vaccination, all were completely or partially immune to challenge. Ten of the 14 animals which failed to seroconvert were immune but the proportion was not significantly different from that in the unvaccinated controls (4/10). Of 29 animals vaccinated and treated simultaneously with a slow-release doxycycline...

  12. Pulmonary immune response of dogs after exposure to 239PuO2

    International Nuclear Information System (INIS)

    This study evaluated the cell-mediated (CMI) and humoral immune responses in four Beagle dogs five to six years after single inhalation exposures to different monodisperse 239PuO2 aerosols (0.72-1.4μm activity median aerodynamic diameter). These exposures resulted in initial lung burdens ranging from 19 to 35kBq. The immune responses induced by lung immunization of dogs that had inhaled 239PuO2 were not suppressed by large doses of chronic alpha irradiation of the lungs and tracheobronchial lymph nodes, indicating that local pulmonary immune responses are preserved despite severe radiation-induced alteration of these tissues. (author)

  13. Interferon-γ: biological function and application for study of cellular immune response

    Directory of Open Access Journals (Sweden)

    A. A. Lutckii

    2015-01-01

    Full Text Available Cellular immune response plays a central role in control of intracellular pathogens like viruses, some bacteria and parasites. Evaluation of presence, specificity and strength of cellular immune response can be done by investigation of reaction of immune cells to specific stimulus, like antigen. The major cellular reactions to antigen stimulation are production of cytokines, proliferation and cytotoxicity. This review is focused on interferon-gamma as one of the central Th1 cytokines: its biology, immunological role and application as marker of cellular immune response.

  14. Effect of oral administration of Lactobacillus paracasei L9 on mouse systemic immunity and the immune response in the intestine

    Directory of Open Access Journals (Sweden)

    Zhu Yuanbo

    2016-01-01

    Full Text Available A probiotic strain Lactobacillus paracasei L9,which was isolated from human intestine, was investigated for its immunomodulatory activity in vivo. Results showed that L9 improved systemic immunity by enhancing the phagocytic activity of peritoneal macrophages, the proliferation ratio of splenocytes, the IgG level in the serum and the level of IgA in the mucosa. Further, L9induced theTh1-polarized immune response by elevating the IFN-γ/IL-4 ratio in the mucosa. This effect was confirmed by the enhanced IL-12-inducing activity of macrophages after in vitro stimulation of L9. Also detected was increased expression of TLR-2mRNA in the mucosa. We predict that L9 could enhance innate immunity by activating TLR-2 in the mucosa, and enhance acquired immunity by promoting Th1 polarization through induced production of IL-12 by macrophages.

  15. Innate immune cell response upon Candida albicans infection.

    Science.gov (United States)

    Qin, Yulin; Zhang, Lulu; Xu, Zheng; Zhang, Jinyu; Jiang, Yuan-Ying; Cao, Yongbing; Yan, Tianhua

    2016-07-01

    Candida albicans is a polymorphic fungus which is the predominant cause of superficial and deep tissue fungal infections. This microorganism has developed efficient strategies to invade the host and evade host defense systems. However, the host immune system will be prepared for defense against the microbe by recognition of receptors, activation of signal transduction pathways and cooperation of immune cells. As a consequence, C. albicans could either be eliminated by immune cells rapidly or disseminate hematogenously, leading to life-threatening systemic infections. The interplay between Candida albicans and the host is complex, requiring recognition of the invaded pathogens, activation of intricate pathways and collaboration of various immune cells. In this review, we will focus on the effects of innate immunity that emphasize the first line protection of host defense against invaded C. albicans including the basis of receptor-mediated recognition and the mechanisms of cell-mediated immunity. PMID:27078171

  16. Effect of therapeutic irradiation on the immune responses

    International Nuclear Information System (INIS)

    The immune responses of 60 patients undergoing therapeutic irradiation were evaluated according to four anatomical sites irradiated. In vitro lymphocyte transformation tests with PHA, Con-A, and PWM and quantitative assays of IgG, IgA, and IgM were performed on blood obtained from each patient before and during therapy, and two weeks, two months, and six months after therapy. At these same testing intervals, skin tests with PPD, mumps antigen, Candida antigen, and SD-SK were performed. During irradiation, the mean values of all lymphocyte transformation tests were depressed, varying from 48 percent to 64 percent of pretreatment baseline. This depression persisted until about two months after completion of treatment. By six months, response rose to pretreatment values. When response was evaluated according to sites irradiated with all mitogens, the pelvic and pelvic plus abdominal groups showed consistently greater depression than the chest or head and neck groups. Radiation effected no significant changes in the mean values of IgG, IgA or IgM. A decrease in skin sensitivity was noted during radiation; 73 percent of the subjects responded positively before therapy while only 53 percent had at least one positive test during therapy. By two months postirradiation, 73 percent of the group clinically free of disease had positive skin tests. A comparison of clinical condition with test results is significant when one considers the 17 patients who developed metastatic disease or died from disease. The depression for all three mitogens during radiation therapy was greater for this group. Of the 17, only four had IgG levels in the normal range, and consistently fewer positive skin tests were demonstrated

  17. Reproductive effort reduces specific immune response and parasite resistance

    OpenAIRE

    Nordling, D.; Andersson, M.; Zohari, S.; Gustafsson, L.

    1998-01-01

    If a trade-off exists between reproductive effort and immune function, life-history decisions may have important implications for parasite resistance. Here, we report effects of experimental manipulation of reproductive effort on subsequent specific immune function and parasite resistance in the collared flycatcher, Ficedula albicollis. Our results show that increased reproductive effort of females immunized with Newcastle disease virus (NDV) vaccine negatively affected the ability to respond...

  18. Behavioural conditioning as the mediator of placebo responses in the immune system

    OpenAIRE

    Vits, Sabine; Cesko, Elvir; Enck, Paul; Hillen, Uwe; Schadendorf, Dirk; Schedlowski, Manfred

    2011-01-01

    Current placebo research postulates that conditioning processes are one of the major mechanisms of the placebo response. Behaviourally conditioned changes in peripheral immune functions have been demonstrated in experimental animals, healthy subjects and patients. The physiological mechanisms responsible for this ‘learned immune response’ are not yet fully understood, but some relevant afferent and efferent pathways in the communication between the brain and the peripheral immune system have ...

  19. Differential Immune Responses of Red Deer (Cervus elaphus) following Experimental Challenge with Mycobacterium avium subsp. paratuberculosis▿

    OpenAIRE

    Robinson, Mark; O'Brien, Rory; Mackintosh, Colin; Griffin, Frank

    2008-01-01

    Immune responses of red deer (Cervus elaphus) that presented with different levels of paucibacillary pathology were profiled to detail immune changes during the progression of Johne's disease. Immune responses were monitored using an immunoglobulin G1 (IgG1) antibody enzyme-linked immunosorbent assay (ELISA), a gamma interferon (IFN-γ) ELISA, and flow cytometry. Animals in the study were divided into outcome groups postmortem according to disease severity. All animals mounted IgG1 antibody an...

  20. The inflammatory an immune response to mousepox (infectious ectromelia) virus

    International Nuclear Information System (INIS)

    The ectromelia virus(EV) has been recognized as the etiological agent of a relatively common infection in laboratory mouse colonies around the world, i.e. Europe (including Poland), U.S.A. and Asia. Due to widespread use of mice in biomedical research, it is important to study the biology of strains characteristic for a given country. This is particularly significant for the diagnosis, prevention and control ectromelia. In severe epizootics, approximately 90% morbidity is observed within colonies and mortality rate exceeding 70% is observed within 4 to 20 days from the appearance of clinical symptoms. The resistance to lethal infection is mouse strain-dependent. Several inbred strains of mice, including C57BL/6 and AKR are resistant to the lethal effects of EV infection, while others, such as A and BALB/c are susceptible. Recent studies indicate that (1) T lymphocytes, natural killer cells and interferon (IFN)-dependent host defenses must operate for the expression of resistance, (2) virus-specific T-cell precursors appear earlier in regional lymph nodes of resistant than susceptible mice, and (3) resistance mechanism are expressed during early stages of infection. Over the past several years, (1) induction of anti-EV cytotoxic CD8+ T lymphocytes responses in vivo in the absence of CD4+ (T helper) cells, (2) importance of some cytokines e.g., IFN-gamma in EV clearance at all stages of infection, and (3) induction of nitric oxide synthase, which is necessary for a substantial antiviral activity of IFN-gamma, have been demonstrated. The effector mechanism by which EV-specific immune cells (T lymphocytes) execute their and inflammatory functions are thought to involve the release of soluble mediators that attract, focus and active cells at the infected sites. It is possible that the skin is the most relevant organ for studying the biology of an EV infection in vivo, yet very little is known concerning EV replication there and the importance of the skin;s innate and

  1. Revaccination of cattle with bacille Calmette-Guérin two years after first vaccination when immunity has waned, boosted protection against challenge with Mycobacterium bovis.

    Science.gov (United States)

    Parlane, Natalie A; Shu, Dairu; Subharat, Supatsak; Wedlock, D Neil; Rehm, Bernd H A; de Lisle, Geoffrey W; Buddle, Bryce M

    2014-01-01

    In both humans and animals, controversy exists concerning the duration of protection induced by BCG vaccine against tuberculosis (TB) and whether revaccination enhances protection. A long-term study was undertaken to determine whether BCG-vaccinated calves would be protected against challenge with Mycobacterium bovis 2½ years after vaccination and to determine the effect of revaccination after 2 years. Seventy-nine calves were divided into five groups (n = 15-17 calves/group) with four of the groups vaccinated subcutaneously with 105 CFU of BCG Danish at 2-4 weeks of age and the fifth group serving as non-vaccinated controls. Three of the four BCG-vaccinated groups were revaccinated 2 years after the initial vaccination. One BCG-vaccinated group was revaccinated with BCG. A second group was vaccinated subcutaneously with a TB protein vaccine consisting of biopolyester particles (Biobeads) displaying two mycobacterial proteins, ESAT-6 and Antigen 85A, mixed with an adjuvant. A third group was vaccinated with TB proteins from M. bovis culture filtrate, mixed with an adjuvant. Twenty-three weeks after the BCG revaccination, all animals were challenged endotracheally with virulent M. bovis and a further 13 weeks later, animals were killed and necropsied to determine protection against TB. The BCG-vaccinated animals produced positive tuberculin caudal fold intradermal (15 of 62 animals) and IFN-γ TB test responses (six of 62 animals) at 6 months after vaccination, but not at subsequent time-points compared to the non-vaccinated animals. Calves receiving a single vaccination with BCG vaccine 2½ years prior to challenge were not protected against TB, while those revaccinated with BCG 2 years after the initial vaccination displayed significant reductions in lung and pulmonary lymph node lesion scores compared to the non-vaccinated animals. In contrast, no reduction in lesion scores was observed in the animals revaccinated with the TB protein vaccines with their immune

  2. Distinct signatures of the immune responses in low risk versus high risk neuroblastoma

    Directory of Open Access Journals (Sweden)

    Wang Ena

    2011-10-01

    Full Text Available Abstract Background Over 90% of low risk (LR neuroblastoma patients survive whereas less than 30% of high risk (HR patients are long term survivors. Age (children younger than 18 months old is associated with LR disease. Considering that adaptive immune system is well developed in older children, and that T cells were shown to be involved in tumor escape and progression of cancers, we sought to determine whether HR patients may tend to show a signature of adaptive immune responses compared to LR patients who tend to have diminished T-cell responses but an intact innate immune response. Methods We performed microarray analysis of RNA extracted from the tumor specimens of HR and LR patients. Flow cytometry was performed to determine the cellular constituents in the blood while multiplex cytokine array was used to detect the cytokine profile in patients' sera. A HR tumor cell line, SK-N-SH, was also used for detecting the response to IL-1β, a cytokines which is involved in the innate immune responses. Results Distinct patterns of gene expression were detected in HR and LR patients indicating an active T-cell response and a diminished adaptive immune response, respectively. A diminished adaptive immune response in LR patients was evident by higher levels of IL-10 in the sera. In addition, HR patients had lower levels of circulating myeloid derived suppressor cells (MDSC compared with a control LR patient. LR patients showed slightly higher levels of cytokines of the innate immune responses. Treatment of the HR tumor line with IL-1β induced expression of cytokines of the innate immune responses. Conclusions This data suggests that adaptive immune responses may play an important role in the progression of HR disease whereas innate immune responses may be active in LR patients.

  3. Isotope-based immunological techniques. Their use in assessment of immune competence and the study of immune responses to pathogens

    International Nuclear Information System (INIS)

    The influence of isotope-based techniques on both assessment of immune competence and immune response to pathogens is discussed. Immunodeficiencies acquired as a result of factors like malnutrition and concomitant disease can severely affect not only attempts to intensify and improve production but also successful immune response against important vaccines such as rinderpest and foot-and-mouth disease. Isotope-based techniques, with their accuracy, speed and small sample volume, are ideally suited for assessing immunocompetence. One of the main drawbacks remains antigen purity, an area where research should now be concentrated. Lymphocyte transformation is widely used to assess cell-mediated immuno-competence but techniques to assess biological functions such as phagocytosis and cell-mediated cytotoxicity could more usefully reflect immune status. These latter techniques utilize isotopes such as 3H, 14C, 32P and 125I. Investigation of specific cell-mediated immune response often requires a labelled target. Suitable isotopes such as 51Cr, 99Tcsup(m), 75Se and 3H are compared for their capacity to label both mammalian and parasite targets. Suggestions are made on a number of areas of research that might usefully be encouraged and supported in order to improve applied veterinary immunology in tropical countries. (author)

  4. Clinical Response of Pelvic and Para-aortic Lymphadenopathy to a Radiation Boost in the Definitive Management of Locally Advanced Cervical Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Rash, Dominique L. [Department of Radiation Oncology, University of California Davis Medical Center, Sacramento, California (United States); Lee, Yongsook C. [Department of Radiation Oncology, University of Kansas School of Medicine, Kansas City, Kansas (United States); Kashefi, Amir [Division of Nuclear Medicine, Department of Radiology, University of California Davis Medical Center, Sacramento, California (United States); Durbin-Johnson, Blythe [Division of Biostatistics, Department of Public Health Sciences, University of California Davis School of Medicine, Sacramento, California (United States); Mathai, Mathew; Valicenti, Richard [Department of Radiation Oncology, University of California Davis Medical Center, Sacramento, California (United States); Mayadev, Jyoti S., E-mail: jyoti.mayadev@ucdmc.ucdavis.edu [Department of Radiation Oncology, University of California Davis Medical Center, Sacramento, California (United States)

    2013-10-01

    Purpose: Optimal treatment with radiation for metastatic lymphadenopathy in locally advanced cervical cancer remains controversial. We investigated the clinical dose response threshold for pelvic and para-aortic lymph node boost using radiographic imaging and clinical outcomes. Methods and Materials: Between 2007 and 2011, 68 patients were treated for locally advanced cervical cancer; 40 patients had clinically involved pelvic and/or para-aortic lymph nodes. Computed tomography (CT) or 18F-labeled fluorodeoxyglucose-positron emission tomography scans obtained pre- and postchemoradiation for 18 patients were reviewed to assess therapeutic radiographic response of individual lymph nodes. External beam boost doses to involved nodes were compared to treatment response, assessed by change in size of lymph nodes by short axis and change in standard uptake value (SUV). Patterns of failure, time to recurrence, overall survival (OS), and disease-free survival (DFS) were determined. Results: Sixty-four lymph nodes suspicious for metastatic involvement were identified. Radiation boost doses ranged from 0 to 15 Gy, with a mean total dose of 52.3 Gy. Pelvic lymph nodes were treated with a slightly higher dose than para-aortic lymph nodes: mean 55.3 Gy versus 51.7 Gy, respectively. There was no correlation between dose delivered and change in size of lymph nodes along the short axis. All lymph nodes underwent a decrease in SUV with a complete resolution of abnormal uptake observed in 68%. Decrease in SUV was significantly greater for lymph nodes treated with ≥54 Gy compared to those treated with <54 Gy (P=.006). Median follow-up was 18.7 months. At 2 years, OS and DFS for the entire cohort were 78% and 50%, respectively. Locoregional control at 2 years was 84%. Conclusions: A biologic response, as measured by the change in SUV for metastatic lymph nodes, was observed at a dose threshold of 54 Gy. We recommend that involved lymph nodes be treated to this minimum dose.

  5. Effects of postoperative immune-enhancing enteral nutrition on the immune system, inflammatory responses, and clinical outcome

    Institute of Scientific and Technical Information of China (English)

    蒋小华; 李宁; 朱维铭; 吴国豪; 全志伟; 黎介寿

    2004-01-01

    Objective This study was conducted to evaluate the effects of postoperative immune enhancing enteral nutrition on the immune system, inflammatory responses, and clinical outcome of patients undergoing major abdominal surgery. Methods This study was designed as a multicenter, prospective,randomized and controlled clinical trial. One hundred twenty-four patients undergoing major abdominal surgery were randomly assigned to receive either an immune enhancing enteral diet or an isocaloric and isonitrogenous control enteral diet for seven days. Enteral feeding was initiated 24 hours after surgery. Host immunity was evaluated by measuring levels of IgG, IgM, IgA, CD4, CD8, and CD4/CD8, and the inflammatory response was determined by assessing IL-1α, IL-2, IL-6, IL-10, and TNF-α levels. Infectious complications were also recorded. Results One hundred twenty patients completed the study and four patients were excluded. On postoperative day 9, among patients receiving an immune enhancing diet,IgG, IgA, CD4 and CD4/CD8 levels were significantly higher and TNF-α and IL-6 concentrations were significantly lower compared to the control group. Moreover, among patients receiving an immune enhancing diet, when comparing preoperation to day 9 postoperation levels, increases in IgA, CD4, and CD4/CD8 levels were significantly higher than in control patients and increases in TNF-α concentrations were significantly lower. No statistically significant differences were found between the two groups with regard to infectious complications.Conclusions Postoperative administration of immune enhancing enteral nutrition in patients undergoing major abdominal surgery can positively modulate postoperative immunosuppressive and inflammatory responses.

  6. Modelling the innate immune response against avian influenza virus in chicken

    NARCIS (Netherlands)

    Hagenaars, T.J.; Fischer, E.A.J.; Jansen, C.A.; Rebel, J.M.J.; Spekreijse, D.; Vervelde, L.; Backer, J.A.; Jong, de M.C.M.; Koets, A.P.

    2016-01-01

    At present there is limited understanding of the host immune response to (low pathogenic) avian influenza virus infections in poultry. Here we develop a mathematical model for the innate immune response to avian influenza virus in chicken lung, describing the dynamics of viral load, interferon-α,

  7. The relationship between metabolism and the autophagy machinery during the innate immune response

    OpenAIRE

    Martinez, Jennifer; Verbist, Katherine; Wang, Ruoning; Green, Douglas R.

    2013-01-01

    The innate immune response is shaped by multiple factors, including both traditional autophagy and LC3-associated phagocytosis (LAP). As the autophagic machinery is engaged during times of nutrient stress, arising from scarcity or pathogens, we examine how autophagy, specifically LAP, and cellular metabolism together influence macrophage function and the innate immune response.

  8. Immune Response in Severe Infection: Could Life-Saving Drugs Be Potentially Harmful?

    OpenAIRE

    Maja Surbatovic; Jasna Jevdjic; Milic Veljovic; Nada Popovic; Dragan Djordjevic; Sonja Radakovic

    2013-01-01

    Critically ill patients suffer a high rate of nosocomial infection with secondary sepsis being a common cause of death. Usage of antibiotics and catecholamines is often necessary, but it can compromise complex immune response to infection. This review explores influence of these life-saving drugs on host immune response to severe infection.

  9. Immune response in mice to ingested soya protein: antibody production, oral tolerance and maternal transfer

    DEFF Research Database (Denmark)

    Christensen, Hanne Risager; Pedersen, Susanne Brix; Frøkiær, Hanne

    2004-01-01

    While allergic reactions to soya are increasingly investigated, the normal immune response to ingested soya is scarcely described. In the present study, we wanted to characterise the soya-specific immune response in healthy mice ingesting soya protein. Mice fed a soya-containing diet (F0) and mic...

  10. Effects of alcohol consumption on the allergen-specific immune response in mice

    DEFF Research Database (Denmark)

    Linneberg, Allan; Roursgaard, Martin; Hersoug, Lars-Georg;

    2008-01-01

    There is evidence that chronic alcohol consumption impairs the T-helper 1 (Th1) lymphocyte-regulated cell-mediated immune response possibly favoring a Th2 deviation of the immune response. Moreover, a few epidemiological studies have linked alcohol consumption to allergen-specific IgE sensitization....

  11. Hemagglutinating virus of Japan envelope (HVJ-E) can enhance the immune responses of swine immunized with killed PRRSV vaccine

    International Nuclear Information System (INIS)

    Highlights: ► We investigated the immunoadjuvant effects of HVJ-E on killed PRRSV vaccine. ► HVJ-E enhanced the humoral and cellular responses of the piglets to PRRSV. ► It is suggested that HVJ-E could be developed as a new-type adjuvant for mammals. -- Abstract: Porcine reproductive and respiratory syndrome virus (PRRSV) is an economically detrimental pig pathogen that causes significant losses for the pig industry. The immunostimulatory effects of hemagglutinating virus of Japan envelope (HVJ-E) in cancer therapy and the adjuvant efficacy of HVJ-E have been previously evaluated. The objective of this study was to investigate the adjuvant effects of HVJ-E on immunization with killed PRRSV vaccine, and to evaluate the protective effects of this immunization strategy against virulent PRRSV infection in piglets. Next, the PRRSV-specific antibody response, lymphocyte proliferation, PRRSV-specific IL-2, IL-10 and IFN-γ production, and the overall protection efficacy were evaluated to assess the immune responses of the piglets. The results showed that the piglets inoculated simultaneously with killed PRRSV vaccine and HVJ-E had a significantly stronger immune response than those inoculated with killed PRRSV vaccine alone. Our results suggest that HVJ-E could be employed as an effective adjuvant to enhance the humoral and cellular responses of piglets to PRRSV.

  12. To boost or not boost in radiotherapy

    International Nuclear Information System (INIS)

    The aim of this paper it to analyse and discuss standard definition of the 'boost' procedure in relation to clinical results and new forms of the boost designed on physical and radiobiological bases. Seventeen sets of clinical data including over 5000 cases cancer with different tumour stages and locations and treated with various forms of 'boost' method have been subtracted from literature. Effectiveness of boost is analyzed regarding its place in combined treatment, timing and subvolume involved. Radiobiological parameter of D10 and normalization method for biologically equivalent doses and dose intensity are used to simulated cold and not subvolumes (hills and dales) and its influence of effectiveness on the boost delivery. Sequential and concomitant boost using external irradiation, although commonly used, offers LTC benefit lower than expected. Brachytherapy, intraoperative irradiation and concurrent chemotherapy boost methods appear more effective. Conformal radiotherapy, with or without dose-intensity modulation, allows heterogeneous increase in dose intensity within the target volume and can be used to integrate the 'boost dose' into baseline treatment (Simultaneous Integrated Boost and SIB). Analysis of interrelationships between boost-dose; boost volume and its timing shows that a TCP benefit from boosting can be expected when a relatively large part of the target volume is involved. Increase in boost dose above 1.2-1.3 of baseline dose using 'standard' methods does not substantially further increase the achieved TCP benefit unless hypoxic cells are a problem. Any small uncertainties in treatment planning can ruin all potential beneficial effect of the boost. For example, a 50% dose deficit in a very small (e.g. 1%) volume of target can decrease TCP to zero. Therefore boost benefits should be carefully weighed against any risk of cold spots in the target volume. Pros and cons in discussion of the role of boost in radiotherapy lead to the important

  13. Inhomogeneous DNA replication kinetics is associated with immune system response

    Science.gov (United States)

    Bechhoefer, John; Gauthier, Michel G.; Norio, Paolo

    2013-03-01

    In eukaryotic organisms, DNA replication is initiated at ``origins,'' launching ``forks'' that spread bidirectionally to replicate the genome. The distribution and firing rate of these origins and the fork progression velocity form the ``replication program.'' Previous models of DNA replication in eukaryotes have assumed firing rates and replication fork velocities to be homogeneous across the genome. But large variations in origin activity and fork velocity do occur. Here, we generalize our replication model to allow for arbitrary spatial variation of initiation rates and fork velocities in a given region of the genome. We derive and solve rate equations for the forks and replication probability, to obtain the mean-field replication program. After testing the model on simulations, we analyze the changes in replication program that occur during B cell development in the mouse. B cells play a major role in the adaptive immune system by producing the antibodies. We show that the process of cell differentiation is associated with a change in replication program, where the zones of high origin initiation rates located in the immunoglobulin heavy-chain locus shift their position as the locus prepares to undergo the recombination events responsible for generating antibody specificity. This work was funded by HSFP and NSERC-Canada (MGG and JB) and by NIH-NIGMS grant R01GM080606 (PN).

  14. Immune response to infection by Leishmania: A mathematical model.

    Science.gov (United States)

    Siewe, Nourridine; Yakubu, Abdul-Aziz; Satoskar, Abhay R; Friedman, Avner

    2016-06-01

    Leishmaniasis is a disease caused by the Leishmania parasites. The injection of the parasites into the host occurs when a sand fly, which is the vector, bites the skin of the host. The parasites, which are obligate, take advantage of the immune system response and invade both the classically activated macrophages (M1) and the alternatively activated macrophages (M2). In this paper, we develop a mathematical model to explain the evolution of the disease. Simulations of the model show that, M2 macrophages steadily increase and M1 macrophages steadily decrease, while M1+M2 reach a steady state which is approximately the same as at healthy state of the host. Furthermore, the ratio of Leishmania parasites to macrophages depends homogeneously on their ratio at the time of the initial infection, in agreement with in vitro experimental data. The model is used to simulate treatment by existing or potential new drugs, and to compare the efficacy of different schedules of drug delivery. PMID:26987853

  15. Autophagy in the immune response to tuberculosis: clinical perspectives.

    LENUS (Irish Health Repository)

    Ní Cheallaigh, C

    2011-06-01

    A growing body of evidence points to autophagy as an essential component in the immune response to tuberculosis. Autophagy is a direct mechanism of killing intracellular Mycobacterium tuberculosis and also acts as a modulator of proinflammatory cytokine secretion. In addition, autophagy plays a key role in antigen processing and presentation. Autophagy is modulated by cytokines; it is stimulated by T helper type 1 (Th1) cytokines such as tumour necrosis factor (TNF)-α and interferon (IFN)-γ, and is inhibited by the Th2 cytokines interleukin (IL)-4 and IL-13 and the anti-inflammatory cytokine IL-10. Vitamin D, via cathelicidin, can also induce autophagy, as can Toll-like receptor (TLR)-mediated signals. Autophagy-promoting agents, administered either locally to the lungs or systemically, could have a clinical application as adjunctive treatment of drug-resistant and drug-sensitive tuberculosis. Moreover, vaccines which effectively induce autophagy could be more successful in preventing acquisition or reactivation of latent tuberculosis.

  16. Quercetin and Its Anti-Allergic Immune Response.

    Science.gov (United States)

    Mlcek, Jiri; Jurikova, Tunde; Skrovankova, Sona; Sochor, Jiri

    2016-01-01

    Quercetin is the great representative of polyphenols, flavonoids subgroup, flavonols. Its main natural sources in foods are vegetables such as onions, the most studied quercetin containing foods, and broccoli; fruits (apples, berry crops, and grapes); some herbs; tea; and wine. Quercetin is known for its antioxidant activity in radical scavenging and anti-allergic properties characterized by stimulation of immune system, antiviral activity, inhibition of histamine release, decrease in pro-inflammatory cytokines, leukotrienes creation, and suppresses interleukin IL-4 production. It can improve the Th1/Th2 balance, and restrain antigen-specific IgE antibody formation. It is also effective in the inhibition of enzymes such as lipoxygenase, eosinophil and peroxidase and the suppression of inflammatory mediators. All mentioned mechanisms of action contribute to the anti-inflammatory and immunomodulating properties of quercetin that can be effectively utilized in treatment of late-phase, and late-late-phase bronchial asthma responses, allergic rhinitis and restricted peanut-induced anaphylactic reactions. Plant extract of quercetin is the main ingredient of many potential anti-allergic drugs, supplements and enriched products, which is more competent in inhibiting of IL-8 than cromolyn (anti-allergic drug disodium cromoglycate) and suppresses IL-6 and cytosolic calcium level increase. PMID:27187333

  17. GMCSF-armed vaccinia virus induces an antitumor immune response.

    Science.gov (United States)

    Parviainen, Suvi; Ahonen, Marko; Diaconu, Iulia; Kipar, Anja; Siurala, Mikko; Vähä-Koskela, Markus; Kanerva, Anna; Cerullo, Vincenzo; Hemminki, Akseli

    2015-03-01

    Oncolytic Western Reserve strain vaccinia virus selective for epidermal growth factor receptor pathway mutations and tumor-associated hypermetabolism was armed with human granulocyte-macrophage colony-stimulating factor (GMCSF) and a tdTomato fluorophore. As the assessment of immunological responses to human transgenes is challenging in the most commonly used animal models, we used immunocompetent Syrian golden hamsters, known to be sensitive to human GMCSF and semipermissive to vaccinia virus. Efficacy was initially tested in vitro on various human and hamster cell lines and oncolytic potency of transgene-carrying viruses was similar to unarmed virus. The hGMCSF-encoding virus was able to completely eradicate subcutaneous pancreatic tumors in hamsters, and to fully protect the animals from subsequent rechallenge with the same tumor. Induction of specific antitumor immunity was also shown by ex vivo co-culture experiments with hamster splenocytes. In addition, histological examination revealed increased infiltration of neutrophils and macrophages in GMCSF-virus-treated tumors. These findings help clarify the mechanism of action of GMCSF-armed vaccinia viruses undergoing clinical trials. PMID:25042001

  18. Quercetin and Its Anti-Allergic Immune Response

    Directory of Open Access Journals (Sweden)

    Jiri Mlcek

    2016-05-01

    Full Text Available Quercetin is the great representative of polyphenols, flavonoids subgroup, flavonols. Its main natural sources in foods are vegetables such as onions, the most studied quercetin containing foods, and broccoli; fruits (apples, berry crops, and grapes; some herbs; tea; and wine. Quercetin is known for its antioxidant activity in radical scavenging and anti-allergic properties characterized by stimulation of immune system, antiviral activity, inhibition of histamine release, decrease in pro-inflammatory cytokines, leukotrienes creation, and suppresses interleukin IL-4 production. It can improve the Th1/Th2 balance, and restrain antigen-specific IgE antibody formation. It is also effective in the inhibition of enzymes such as lipoxygenase, eosinophil and peroxidase and the suppression of inflammatory mediators. All mentioned mechanisms of action contribute to the anti-inflammatory and immunomodulating properties of quercetin that can be effectively utilized in treatment of late-phase, and late-late-phase bronchial asthma responses, allergic rhinitis and restricted peanut-induced anaphylactic reactions. Plant extract of quercetin is the main ingredient of many potential anti-allergic drugs, supplements and enriched products, which is more competent in inhibiting of IL-8 than cromolyn (anti-allergic drug disodium cromoglycate and suppresses IL-6 and cytosolic calcium level increase.

  19. CD40/CD40 LIGAND INTERACTIONS IN IMMUNE RESPONSES AND PULMONARY IMMUNITY

    OpenAIRE

    Kawabe, Tsutomu; Matsushima, Miyoko; Hashimoto, Naozumi; Imaizumi, Kazuyoshi; Hasegawa, Yoshinori

    2011-01-01

    ABSTRACT The CD40 ligand/CD40 pathway is widely recognized for its prominent role in immune regulation and homeostasis. CD40, a member of the tumor necrosis factor receptor family, is expressed by antigen-presenting cells, as well as non-immune cells and tumors. The engagement of the CD40 and CD40 ligands, which are transiently expressed on T cells and other non-immune cells under inflammatory conditions, regulates a wide spectrum of molecular and cellular processes, including the initiation ...

  20. Control Strategy for Discontinuous Conduction Mode Boost Rectifier with Low Total Harmonic Distortion and Improved Dynamic Response

    Directory of Open Access Journals (Sweden)

    H. S. Athab

    2008-01-01

    Full Text Available Due to its simplicity, the discontinuous conduction mode boost rectifier is potentially the least expensive active line-harmonics reducing circuit. Problem statement: The line current however, shows considerable distortion when the peak input voltage is close to the output voltage, As a result, the input power factor is poor. This study proposes a simple, low-cost method to reduce the line harmonics. Approach: A periodic voltage signal was injected in the control circuit to vary the duty cycle of the boost switch within a line cycle so that the third-order harmonic of the input current is reduced and the THD is improved. The proposed technique eliminates the additional harmonic generator, phase detecting and phase-locking circuits, which was proposed in the literature. Instead we can utilize the bridge rectifier's output voltage of the boost converter to modulate the duty cycle of the boost switch. As a result, the injected signal is naturally synchronized with line current. In addition, to obtain nearly constant harmonic content over a wide range of load variation, a modulation index m is used to update the injected signal with a fraction of duty cycle which reflects the load changes. Results: The results proved that third-order harmonic, which was the Lowest Order Harmonic (LOH, can be attenuated by adjusting the modulation index of the injected signal. Moreover, the rectifier shows a good transient performance where the converter's output voltage overshoots during load and input voltage transients is reduced. Conclusions/Recommendations: The proposed circuit can be used as a front-end converter for DC/DC or DC/AC converters in order to improve the power factor of the input current. Also the proposed control circuit could be integrated in a single chip in order to reduce the cost of the industrial implementation.

  1. Children with asthma by school age display aberrant immune responses to pathogenic airway bacteria as infants

    DEFF Research Database (Denmark)

    Larsen, Jeppe Madura; Pedersen, Susanne Brix; Thysen, Anna Hammerich;

    2014-01-01

    (P = .001), and IL-10 (P = .028), whereas there were no differences in T-cell activation or peripheral T-cell composition. ConclusionsChildren with asthma by school age exhibited an aberrant immune response to pathogenic bacteria in infancy. We propose that an abnormal immune response to pathogenic...... Prospective Studies on Asthma in Childhood birth cohort was followed prospectively, and asthma was diagnosed at age 7 years. The immune response to H influenzae, M catarrhalis, and S pneumoniae was analyzed in 292 infants using PBMCs isolated and stored since the age of 6 months. The immune response was...... assessed based on the pattern of cytokines produced and T-cell activation. ResultsThe immune response to pathogenic bacteria was different in infants with asthma by 7 years of age (P = .0007). In particular, prospective asthmatic subjects had aberrant production of IL-5 (P = .008), IL-13 (P = .057), IL-17...

  2. Arterial hypertension aggravates innate immune responses after experimental stroke

    Directory of Open Access Journals (Sweden)

    Karoline Möller

    2015-11-01

    Full Text Available Arterial hypertension is not only the leading risk factor for stroke, but also attribute to impaired recovery and poor outcome. The latter could be explained by hypertensive vascular remodeling that aggravates perfusion deficits and blood brain barrier disruption. However, besides vascular changes, one could hypothesize that activation of the immune system due to pre-existing hypertension may negatively influence post-stroke inflammation and thus stroke outcome. To test this hypothesis, male adult spontaneously hypertensive rats (SHR and normotensive Wistar Kyoto rats (WKY were subjected to photothrombotic stroke. One and three days after stroke, infarct volume and functional deficits were evaluated by magnetic resonance imaging and behavioral tests. Expression levels of adhesion molecules and chemokines, along with the post-stroke inflammatory response was analyzed by flow cytometry, quantitative real-time PCR and immunohistochemistry in rat brains four days after stroke. Although comparable at day one, lesion volumes were significantly larger in SHR at day three. The infarct volume showed a strong correlation with the amount of CD45 highly positive leukocytes present in the ischemic hemispheres. Functional deficits were comparable between SHR and WKY. Brain endothelial expression of intercellular adhesion molecule 1 (ICAM-1, vascular cell adhesion molecule 1 (VCAM-1 and P-selectin (CD62P was neither increased by hypertension nor by stroke. However, in SHR, brain infiltrating myeloid leukocytes showed significantly higher surface expression of ICAM-1 which may augment leukocyte transmigration by leukocyte-leukocyte interactions. The expression of chemokines that primarily attract monocytes and granulocytes was significantly increased by stroke and, furthermore, by hypertension. Accordingly, ischemic hemispheres of SHR contain considerably higher numbers of monocytes, macrophages and granulocytes. Exacerbated brain inflammation in SHR may

  3. Immune response to enzyme replacement therapies in lysosomal storage diseases and the role of immune tolerance induction.

    Science.gov (United States)

    Kishnani, Priya S; Dickson, Patricia I; Muldowney, Laurie; Lee, Jessica J; Rosenberg, Amy; Abichandani, Rekha; Bluestone, Jeffrey A; Burton, Barbara K; Dewey, Maureen; Freitas, Alexandra; Gavin, Derek; Griebel, Donna; Hogan, Melissa; Holland, Stephen; Tanpaiboon, Pranoot; Turka, Laurence A; Utz, Jeanine J; Wang, Yow-Ming; Whitley, Chester B; Kazi, Zoheb B; Pariser, Anne R

    2016-02-01

    The US Food and Drug Administration (FDA) and National Organization for Rare Disease (NORD) convened a public workshop titled "Immune Responses to Enzyme Replacement Therapies: Role of Immune Tolerance Induction" to discuss the impact of anti-drug antibodies (ADAs) on efficacy and safety of enzyme replacement therapies (ERTs) intended to treat patients with lysosomal storage diseases (LSDs). Participants in the workshop included FDA staff, clinicians, scientists, patients, industry, and advocacy group representatives. The risks and benefits of implementing prophylactic immune tolerance induction (ITI) to reduce the potential clinical impact of antibody development were considered. Complications due to immune responses to ERT are being recognized with increasing experience and lengths of exposure to ERTs to treat several LSDs. Strategies to mitigate immune responses and to optimize therapies are needed. Discussions during the workshop resulted in the identification of knowledge gaps and future areas of research, as well as the following proposals from the participants: (1) systematic collection of longitudinal data on immunogenicity to better understand the impact of ADAs on long-term clinical outcomes; (2) development of disease-specific biomarkers and outcome measures to assess the effect of ADAs and ITI on efficacy and safety; (3) development of consistent approaches to ADA assays to allow comparisons of immunogenicity data across different products and disease groups, and to expedite reporting of results; (4) establishment of a system to widely share data on antibody titers following treatment with ERTs; (5) identification of components of the protein that are immunogenic so that triggers and components of the immune responses can be targeted in ITI; and (6) consideration of early ITI in patients who are at risk of developing clinically relevant ADA that have been demonstrated to worsen treatment outcomes. PMID:26597321

  4. Ganoderma lucidum polysaccharides encapsulated in liposome as an adjuvant to promote Th1-bias immune response.

    Science.gov (United States)

    Liu, Zhenguang; Xing, Jie; Zheng, Sisi; Bo, Ruonan; Luo, Li; Huang, Yee; Niu, Yale; Li, Zhihua; Wang, Deyun; Hu, Yuanliang; Liu, Jiaguo; Wu, Yi

    2016-05-20

    Liposome-based vaccine delivery systems are known to enhance immune responses. Ganoderma lucidum polysaccharides (GLP) have been widely studied as immunomodulator and it could be as inducers of strong immune responses. In the research, GLP and ovalbumin (OVA) were encapsulated into liposome as vaccine and inoculated to mice. The magnitude and kinetics of the humoral and cellular immune responses were investigated. The results showed that GLP-OVA-loaded liposomes (GLPL/OVA) could induce more powerful antigen-specific immune responses than each single-component formulation. Mice immunized with GLPL/OVA displayed higher antigen-specific IgG antibodies, better splenocytes proliferation, higher cytokine secretion by splenocytes and significant activation of CD3+CD4+ and CD3+CD8+ T cells. Thus the GLPL/OVA formulation produced a heightened humoral and cellular immune response, with an overall Th1 bias. Enhanced immune responses elicited by the GLPL/OVA formulation might be attributed to effective activation and mature of DC in draining lymph nodes. Overall, these findings indicate that GLPL have the potential to enhance immune responses as vaccine delivery systems. PMID:26917384

  5. Persistent immune responses induced by a human immunodeficiency virus DNA vaccine delivered in association with electroporation in the skin of nonhuman primates.

    Science.gov (United States)

    Martinon, Frédéric; Kaldma, Katrin; Sikut, Rein; Culina, Slobodan; Romain, Gabrielle; Tuomela, Mari; Adojaan, Maarja; Männik, Andres; Toots, Urve; Kivisild, Toomas; Morin, Julie; Brochard, Patricia; Delache, Benoît; Tripiciano, Antonella; Ensoli, Fabrizio; Stanescu, Ioana; Le Grand, Roger; Ustav, Mart

    2009-11-01

    Strategies to improve vaccine efficacy are still required, especially in the case of chronic infections, including human immunodeficiency virus (HIV). DNA vaccines have potential advantages over conventional vaccines; however, low immunological efficacy has been demonstrated in many experiments involving large animals and in clinical trials. To improve the immunogenicity of DNA vaccines, we have designed a plasmid vector exploiting the binding capacity of the bovine papillomavirus E2 protein and we have used electroporation (EP) to increase DNA uptake after intradermal inoculation. We demonstrated, in nonhuman primates (NHPs), efficient induction of anti-HIV immunity with an improved DNA vaccine vector encoding an artificial fusion protein, consisting of several proteins and selected epitopes from HIV-1. We show that a DNA vaccine delivery method combining intradermal injection and noninvasive EP dramatically increased expression of the vaccine antigen selectively in the epidermis, and our observations strongly suggest the involvement of Langerhans cells in the strength and quality of the anti-HIV immune response. Although the humoral responses to the vaccine were transient, the cellular responses were exceptionally robust and persisted, at high levels, more than 2 years after the last vaccine boost. The immune responses were characterized by the induction of significant proportions of T cells producing both interferon-gamma and interleukin-2 cytokines, in both subpopulations, CD4(+) and CD8(+). This strategy is an attractive approach for vaccination in humans because of its high efficacy and the possible use of newly developed devices for EP. PMID:19627235

  6. Role of IL-12 and IFN-γ in immune response to toxoplasma gondii infection

    International Nuclear Information System (INIS)

    Interlenkin 12 (IL-12) is a potent immunoregulatory molecule that is critically involved in a wide range of diseases. In several murine models of intracellular infection, endogenous IL-12 has been shown to be crucial for the generation of a protective Th1 response in a primary infection for a intracellular pathogens. Interferon-gamma (IFN-γ) is also an important mediator of cellular immunity against microbial pathogens and tumor cells due to its potent capacity to activate macrophages for enhanced cytotoxicity. The aim of the present study is to evaluate the immune response to toxoplasma gondii after primary inflection (infected groups and secondary infection (re-infected groups for over 19 weeks (the time of the experiment). the evaluation was assessed by measurements of levels of IL-12 and IFN-γ using ELISA technique in the sera of these infected rats. The results demonstrated that the primary immune response induced a fluctuation in the levels of IL-12 in the sera of infected rats, which reached maximum value of 122.6 ±1.4 pg/ml after 15 weeks of primary infection. While, in the challenged groups (secondary immune response, re-infected groups) the levels of IL-12 were generally lower than that of the primary immune response. On the other hand, IFN-γ levels increased significantly in the secondary immune response (re-infected groups) as compared to primary immune response 9 infected groups) In conclusion, the results suggest that IL-12 might have a role in the defense mechanism against intracellular infection with T-gondii especially in primary immune response than in the secondary immune response. This is in contrast to IFN-γ that takes the up-hand in secondary immune response to T-gondii infection

  7. Immunization of neonatal mice with LAMP/p55 HIV gag DNA elicits robust immune responses that last to adulthood

    International Nuclear Information System (INIS)

    Successful T cell priming in early postnatal life that can generate effective long-lasting responses until adulthood is critical in HIV vaccination strategies because it prevents early sexual initiation and breastfeeding transmission of HIV. A chimeric DNA vaccine encoding p55 HIV gag associated with lysosome-associated membrane protein 1 (LAMP-1; which drives the antigen to the MIIC compartment), has been used to enhance cellular and humoral antigen-specific responses in adult mice and macaques. Herein, we investigated LAMP-1/gag vaccine immunogenicity in the neonatal period in mice and its ability to generate long-lasting effects. Neonatal vaccination with chimeric LAMP/gag generated stronger Gag-specific immune responses, as measured by the breadth of the Gag peptide-specific IFN-γ, proliferative responsiveness, cytokine production and antibody production, all of which revealed activation of CD4+ T cells as well as the generation of a more robust CTL response compared to gag vaccine alone. To induce long-lived T and B cell memory responses, it was necessary to immunize neonates with the chimeric LAMP/gag DNA vaccine. The LAMP/gag DNA vaccine strategy could be particularly useful for generating an anti-HIV immune response in the early postnatal period capable of inducing long-term immunological memory.

  8. Simultaneous immunization of cattle with foot-and-mouth disease (FMD and live anthrax vaccines do not interfere with FMD booster responses

    Directory of Open Access Journals (Sweden)

    Myrian Trotta

    2015-01-01

    Full Text Available Foot-and-mouth disease (FMD vaccination in Argentina is compulsory for most of the cattle population and conducted by certified veterinarians. This organized campaign may facilitate the controlled application of other vaccines against endemic diseases, provided immune responses against FMD are not hindered. There is no published information on the interference of immunity against FMD vaccines when applied together with a live bacterial vaccine. In this study we evaluated if the simultaneous application of a Bacillus anthracis live vaccine with a commercial tetravalent oil-based FMD vaccine (FMD-vac used in Argentina, modifies the antibody booster responses against FMD virus (FMDV in cattle. Two groups of 16 heifers with comparable liquid phase blocking ELISA (LPBE titers were immunized with the FMD-vac alone or simultaneously with a commercial attenuated bovine anthrax Sterne strain vaccine (ABV. Serum samples were obtained at 0, 25, 60 and 90 days post vaccination (dpv and specific antibodies against two FMDV vaccine strains were assessed by LPBE, avidity and IgG-isotype ELISAs. Bovines immunized with FMD-vac or FMDV-V + ABV responded with a boost in the LPBE antibody titers and avidity at 25 dpv, and remained within similar levels up to the end of the study. Animals vaccinated with FMD-vac + ABV had significantly higher LPBE titers at 25 dpv, compared to those immunized with FMD-vac alone; which was due to an increase in IgG2 titers. Overall, antibody titers elicited in both groups were similar and followed comparable kinetics over time. We conclude that the simultaneous application of a live anthrax vaccine with the current FMD tetravalent vaccine used in Argentina in cattle previously immunized against FMD, did not counteract the serological response induced by FMD vaccination.

  9. Immune evasion strategies of ranaviruses and innate immune responses to these emerging pathogens.

    Science.gov (United States)

    Grayfer, Leon; Andino, Francisco De Jesús; Chen, Guangchun; Chinchar, Gregory V; Robert, Jacques

    2012-07-01

    Ranaviruses (RV, Iridoviridae) are large double-stranded DNA viruses that infect fish, amphibians and reptiles. For ecological and commercial reasons, considerable attention has been drawn to the increasing prevalence of ranaviral infections of wild populations and in aquacultural settings. Importantly, RVs appear to be capable of crossing species barriers of numerous poikilotherms, suggesting that these pathogens possess a broad host range and potent immune evasion mechanisms. Indeed, while some of the 95-100 predicted ranavirus genes encode putative evasion proteins (e.g., vIFα, vCARD), roughly two-thirds of them do not share significant sequence identity with known viral or eukaryotic genes. Accordingly, the investigation of ranaviral virulence and immune evasion strategies is promising for elucidating potential antiviral targets. In this regard, recombination-based technologies are being employed to knock out gene candidates in the best-characterized RV member, Frog Virus (FV3). Concurrently, by using animal infection models with extensively characterized immune systems, such as the African clawed frog, Xenopus laevis, it is becoming evident that components of innate immunity are at the forefront of virus-host interactions. For example, cells of the macrophage lineage represent important combatants of RV infections while themselves serving as targets for viral infection, maintenance and possibly dissemination. This review focuses on the recent advances in the understanding of the RV immune evasion strategies with emphasis on the roles of the innate immune system in ranaviral infections. PMID:22852041

  10. Immune Evasion Strategies of Ranaviruses and Innate Immune Responses to These Emerging Pathogens

    Directory of Open Access Journals (Sweden)

    Leon Grayfer

    2012-06-01

    Full Text Available Ranaviruses (RV, Iridoviridae are large double-stranded DNA viruses that infect fish, amphibians and reptiles. For ecological and commercial reasons, considerable attention has been drawn to the increasing prevalence of ranaviral infections of wild populations and in aquacultural settings. Importantly, RVs appear to be capable of crossing species barriers of numerous poikilotherms, suggesting that these pathogens possess a broad host range and potent immune evasion mechanisms. Indeed, while some of the 95–100 predicted ranavirus genes encode putative evasion proteins (e.g., vIFα, vCARD, roughly two-thirds of them do not share significant sequence identity with known viral or eukaryotic genes. Accordingly, the investigation of ranaviral virulence and immune evasion strategies is promising for elucidating potential antiviral targets. In this regard, recombination-based technologies are being employed to knock out gene candidates in the best-characterized RV member, Frog Virus (FV3. Concurrently, by using animal infection models with extensively characterized immune systems, such as the African clawed frog, Xenopus laevis, it is becoming evident that components of innate immunity are at the forefront of virus-host interactions. For example, cells of the macrophage lineage represent important combatants of RV infections while themselves serving as targets for viral infection, maintenance and possibly dissemination. This review focuses on the recent advances in the understanding of the RV immune evasion strategies with emphasis on the roles of the innate immune system in ranaviral infections.

  11. Memory and effector T cells modulate subsequently primed immune responses to unrelated antigens

    OpenAIRE

    Tian, Jide D; LU, Y. X.; Hanssen, L.; Dang, H.; Kaufman, D L

    2003-01-01

    Memory and effector T cells modulate subsequently primed T cell responses to the same antigen. However, little is known about the impact of pre-existing memory and effector T cell immunity on subsequently primed immune responses to unrelated antigens. Here, we show that an antigen-primed first wave of Th1 and Th2 immunity enhanced or inhibited the subsequently primed T cell immunity to an unrelated Antigen, depending on whether the second antigen was administered in the same or opposite type ...

  12. Distinct Mechanisms Underlie Boosted Polysaccharide-Specific IgG Responses Following Secondary Challenge with Intact Gram-Negative versus Gram-Positive Extracellular Bacteria.

    Science.gov (United States)

    Kar, Swagata; Arjunaraja, Swadhinya; Akkoyunlu, Mustafa; Pier, Gerald B; Snapper, Clifford M

    2016-06-01

    Priming of mice with intact, heat-killed cells of Gram-negative Neisseria meningitidis, capsular serogroup C (MenC) or Gram-positive group B Streptococcus, capsular type III (GBS-III) bacteria resulted in augmented serum polysaccharide (PS)-specific IgG titers following booster immunization. Induction of memory required CD4(+) T cells during primary immunization. We determined whether PS-specific memory for IgG production was contained within the B cell and/or T cell populations, and whether augmented IgG responses following booster immunization were also dependent on CD4(+) T cells. Adoptive transfer of purified B cells from MenC- or GBS-III-primed, but not naive mice resulted in augmented PS-specific IgG responses following booster immunization. Similar responses were observed when cotransferred CD4(+) T cells were from primed or naive mice. Similarly, primary immunization with unencapsulated MenC or GBS-III, to potentially prime CD4(+) T cells, failed to enhance PS-specific IgG responses following booster immunization with their encapsulated isogenic partners. Furthermore, in contrast to GBS-III, depletion of CD4(+) T cells during secondary immunization with MenC or another Gram-negative bacteria, Acinetobacter baumannii, did not inhibit augmented PS-specific IgG booster responses of mice primed with heat-killed cells. Also, in contrast with GBS-III, booster immunization of MenC-primed mice with isolated MenC-PS, a TI Ag, or a conjugate of MenC-PS and tetanus toxoid elicited an augmented PS-specific IgG response similar to booster immunization with intact MenC. These data demonstrate that memory for augmented PS-specific IgG booster responses to Gram-negative and Gram-positive bacteria is contained solely within the B cell compartment, with a differential requirement for CD4(+) T cells for augmented IgG responses following booster immunization. PMID:27183619

  13. DMPD: Toll-like receptors are key participants in innate immune responses. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18064347 Toll-like receptors are key participants in innate immune responses. Aranc...Epub 2007 Nov 21. (.png) (.svg) (.html) (.csml) Show Toll-like receptors are key participants in innate immune response...s. PubmedID 18064347 Title Toll-like receptors are key participants in innate immune response

  14. New immune systems: pathogen-specific host defence, life history strategies and hypervariable immune-response genes of invertebrates

    OpenAIRE

    L Bowden; NM Dheilly; DA Raftos; SV Nair

    2007-01-01

    Our understanding of invertebrate immune systems is undergoing a paradigm shift. Until recently, the host defence responses of invertebrates were thought to rely on limited molecular diversity that could not tailor reactions toward specific microbes. This view is now being challenged. Highly discriminatory defence responses, and hypervariable gene systems with the potential to drive them, have been identified in a number of invertebrate groups. These systems seem to be quite distinct, suggest...

  15. Revaccination of cattle with bacille Calmette-Guerin two years after first vaccination when immunity has waned, boosted protection against challenge with Mycobacterium bovis.

    Directory of Open Access Journals (Sweden)

    Natalie A Parlane

    their immune responses biased towards induction of antibody.

  16. Qualitative and quantitative evaluation of donkeys responses to immunization by rabbits' IgG

    International Nuclear Information System (INIS)

    In this study two apparently healthy donkeys were immunized with highly pure rabbit's 1gG using a revised protocol. Qualitative test using the same immuno gen was done as a primary test to eva lute the immune system response. However, the same 1gG was iodinated with 125I using chloramine T method and the labeled 1gG was used to quantitatively study the immune response. The two donkeys showed good response with the younger one having the best response. The obtained donkey anti rabbit sera was used as separating agent for RIA assay for human PRL. (Author)

  17. The Murine Humoral Immune Response to Hepatitis B Surface Antigen: Idiotype Network Pathways.

    Science.gov (United States)

    Schick, Michael Roy

    Recognition of a wide spectrum in disease outcomes following Hepatitis B Virus (HBV) infection has led to the suggestion that individual differences may be due to characteristics of the immune response. HBV, a hepatotropic virus, is not directly cytopathic to the host hepatocytes but the cellular damage which does not occur may be due to the host's own immune response. It is this variety in immune response capabilities following natural infection or vaccination which led to the present study in which the murine humoral immune response to hepatitis B surface antigen (HBsAg) was examined. Following immunization with purified HBsAg an anti-HBs response could be detected in 19 inbred strains of mice. The response, which varied among the strains, was linked to the major histocompatibility complex (MHC). Among high responders to HBsAg were two strains in which a poor response to a single epitope could be detected. Although quantitatively serum from these strains resembled serum from other high responders, there was a major difference in the qualitative aspects. Included within this study was the role of idotype networks within the murine anti-HBs response. By directly targeting HBsAg-specific B cells within the framework of an idiotype network by an Ab-2, it was possible to circumvent T cell-dependent regulation of an immune response. In each of five inbred strains of mice immunized with a polyclonal rabbit Ab-2 an Ab-3 population with HBsAg-specificity (Ab -1^') was induced. These mice were also immunized with HBsAg resulting in a higher anti-HBs response as compared to HBsAg immunization alone in all of the strains tested except for one. The response in this strain, normally a low responder to HBsAg, indicated that the mechanisms for genetic restriction of the anti -HBs response was still active, although it was not apparent during anti-Id immunization. The effects of an anti-Id on the murine antibody response to HBsAg may lead to insights on the presence of idiotype

  18. Immunization with Paracoccidioides brasiliensis radioattenuated yeast cells induces Th1 immune response in Balb/C mice

    International Nuclear Information System (INIS)

    Paracoccidioides brasiliensis is the agent of paracoccidioidomycosis, the most prevalent mycosis in Latin America. To date, there is no effective vaccine. In our laboratory yeast cells of P. brasiliensis were attenuated by gamma irradiation. We defined an absorbed dose in which the pathogen loses the reproductive ability, while retaining the morphology, the synthesis and secretion of proteins and the oxidative metabolism. The immunization with these cells was able to confer protection in BALB/c mice. The aim of the present work was evaluate the immune response pathway activated in mice immunized with P. brasiliensis radioattenuated yeast cells. The protector effect was evaluated in BALB/c mice groups immunized once or twice, respectively. Each group was divided in three sub groups that were challenge 30, 45 or 60 days after the immunization. These groups were called G1A, G1B and G1C in the group immunized once and G2A, G2B and G2C in the group immunized twice. Recovery of CFUs and cytokines determination (IFN - γ, IL - 10 and IL IV 4) were performed three months post challenge. Quantitative RT-PCR was the method of choice used to quantify the expression of cytokines. The sera were collected weekly to evaluate the IgG antibody titers and the IgG1 and IgG2a pattern in the course of infection. A significant reduction in CFUs recovery was verified 90 days post challenge in mice submitted to one immunization: 73.0%, 96.0% and 76.3% for sub-groups G1A, G1B and G1C, respectively. In the group submitted to two immunizations, a remarkable increase in the protection was obtained. No CFUs was recovered from sub-groups G2B and G2C and very few CFUs (reduction of 98.6%) were recovered from the lungs of sub group G2A. In mice submitted to one immunization, Th1 and Th2 cytokines were simultaneously produced. In the group submitted to two immunizations, levels of IL-10 and IL-4 were very low, while IFN-γ production was maintained indicating that a Th1 pattern was dominant. For

  19. Immunization with Paracoccidioides brasiliensis radioattenuated yeast cells induces Th1 immune response in Balb/C mice

    Energy Technology Data Exchange (ETDEWEB)

    Martins, Estefania M.N.; Andrade, Antero S.R. [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN-CNEN/MG), Belo Horizonte, MG (Brazil)], e-mail: estefaniabio@yahoo.com.br, e-mail: antero@cdtn.br; Resende, Maria Aparecida de [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Dept. de Microbiologia], e-mail: maresend@mono.icb.ufmg.br; Reis, Bernardo S.; Goes, Alfredo M. [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Dept. de Bioquimica e Imunologia], e-mail: goes@mono.icb.ufmg.br, e-mail: brsgarbi@mono.icb.ufmg.br

    2009-07-01

    Paracoccidioides brasiliensis is the agent of paracoccidioidomycosis, the most prevalent mycosis in Latin America. To date, there is no effective vaccine. In our laboratory yeast cells of P. brasiliensis were attenuated by gamma irradiation. We defined an absorbed dose in which the pathogen loses the reproductive ability, while retaining the morphology, the synthesis and secretion of proteins and the oxidative metabolism. The immunization with these cells was able to confer protection in BALB/c mice. The aim of the present work was evaluate the immune response pathway activated in mice immunized with P. brasiliensis radioattenuated yeast cells. The protector effect was evaluated in BALB/c mice groups immunized once or twice, respectively. Each group was divided in three sub groups that were challenge 30, 45 or 60 days after the immunization. These groups were called G1A, G1B and G1C in the group immunized once and G2A, G2B and G2C in the group immunized twice. Recovery of CFUs and cytokines determination (IFN - {gamma}, IL - 10 and IL IV 4) were performed three months post challenge. Quantitative RT-PCR was the method of choice used to quantify the expression of cytokines. The sera were collected weekly to evaluate the IgG antibody titers and the IgG1 and IgG2a pattern in the course of infection. A significant reduction in CFUs recovery was verified 90 days post challenge in mice submitted to one immunization: 73.0%, 96.0% and 76.3% for sub-groups G1A, G1B and G1C, respectively. In the group submitted to two immunizations, a remarkable increase in the protection was obtained. No CFUs was recovered from sub-groups G2B and G2C and very few CFUs (reduction of 98.6%) were recovered from the lungs of sub group G2A. In mice submitted to one immunization, Th1 and Th2 cytokines were simultaneously produced. In the group submitted to two immunizations, levels of IL-10 and IL-4 were very low, while IFN-{gamma} production was maintained indicating that a Th1 pattern was

  20. Biochemical and Functional Insights into the Integrated Regulation of Innate Immune Cell Responses by Teleost Leukocyte Immune-Type Receptors

    Directory of Open Access Journals (Sweden)

    Chenjie Fei

    2016-03-01

    Full Text Available Across vertebrates, innate immunity consists of a complex assortment of highly specialized cells capable of unleashing potent effector responses designed to destroy or mitigate foreign pathogens. The execution of various innate cellular behaviors such as phagocytosis, degranulation, or cell-mediated cytotoxicity are functionally indistinguishable when being performed by immune cells isolated from humans or teleost fishes; vertebrates that diverged from one another more than 450 million years ago. This suggests that vital components of the vertebrate innate defense machinery are conserved and investigating such processes in a range of model systems provides an important opportunity to identify fundamental features of vertebrate immunity. One characteristic that is highly conserved across vertebrate systems is that cellular immune responses are dependent on specialized immunoregulatory receptors that sense environmental stimuli and initiate intracellular cascades that can elicit appropriate effector responses. A wide variety of immunoregulatory receptor families have been extensively studied in mammals, and many have been identified as cell- and function-specific regulators of a range of innate responses. Although much less is known in fish, the growing database of genomic information has recently allowed for the identification of several immunoregulatory receptor gene families in teleosts. Many of these putative immunoregulatory receptors have yet to be assigned any specific role(s, and much of what is known has been based solely on structural and/or phylogenetic relationships with mammalian receptor families. As an attempt to address some of these shortcomings, this review will focus on our growing understanding of the functional roles played by specific members of the channel catfish (Ictalurus punctatus leukocyte immune-type receptors (IpLITRs, which appear to be important regulators of several innate cellular responses via classical as well

  1. NYVAC vector modified by C7L viral gene insertion improves T cell immune responses and effectiveness against leishmaniasis.

    Science.gov (United States)

    Sánchez-Sampedro, L; Mejías-Pérez, E; S Sorzano, Carlos Óscar; Nájera, J L; Esteban, M

    2016-07-15

    The NYVAC poxvirus vector is used as vaccine candidate for HIV and other diseases, although there is only limited experimental information on its immunogenicity and effectiveness for use against human pathogens. Here we defined the selective advantage of NYVAC vectors in a mouse model by comparing the immune responses and protection induced by vectors that express the LACK (Leishmania-activated C-kinase antigen), alone or with insertion of the viral host range gene C7L that allows the virus to replicate in human cells. Using DNA prime/virus boost protocols, we show that replication-competent NYVAC-LACK that expresses C7L (NYVAC-LACK-C7L) induced higher-magnitude polyfunctional CD8(+) and CD4(+) primary adaptive and effector memory T cell responses (IFNγ, TNFα, IL-2, CD107a) to LACK antigen than non-replicating NYVAC-LACK. Compared to NYVAC-LACK, the NYVAC-LACK-C7L-induced CD8(+) T cell population also showed higher proliferation when stimulated with LACK antigen. After a challenge by subcutaneous Leishmania major metacyclic promastigotes, NYVAC-LACK-C7L-vaccinated mouse groups showed greater protection than the NYVAC-LACK-vaccinated group. Our results indicate that the type and potency of immune responses induced by LACK-expressing NYVAC vectors is improved by insertion of the C7L gene, and that a replication-competent vector as a vaccine renders greater protection against a human pathogen than a non-replicating vector. PMID:27036935

  2. Phase I trial of recombinant adenovirus gene transfer in lung cancer. Longitudinal study of the immune responses to transgene and viral products.

    Science.gov (United States)

    Gahéry-Ségard, H; Molinier-Frenkel, V; Le Boulaire, C; Saulnier, P; Opolon, P; Lengagne, R; Gautier, E; Le Cesne, A; Zitvogel, L; Venet, A; Schatz, C; Courtney, M; Le Chevalier, T; Tursz, T; Guillet, J G; Farace, F

    1997-01-01

    Animal studies indicate that the use of replication-deficient adenovirus for human gene therapy is limited by host antivector immune responses that result in transient recombinant protein expression and blocking of gene transfer when rechallenged. Therefore, we have examined immune responses to an adenoviral vector and to the beta-galactosidase protein in four patients with lung cancer given a single intratumor injection of 10(9) plaque-forming units of recombinant adenovirus. The beta-galactosidase protein was expressed in day-8 tumor biopsies from all patients at variable levels. Recombinant virus DNA was detected by PCR in day-30 and day-60 tumor biopsies from all patients except patient 1. A high level of neutralizing antiadenovirus antibodies was detected in patient 1 before Ad-beta-gal injection whereas it was low (patient 3) or undetectable in the other two patients. All patients developed potent CD4 type 1 helper T cell (Th1) responses to adenoviral particles which increased gradually over time after injection. Antiadenovirus cytotoxic T lymphocyte responses were consistently boosted in the two patients examined (patients 3 and 4). Sustained production of anti-beta-galactosidase IgG was observed in all patients except patient 1. Consistent with anti-beta-gal antibody production, all patients except patient 1 developed intense, dose-dependent Th1 responses to soluble beta-galactosidase which increased over time. Strong beta-galactosidase-specific cytotoxic T lymphocyte responses were detected in patients 2, 3, and 4. Our results clearly show that despite the intensity of antiadenovirus responses, transgene protein expression was sufficient to induce strong and prolonged immunity in three patients. Recombinant adenovirus injected directly into the tumor is a highly efficient vector for immunizing patients against the transgene protein. PMID:9410899

  3. Deprivation of human natural killer cells and antitumor immune response

    Directory of Open Access Journals (Sweden)

    Vyacheslav Ogay

    2014-01-01

    Full Text Available Introduction: Cell-based immunotherapy has been given increased attention as a treatment for cancer. Human natural killer (NK cells are resident lymphocyte populations. They exhibit potent antitumor activity without human leukocyte antigen matching and without prior antigen exposure. They also are a promising tool for immunotherapy of solid and hematologic cancers. However, most cancer patients do not have enough NK cells to induce an effective antitumor immune response. This demonstrates a need for a source of NK cells that can supplement the endogenous cell population. Material and methods: In this study, we derived induced pluripotent stem cells (iPSCs from peripheral blood T-lymphocytes using Sendai virus vectors. Results: Generated iPSCs exhibited monoclonal T cell receptors (TCR rearrangement in their genome, a hallmark of mature terminally differentiated T cells. These iPSCs were differentiated into NK cells using a two-stage coculture system: iPSCs into hematopoietic CD34+ cells with feeder cells M210-B4 (ATCC, USA and CD34+ cells into mature NK cells with AFT024 cells (ATCC, USA. Our results showed that iPSC-derived NK cells expressed CD56, CD16, NKp 44 and NKp 46, possessed high cytotoxic activity  and produced high level of interferon-γ. Conclusion: Based on our data, derivation of NK cells from induced pluripotent stem cells should be considered in the treatment of oncologic diseases.This would allow for the development of cell therapy for cancer using immunologically compatible NK cells derived from iPSCs. This may contribute to a more efficient treatment of oncologic diseases in addition to traditional cancer treatment.

  4. Mirtazapine inhibits tumor growth via immune response and serotonergic system.

    Directory of Open Access Journals (Sweden)

    Chun-Kai Fang

    Full Text Available To study the tumor inhibition effect of mirtazapine, a drug for patients with depression, CT26/luc colon carcinoma-bearing animal model was used. BALB/c mice were randomly divided into six groups: two groups without tumors, i.e. wild-type (no drug and drug (mirtazapine, and four groups with tumors, i.e. never (no drug, always (pre-drug, i.e. drug treatment before tumor inoculation and throughout the experiment, concurrent (simultaneously tumor inoculation and drug treatment throughout the experiment, and after (post-drug, i.e. drug treatment after tumor inoculation and throughout the experiment. The "psychiatric" conditions of mice were observed from the immobility time with tail suspension and spontaneous motor activity post tumor inoculation. Significant increase of serum interleukin-12 (sIL-12 and the inhibition of tumor growth were found in mirtazapine-treated mice (always, concurrent, and after as compared with that of never. In addition, interferon-γ level and immunocompetent infiltrating CD4+/CD8+ T cells in the tumors of mirtazapine-treated, tumor-bearing mice were significantly higher as compared with that of never. Tumor necrosis factor-α (TNF-α expressions, on the contrary, are decreased in the mirtazapine-treated, tumor-bearing mice as compared with that of never. Ex vivo autoradiography with [(123I]ADAM, a radiopharmaceutical for serotonin transporter, also confirms the similar results. Notably, better survival rates and intervals were also found in mirtazapine-treated mice. These findings, however, were not observed in the immunodeficient mice. Our results suggest that tumor growth inhibition by mirtazapine in CT26/luc colon carcinoma-bearing mice may be due to the alteration of the tumor microenvironment, which involves the activation of the immune response and the recovery of serotonin level.

  5. INVOLVEMENT OF PEPTIDOGLYCAN RECOGNITION PROTEIN L6 IN ACTIVATION OF IMMUNE DEFICIENCY PATHWAY IN THE IMMUNE RESPONSIVE SILKWORM CELLS.

    Science.gov (United States)

    Tanaka, Hiromitsu; Sagisaka, Aki

    2016-06-01

    The immune deficiency (Imd) signaling pathway is activated by Gram-negative bacteria for producing antimicrobial peptides (AMPs). In Drosophila melanogaster, the activation of this pathway is initiated by the recognition of Gram-negative bacteria by peptidoglycan (PGN) recognition proteins (PGRPs), PGRP-LC and PGRP-LE. In this study, we found that the Imd pathway is involved in enhancing the promoter activity of AMP gene in response to Gram-negative bacteria or diaminopimelic (DAP) type PGNs derived from Gram-negative bacteria in an immune responsive silkworm cell line, Bm-NIAS-aff3. Using gene knockdown experiments, we further demonstrated that silkworm PGRP L6 (BmPGRP-L6) is involved in the activation of E. coli or E. coli-PGN mediated AMP promoter activation. Domain analysis revealed that BmPGRP-L6 contained a conserved PGRP domain, transmembrane domain, and RIP homotypic interaction motif like motif but lacked signal peptide sequences. BmPGRP-L6 overexpression enhances AMP promoter activity through the Imd pathway. BmPGRP-L6 binds to DAP-type PGNs, although it also binds to lysine-type PGNs that activate another immune signal pathway, the Toll pathway in Drosophila. These results indicate that BmPGRP-L6 is a key PGRP for activating the Imd pathway in immune responsive silkworm cells. PMID:26991439

  6. Role of nutrients in the development of neonatal immune response

    OpenAIRE

    Cunningham-Rundles, Susanna; Lin, Hong; Ho-Lin, Deborah; Dnistrian, Ann; Cassileth, Barrie R.; Perlman, Jeffrey M

    2009-01-01

    Nutrients exert unique regulatory effects in the perinatal period that mold the developing immune system. The interactions of micronutrients and microbial and environmental antigens condition the post-birth maturation of the immune system, influencing reactions to allergens, fostering tolerance towards the emerging gastrointestinal flora and ingested antigens, and defining patterns of host defense against potential pathogens. The shared molecular structures that are present on microbes or cer...

  7. The innate immune response in ischemic acute kidney injury

    OpenAIRE

    Jang, Hye Ryoun; Rabb, Hamid

    2008-01-01

    Kidney ischemia reperfusion injury is a major cause of morbidity in both allograft and native kidneys. Ischemia reperfusion-induced acute kidney injury is characterized by early, allo-antigen independent inflammation. Major components of the innate immune system are activated and participate in the pathogenesis of acute kidney injury, plus prime the allograft kidney for rejection. Soluble members of innate immunity implicated in acute kidney injury include the complement system, cytokines, an...

  8. A specific primed immune response in Drosophila is dependent on phagocytes.

    Directory of Open Access Journals (Sweden)

    Linh N Pham

    2007-03-01

    Full Text Available Drosophila melanogaster, like other invertebrates, relies solely on its innate immune response to fight invading microbes; by definition, innate immunity lacks adaptive characteristics. However, we show here that priming Drosophila with a sublethal dose of Streptococcus pneumoniae protects against an otherwise-lethal second challenge of S. pneumoniae. This protective effect exhibits coarse specificity for S. pneumoniae and persists for the life of the fly. Although not all microbial challenges induced this specific primed response, we find that a similar specific protection can be elicited by Beauveria bassiana, a natural fly pathogen. To characterize this primed response, we focused on S. pneumoniae-induced protection. The mechanism underlying this protective effect requires phagocytes and the Toll pathway. However, activation of the Toll pathway is not sufficient for priming-induced protection. This work contradicts the paradigm that insect immune responses cannot adapt and will promote the search for similar responses overlooked in organisms with an adaptive immune response.

  9. Safety and Immunogenicity of Boosting BCG Vaccinated Subjects with BCG: Comparison with Boosting with a New TB Vaccine, MVA85A

    OpenAIRE

    Whelan, KT; Pathan, AA; Sander, CR; Fletcher, HA; Poulton, I; Alder, NC; Hill, AV; Mcshane, H.

    2009-01-01

    OBJECTIVES To investigate the safety and immunogenicity of a booster BCG vaccination delivered intradermally in healthy, BCG vaccinated subjects and to compare with a previous clinical trial where BCG vaccinated subjects were boosted with a new TB vaccine, MVA85A. DESIGN Phase I open label observational trial, in the UK. Healthy, HIV-negative, BCG vaccinated adults were recruited and vaccinated with BCG. The primary outcome was safety; the secondary outcome was cellular immune responses ...

  10. Immune Responses to Virulent and Vaccine Strains of Infectious Bronchitis Viruses in Chickens.

    Science.gov (United States)

    Chhabra, Rajesh; Chantrey, Julian; Ganapathy, Kannan

    2015-11-01

    Infectious bronchitis (IB) is an acute and highly contagious chicken viral disease, causing severe economic losses to poultry producers worldwide. In the last few decades, infectious bronchitis virus (IBV) has been extensively studied, but knowledge of immune responses to virulent or vaccine strains of IBVs remains limited. This review focuses on fundamental aspects of immune responses against IBV, including the role of pattern recognition receptors (PRRs) in identification of conserved viral structures and the role of different components of innate immunity (e.g., heterophils, macrophages, dendritic cells, acute phase protein, and cytokines). Studies on adaptive immune activation and the role of humoral and cellular immunity in IBV clearance are also reviewed. Multiple interlinking immune responses are essential for protection against virulent IBVs, including passive, innate, adaptive, and effector T cells active at mucosal surfaces. Although the development of approaches for chicken transcriptome and proteome analyses have greatly helped the understanding of the underlying genetic mechanisms for immunity, there are still major knowledge gaps, such as the role of mucosal and cellular responses to IBVs. In view of recent reports of emergent IBV variants in many countries, there is renewed interest in a more complete understanding of poultry immune responses to both virulent and vaccine strains of IBVs. This will be critical for developing new vaccine or vaccination strategies and other intervention programs. PMID:26301315

  11. The host immune response in respiratory virus infection: balancing virus clearance and immunopathology.

    Science.gov (United States)

    Newton, Amy H; Cardani, Amber; Braciale, Thomas J

    2016-07-01

    The respiratory tract is constantly exposed to the external environment, and therefore, must be equipped to respond to and eliminate pathogens. Viral clearance and resolution of infection requires a complex, multi-faceted response initiated by resident respiratory tract cells and innate immune cells and ultimately resolved by adaptive immune cells. Although an effective immune response to eliminate viral pathogens is essential, a prolonged or exaggerated response can damage the respiratory tract. Immune-mediated pulmonary damage is manifested clinically in a variety of ways depending on location and extent of injury. Thus, the antiviral immune response represents a balancing act between the elimination of virus and immune-mediated pulmonary injury. In this review, we highlight major components of the host response to acute viral infection and their role in contributing to mitigating respiratory damage. We also briefly describe common clinical manifestations of respiratory viral infection and morphological correlates. The continuing threat posed by pandemic influenza as well as the emergence of novel respiratory viruses also capable of producing severe acute lung injury such as SARS-CoV, MERS-CoV, and enterovirus D68, highlights the need for an understanding of the immune mechanisms that contribute to virus elimination and immune-mediated injury. PMID:26965109

  12. Heterologous prime-boost immunization regimens using adenovirus vector and virus-like particles induce broadly neutralizing antibodies against H5N1 avian influenza viruses.

    Science.gov (United States)

    Lin, Shih-Chang; Liu, Wen-Chun; Lin, Yu-Fen; Huang, Yu-Hsuan; Liu, Jin-Hwang; Wu, Suh-Chin

    2013-11-01

    Highly pathogenic avian influenza (HPAI) H5N1 viruses continue to trigger severe diseases in poultry and humans, prompting efforts to develop an effective vaccine. Toward that goal, we constructed a recombinant adenovirus vector encoding influenza hemagglutin (rAd-HA) and a flagellin-containing virus-like particle (FliC-VLP). Using a murine model, we investigated a heterologous prime-boost vaccination regimen combining these two vectors. Our results indicate that priming with the rAd-HA vector followed by a FliC-VLP booster induced the highest HA-specific total IgG, IgG1and IgG2a. Maximum neutralizing antibody titers against homologous and heterologous clades of H5N1 virus strains and hemagglutination inhibition resulted from the heterologous vaccination strategy. Our results are likely to contribute to the development of more effective H5N1 vaccines. PMID:23813782

  13. Chronic spinal cord injury impairs primary antibody responses, but spares existing humoral immunity in mice

    OpenAIRE

    Oropallo, Michael A.; HELD, KATHERINE S.; Goenka, Radhika; Ahmad, Sifat A.; O’Neill, Patrick J.; Steward, Oswald; Lane, Thomas E.; Cancro, Michael P.

    2012-01-01

    Spinal cord injury (SCI) results in immune depression. To better understand how injury inhibits humoral immunity, the effects of chronic thoracic SCI on B cell development and immune responses to thymus-independent (TI) type-2 and thymus-dependent (TD) antigens were determined. Mice received complete crush injury or control laminectomy at either thoracic level 3 (T3), which disrupts descending autonomic control of the spleen, or at T9, which conserves most splenic sympathetic activity. Althou...

  14. Early suppression of immune response in Heliothis virescens larvae by the endophagous

    OpenAIRE

    R Ferrarese; Brivio, M.; T Congiu; P Falabella; Grimaldi, A.; Mastore, M; PERLETTI, G.; Pennacchio, F.; Sciacca, L.; Tettamanti, G.; R Valvassori; M de Eguileor

    2005-01-01

    Toxoneuron nigriceps is an endophagous parasitoid of larval stages of the noctuid moth Heliothisvirescens. As all parasitoids, this wasp avoid host immune reaction by a combination of several passiveand active mechanisms. Secretions injected by ovipositing females, which contain venom, calyx fluid andpolydnaviruses, are the most probably factors actively disrupting Heliothis virescens immune system. Thispaper describes the main alterations of the host immune response observed shortly after ov...

  15. Genetic variants within the MHC region are associated with immune responsiveness to childhood vaccinations☆

    OpenAIRE

    Yucesoy, Berran; Talzhanov, Yerkebulan; Johnson, Victor J.; Wilson, Nevin W.; Biagini, Raymond E.; Wang, Wei; Frye, Bonnie; Weissman, David N.; Germolec, Dori R.; Luster, Michael I; Barmada, Michael M.

    2013-01-01

    The influence of genetic variability within the major histocompatibility complex (MHC) region on variations in immune responses to childhood vaccination was investigated. The study group consisted of 135 healthy infants who had been immunized with hepatitis B (HBV), 7-valent pneumococcal conjugate (PCV7), and diphtheria, tetanus, acellular pertussis (DTaP) vaccines according to standard childhood immunization schedules. Genotype analysis was performed on genomic DNA using Illumina Goldengate ...

  16. Regulation of Intestinal Immune Responses through TLR Activation: Implications for Pro- and Prebiotics

    OpenAIRE

    de Kivit, Sander; Tobin, Mary C.; Forsyth, Christopher B.; Keshavarzian, Ali; Landay, Alan L.

    2014-01-01

    The intestinal mucosa is constantly facing a high load of antigens including bacterial antigens derived from the microbiota and food. Despite this, the immune cells present in the gastrointestinal tract do not initiate a pro-inflammatory immune response. Toll-like receptors (TLRs) are pattern recognition receptors expressed by various cells in the gastrointestinal tract, including intestinal epithelial cells (IEC) and resident immune cells in the lamina propria. Many diseases, including chron...

  17. Repeated Aerosolized-Boosting with Gamma-Irradiated Mycobacterium bovis BCG Confers Improved Pulmonary Protection against the Hypervirulent Mycobacterium tuberculosis Strain HN878 in Mice.

    Science.gov (United States)

    Cha, Seung Bin; Kim, Woo Sik; Kim, Jong-Seok; Kim, Hongmin; Kwon, Kee Woong; Han, Seung Jung; Eum, Seok-Yong; Cho, Sang-Nae; Shin, Sung Jae

    2015-01-01

    Mycobacterium bovis bacillus Calmette-Guerin (BCG), the only licensed vaccine, shows limited protection efficacy against pulmonary tuberculosis (TB), particularly hypervirulent Mycobacterium tuberculosis (Mtb) strains, suggesting that a logistical and practical vaccination strategy is urgently required. Boosting the BCG-induced immunity may offer a potentially advantageous strategy for advancing TB vaccine development, instead of replacing BCG completely. Despite the improved protection of the airway immunization by using live BCG, the use of live BCG as an airway boosting agent may evoke safety concerns. Here, we analyzed the protective efficacy of γ-irradiated BCG as a BCG-prime boosting agent for airway immunization against a hypervirulent clinical strain challenge with Mycobacterium tuberculosis HN878 in a mouse TB model. After the aerosol challenge with the HN878 strain, the mice vaccinated with BCG via the parenteral route exhibited only mild and transient protection, whereas BCG vaccination followed by multiple aerosolized boosting with γ-irradiated BCG efficiently maintained long-lasting control of Mtb in terms of bacterial reduction and pathological findings. Further immunological investigation revealed that this approach resulted in a significant increase in the cellular responses in terms of a robust expansion of antigen (PPD and Ag85A)-specific CD4+ T cells concomitantly producing IFN-γ, TNF-α, and IL-2, as well as a high level of IFN-γ-producing recall response via both the local and systemic immune systems upon further boosting. Collectively, aerosolized boosting of γ-irradiated BCG is able to elicit strong Th1-biased immune responses and confer enhanced protection against a hypervirulent Mycobacterium tuberculosis HN878 infection in a boosting number-dependent manner. PMID:26509812

  18. Intracellular delivery of lipopolysaccharide induces effective Th1-immune responses independent of IL-12.

    Directory of Open Access Journals (Sweden)

    Sachiko Watanabe

    Full Text Available Lipopolysaccharide (LPS is responsible for many of the inflammatory responses and pathogenic effects of Gram-negative bacteria, however, it also induces protective immune responses. LPS induces the production of inflammatory cytokines such as TNF-α, IL-6, and IL-12 from dendritic cells (DCs and macrophages. It is thought that IL-12 is required for one of the protective immune responses induced by LPS, the T helper 1 (Th1-immune response, which include the production of IFN-γ from Th1cells and IgG2c class switching. Here, we clearly demonstrate that intracellular delivery of LPS by LPS-formulated liposomes (LPS-liposomes does not induce the production of inflammatory cytokines from DCs, but enhances Th1-immune responses via type-I IFNs, independent of IL-12. Collectively, our results strongly suggest that LPS-liposomes can effectively induce Th1-immune responses without inducing unnecessary inflammation, and may be useful as an immune adjuvant to induce protective immunity.

  19. Synthetic DNA immunogen encoding hepatitis B core antigen drives immune response in liver.

    Science.gov (United States)

    Obeng-Adjei, N; Choo, D K; Saini, J; Yan, J; Pankhong, P; Parikh, A; Chu, J S; Weiner, D B

    2012-11-01

    The prevalence of hepatitis B virus (HBV) infection in Asia and sub-Sahara Africa is alarming. With quarter of a billion people chronically infected worldwide and at risk of developing liver cancer, the need for a prophylactic or therapeutic vaccination approach that can effectively induce protective responses against the different genotypes of HBV is more important than ever. Such a strategy will require both the induction of a strong antigen-specific immune response and the subsequent deployment of immune response towards the liver. Here, we assessed the ability of a synthetic DNA vaccine encoding a recombinant consensus plasmid from genotype A through E of the HBV core antigen (HBcAg), to drive immunity in the liver. Intramuscular vaccination induced both strong antigen-specific T cell and high titer antibody responses systematically and in the liver. Furthermore, immunized mice showed strong cytotoxic responses that eliminate adoptively transferred HBV-coated target cells. Importantly, vaccine-induced immune responses provided protection from HBcAg plasmid-based liver transfection in a hydrodynamic liver transfection model. These data provide important insight into the generation of peripheral immune responses that are recruited to the liver-an approach that can be beneficial in the search for vaccines or immune-therapies to liver disease. PMID:23037809

  20. Study of the integrated immune response induced by an inactivated EV71 vaccine.

    Directory of Open Access Journals (Sweden)

    Longding Liu

    Full Text Available UNLABELLED: Enterovirus 71 (EV71, a major causative agent of hand-foot-and-mouth disease (HFMD, causes outbreaks among children in the Asia-Pacific region. A vaccine is urgently needed. Based on successful pre-clinical work, phase I and II clinical trials of an inactivated EV71 vaccine, which included the participants of 288 and 660 respectively, have been conducted. In the present study, the immune response and the correlated modulation of gene expression in the peripheral blood mononuclear cells (PBMCs of 30 infants (6 to 11 months immunized with this vaccine or placebo and consented to join this study in the phase II clinical trial were analyzed. The results showed significantly greater neutralizing antibody and specific T cell responses in vaccine group after two inoculations on days 0 and 28. Additionally, more than 600 functional genes that were up- or down-regulated in PBMCs were identified by the microarray assay, and these genes included 68 genes associated with the immune response in vaccine group. These results emphasize the gene expression profile of the immune system in response to an inactivated EV71 vaccine in humans and confirmed that such an immune response was generated as the result of the positive mobilization of the immune system. Furthermore, the immune response was not accompanied by the development of a remarkable inflammatory response. CLINICAL TRIAL REGISTRATION: NCT01391494 and NCT01512706.

  1. Heterologous Prime-Boost HIV-1 Vaccination Regimens in Pre-Clinical and Clinical Trials

    Directory of Open Access Journals (Sweden)

    Julia L. Hurwitz

    2010-02-01

    Full Text Available Currently, there are more than 30 million people infected with HIV-1 and thousands more are infected each day. Vaccination is the single most effective mechanism for prevention of viral disease, and after more than 25 years of research, one vaccine has shown somewhat encouraging results in an advanced clinical efficacy trial. A modified intent-to-treat analysis of trial results showed that infection was approximately 30% lower in the vaccine group compared to the placebo group. The vaccine was administered using a heterologous prime-boost regimen in which both target antigens and delivery vehicles were changed during the course of inoculations. Here we examine the complexity of heterologous prime-boost immunizations. We show that the use of different delivery vehicles in prime and boost inoculations can help to avert the inhibitory effects caused by vector-specific immune responses. We also show that the introduction of new antigens into boost inoculations can be advantageous, demonstrating that the effect of ‘original antigenic sin’ is not absolute. Pre-clinical and clinical studies are reviewed, including our own work with a three-vector vaccination regimen using recombinant DNA, virus (Sendai virus or vaccinia virus and protein. Promising preliminary results suggest that the heterologous prime-boost strategy may possibly provide a foundation for the future prevention of HIV-1 infections in humans.

  2. InnateDB: facilitating systems-level analyses of the mammalian innate immune response

    OpenAIRE

    Lynn, David J.; Winsor, Geoffrey L.; Chan, Calvin; Richard, Nicolas; Laird, Matthew R; Barsky, Aaron; Gardy, Jennifer L; Roche, Fiona M.; Chan, Timothy H W; Shah, Naisha; Lo, Raymond; Naseer, Misbah; Que, Jaimmie; Yau, Melissa; Acab, Michael

    2008-01-01

    Although considerable progress has been made in dissecting the signaling pathways involved in the innate immune response, it is now apparent that this response can no longer be productively thought of in terms of simple linear pathways. InnateDB (www.innatedb.ca) has been developed to facilitate systems-level analyses that will provide better insight into the complex networks of pathways and interactions that govern the innate immune response. InnateDB is a publicly available, manually curate...

  3. Dysregulation of mucosal immune response in pathogenesis of inflammatory bowel disease

    OpenAIRE

    Xu, Xiao-rong; Liu, Chang-Qin; Feng, Bai-Sui; Liu, Zhan-Ju

    2014-01-01

    Inflammatory bowel disease (IBD) includes Crohn’s disease and ulcerative colitis. The exact etiology and pathology of IBD remain unknown. Available evidence suggests that an abnormal immune response against the microorganisms in the intestine is responsible for the disease in genetically susceptible individuals. Dysregulation of immune response in the intestine plays a critical role in the pathogenesis of IBD, involving a wide range of molecules including cytokines. On the other hand, besides...

  4. Hemocyte differentiation mediates the mosquito late-phase immune response against Plasmodium in Anopheles gambiae

    OpenAIRE

    Smith, Ryan C.; Barillas-Mury, Carolina; Jacobs-Lorena, Marcelo

    2015-01-01

    The innate immune response is a major determinant of malaria parasite success in its mosquito host. Previous experiments have implicated LPS-induced TNFα transcription factor (LITAF)-like 3 (LL3) as an integral component of the mosquito immune response to the malaria parasite. This study reports that LL3 influences oocyst survival and demonstrates its role in mosquito blood cell (hemocyte) differentiation in response to parasite infection. Integrating previous data, we provide evidence that h...

  5. Ear Pinna : a privileged DNA electroporation site for inducing strong Th1 immune responses

    OpenAIRE

    Ni, Jing; Nolte, Britta; Vandermeulen, Gaëlle; Préat, Véronique; Scherman, Daniel; SCHIRRMACHER, VOLKER; Fournier, Philippe

    2009-01-01

    DNA vaccination appears a very attractive approach for inducing immune responses towards the encoded antigen, but studies in large animals and in humans revealed weaknesses of such responses. In this study, we evaluated a new approach based on a new device combining DNA vaccination with electroporation (EP) at the ear pinna site. Under optimal EP conditions, the expression of the DNA encoded antigen and the induced immune responses were considerably increased. Very interestingly, DNA vaccinat...

  6. Antioxidants Enhancement to the Immune Response of NIH Mice to Vero Cell Grown Rabies Virus Vaccine

    Directory of Open Access Journals (Sweden)

    Aly Fahmy Mohamed

    2006-06-01

    Full Text Available Introduction: Rabies cell culture vaccine (Vero-Rab showed to be more immunogenic and a higher and faster release of antibody titer could be detected than in case of using Fermi type vaccine, DEV and CECV. Result: The immune response of NIH mice immunized intramuscularly using both vE - Se adjuvated and non adjuvated Vero cell rabies virus vaccine (Vero-Rab showed an elevation of antibody level of vaccinated mice groups more than the limits decided by WHO for a potent rabies virus vaccine. Also, two different immunization regimens were achieved, 5 single doses and 3 double doses of vE-selenium adjuvated and non adjuvated Vero cell rabies virus vaccine. The antibodies developed against rabies virus vaccine could be detected 14 days post immunization using ELISA and IFA. The antibody level developed in sera of mice immunized, with either adjuvated and non adjuvanted Vero-Rab., using different immunization regimens, could protect mice against the challenge with 100 MICLD50 of the challenge virus standard (CVS after the end of the experiment, (6 months of the prim-vaccination.Conclusion: vE-Se as immune potentiator can enhance the immune response and single dose immunization regimen without vE-Se as immune stimulant was preferred than double dose regimen.

  7. Vaccination with lipid core peptides fails to induce epitope-specific T cell responses but confers non-specific protective immunity in a malaria model.

    Directory of Open Access Journals (Sweden)

    Simon H Apte

    Full Text Available Vaccines against many pathogens for which conventional approaches have failed remain an unmet public health priority. Synthetic peptide-based vaccines offer an attractive alternative to whole protein and whole organism vaccines, particularly for complex pathogens that cause chronic infection. Previously, we have reported a promising lipid core peptide (LCP vaccine delivery system that incorporates the antigen, carrier, and adjuvant in a single molecular entity. LCP vaccines have been used to deliver several peptide subunit-based vaccine candidates and induced high titre functional antibodies and protected against Group A streptococcus in mice. Herein, we have evaluated whether LCP constructs incorporating defined CD4(+ and/or CD8(+ T cell epitopes could induce epitope-specific T cell responses and protect against pathogen challenge in a rodent malaria model. We show that LCP vaccines failed to induce an expansion of antigen-specific CD8(+ T cells following primary immunization or by boosting. We further demonstrated that the LCP vaccines induced a non-specific type 2 polarized cytokine response, rather than an epitope-specific canonical CD8(+ T cell type 1 response. Cytotoxic responses of unknown specificity were also induced. These non-specific responses were able to protect against parasite challenge. These data demonstrate that vaccination with lipid core peptides fails to induce canonical epitope-specific T cell responses, at least in our rodent model, but can nonetheless confer non-specific protective immunity against Plasmodium parasite challenge.

  8. The immune system strikes back: cellular immune responses against indoleamine 2,3-dioxygenase

    DEFF Research Database (Denmark)

    Sørensen, Rikke Baek; Berge-Hansen, Linda; Junker, Niels;

    2009-01-01

    BACKGROUND: The enzyme indoleamine 2,3-dioxygenase (IDO) exerts an well established immunosuppressive function in cancer. IDO is expressed within the tumor itself as well as in antigen-presenting cells in tumor-draining lymph nodes, where it promotes the establishment of peripheral immune toleran...... the major immune suppressive cell populations. CONCLUSION: IDO may serve as an important and widely applicable target for anti-cancer immunotherapeutic strategies. Furthermore, as emerging evidence suggests that IDO constitutes a significant counter-regulatory mechanism induced by pro...

  9. Evaluation of the immune response to recombinant DNA vaccine and adenoviral vaccine co-expressing the M1 and HA genes of H5N1 influenza virus in mice.

    Science.gov (United States)

    Guo, Jianqiang; Yao, Lihong; Chen, Aijun; Liu, Xiaoyu; Fu, Jinqi; Xu, Pengwei; Zhang, Zhiqing

    2011-06-01

    In order to evaluate the response to vector-expressed M1 and HA genes of influenza virus in mice, we prepared recombinant plasmid pStar-M1/HA and recombinant adenovirus Ad-M1/HA containing both the full-length matrix protein 1(M1) and hemagglutinin (HA) genes of human H5N1 influenza virus strain A/Anhui/1/2005. We then combined the DNA vaccine and adenoviral vaccine in immunization of BALB/c mice with a prime-boost regime. We immunized the mice with DNA vaccine at day 0 and 28 and with recombinant adenoviral vaccines at day 14 and 42. We took blood samples before each injection and 14 days after the final injection for detection of humoral immune responses. At day 56, we sacrificed the mice and collected splenocytes for detection of cellular immune responses. ELISA and hemagglutination inhibition (HI) assay showed that specific IgG Abs against H5N1 influenza virus was induced in serum of the immunized mice. ELISPOT results confirmed that the specific cellular immune responses were successfully induced against the M1 and HA proteins of H5N1 influenza virus. This study provides new strategy for development of novel influenza vaccines. PMID:22034816

  10. Effect of partial and complete variable loop deletions of the human immunodeficiency virus type 1 envelope glycoprotein on the breadth of gp160-specific immune responses

    International Nuclear Information System (INIS)

    Induction of cross-reactive cellular and humoral responses to the HIV-1 envelope (env) glycoprotein was examined after DNA immunization of BALB/c mice with gp14089.6-derived constructs exhibiting partial or complete deletions of the V1, V2, and V3 domains. It was demonstrated that specific modification of the V3 loop (mV3) in combination with the V2-modified (mV2) or V1/V2-deleted (ΔV1/V2) region elicited increased levels of cross-reactive CD8+ T cell responses. Mice immunized with the mV2/mV3 or ΔV1/V2/mV3 gp14089.6 plasmid DNA were greater than 50-fold more resistant to challenge with recombinant vaccinia virus (rVV) expressing heterologous env gene products than animals immunized with the wild-type (WT) counterpart. Sera from mV2/mV3- and ΔV1/V2/mV3-immunized mice exhibited the highest cross-neutralizing activity and displayed intermediate antibody avidity values which were further enhanced by challenge with rVV expressing the homologous gp160 glycoprotein. In contrast, complete deletion of the variable regions had little or no effect on the cross-reactive antibody responses. The results of these experiments indicate that the breadth of antibody responses to the HIV-1 env glycoprotein may not be increased by removal of the variable domains. Instead, partial deletions within these regions may redirect specific responses toward conserved epitopes and facilitate approaches for boosting cross-reactive cellular and antibody responses to the env glycoprotein

  11. Enhancement of mucosal immune responses by chimeric influenza HA/SHIV virus-like particles

    International Nuclear Information System (INIS)

    To enhance mucosal immune responses using simian/human immunodeficiency virus-like particles (SHIV VLPs), we have produced novel phenotypically mixed chimeric influenza HA/SHIV VLPs and used them to immunize C57BL/6J mice intranasally. Antibody and cytotoxic T-cell (CTL) responses as well as cytokine production in both systemic and mucosal sites were compared after immunization with SHIV VLPs or chimeric HA/SHIV VLPs. By using enzyme-linked immunosorbent assay (ELISA), the levels of serum IgG and mucosal IgA to the HIV envelope protein (Env) were found to be highest in the group immunized with chimeric HA/SHIV VLPs. Furthermore, the highest titer of serum neutralizing antibody against HIV Env was found with the group immunized with chimeric HA/SHIV VLPs. Analysis of the IgG1/IgG2a ratio indicated that a TH1-oriented immune response resulted from these VLP immunizations. HA/SHIV VLP-immunized mice also showed significantly higher CTL responses than those observed in SHIV VLP-immunized mice. Moreover, a MHC class I restricted T-cell activation ELISPOT assay showed a mixed type of TH1/TH2 cytokines in the HA/SHIV VLP-immunized mice, indicating that the chimeric VLPs can enhance both humoral and cellular immune responses to the HIV Env protein at multiple mucosal and systemic sites. The results indicate that incorporation of influenza HA into heterotypic VLPs may be highly effective for targeting vaccines to mucosal surfaces

  12. Immune-mediated mechanisms influencing the efficacy of anticancer therapies.

    Science.gov (United States)

    Coffelt, Seth B; de Visser, Karin E

    2015-04-01

    Conventional anticancer therapies, such as chemotherapy, radiotherapy, and targeted therapy, are designed to kill cancer cells. However, the efficacy of anticancer therapies is not only determined by their direct effects on cancer cells but also by off-target effects within the host immune system. Cytotoxic treatment regimens elicit several changes in immune-related parameters including the composition, phenotype, and function of immune cells. Here we discuss the impact of innate and adaptive immune cells on the success of anticancer therapy. In this context we examine the opportunities to exploit host immune responses to boost tumor clearing, and highlight the challenges facing the treatment of advanced metastatic disease. PMID:25857662

  13. LV305, a dendritic cell-targeting integration-deficient ZVex(TM)-based lentiviral vector encoding NY-ESO-1, induces potent anti-tumor immune response.

    Science.gov (United States)

    Albershardt, Tina Chang; Campbell, David James; Parsons, Andrea Jean; Slough, Megan Merrill; Ter Meulen, Jan; Berglund, Peter

    2016-01-01

    We have engineered an integration-deficient lentiviral vector, LV305, to deliver the tumor antigen NY-ESO-1 to human dendritic cells in vivo through pseudotyping with a modified Sindbis virus envelop protein. Mice immunized once with LV305 developed strong, dose-dependent, multifunctional, and cytotoxic NY-ESO-1-specific cluster of differentiation 8 (CD8) T cells within 14 days post-immunization and could be boosted with LV305 at least twice to recall peak-level CD8 T-cell responses. Immunization with LV305 protected mice against tumor growth in an NY-ESO-1-expressing CT26 lung metastasis model, with the protective effect abrogated upon depletion of CD8 T cells. Adoptive transfer of CD8 T cells, alone or together with CD4 T cells or natural killer cells, from LV305-immunized donor mice to tumor-bearing recipient mice conferred significant protection against metastatic tumor growth. Biodistribution of injected LV305 in mice was limited to the site of injection and the draining lymph node, and injected LV305 exhibited minimal excretion. Mice injected with LV305 developed little to no adverse effects, as evaluated by toxicology studies adherent to good laboratory practices. Taken together, these data support the development of LV305 as a clinical candidate for treatment against tumors expressing NY-ESO-1. PMID:27626061

  14. Immune responses to hair dyes containing toluene-2,5-diamine

    DEFF Research Database (Denmark)

    Schmidt, J D; Johansen, J D; Nielsen, M M;

    2014-01-01

    BACKGROUND: Toluene-2,5-diamine (PTD) is the most frequently used dye in oxidative hair dyes on the Scandinavian market. However, little is known about immune responses to PTD-containing oxidative hair dyes. OBJECTIVES: To study immune responses induced by PTD-containing hair dyes in mice. METHODS......: Immune responses against two different permanent hair dye products containing 1·60% (w/w) and 0·48% (w/w) PTD within the colour gel, and various concentrations of pure PTD were studied. The local inflammatory response was measured by ear swelling and cell infiltration, and T- and B-cell infiltration and...... proliferation was determined in the draining lymph nodes. RESULTS: Concentration-dependent immune responses were seen to PTD both in the skin and draining lymph nodes. The hair dye containing 1·60% PTD induced strong local inflammation and caused T- and B-cell infiltration and proliferation as well as an...

  15. Effect of petroleum hydrocarbons and oil spill dispersants on immune responses in mussels

    Energy Technology Data Exchange (ETDEWEB)

    Hamoutene, D.; Payne, J.F. [Department of Fisheries and Oceans, St. John' s, NF (Canada). Science Branch; Rahimtula, A. [Memorial Univ. of Newfoundland, St. John' s, NF (Canada); French, B. [Oceans Ltd., St. John' s, NF (Canada); Lee, K. [Department of Fisheries and Oceans, Dartmouth, NS (Canada). Bedford Inst. of Oceanography

    2002-07-01

    A study was conducted to examine the effect of water soluble fractions of diesel oil and emulsions of Corexit 9527 on the cellular immune responses in mussels. The potential use of cytoskeleton labelling tests in mussel immunity assessment was also demonstrated. Corexit 9527 is an oil spill dispersant or surfactant that may be linked to anthropogenic stress that has increased the incidence of disease in shellfish. Various immune responses were examined in hemocytes which were preincubated in vitro with diesel water soluble fractions and Corexit 9527 emulsions before measuring phagocytosis cytoskeleton integrity. Animals were exposed to water soluble fractions of diesel and Corexit emulsions to study the in vivo immune response to determine the dose-response association. The animals were also injected with zymosan particles, followed by the measuring of the phagocytosis and cell numbers before and after exposure to water soluble fraction of diesel and Corexit emulsions. Results indicate there is an effect of dispersant and petroleum hydrocarbons on some stage of the hemocytes immune response. Dispersant concentrations that result in changes in the immune functions of mussels were greater than 100 mg per litre. This suggests that Corexit 9527 would not affect cellular mussel functions if used in operational doses in the event of an oil spill. However, the diesel water soluble fraction could pose a threat to the immune responses of mussels because the effective doses obtained in this study was found to be comparable or higher than those expected in the water column during the treatment of an oil spill.

  16. Effect of petroleum hydrocarbons and oil spill dispersants on immune responses in mussels

    International Nuclear Information System (INIS)

    A study was conducted to examine the effect of water soluble fractions of diesel oil and emulsions of Corexit 9527 on the cellular immune responses in mussels. The potential use of cytoskeleton labelling tests in mussel immunity assessment was also demonstrated. Corexit 9527 is an oil spill dispersant or surfactant that may be linked to anthropogenic stress that has increased the incidence of disease in shellfish. Various immune responses were examined in hemocytes which were preincubated in vitro with diesel water soluble fractions and Corexit 9527 emulsions before measuring phagocytosis cytoskeleton integrity. Animals were exposed to water soluble fractions of diesel and Corexit emulsions to study the in vivo immune response to determine the dose-response association. The animals were also injected with zymosan particles, followed by the measuring of the phagocytosis and cell numbers before and after exposure to water soluble fraction of diesel and Corexit emulsions. Results indicate there is an effect of dispersant and petroleum hydrocarbons on some stage of the hemocytes immune response. Dispersant concentrations that result in changes in the immune functions of mussels were greater than 100 mg per litre. This suggests that Corexit 9527 would not affect cellular mussel functions if used in operational doses in the event of an oil spill. However, the diesel water soluble fraction could pose a threat to the immune responses of mussels because the effective doses obtained in this study was found to be comparable or higher than those expected in the water column during the treatment of an oil spill

  17. Altered immune response in mallard ducklings exposed to lead through maternal transfer in the wild

    International Nuclear Information System (INIS)

    Lead (Pb) poisoning has caused significant mortality in waterfowl populations worldwide. In spite of having been banned since 2003, prevalence of Pb shot ingestion in mallards (Anas platyrhynchos) from the Ebro delta was still 15.5% in 2011–12. We collected mallard eggs from this area to study the effects of maternally transferred Pb on eggshell properties and on immune response and oxidative balance of ducklings. Eggshell Pb levels were positively correlated with Pb levels in the blood of ducklings. Ducklings with blood Pb levels above 180 ng mL−1 showed reduced body mass and died during the first week post hatching. Blood Pb levels positively correlated with humoral immune response, endogenous antioxidants and oxidative stress biomarkers, and negatively correlated with cellular immune response. Pb shot ingestion in birds can result in maternal transfer to the offspring that can affect their developing immune system and reduce their survival in early life stages. - Highlights: • Pb was transferred from mallard hens to eggs and ducklings. • Maternal Pb transfer was enough to inhibit blood ALAD activity in ducklings. • Cellular immune response was negatively affected by blood Pb levels. • Humoral immune response was exacerbated by Pb exposure. • Pb induced oxidative stress and increased levels of antioxidants in blood. - Maternal transfer of Pb alters immune responses and oxidative balance of ducklings and compromises the survival of individuals

  18. Complement activation pathways: a bridge between innate and adaptive immune responses in asthma.

    Science.gov (United States)

    Wills-Karp, Marsha

    2007-07-01

    Although it is widely accepted that allergic asthma is driven by T helper type 2 (Th2)-polarized immune responses to innocuous environmental allergens, the mechanisms driving these aberrant immune responses remain elusive. Recent recognition of the importance of innate immune pathways in regulating adaptive immune responses have fueled investigation into the role of innate immune pathways in the pathogenesis of asthma. The phylogenetically ancient innate immune system, the complement system, is no exception. The emerging paradigm is that C3a production at the airway surface serves as a common pathway for the induction of Th2-mediated inflammatory responses to a variety of environmental triggers of asthma (i.e., allergens, pollutants, viral infections, cigarette smoke). In contrast, C5a plays a dual immunoregulatory role by protecting against the initial development of a Th2-polarized adaptive immune response via its ability to induce tolerogenic dendritic cell subsets. On the other hand, C5a drives type 2-mediated inflammatory responses once inflammation ensues. Thus, alterations in the balance of generation of the various components of the complement pathway either due to environmental exposure changes or genetic alterations in genes of the complement cascade may underlie the recent rise in asthma prevalence in westernized countries. PMID:17607007

  19. Energetic and developmental costs of mounting an immune response in greenfinches (Carduelis chloris)

    NARCIS (Netherlands)

    Amat, Juan A.; Aguilera, Eduardo; Visser, G. Henk

    2007-01-01

    It is assumed that there is a trade-off between the costs allocated to mounting an immune defence and those allocated to costly functions such as breeding and moulting. The physiological basis for this is that mounting an immune response to pathogen challenge has energetic and/or nutrient costs whic

  20. The Nanoscience of Polyvalent Binding by Proteins in the Immune Response

    DEFF Research Database (Denmark)

    Vorup-Jensen, Thomas

    2016-01-01

    Recent research has demonstrated that the successful use of nanometer-scaled material, such as nanoparticles, as medicines is often challenged by the host immune system. Mechanisms of the innate immunity seem to provide a swift response to administration of particulate nanomedicines, which may cl...