WorldWideScience

Sample records for humoral immune suppression

  1. Antibiotic Treatment Suppresses Rotavirus Infection and Enhances Specific Humoral Immunity

    Science.gov (United States)

    Uchiyama, Robin; Chassaing, Benoit; Zhang, Benyue; Gewirtz, Andrew T.

    2014-01-01

    Background. Rotavirus causes 500 000 deaths and millions of physician visits and hospitalizations per year, with worse outcomes and reduced vaccine efficacy in developing countries. We hypothesized that the gut microbiota might modulate rotavirus infection and/or antibody response and thus potentially play a role in such regional differences. Methods. The microbiota was ablated via germ-free or antibiotic approaches. Enhanced exposure to microbiota was achieved via low-dose dextran sodium sulfate (DSS) treatment. Rotavirus infection and replication was assessed by enzyme-linked immunosorbent assay (ELISA) and quantitative reverse-transcription polymerase chain reaction. Diarrhea was scored visually. Humoral responses to rotavirus were measured by ELISA and enzyme-linked immunosorbent spot assay. Results. Microbiota elimination delayed infection and reduced infectivity by 42%. Antibiotics did not alter ratios of positive-sense to negative-sense strands, suggesting that entry rather than replication was influenced. Antibiotics reduced the diarrhea incidence and duration, indicating that the reduction in the level of rotavirus antigen was biologically significant. Despite lowered antigen level, antibiotics resulted in a more durable rotavirus mucosal/systemic humoral response. Increased rotavirus antibody response durability correlated with increased small intestinal rotavirus-specific, immunoglobulin A–producing antibody-secreting cell concentration in antibiotic-treated mice. Conversely, DSS treatment impaired generation of rotavirus-specific antibodies. Conclusions. Microbiota ablation resulted in reduced rotavirus infection/diarrhea and a more durable rotavirus antibody response, suggesting that antibiotic administration before rotavirus vaccination could raise low seroconversion rates that correlate with the vaccine's inefficacy in developing regions. PMID:24436449

  2. Cyclolinopeptide derivatives modify methotrexate-induced suppression of the humoral immune response in mice.

    Science.gov (United States)

    Katarzyńska, Joanna; Mazur, Adam; Rudzińska, Ewa; Artym, Jolanta; Zimecki, Michał; Jankowski, Stefan; Zabrocki, Janusz

    2011-09-01

    High doses of chemotherapeutics in clinical treatment, leading to cell toxicity, can be lowered by co-administration of other immunoregulatory drugs. The aim of this study was to evaluate effects of several derivatives of cyclolinopeptide A (CLA), derived from linen seeds, on the suppressive action of metothrexate (MTX) in a mouse model of humoral immune response in vitro. New CLA analogues 1 and 2, and their linear precursors 3 and 4, containing conformationally restricted dipeptide fragment Phe-Phe or D-Phe-D-Phe with ethylene bridge (-CH(2)-CH(2)-) between phenylalanine nitrogens were synthesized. NMR studies and theoretical calculations showed that introduction of locally constraining fragment into CLA molecule increased its overall conformational flexibility. The bioactivity of new CLA analogues was examined in the mouse model of the in vitro secondary humoral immune response, suppressed by methotrexate (MTX). The results revealed differential actions of the peptides such as 1/augmentation of the suppressive activity of MTX or 2/antagonistic effects of the peptides on MTX-induced suppression. Potential advantages for the application of CLA-derived peptides in therapy and structure-activity relationships were discussed. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  3. Maternal antibody transfer can lead to suppression of humoral immunity in developing zebra finches (Taeniopygia guttata).

    Science.gov (United States)

    Merrill, Loren; Grindstaff, Jennifer L

    2014-01-01

    Maternally transferred antibodies have been documented in a wide range of taxa and are thought to adaptively provide protection against parasites and pathogens while the offspring immune system is developing. In most birds, transfer occurs when females deposit immunoglobulin Y into the egg yolk, and it is proportional to the amount in the female's plasma. Maternal antibodies can provide short-term passive protection as well as specific and nonspecific immunological priming, but high levels of maternal antibody can result in suppression of the offspring's humoral immune response. We injected adult female zebra finches (Taeniopygia guttata) with one of two antigens (lipopolysaccharide [LPS] or keyhole limpet hemocyanin [KLH]) or a control and then injected offspring with LPS, KLH, or a control on days 5 and 28 posthatch to examine the impact of maternally transferred antibodies on the ontogeny of the offspring's humoral immune system. We found that offspring of females exposed to KLH had elevated levels of KLH-reactive antibody over the first 17-28 days posthatch but reduced KLH-specific antibody production between days 28 and 36. We also found that offspring exposed to either LPS or KLH exhibited reduced total antibody levels, compared to offspring that received a control injection. These results indicate that high levels of maternal antibodies or antigen exposure during development can have negative repercussions on short-term antibody production and may have long-term fitness repercussions for the offspring.

  4. Effect of lactoferrin on the methotrexate-induced suppression of the cellular and humoral immune response in mice.

    Science.gov (United States)

    Artym, Jolanta; Zimecki, Michal; Kruzel, Marian L

    2004-01-01

    Our previous studies revealed that lactoferrin (LF) reconstitutes the cellular and humoral immune response in cyclophosphamide-treated mice. The aim of this investigation was to establish whether the suppressory effects of methotrexate (MTX) on the cellular and humoral immune response can be modulated by LF. We found that MTX, given intraperitoneally (i.p.) at a dose of 200 mg/kg b.w., 48 h following sensitization of CBA mice with ovalbumin (OVA), reduced by 80% the delayed type hypersensitivity (DTH) response. Co-administration of LF in drinking water (0.5% solution) for the duration of the experiment (4 days) restored the DTH response almost to the control level. However, LF was not able to restore the primary humoral immune response, measured by the number of antibody-forming cells (AFC) to sheep erythrocytes (SRBC) in the spleens when MTX (1 mg/kg b.w.) was administered to mice i.p. 48h post immunization. On the other hand, mice treated with LF after second challenge with SRBC showed significant restoration of the MTX-suppressed humoral immune response following the booster immunization. In addition, LF (1 microg/ml) restored the secondary humoral immune response to SRBC in vitro when MTX (0.05-1 mM) was added to cell cultures on day 2 following cell culture initiation. These data demonstrate that LF preferentially restores the cellular immune response impaired by MTX treatment. It seems that LF also prevents the block of the activity of T memory cells in the secondary, humoral immune response. Taken together, we demonstrated that LF given orally can reduce the toxic effects of MTX.

  5. Suppression of Long-Lived Humoral Immunity Following Borrelia burgdorferi Infection.

    Directory of Open Access Journals (Sweden)

    Rebecca A Elsner

    2015-07-01

    Full Text Available Lyme Disease caused by infection with Borrelia burgdorferi is an emerging infectious disease and already by far the most common vector-borne disease in the U.S. Similar to many other infections, infection with B. burgdorferi results in strong antibody response induction, which can be used clinically as a diagnostic measure of prior exposure. However, clinical studies have shown a sometimes-precipitous decline of such antibodies shortly following antibiotic treatment, revealing a potential deficit in the host's ability to induce and/or maintain long-term protective antibodies. This is further supported by reports of frequent repeat infections with B. burgdorferi in endemic areas. The mechanisms underlying such a lack of long-term humoral immunity, however, remain unknown. We show here that B. burgdorferi infected mice show a similar rapid disappearance of Borrelia-specific antibodies after infection and subsequent antibiotic treatment. This failure was associated with development of only short-lived germinal centers, micro-anatomical locations from which long-lived immunity originates. These showed structural abnormalities and failed to induce memory B cells and long-lived plasma cells for months after the infection, rendering the mice susceptible to reinfection with the same strain of B. burgdorferi. The inability to induce long-lived immune responses was not due to the particular nature of the immunogenic antigens of B. burgdorferi, as antibodies to both T-dependent and T-independent Borrelia antigens lacked longevity and B cell memory induction. Furthermore, influenza immunization administered at the time of Borrelia infection also failed to induce robust antibody responses, dramatically reducing the protective antiviral capacity of the humoral response. Collectively, these studies show that B. burgdorferi-infection results in targeted and temporary immunosuppression of the host and bring new insight into the mechanisms underlying the failure

  6. Suppression of cell-mediated and humoral immune responses by an interleukin-2-immunoglobulin fusion protein in mice.

    Science.gov (United States)

    Kunzendorf, U; Pohl, T; Bulfone-Paus, S; Krause, H; Notter, M; Onu, A; Walz, G; Diamantstein, T

    1996-01-01

    Interleukin-2 (IL-2) plays a pivotal role in the cellular and humoral immune responses directed against foreign antigens. We characterized the in vitro and in vivo properties of a chimeric protein consisting of mouse IL-2 fused to the mouse IgG2b Fc domains. This fusion protein binds to IL-2 and Fc receptors and supports IL-2-dependent cell proliferation but does not mediate lysis of IL-2 receptor-positive cells in the presence of murine complement in vitro. However, in vivo the IL2-IgG2b fusion protein suppresses both cellular and humoral immune responses after immunization with sheep erythrocytes. Surprisingly, delayed hypersensitivity is inhibited despite a dramatic increase of splenic CD3+ and NK1.1+ lymphocytes, indicating that altered homing of IL2-IgG2b-activated lymphocytes rather than cytolysis prevents these cells from accumulating in areas of inflammation. Although in vitro the IL2-IgG2b fusion protein does not alter proliferation of B cells in response to mitogenic stimulation, IgM production in response to sheep erythrocytes is profoundly inhibited in mice treated with the IL2-IgG2b fusion protein. Since no side effects are observed, the IL2-IgG2b fusion protein may expand the therapeutic repertoire of reagents used for the treatment of allograft rejection and autoimmune diseases. PMID:8636431

  7. Humoral immunity in Hansen's Disease

    Directory of Open Access Journals (Sweden)

    Waldenise Cossermelli-Messina

    Full Text Available For many years immune response in leprosy has been studied. Since 1960 several reports dealing with humoral immunity have been described in the literature. Different autoantibody rates occur in leprosy. There is an increase in the prevalence of autoantibodies in elderly patients with long standing disease, in lepromatous leprosy and in those with reactional states. The diferences in rates among various studies are attributed to different methods and variations among patient samples concerning age, gender, polar forms, therapy and other elements. The prevalence of numerous antibodies, immune complexes, cryoglobulins and complement levels have been studied by many authors. This also highlights the importance of the more recent reviews of anti-Mycobacterium leprae glycolipid antibodies such as the anti-phenolic glycolipid-I antibodies in which titers are variable and depend on genetic factors.

  8. Transient suppression of the humoral immune response mediated by a factor derived from specifically activated, doubly primed lymphoid cells.

    Science.gov (United States)

    Kempf, K E; Rubin, A S

    1977-08-01

    In cultures of sheep erythrocyte- (SRBC) stimulated spleen cells from mice immunized with tetanus toxoid (TT) and horse erythrocytes (HRBC) 30 to 90 days earlier, the addition of both HRBC (day 0) and TT (day 2) resulted in significant suppression of the anti-SRBC plaque-forming cell (PFC) response compared to the response of similar cultures maintained without the priming antigens. The observed inhibition was due to the presence of a soluble factor that was released into the supernatant fluid of the specifically stimulated, primed population of lymphoid cells between 72 and 120 hr after culture initiation. The active mediator, a macromolecule of approximately 24,000 daltons as determined by gel filtration over Sephadex G-150 and Ultrogel AcA 44, was suppressive when added within 24 hr, but not 48 hr, of assay for PFC against the reference SRBC antigen. The transiently acting soluble suppressor (TASS) was not overtly cytotoxic since total cell recovery and viability were unaffected in its presence. The results presented here are discussed in relation to a possible mechanism of action in which the negative regulation of immunoglobulin production is favored once a minimum level of immune reactivity is reached.

  9. Subchronic exposure to ellagic acid impairs cytotoxic T-cell function and suppresses humoral immunity in mice.

    Science.gov (United States)

    Allen, C T; Peden-Adams, M M; EuDaly, J; Keil, D E

    2003-08-01

    Ellagic acid (EA) is present in a variety of foods such as grapes, strawberries, raspberries, and nuts. It is a dietary plant phenol that has been shown to inhibit oxidative stress and chemical carcinogenesis. Although several studies have examined the protective mechanisms of dietary EA including the induction of detoxifying enzymes, regulation of cell cycle, chelation of nickel, and prevention of DNA methylation, none have addressed the role of EA in immunological surveillance. This study investigates the status of immune function in B6C3F1 mice exposed continuously to EA in drinking water at 0.5, 1.0, or 2.0 mg/kg/day for 28 days. Although this range of exposure is above the estimated human daily intake (approximately 940 microg/day for 70 kg person or 13.4 microg/kg/day), these levels would not be unreasonable if EA were used as a dietary supplement or as a chemotherapeutic agent. Previous reports have demonstrated the anticarcinogenic effects of EA at levels 10- to 250-fold greater than those applied in this study. Immunological parameters assessed included natural killer (NK) cell activity, cytotoxic T lymphocyte (CTL) activity, IgM antibody plaque forming cell (PFC) response, thymus, spleen, kidney, and liver mass, and total cellularity for the thymus and spleen. Subchronic exposure to EA for 28 days in drinking water caused significant suppression of specific IgM antibody responses in the 2.0 mg/kg EA treatment group and suppressed cytotoxic T-cell function in the 0.5 and 1.0 mg/kg EA treatment groups. All other immunological parameters were within normal ranges. Kidney and liver mass were not altered after treatment with EA. The results from this study indicate that EA suppressed both IgM antibody responses and CTLs. These observations suggest important implications on human health should EA be prescribed as a chemotherapeutic agent or a preventative dietary supplement for cancer.

  10. 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.

  11. Suppression of humoral immunity and lymphocyte responsiveness during experimental trypanosoma cruzi infections Supresión de la inmunidade humoral y de la respuesta linfocitaria durante la infección experimental con Trypanosoma cruzi

    Directory of Open Access Journals (Sweden)

    José A. O'daly

    1984-04-01

    Full Text Available C3H/He and C57B1/6 mice were inoculated with 500 Trypanosoma cruzi trypomastigotes (Strain Y. During the acute phase infected mice presented parasitemia and enlargement of lymph nodes and spleens and intracellular parasites were observed in the heart. Examinations of cells derived from spleen and lymph nodes showed increased numbers of IgM and IgG-bearing cells. During the peak of splenomegaly, about day 17 post-infections, splenic lymphocytes showed a marked decrease in responsiveness to T and B-cell mitogens, parasite antigens and plaque forming cells (PFC to sheep red blood cells (SRBC. Unfractionated or plastic adherent splenic cells from mice, obtained during the acute phase were able to suppress the response to mitogens by lymphocytes from uninfected mice. During the chronic phase. Disappearance of parasitemia and intracellular parasites in the hearts as well as a decrease in spleen size, was observed. These changes preceded the complete recovery of responsiveness to mitogens and T. cruzi antigens by C57B1/6 splenic lymphocytes. However, this recovery was only partial in the C3H/He mice, known to be more sensitive to T. cruzi infection. Partial recovery of humoral immune response also occurred in both strains of mice during the chronic phase.Ratones C3H/He y C57B1/6 inoculados con 500 tripomastigotes de la cepa Y de T. cruzi muestran durante la fase aguda de la enferme-dad, parasitemia, aumento del bazo y gânglios linfáticos así como parásitos intracelulares en el corazón. Análisis de las células presentes en ganglios linfáticos y bazo presenta aumento de células IgM e IgG. Cuando la esplenomegalia es mayor, alrededor del día 17 postínfección, los linfocitos esplénicos mostraron un descenso marcado en la respuesta a mitógenos de células B y T, antígenos de T. cruzi y células formadoras de placas contra glóbulos rojos de carnero. Células de bazo o células esplénicas adherentes a plástico, obtenidas de ratones durante

  12. The immortality of humoral immunity.

    Science.gov (United States)

    Elgueta, Raul; de Vries, Victor C; Noelle, Randolph J

    2010-07-01

    Decades of high-titered antibody are sustained due to the persistence of memory B cells and long-lived plasma cells (PCs). The differentiation of each of these subsets is antigen- and T-cell driven and is dependent on signals acquired and integrated during the germinal center response. Inherent in the primary immune response must be the delivery of signals to B cells to create these populations, which have virtual immortality. Differences in biology and chemotactic behavior disperse memory B cells and long-lived PCs to a spectrum of anatomic sites. Each subset must rely on survival factors that can support their longevity. This review focuses on the generation of each of these subsets, their survival, and renewal, which must occur to sustain serological memory. In this context, we discuss the role of antigen, bystander inflammation, and cellular niches. The contribution of BAFF (B-cell activating factor belonging to the tumor necrosis factor family) and APRIL (a proliferation-inducing ligand) to the persistence of memory B cells and PCs are also detailed. Insights that have been provided over the past few years in the regulation of long-lived B-cell responses will have profound impact on vaccine development, the treatment of pre-sensitized patients for organ transplantation, and therapeutic interventions in both antibody- and T-cell-mediated autoimmunity.

  13. Intrathecal humoral immunity to encephalitic RNA viruses.

    Science.gov (United States)

    Phares, Timothy W; Stohlman, Stephen A; Bergmann, Cornelia C

    2013-02-15

    The nervous system is the target for acute encephalitic viral infections, as well as a reservoir for persisting viruses. Intrathecal antibody (Ab) synthesis is well documented in humans afflicted by infections associated with neurological complications, as well as the demyelinating disease, multiple sclerosis. This review focuses on the origin, recruitment, maintenance, and biological relevance of Ab-secreting cells (ASC) found in the central nervous system (CNS) following experimental neurotropic RNA virus infections. We will summarize evidence for a highly dynamic, evolving humoral response characterized by temporal alterations in B cell subsets, proliferation, and differentiation. Overall local Ab plays a beneficial role via complement-independent control of virus replication, although cross or self-reactive Ab to CNS antigens may contribute to immune-mediated pathogenesis during some infections. Importantly, protective Ab exert anti-viral activity not only by direct neutralization, but also by binding to cell surface-expressed viral glycoproteins. Ab engagement of viral glycoproteins blocks budding and mediates intracellular signaling leading to restored homeostatic and innate functions. The sustained Ab production by local ASC, as well as chemokines and cytokines associated with ASC recruitment and retention, are highlighted as critical components of immune control.

  14. Sculpting humoral immunity through dengue vaccination to enhance protective immunity

    Directory of Open Access Journals (Sweden)

    Wayne eCrill

    2012-11-01

    Full Text Available Dengue viruses (DENV are the most important mosquito transmitted viral pathogens infecting humans. DENV infection produces a spectrum of disease, most commonly causing a self-limiting flu-like illness known as dengue fever; yet with increased frequency, manifesting as life-threatening dengue hemorrhagic fever (DHF. Waning cross-protective immunity from any of the four dengue serotypes may enhance subsequent infection with another heterologous serotype to increase the probability of DHF. Decades of effort to develop dengue vaccines are reaching the finishing line with multiple candidates in clinical trials. Nevertheless, concerns remain that imbalanced immunity, due to the prolonged prime-boost schedules currently used in clinical trials, could leave some vaccinees temporarily unprotected or with increased susceptibility to enhanced disease. Here we develop a DENV serotype 1 (DENV-1 DNA vaccine with the immunodominant cross-reactive B cell epitopes associated with immune enhancement removed. We compare wild-type (WT with this cross-reactivity reduced (CRR vaccine and demonstrate that both vaccines are equally protective against lethal homologous DENV-1 challenge. Under conditions mimicking natural exposure prior to acquiring protective immunity, WT vaccinated mice enhanced a normally sub-lethal heterologous DENV-2 infection resulting in DHF-like disease and 95% mortality in AG129 mice. However, CRR vaccinated mice exhibited redirected serotype-specific and protective immunity, and significantly reduced morbidity and mortality not differing from naïve mice. Thus, we demonstrate in an in vivo DENV disease model, that non-protective vaccine-induced immunity can prime vaccinees for enhanced DHF-like disease and that CRR DNA immunization significantly reduces this potential vaccine safety concern. The sculpting of immune memory by the modified vaccine and resulting redirection of humoral immunity provide insight into DENV vaccine induced immune

  15. Humoral and cellular immune responses to modified hepatitis B ...

    African Journals Online (AJOL)

    Keywords: Hepatitis B virus, Plasmid DNA, Vaccine, Spleen cytokines, Humoral and cellular immune responses. Tropical Journal of Pharmaceutical Research is indexed by Science Citation Index (SciSearch), Scopus,. International Pharmaceutical Abstract, Chemical Abstracts, Embase, Index Copernicus, EBSCO, African.

  16. Humoral and cellular immune responses to modified hepatitis B ...

    African Journals Online (AJOL)

    Humoral and cellular immune responses to modified hepatitis B plasmid DNA vaccine in mice. Mounir M Salem-Bekhit, Mohamed Osman Gad El Rab, Mahmoud M Tawfick, Mohammad Raish, Mohamed Dahmani Fathallah, Mohsen Bayomi ...

  17. Changes in Humoral and Cellular Immunity in Tertiary Peritonitis

    OpenAIRE

    Matviychuk, Oleh

    2017-01-01

    The objective of the research was to give a comparative characteristic of parameters of humoral and cellular immunity in the development of secondary and tertiary peritonitis.Materials and methods. The research enrolled 109 patients with secondary peritonitis, 20 of whom developed tertiary peritonitis. Changes in humoral and cellular immunity were evaluated by serial blood tests for the determination of leukocyte count, the relative number of lymphocytes, Ig A, M, and G levels, as well as by ...

  18. Characterization of the effect of Cr(VI) on humoral innate immunity using Drosophila melanogaster.

    Science.gov (United States)

    Pragya, P; Shukla, A K; Murthy, R C; Abdin, M Z; Kar Chowdhuri, D

    2015-11-01

    With the advancement of human race, different anthropogenic activities have heaped the environment with chemicals that can cause alteration in the immune system of exposed organism. As a first line of barrier, the evolutionary conserved innate immunity is crucial for the health of an organism. However, there is paucity of information regarding in vivo assessment of the effect of environmental chemicals on innate immunity. Therefore, we examined the effect of a widely used environmental chemical, Cr(VI), on humoral innate immune response using Drosophila melanogaster. The adverse effect of Cr(VI) on host humoral response was characterized by decreased gene expression of antimicrobial peptides (AMPs) in the exposed organism. Concurrently, a significantly decreased transcription of humoral pathway receptors (Toll and PGRP) and triglyceride level along with inhibition of antioxidant enzyme activities were observed in exposed organism. This in turn weakened the immune response of exposed organism that was manifested by their reduced resistance against bacterial infection. In addition, overexpression of the components of humoral immunity particularly Diptericin benefits Drosophila from Cr(VI)-induced humoral immune-suppressive effect. To our knowledge, this is the first report regarding negative impact of an environmental chemical on humoral innate immune response of Drosophila along with subsequent protection by AMPs, which may provide novel insight into host-chemical interactions. Also, our data validate the utility and sensitivity of Drosophila as a model that could be used for screening the possible risk of environmental chemicals on innate immunity with minimum ethical concern that can be further extrapolated to higher organisms. © 2014 Wiley Periodicals, Inc.

  19. Evidence of a humoral immune response against the prokaryotic ...

    Indian Academy of Sciences (India)

    Although the BVDV non-structural N-terminal protease (Npro) acts as an interferon antagonist and subverts the host innate immunity, little is known about its immunogenicity. Hence, we expressed a recombinant BVDV Npro–His fusion protein (28 kDa) in E. coli and determined the humoral immune response generated by it ...

  20. Humoral and cellular immune responses to modified hepatitis B ...

    African Journals Online (AJOL)

    assay (ELISA), while cellular immune response was investigated by analysis of spleen cytokine profile. (TNFα, IFN γ and IL2) ... Keywords: Hepatitis B virus, Plasmid DNA, Vaccine, Spleen cytokines, Humoral and cellular immune responses. Tropical ..... factors associated with non-response to hepatitis. B vaccine included ...

  1. Oestrogen levels and humoral immune parameters in Nigerian ...

    African Journals Online (AJOL)

    Objectives: Endocrine and immune interactions mediate breast cancer which is currently incurable. This study attempts at elucidating mechanisms by which breast cancer progresses by determining the levels of oestradiol and humoral immune parameters at different stages of breast cancer compared with women without ...

  2. Q fever in pregnant goats: humoral and cellular immune responses

    NARCIS (Netherlands)

    Roest, H.I.J.; Post, J.; Gelderen, van E.; Zijderveld, van F.G.; Rebel, J.M.J.

    2013-01-01

    Q fever is a zoonosis caused by the intracellular bacterium Coxiella burnetii. Both humoral and cellular immunity are important in the host defence against intracellular bacteria. Little is known about the immune response to C. burnetii infections in domestic ruminants even though these species are

  3. Immune suppression and immune activation in depression.

    Science.gov (United States)

    Blume, Joshua; Douglas, Steven D; Evans, Dwight L

    2011-02-01

    Depression has been characterized as a disorder of both immune suppression and immune activation. Markers of impaired cellular immunity (decreased natural killer cell cytotoxicity) and inflammation (elevated IL-6, TNFα, and CRP) have been associated with depression. These immunological markers have been associated with other medical illnesses, suggesting that immune dysregulation may be a central feature common to both depression and to its frequent medical comorbidities. Yet the significant associations of findings of both immune suppression and immune activation with depression raise questions concerning the relationship between these two classes of immunological observations. Depressed populations are heterogeneous groups, and there may be differences in the immune profiles of populations that are more narrowly defined in terms of symptom profile and/or demographic features. There have been few reports concurrently investigating markers of immune suppression and immune activation in the same depressed individuals. An emerging pre-clinical literature suggests that chronic inflammation may directly contribute to the pathophysiology of immune suppression in the context of illnesses such as cancer and rheumatoid arthritis. This literature provides us with specific immunoregulatory mechanisms mediating these relationships that could also explain differences in immune disturbances between subsets of depressed individuals We propose a research agenda emphasizing the assessment of these immunoregulatory mechanisms in large samples of depressed subjects as a means to define the relationships among immune findings (suppression and/or activation) within the same depressed individuals and to characterize subsets of depressed subjects based on shared immune profiles. Such a program of research, building on and integrating our knowledge of the psychoneuroimmunology of depression, could lead to innovation in the assessment and treatment of depression and its medical

  4. Effects of corticosterone on innate and humoral immune functions and oxidative stress in barn owl nestlings.

    Science.gov (United States)

    Stier, Kim Silvana; Almasi, Bettina; Gasparini, Julien; Piault, Romain; Roulin, Alexandre; Jenni, Lukas

    2009-07-01

    The costs of coping with stressful situations are traded-off against other functions such as immune responses. This trade-off may explain why corticosterone secretion reduces immune reactions. Corticosterone differentially affects various immunity components. However, which component is suppressed varies between studies. It remains unclear whether the trade-off in energy, nutrition, autoimmunity or oxidative stress accounts for differential immunosuppression. In this study, we investigated whether corticosterone differentially affects the constitutive innate and humoral acquired immunity. We used barn owl nestlings, implanting 50% with a corticosterone-releasing pellet and the other 50% with a placebo pellet. To measure the effect on humoral immunity we vaccinated 50% of the corticosterone-nestlings and 50% of the placebo-nestlings with the antigens 'Tetravac' and the other 50% were injected with PBS. To assess the costs of elevated corticosterone, we measured body mass and resistance to oxidative stress. Administration of corticosterone increased corticosterone levels whereas vaccination induced the production of antibodies. Corticosterone reduced the production of antibodies, but it did not significantly affect the constitutive innate immunity. Corticosterone reduced body growth and resistance to oxidative stress. Under stressful conditions barn owl nestlings seem to keep the constitutive innate immunity, whereas elevated corticosterone levels negatively affected inducible immune responses. We found evidence that mounting a humoral immune reaction is not costly in terms of growth, but reduces the resistance to oxidative stress independently of corticosterone administration. We suggest that humoral immunity is suppressed because the risk of immunopathologies may be disproportionately high when mounting an antibody response under stressful situations.

  5. Saccharomyces uvarum mannoproteins stimulate a humoral immune response in mice

    Directory of Open Access Journals (Sweden)

    Fernanda Patrícia Brito Darpossolo

    2012-08-01

    Full Text Available Yeasts discarded in industrial processes can be used as a nutritional supplement and to extract cellular components with biotechnological aims. In this study, the humoral immune response of Swiss mice treated with mannoproteins (MP from the yeast Saccharomyces uvarum was evaluated. The mice were treated with MPs at different doses and times and inoculated with 2% sheep red blood cells. An increase in total Ig in mice treated with 100 μg of MP at the time of immunization or 24 h before was observed in the primary immune response; in the secondary immune response, an increase was observed in total Ig values for all groups, and an increase of IgG was observed in the mice treated with MPs (100 μg at the time of immunization or 24 h before. These results show that S. uvarum MPs present an immunostimulatory action on the humoral immune response in mice.

  6. Hibernation is associated with depression of T-cell independent humoral immune responses in the 13-lined ground squirrel

    NARCIS (Netherlands)

    Bouma, Hjalmar R.; Henning, Robert H.; Kroese, Frans G. M.; Carey, Hannah V.

    Mammalian hibernation consists of periods of low metabolism and body temperature (torpor), interspersed by euthermic arousal periods. The function of both the innate and adaptive immune system is suppressed during hibernation. In this study, we analyzed the humoral adaptive immune response to a

  7. Targeting the humoral immune system of patients with rheumatoid arthritis

    NARCIS (Netherlands)

    Teng, Yoe Kie Onno

    2008-01-01

    The aim of this thesis was to unravel the role of the humoral immune system in rheumatoid arthritis patients by employing new immunosuppressive strategies, i.e. specific B-cell depletion with Rituximab and non-specific lymfoablative treatment with high dose chemotherapy and hematopoeietic stem cell

  8. Humoral and cellular immune responses to modified hepatitis B ...

    African Journals Online (AJOL)

    Humoral and cellular immune responses to modified hepatitis B plasmid DNA vaccine in mice. ... Journal Home > Vol 15, No 4 (2016) > ... The PDF file you selected should load here if your Web browser has a PDF reader plug-in installed (for ...

  9. Heterogeneity of the humoral immune response following Staphylococcus aureus bacteremia

    NARCIS (Netherlands)

    N.J. Verkaik (Nelianne); H.A.M. Boelens (Hélène); C.P. de Vogel (Corné); M. Tavakol (Mehri); L.G.M. Bode (Lonneke); H.A. Verbrugh (Henri); A.F. van Belkum (Alex); W.J.B. van Wamel (Willem)

    2010-01-01

    textabstractExpanding knowledge on the humoral immune response in Staphylococcus aureus-infected patients is a mandatory step in the development of vaccines and immunotherapies. Here, we present novel insights into the antibody responses following S. aureus bacteremia. Fifteen bacteremic patients

  10. [Environmental influences on cellular and humoral immunity in athletes].

    Science.gov (United States)

    Sashenkov, S L; Pylaeva, I L; Kolupaev, V A; Dolgushin, I I

    2012-01-01

    The study of seasonal changes in the state of cellular and humoral immunity in trained athletes with predominantly aerobic energy supply of muscle activity, but different different dynamics of the level of physical activity in the annual cycle has been performed. The immune status of athletes, the level of several hormones and interleukins have been established to undergo significant, regular fluctuations training--competitive load throughout the annual cycle that may affect the level of morbidity of athletes.

  11. Humoral immunity is involved in the development of pericentral fibrosis after pediatric live donor liver transplantation.

    Science.gov (United States)

    Yamada, Hiroyuki; Kondou, Hiroki; Kimura, Takeshi; Ikeda, Kayo; Tachibana, Makiko; Hasegawa, Yasuhiro; Kiyohara, Yuki; Ueno, Takehisa; Miyoshi, Yoko; Mushiake, Sotaro; Ozono, Keiichi

    2012-12-01

    Although LT can be successful for treating end-stage liver disease in children, some patients develop fibrosis around the central vein area (PCF). This raises the possibility that PCF could lead to later cirrhosis and graft failure. Here, we report a retrospective immunohistochemical study of 28 patients who received a live donor liver transplant. We assessed the incidence and etiology of PCF using CD3, CD20, HLA-DR, and C4d-specific antibodies. Histological evidence of PCF was found in 13 cases (46.4%), of which 11 (84.6%) had experienced ACR and/or CP events post-transplant. Immunohistochemical evaluation revealed significantly stronger staining with these antibodies in the central vein area in PCF, especially for CD20 and C4d. This implies humoral immunopathology and suggests involvement of humoral immunity in the development of PCF. These results further imply that suppression of cellular immunity alone is insufficient to prevent PCF. We therefore suggest that suppression of both humoral and cellular immunity in combination would be required for prevention of PCF. © 2012 John Wiley & Sons A/S.

  12. Targeting the humoral immune system of patients with rheumatoid arthritis

    OpenAIRE

    Teng, Yoe Kie Onno

    2008-01-01

    The aim of this thesis was to unravel the role of the humoral immune system in rheumatoid arthritis patients by employing new immunosuppressive strategies, i.e. specific B-cell depletion with Rituximab and non-specific lymfoablative treatment with high dose chemotherapy and hematopoeietic stem cell transplantation. This thesis evaluates the clinical benefit of these strategies as well as the immunological changes that coincide with clinical improvement. By combining clinical outcome with immu...

  13. Norovirus P particle efficiently elicits innate, humoral and cellular immunity.

    Directory of Open Access Journals (Sweden)

    Hao Fang

    Full Text Available Norovirus (NoV P domain complexes, the 24 mer P particles and the P dimers, induced effective humoral immunity, but their role in the cellular immune responses remained unclear. We reported here a study on cellular immune responses of the two P domain complexes in comparison with the virus-like particle (VLP of a GII.4 NoV (VA387 in mice. The P domain complexes induced significant central memory CD4(+ T cell phenotypes (CD4(+ CD44(+ CD62L(+ CCR7(+ and activated polyclonal CD4(+ T cells as shown by production of Interleukin (IL-2, Interferon (IFN-γ, and Tumor Necrosis Factor (TNF-α. Most importantly, VA387-specific CD4(+ T cell epitope induced a production of IFN-γ, indicating an antigen-specific CD4(+ T cell response in P domain complex-immunized mice. Furthermore, P domain complexes efficiently induced bone marrow-derived dendritic cell (BMDC maturation, evidenced by up-regulation of co-stimulatory and MHC class II molecules, as well as production of IL-12 and IL-1β. Finally, P domain complex-induced mature dendritic cells (DCs elicited proliferation of specific CD4(+ T cells targeting VA387 P domain. Overall, we conclude that the NoV P domain complexes are efficiently presented by DCs to elicit not only humoral but also cellular immune responses against NoVs. Since the P particle is highly effective for both humoral and cellular immune responses and easily produced in Escherichia coli (E. coli, it is a good choice of vaccine against NoVs and a vaccine platform against other diseases.

  14. Augmented primary humoral immune response and decreased cell-mediated immunity by Murraya koenigii in rats.

    Science.gov (United States)

    Kaur, Inderjit; Bhatia, Sneh; Bhati, Yogendra; Sharma, Vinay; Mediratta, Pramod K; Bhattacharya, Swapan K

    2014-05-01

    Murraya koenigii (Rutaceae) (curry patta: Hindi) of the family Rutaceae is used in the traditional Indian system of medicine for its immunomodulatory properties. The essential oil of the leaves of M. koenigii possesses antimicrobial, antifungal, and pesticidal activities and is used for the treatment of amebiasis, diabetes, and hepatitis. The present study was performed to evaluate the effect of M. koenigii on humoral and cell-mediated immune responses in rats. Aqueous extract of M. koenigii leaves was administered orally in a dose of 350 mg/kg. Cell-mediated immunity was assessed by measuring foot pad thickness following sensitization by injection of keyhole limpet hemocyanin and subsequent challenge by the same. Humoral immunity was assessed by measurement of hemagglutination titer to sheep red blood cells (SRBCs). In the humoral immune response, the administration of M. koenigii [350 mg/kg per os (p.o.)] from day 1 to day 7 after sensitization with SRBC on day 0 caused a significant increase in the primary anti-SRBC titer. However, the secondary immune response was decreased significantly (pkoenigii (350 mg/kg, p.o.), when administered for 14 days, produced a significant (pkoenigii augments primary humoral immune response and decreases cell-mediated immunity.

  15. Selenium supplementation restores innate and humoral immune responses in footrot-affected sheep.

    Science.gov (United States)

    Hall, Jean A; Vorachek, William R; Stewart, Whitney C; Gorman, M Elena; Mosher, Wayne D; Pirelli, Gene J; Bobe, Gerd

    2013-01-01

    Dietary selenium (Se) alters whole-blood Se concentrations in sheep, dependent upon Se source and dosage administered, but little is known about effects on immune function. We used footrot (FR) as a disease model to test the effects of supranutritional Se supplementation on immune function. To determine the effect of Se-source (organic Se-yeast, inorganic Na-selenite or Na-selenate) and Se-dosage (1, 3, 5 times FDA-permitted level) on FR severity, 120 ewes with and 120 ewes without FR were drenched weekly for 62 weeks with different Se sources and dosages (30 ewes/treatment group). Innate immunity was evaluated after 62 weeks of supplementation by measuring neutrophil bacterial killing ability. Adaptive immune function was evaluated by immunizing sheep with keyhole limpet hemocyanin (KLH). The antibody titer and delayed-type hypersensitivity skin test to KLH were used to assess humoral immunity and cell-mediated immunity, respectively. At baseline, FR-affected ewes had lower whole-blood and serum-Se concentrations; this difference was not observed after Se supplementation. Se supplementation increased neutrophil bacterial killing percentages in FR-affected sheep to percentages observed in supplemented and non-supplemented healthy sheep. Similarly, Se supplementation increased KLH antibody titers in FR-affected sheep to titers observed in healthy sheep. FR-affected sheep demonstrated suppressed cell-mediated immunity at 24 hours after intradermal KLH challenge, although there was no improvement with Se supplementation. We did not consistently prevent nor improve recovery from FR over the 62 week Se-treatment period. In conclusion, Se supplementation does not prevent FR, but does restore innate and humoral immune functions negatively affected by FR.

  16. Immune response and histology of humoral rejection in kidney transplantation.

    Science.gov (United States)

    González-Molina, Miguel; Ruiz-Esteban, Pedro; Caballero, Abelardo; Burgos, Dolores; Cabello, Mercedes; Leon, Miriam; Fuentes, Laura; Hernandez, Domingo

    2016-01-01

    The adaptive immune response forms the basis of allograft rejection. Its weapons are direct cellular cytotoxicity, identified from the beginning of organ transplantation, and/or antibodies, limited to hyperacute rejection by preformed antibodies and not as an allogenic response. This resulted in allogenic response being thought for decades to have just a cellular origin. But the experimental studies by Gorer demonstrating tissue damage in allografts due to antibodies secreted by B lymphocytes activated against polymorphic molecules were disregarded. The special coexistence of binding and unbinding between antibodies and antigens of the endothelial cell membranes has been the cause of the delay in demonstrating the humoral allogenic response. The endothelium, the target tissue of antibodies, has a high turnover, and antigen-antibody binding is non-covalent. If endothelial cells are attacked by the humoral response, immunoglobulins are rapidly removed from their surface by shedding and/or internalization, as well as degrading the components of the complement system by the action of MCP, DAF and CD59. Thus, the presence of complement proteins in the membrane of endothelial cells is transient. In fact, the acute form of antibody-mediated rejection was not demonstrated until C4d complement fragment deposition was identified, which is the only component that binds covalently to endothelial cells. This review examines the relationship between humoral immune response and the types of acute and chronic histological lesion shown on biopsy of the transplanted organ. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  17. Orally administered lactoferrin restores humoral immune response in immunocompromised mice.

    Science.gov (United States)

    Artym, Jolanta; Zimecki, Michal; Paprocka, Maria; Kruzel, Marian L

    2003-10-09

    Cyclophosphamide (CP) is an anti-tumor drug commonly used in the chemotherapy of human cancer and autoimmune diseases. In our previous studies, we have demonstrated that lactoferrin (LF), given orally to CP-immunosuppressed mice, could reconstitute a T cell mediated immune response by the renewal of the T cell population. The aim of this present study was to evaluate the effects of LF on humoral responses in mice treated with cyclophosphamide. We demonstrate that a single, sublethal dose of cyclophosphamide (400 mg/kg body weight) profoundly inhibited the humoral immune response of CBA mice to sheep red blood cells (SRBC), as measured by the number of antibody forming cells (AFC) in the spleen after 5 weeks following CP treatment. Administration of 0.5% bovine LF in drinking water for 5 weeks partially reconstituted the AFC number (30-40% of the control values, but 7-10x more than in CP-treated controls). Determination of T and B cell levels in the spleens by flow cytometry revealed that the content of CD3+ and CD4+ as well as Ig+ splenocytes was elevated in the immunocompromised mice treated with LF. In addition, the number of peritoneal macrophages was partially restored following LF treatment. Evaluation of the proliferative response to concanavalin A (ConA) and pokeweed mitogen (PWM) demonstrated that the diminished reactivity of splenocytes from CP-treated mice was significantly enhanced by LF. In summary, we conclude that the prolonged, oral treatment of immunocompromised mice with LF led to partial reconstitution of the humoral response, associated with elevation of T and B cell and macrophage content and the proliferative response of splenocytes to mitogens.

  18. Assessment of the humoral immune system in adults with respiratory tract disease

    NARCIS (Netherlands)

    Kessel, D.A. van; Rijkers, G.T.; Zanen, P.

    2017-01-01

    Recurrent respiratory tract infections are a common problem, and can have various causes, including an underlying immunodeficiency. This thesis investigates the value of humoral immune status assessment in patients with respiratory tract infections, lung transplant candidates/recipients and the

  19. Sense of humor, childhood cancer stressors, and outcomes of psychosocial adjustment, immune function, and infection.

    Science.gov (United States)

    Dowling, Jacqueline S; Hockenberry, Marilyn; Gregory, Richard L

    2003-01-01

    The diagnosis, treatment, and side effects of childhood cancer have been described as extremely stressful experiences in the life of a child. Anecdotally, children report that a sense of humor helps them cope with the daily experiences of living with cancer; however, no research has examined sense of humor and childhood cancer stressors. This study investigated the effect of sense of humor on the relationship between cancer stressors and children's psychosocial adjustment to cancer, immune function, and infection using Lazarus and Folkman's theory of stress, appraisal, and coping. A direct relationship was observed between sense of humor and psychosocial adjustment to cancer, such that children with a high sense of humor had greater psychological adjustment, regardless of the amount of cancer stressors. A moderating effect was observed for incidence of infection. As childhood cancer stressors increase, children with high coping humor scores reported fewer incidences of infection than low scorers.

  20. AGE-DEPENDENT FEATURES OF EVOLVING HUMORAL IMMUNITY IN CHILDREN

    Directory of Open Access Journals (Sweden)

    A. P. Toptygina

    2012-01-01

    Full Text Available Abstract. Age dynamics of humoral immunity was studied in healthy children, i.e., 11 newborns, 33 infants of 4 to 8 months, 32 children of 1 to 2 years old,, 17 children of 4 to 5 years old, 25 children of 6 to 8 years old, 15 children of 9 to 11 years old, and 28 adolescents of 14 to 16 years old. Evaluation of membrane receptors on B cells was performed by means of three-colour fluorescent label and allowed of characterizing B1 subpopulations (CD19+CD5+CD27-, naпve B2 cells (CD19+CD5-CD27-, and B2 memory cells (CD19+CD5-CD27+. B1 cells have been shown to dominate in blood of newborns and younger children (up to 5 years old. By the contrary, B2 memory cells were nearly undetectable in newborns, and exceeded 20% in adolescents (by 15 years old. Meanwhile, it has been revealed that the amounts of IgG1 and IgG3 subclasses did progressively increase with age, whereas IgG2 remained decreased to 50% of adult values for a long time, and reached them by 11 years and later. We suggest that the age dynamics of IgG subclasses is connected with age-dependent changes in B cell subpopulations.

  1. Dissecting polyclonal vaccine-induced humoral immunity against HIV using Systems Serology

    Science.gov (United States)

    Chung, Amy W.; Kumar, Manu P.; Arnold, Kelly B.; Yu, Wen Han; Schoen, Matthew K.; Dunphy, Laura J.; Suscovich, Todd J.; Frahm, Nicole; Linde, Caitlyn; Mahan, Alison E.; Hoffner, Michelle; Streeck, Hendrik; Ackerman, Margaret E.; McElrath, M. Juliana; Schuitemaker, Hanneke; Pau, Maria G.; Baden, Lindsey R.; Kim, Jerome H.; Michael, Nelson L.; Barouch, Dan H.; Lauffenburger, Douglas A.; Alter, Galit

    2017-01-01

    While antibody titers and neutralization are considered the gold standard for the selection of successful vaccines, these parameters are often inadequate predictors of protective immunity. As antibodies mediate an array of extra-neutralizing Fc-functions, when neutralization fails to predict protection, investigating Fc-mediated activity may help identify immunological correlates and mechanism(s) of humoral protection. Here, we used an integrative approach termed Systems Serology to analyze relationships among humoral responses elicited in four HIV vaccine-trials. Each vaccine regimen induced a unique humoral “Fc-fingerprint”. Moreover, analysis of case:control data from the first moderately protective HIV vaccine trial, RV144, pointed to mechanistic insights into immune complex composition that may underlie protective immunity to HIV. Thus, multi-dimensional relational comparisons of vaccine humoral fingerprints offer a unique approach for the evaluation and design of novel vaccines against pathogens for which correlates of protection remain elusive. PMID:26544943

  2. Helminth Protein Vaccine Induced Follicular T Helper Cell for Enhancement of Humoral Immunity against Schistosoma japonicum

    Directory of Open Access Journals (Sweden)

    Jingyao Zhang

    2013-01-01

    Full Text Available Protein vaccines combined with adjuvants have been widely used to induce immune responses, especially the humoral immune response, against molecular targets including parasites. Follicular T helper (Tfh cells are the specialized providers of B-cell help, however, the induction of Tfh cells in protein vaccination has been rarely studied. Here, we report that the Schistosoma japonicum recombinant protein (SjGST-32 combined with tacrolimus (FK506 augmented the induction of Tfh cells, which expressed the canonical markers CXCR5, BCL6, and IL-21, and enhanced the humoral immune responses in BALB/c mice. Furthermore, the expression of IL-21R on germinal center (GC B cells and memory B cells increased in immunized mice, which indicated that IL-21 from the induced Tfh cells interacted with IL-21R for activation of B cells and maintenance of long-lived humoral immunity. Our results suggest that helminth protein vaccine combined with FK506 induces Tfh cell for stimulating humoral immune responses and inducing long-lived humoral immunity.

  3. Effector mechanisms of humoral immunity to porcine reproductive and respiratory syndrome virus.

    Science.gov (United States)

    Rahe, Michael C; Murtaugh, Michael P

    2017-04-01

    Porcine reproductive and respiratory syndrome virus (PRRSV) continues to afflict swine nearly 30 years after it was first discovered as the causative agent of "mystery swine disease". Immunological tools of vaccination and exposure to virulent viruses have not succeeded in achieving control and prevention of PRRSV. Humoral immunity, mediated by antibodies, is a hallmark of anti-viral immunity, but little is known about the effector mechanisms of humoral immunity against PRRSV. It is essential to understand the immunological significance of antibody functions, including recently described broadly neutralizing antibodies and potential non-neutralizing activities, in the immune response to PRRSV. Here, we review recent research from PRRSV and other host-pathogen interactions to inform novel routes of exploration into PRRSV humoral immunity which may be important for identifying the immunological correlates of protection against PRRSV infection. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Humoral immune responses of pregnant Guinea pigs Immunized with live attenuated Rhodococcus equi

    Directory of Open Access Journals (Sweden)

    Mawlood Abass Ali Al- Graibawi

    2018-02-01

    Full Text Available The potential to increase passive transfer of specific Rhodococcus equi (R.equi humoral immunity to newborn by preparturient vaccination of their dams was investigated in Pregnant Guinea pigs as a pilot study. Attenuated autogenous vaccine was prepared from a Congo red negative (CR- R.equi local isolate mixed with adjuvant (potassium alum sulphate, tested for sterility, safety and potency prior to vaccination .Two groups of pregnant G. pigs were used, the first group was vaccinated twice subcutaneously (S.C with the prepared vaccine at five and three weeks prior parturition, the second group was inoculated with adjuvant plus phosphate buffer saline (PBS twice s.c and kept as control. Offspring from the vaccinated dams had revealed high titers of specific R. equi antibody as detected by tube agglutination (TA and passive haemagglutination (PH test and showed protection against challenge dose. The results revealed that vaccination of pregnant G. pigs with the prepared attenuated vaccine was safe and efficient method to protect their offspring against experimental challenge with virulent R.equi. Vaccination was associated with increased humoral immune response in vaccinated group.

  5. Increased humoral immunity by DNA vaccination using an alpha-tocopherol-based adjuvant

    DEFF Research Database (Denmark)

    Karlsson, Ingrid; Borggren, Marie; Nielsen, Jens

    2017-01-01

    DNA vaccines induce broad immunity, which involves both humoral and strong cellular immunity, and can be rapidly designed for novel or evolving pathogens such as influenza. However, the humoral immunogenicity in humans and higher animals has been suboptimal compared to that of traditional vaccine......). The animals received two intracutaneous immunizations spaced 3 weeks apart. When combined with Diluvac Forte® or the emulsion containing alpha-tocopherol, the DNA vaccine induced a more potent and balanced immunoglobulin G (IgG)1 and IgG2c response, and both IgG subclass responses were significantly enhanced...... constituent alpha-tocopherol plays an important role in this immunogenicity. This induction of a potent and balanced humoral response without impairment of cellular immunity constitutes an important advancement toward effective DNA vaccines....

  6. Human breast milk feeding induces stronger humoral immune response than formula feeding in neonatal porcine model

    Science.gov (United States)

    Several studies indicate stronger humoral immune responses in breast-fed than formula-fed infants. The key to the beneficial impact of breastmilk on the gastrointestinal (GI) tract and immune system development is the interaction between diet and the gut microbiome. A more comprehensive, mechanistic...

  7. Mucosal Immunization with Liposome-Nucleic Acid Adjuvants Generates Effective Humoral and Cellular Immunity

    Science.gov (United States)

    Henderson, Angela; Propst, Katie; Kedl, Ross; Dow, Steven

    2012-01-01

    Development of effective new mucosal vaccine adjuvants has become a priority with the increase in emerging viral and bacterial pathogens. We previously reported that cationic liposomes complexed with non-coding plasmid DNA (CLDC) were effective parenteral vaccine adjuvants. However, little is known regarding the ability of liposome-nucleic acid complexes to function as mucosal vaccine adjuvants, or the nature of the mucosal immune responses elicited by mucosal liposome-nucleic acid adjuvants. To address these questions, antibody and T cell responses were assessed in mice following intranasal immunization with CLDC-adjuvanted vaccines. The effects of CLDC adjuvant on antigen uptake, trafficking, and cytokine responses in the airways and draining lymph nodes were also assessed. We found that mucosal immunization with CLDC-adjuvanted vaccines effectively generated potent mucosal IgA antibody responses, as well as systemic IgG responses. Notably, mucosal immunization with CLDC adjuvant was very effective in generating strong and sustained antigen-specific CD8+ T cell responses in the airways of mice. Mucosal administration of CLDC vaccines also induced efficient uptake of antigen by DCs within the mediastinal lymph nodes. Finally, a killed bacterial vaccine adjuvanted with CLDC induced significant protection from lethal pulmonary challenge with Burkholderia pseudomallei. These findings suggest that liposome-nucleic acid adjuvants represent a promising new class of mucosal adjuvants for non-replicating vaccines, with notable efficiency at eliciting both humoral and cellular immune responses following intranasal administration. PMID:21600950

  8. Genome-Wide Profiling of Humoral Immune Response to Coxiella burnetii Infection by Protein Microarray

    Science.gov (United States)

    2010-01-01

    Revised: March 5, 2010 Accepted: March 18, 2010 Keywords: Antibody I Coxiella burnetii I Humoral/ Microarray I Protein arrays I 0 fever 1 Introduction... Coxiella burnetii is a gram-negative, obligate intracellular bacteria, and the etiological agent of Q fever [1 ]. Distribution of C. burnetii is...4. TITLE AND SUBTITLE Genome-wide profiling of humoral immune response to Coxiella burnetii infection by protein microarray 5a. CONTRACT NUMBER 5b

  9. Targeting Immune Regulatory Networks to Counteract Immune Suppression in Cancer

    Directory of Open Access Journals (Sweden)

    Chiara Camisaschi

    2016-11-01

    Full Text Available The onset of cancer is unavoidably accompanied by suppression of antitumor immunity. This occurs through mechanisms ranging from the progressive accumulation of regulatory immune cells associated with chronic immune stimulation and inflammation, to the expression of immunosuppressive molecules. Some of them are being successfully exploited as therapeutic targets, with impressive clinical results achieved in patients, as in the case of immune checkpoint inhibitors. To limit immune attack, tumor cells exploit specific pathways to render the tumor microenvironment hostile for antitumor effector cells. Local acidification might, in fact, anergize activated T cells and facilitate the accumulation of immune suppressive cells. Moreover, the release of extracellular vesicles by tumor cells can condition distant immune sites contributing to the onset of systemic immune suppression. Understanding which mechanisms may be prevalent in specific cancers or disease stages, and identifying possible strategies to counterbalance would majorly contribute to improving clinical efficacy of cancer immunotherapy. Here, we intend to highlight these mechanisms, how they could be targeted and the tools that might be available in the near future to achieve this goal.

  10. Elevated humoral response to cytomegalovirus in HIV-infected individuals with poor CD4+ T-cell immune recovery.

    Directory of Open Access Journals (Sweden)

    Elisabet Gómez-Mora

    Full Text Available Some HIV-infected c-ART-suppressed individuals show incomplete CD4+ T-cell recovery, abnormal T-cell activation and higher mortality. One potential source of immune activation could be coinfection with cytomegalovirus (CMV. IgG and IgM levels, immune activation, inflammation and T-cell death in c-ART-suppressed individuals with CD4+ T-cell counts >350 cells/μL (immunoconcordant, n = 133 or <350 cells/μL (immunodiscordant, n = 95 were analyzed to evaluate the effect of CMV humoral response on immune recovery. In total, 27 HIV-uninfected individuals were included as controls. In addition, the presence of CMV IgM antibodies was retrospectively analyzed in 58 immunoconcordant individuals and 66 immunodiscordant individuals. Increased CMV IgG levels were observed in individuals with poor immune reconstitution (p = 0.0002. Increased CMV IgG responses were significantly correlated with lower nadir and absolute CD4+ T-cell counts. In contrast, CMV IgG responses were positively correlated with activation (HLA-DR+ and death markers in CD4+ T-cells and activated memory CD8+ T-cells (CD45RA-CD38+. Longitudinal subanalysis revealed an increased frequency of IgM+ samples in individuals with poor CD4+ T-cell recovery, and an association was observed between retrospective IgM positivity and the current level of IgG. The magnitude of the humoral immune response to CMV is associated with nadir CD4+ T-cell counts, inflammation, immune activation and CD4+ T-cell death, thus suggesting that CMV infection may be a relevant driving force in the increased morbidity/mortality observed in HIV+ individuals with poor CD4+ T-cell recovery.

  11. Gut Microbiota Co-microevolution with Selection for Host Humoral Immunity

    Directory of Open Access Journals (Sweden)

    Lingyu Yang

    2017-07-01

    Full Text Available To explore coevolution between the gut microbiota and the humoral immune system of the host, we used chickens as the model organism. The host populations were two lines (HAS and LAS developed from a common founder that had undergone 40 generations of divergent selection for antibody titers to sheep red blood cells (SRBC and two relaxed sublines (HAR and LAR. Analysis revealed that microevolution of host humoral immunity contributed to the composition of gut microbiota at the taxa level. Relaxing selection enriched some microorganisms whose functions were opposite to host immunity. Particularly, Ruminococcaceae and Oscillospira enriched in high antibody relaxed (HAR and contributed to reduction in antibody response, while Lactobacillus increased in low antibody relaxed (LAR and elevated the antibody response. Microbial functional analysis showed that alterations were involved in pathways relating to the immune system and infectious diseases. Our findings demonstrated co-microevolution relationships of host-microbiota and that gut microorganisms influenced host immunity.

  12. IFNAR1-Signalling Obstructs ICOS-mediated Humoral Immunity during Non-lethal Blood-Stage Plasmodium Infection.

    Directory of Open Access Journals (Sweden)

    Ismail Sebina

    2016-11-01

    Full Text Available Parasite-specific antibodies protect against blood-stage Plasmodium infection. However, in malaria-endemic regions, it takes many months for naturally-exposed individuals to develop robust humoral immunity. Explanations for this have focused on antigenic variation by Plasmodium, but have considered less whether host production of parasite-specific antibody is sub-optimal. In particular, it is unclear whether host immune factors might limit antibody responses. Here, we explored the effect of Type I Interferon signalling via IFNAR1 on CD4+ T-cell and B-cell responses in two non-lethal murine models of malaria, P. chabaudi chabaudi AS (PcAS and P. yoelii 17XNL (Py17XNL infection. Firstly, we demonstrated that CD4+ T-cells and ICOS-signalling were crucial for generating germinal centre (GC B-cells, plasmablasts and parasite-specific antibodies, and likewise that T follicular helper (Tfh cell responses relied on B cells. Next, we found that IFNAR1-signalling impeded the resolution of non-lethal blood-stage infection, which was associated with impaired production of parasite-specific IgM and several IgG sub-classes. Consistent with this, GC B-cell formation, Ig-class switching, plasmablast and Tfh differentiation were all impaired by IFNAR1-signalling. IFNAR1-signalling proceeded via conventional dendritic cells, and acted early by limiting activation, proliferation and ICOS expression by CD4+ T-cells, by restricting the localization of activated CD4+ T-cells adjacent to and within B-cell areas of the spleen, and by simultaneously suppressing Th1 and Tfh responses. Finally, IFNAR1-deficiency accelerated humoral immune responses and parasite control by boosting ICOS-signalling. Thus, we provide evidence of a host innate cytokine response that impedes the onset of humoral immunity during experimental malaria.

  13. IFNAR1-Signalling Obstructs ICOS-mediated Humoral Immunity during Non-lethal Blood-Stage Plasmodium Infection.

    Science.gov (United States)

    Sebina, Ismail; James, Kylie R; Soon, Megan S F; Fogg, Lily G; Best, Shannon E; Labastida Rivera, Fabian de; Montes de Oca, Marcela; Amante, Fiona H; Thomas, Bryce S; Beattie, Lynette; Souza-Fonseca-Guimaraes, Fernando; Smyth, Mark J; Hertzog, Paul J; Hill, Geoffrey R; Hutloff, Andreas; Engwerda, Christian R; Haque, Ashraful

    2016-11-01

    Parasite-specific antibodies protect against blood-stage Plasmodium infection. However, in malaria-endemic regions, it takes many months for naturally-exposed individuals to develop robust humoral immunity. Explanations for this have focused on antigenic variation by Plasmodium, but have considered less whether host production of parasite-specific antibody is sub-optimal. In particular, it is unclear whether host immune factors might limit antibody responses. Here, we explored the effect of Type I Interferon signalling via IFNAR1 on CD4+ T-cell and B-cell responses in two non-lethal murine models of malaria, P. chabaudi chabaudi AS (PcAS) and P. yoelii 17XNL (Py17XNL) infection. Firstly, we demonstrated that CD4+ T-cells and ICOS-signalling were crucial for generating germinal centre (GC) B-cells, plasmablasts and parasite-specific antibodies, and likewise that T follicular helper (Tfh) cell responses relied on B cells. Next, we found that IFNAR1-signalling impeded the resolution of non-lethal blood-stage infection, which was associated with impaired production of parasite-specific IgM and several IgG sub-classes. Consistent with this, GC B-cell formation, Ig-class switching, plasmablast and Tfh differentiation were all impaired by IFNAR1-signalling. IFNAR1-signalling proceeded via conventional dendritic cells, and acted early by limiting activation, proliferation and ICOS expression by CD4+ T-cells, by restricting the localization of activated CD4+ T-cells adjacent to and within B-cell areas of the spleen, and by simultaneously suppressing Th1 and Tfh responses. Finally, IFNAR1-deficiency accelerated humoral immune responses and parasite control by boosting ICOS-signalling. Thus, we provide evidence of a host innate cytokine response that impedes the onset of humoral immunity during experimental malaria.

  14. Humoral and cellular immunity in cosmonauts after the ISS missions

    Science.gov (United States)

    Rykova, M. P.; Antropova, E. N.; Larina, I. M.; Morukov, B. V.

    Spaceflight effects on the immune system were studied in 30 cosmonauts flown onto the International Space Station (ISS) for long- (125-195 d, n=15) and short-term (8-10 d, n=15) missions. Immunological investigations before launch and after landing were performed by using methods for quantitative and functional evaluation of the immunologically competent cells. Specific assays include: peripheral leukocyte distribution, natural killer (NK) cell cytotoxic activity, phagocytic activity of monocytes and granulocytes, proliferation of T-cells in response to a mitogen, levels of immunoglobulins IgA, IgM, IgG, virus-specific antibody and cytokine in serum. It was noticed that after long-term spaceflights the percentage of NK (CD3-/CD16+/CD56+) cells was significantly reduced compared with pre-flight data (pNK activity was suppressed by 20-85% as compared with pre-flight data in 12 out of 15 cosmonauts. T-lymphocyte activity was decreased by 25-39% as compared with pre-flight data in 5 out of 13 cosmonauts. However, the relative number of CD3+, CD4+ and CD8+ T-cells did not change. The functional activity of NK and T-cells decreased in some of the cosmonauts after short-term missions. On the other hand, a moderate trend upward of NK cytotoxic activity and proliferative activity of T-cells was observed in some individuals. Concentrations immunoglobulins (IgA, IgM, IgG) and levels of M and G antibodies to herpes simplex virus (HSV), cytomegalovirus (CMV), Epstein-Barr virus (EBV) and herpes virus type 6 (HV6) in serum did not reveal significant changes after long- and short-term flights. Concentrations of cytokines (IL- 1β, IL-2, IL-4 and TNF- α) in serum changed in an apparently random manner as compared with values before long- and short-term missions. Despite the fact that many improvements have been made to the living conditions of aboard the ISS our investigations demonstrate the remarkable depression of the immunological function after the ISS missions. These

  15. 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

    is still a problem worldwide. The broad host range of CDV creates a constant viral reservoir among wildlife animals. Our results demonstrated early humoral and cell-mediated immune responses (IFN-gamma) in DNA vaccinated mink compared to mock-vaccinated mink after challenge with a Danish wild-type CDV...

  16. Characterization of Humoral and Cellular Immunity to Rubella Vaccine in Four Distinct Cohorts

    Science.gov (United States)

    Lambert, Nathaniel; Haralambieva, Iana; Ovsyannikova, Inna; Larrabee, Beth; Pankratz, V. Shane; Poland, Gregory

    2014-01-01

    Although vaccination campaigns have significantly reduced the global burden of rubella disease, there are still regional outbreaks and cases of congenital rubella syndrome (CRS). Rubella vaccination elicits a strong humoral, as well as cellular, response. The relationship between these two measures in response to rubella vaccine is poorly understood. We have previously reported no correlation between rubella virus-specific cytokine secretion and IgG antibody levels after rubella vaccination. In the current study, we extend our previous work to report correlations between secreted cytokines and functional neutralizing antibodies after rubella vaccination in four distinct cohorts. There was evidence of significant differences (p rubella virus-specific humoral and cellular responses between cohorts. When investigating relationships between rubella vaccine-specific humoral and cellular immunity, we observed a significant correlation between neutralizing antibodies and IFN-γ (rs = 0.21, p = 0.0004). We also observed correlations in subjects with extreme humoral immune phenotypes and IFN-γ levels in two of the four cohorts (rs = 0.32, p = 0.01; rs = 0.36, p = 0.01, respectively). These findings indicate that there is a high level of heterogeneity in rubella-specific immune responses between study populations. We believe that the novel correlation discovered between IFN-γ and neutralizing antibody titers will give future insight into the functional mechanisms of immunity induced by rubella virus and other live viral vaccines. PMID:24375276

  17. The effect of Aloe vera extract on humoral and cellular immune ...

    African Journals Online (AJOL)

    tonukari sunday

    2011-06-13

    Jun 13, 2011 ... Some plant polysaccharides are well known to possess immunostimulatory effects. Aloe vera possesses confirmed curative or healing actions. The aim of this study was to evaluate the effect of the administration of A. vera plant extract on cellular and humoral immune response in rabbits. 20 healthy.

  18. The effect of Aloe vera extract on humoral and cellular immune ...

    African Journals Online (AJOL)

    Some plant polysaccharides are well known to possess immunostimulatory effects. Aloe vera possesses confirmed curative or healing actions. The aim of this study was to evaluate the effect of the administration of A. vera plant extract on cellular and humoral immune response in rabbits. 20 healthy male New Zealand white ...

  19. Chronic spinal cord injury impairs primary antibody responses, but spares existing humoral immunity in mice

    Science.gov (United States)

    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. Although mature B cell numbers were only mildly reduced, bone marrow B cell production was transiently but profoundly depressed immediately after injury. Despite the return of normal B cell production four weeks after SCI, mice receiving T3-injury showed a significant reduction in their ability to mount primary TI-2 or TD immune responses. The latter were marked by decreases in germinal center B cells as well as class switched high-affinity antibody secreting cells. Importantly, injury did not affect affinity maturation per se, pre-existing B cell memory, or secondary humoral immune responses. Together, these findings show that chronic high thoracic SCI impairs the ability to mount optimal antibody responses to new antigenic challenges, but spares previously established humoral immunity. PMID:22523388

  20. Long-term exposure to arsenic affects head kidney and impairs humoral immune responses of Clarias batrachus

    Energy Technology Data Exchange (ETDEWEB)

    Ghosh, Debabrata [Immunobiology Laboratory, School of Life Sciences, Visva-Bharati University, Santiniketan 731235 (India); Datta, Soma [Immunobiology Laboratory, School of Life Sciences, Visva-Bharati University, Santiniketan 731235 (India); Bhattacharya, Shelley [Environmental Toxicology Laboratory, School of Life Sciences, Visva-Bharati University, Santiniketan 731235 (India); Mazumder, Shibnath [Immunobiology Laboratory, School of Life Sciences, Visva-Bharati University, Santiniketan 731235 (India)]. E-mail: shibnath1@yahoo.co.in

    2007-02-15

    The present study was aimed at determining the effects of long-term arsenic exposure on the head kidney (HK) and ensuing humoral immune responses in Clarias batrachus L. Long-term exposure (150 days) to non-lethal concentrations of arsenic (42.42 {mu}M) resulted in significant time-dependent alterations in HK cell number eventually affecting the HK somatic index. Prolonged exposure to arsenic also suppressed HK-B cell proliferation and led to significant reduction in serum immunoglobulin levels and antigen-specific serum bacterial agglutinin titers. A decline in the number of antigen-specific plaque-forming cells with duration of arsenic exposure was noted in the HK. Enzyme linked immunosorbent assays further revealed that arsenic exposure inhibited the release of 'IL-4 like factors' from HK-T cells. Histological studies documented time-dependent changes in the structure and cellular composition of HK characterized by extensive lymphocytopenia, decrease in melano-macrophage population and hemosiderin accumulation. From exposure-challenge studies with Aeromonas hydrophila it was evident that pathogens could efficiently disseminate and colonize distant host tissues in the exposed fish. Moreover, the ability to decrease the pathogen load was also significantly reduced in the arsenic-exposed fish. Thus long-term exposure to non-lethal concentrations of arsenic affects HK and interferes with the humoral immune system of C. batrachus rendering them immunocompromised and susceptible to pathogenic challenge.

  1. Ceftiofur hydrochloride affects the humoral and cellular immune response in pigs after vaccination against swine influenza and pseudorabies.

    Science.gov (United States)

    Pomorska-Mól, Małgorzata; Czyżewska-Dors, Ewelina; Kwit, Krzysztof; Wierzchosławski, Karol; Pejsak, Zygmunt

    2015-10-22

    significant delay in the development of humoral response against pseudorabies virus (PRV) as well as a significant suppression of production of antibodies against swine influenza virus (SIV) was found in pigs receiving ceftiofur hydrochloride at the time of vaccination. The cellular immune response against PRV was also significantly affected by ceftiofur. In contrast, there were no significant differences between vaccinated groups with regard to the T-cell response against SIV. From day 28 of study to day 70, the concentration of INF-γ in culture supernatants were significantly lower in group treated with ceftiofur after restimulation with PRV. While, no significant differences were observed after restimulation of PBMC with H3N2 SIV. The effect of an antibiotic therapy with ceftiofur hydrochloride on the humoral and cellular post-vaccinal immune responses in pigs was investigated. Ceftiofur hydrochloride was given in therapeutic doses. The results of the present study indicate that both, humoral and cell-mediated post-vaccinal immune responses can be modulated by treatment with ceftiofur hydrochloride. The results of our study point out that caution should be taken when administered this antibiotic during vaccination of pigs.

  2. Germinal center texture entropy as possible indicator of humoral immune response: immunophysiology viewpoint.

    Science.gov (United States)

    Pantic, Igor; Pantic, Senka

    2012-10-01

    In this article, we present the results indicating that spleen germinal center (GC) texture entropy determined by gray-level co-occurrence matrix (GLCM) method is related to humoral immune response. Spleen tissue was obtained from eight outbred male short-haired guinea pigs previously immunized by sheep red blood cells (SRBC). A total of 312 images from 39 germinal centers (156 GC light zone images and 156 GC dark zone images) were acquired and analyzed by GLCM method. Angular second moment, contrast, correlation, entropy, and inverse difference moment were calculated for each image. Humoral immune response to SRBC was measured using T cell-dependent antibody response (TDAR) assay. Statistically highly significant negative correlation was detected between light zone entropy and the number of TDAR plaque-forming cells (r (s) = -0.86, p Germinal center texture entropy may be a powerful indicator of humoral immune response. This study is one of the first to point out the potential scientific value of GLCM image texture analysis in lymphoid tissue cytoarchitecture evaluation. Lymphoid tissue texture analysis could become an important and affordable addition to the conventional immunophysiology techniques.

  3. PBMC transcription profiles of pigs with divergent humoral immune responses and lean growth performance.

    Science.gov (United States)

    Adler, Marcel; Murani, Eduard; Ponsuksili, Siriluck; Wimmers, Klaus

    2013-01-01

    The identification of key genes and regulatory networks in the transcriptomic responses of blood cells to antigen stimulation could facilitate the understanding of host defence and disease resistance. Moreover, genetic relationships between immunocompetence and the expression of other phenotypes, such as those of metabolic interest, are debated but incompletely understood in farm animals. Both positive and negative associations between immune responsiveness and performance traits such as weight gain or lean growth have been reported. We designed an in vivo microarray study of transcriptional changes in porcine peripheral blood mononuclear cells (PBMCs) during the immune response to tetanus toxoid (TT) as a model antigen for combined cellular (Th1) and humoral (Th2) responses. The aim of the study was to investigate the responsiveness of PBMCs against the background of divergent lean growth (LG) performance and anti-TT antibody (AB) titers and to compare lean growth and humoral immune performance phenotypes. In general, high LG phenotypes had increased cellular immune response transcripts, while low AB phenotypes had increased transcripts for canonical pathways that represented processes of intracellular and second messenger signaling and immune responses. Comparison of lean growth phenotypes in the context of high AB titers revealed higher cellular immune response transcripts in high LG phenotypes. Similar comparisons in the context of low AB titers failed to identify any corresponding pathways. When high and low AB titer phenotypes were differentially compared, low AB phenotypes had higher cellular immune response transcripts on a low LG background and higher cell signaling, growth, and proliferation transcripts on a high LG background. Divergent phenotypes of both lean growth performance and humoral immune response are affected by significant and functional transcript abundance changes throughout the immune response. The selected high-performance phenotypes

  4. Humoral and cellular immunity in progressive systemic sclerosis.

    Science.gov (United States)

    Sierakowski, S; Bernacka, K

    1987-01-01

    There is ever increasing evidence that immune disturbances can play an essential role in the pathogenesis of progressive systemic sclerosis. However, there are still a great many controversial opinions and complex studies in this domain are few. Tests of lymphocyte blastic transformation and of leukocyte migration inhibition as well as E and EAC rosette tests were performed and the serum level of A, G and M immunoglobulins and complement were estimated in 13 patients with progressive systemic sclerosis. The increase of serum IgA, IgG and IgM and the decrease of early and delayed E rosette formation was observed in the patients as compared with the control group. The patients also presented increase spontaneous and PHA induced lymphocyte blastic transformation. The results support the hypothesis of the role played by immune disturbances in the pathogenesis of progressive systemic sclerosis.

  5. Stability of a general delayed virus dynamics model with humoral immunity and cellular infection

    Science.gov (United States)

    Elaiw, A. M.; Raezah, A. A.; Alofi, A. S.

    2017-06-01

    In this paper, we investigate the dynamical behavior of a general nonlinear model for virus dynamics with virus-target and infected-target incidences. The model incorporates humoral immune response and distributed time delays. The model is a four dimensional system of delay differential equations where the production and removal rates of the virus and cells are given by general nonlinear functions. We derive the basic reproduction parameter R˜0 G and the humoral immune response activation number R˜1 G and establish a set of conditions on the general functions which are sufficient to determine the global dynamics of the models. We use suitable Lyapunov functionals and apply LaSalle's invariance principle to prove the global asymptotic stability of the all equilibria of the model. We confirm the theoretical results by numerical simulations.

  6. Growing bacteria shed elicitors of Drosophila humoral immunity.

    Science.gov (United States)

    Karlsson, Jenny; Oldenvi, Sandra; Fahlander, Carina; Daenthanasanmak, Anusara; Steiner, Håkan

    2012-01-01

    It has been much debated how the Drosophila immune system can recognize bacterial peptidoglycan that is often hidden. We show that bacteria separated from Drosophila S2 cells by a semipermeable membrane can upregulate the Imd pathway. Supernatants from exponentially growing but not from stationary-phase bacterial cultures induce antimicrobial peptides. It is also made likely that the shed elicitors are of peptidoglycan nature. Copyright © 2011 S. Karger AG, Basel.

  7. Humoral and cell-mediated immune response to crude antigens of Dermatophilus congolensis during experimental infection of rabbits.

    Science.gov (United States)

    Makinde, A A; Wilkie, B N

    1979-01-01

    Rabbits were infected with Dermatophilus congolensis and tested for humoral immune response by indirect haemagglutination and for cell-mediated immune response to crude antigens of D. congolensis. Lymphocyte transformation and macrophage migration inhibition assays were used as in vitro correlates of cell-mediated immune response while cutaneous delayed hypersensitivity was used in vivo. Endo-antigen and whole cell antigen were found to significantly induce cell-mediated immune response. In contrast, humoral responses were found to be more significantly induced by exo-antigen. A biphasic immune response was revealed by the lymphocyte transformation test.

  8. Humoral immune response to campylobacter jejuni in patients with enterocolitis and Guillain-Barré syndrome

    OpenAIRE

    Ristić Ljiljana; Kocić Branislava; Babić Tatjana; Apostolski S.; Spasić Mirjana; Miljković-Selimović Biljana

    2012-01-01

    Campylobacter jejuni is one of the most important causes of diarrheal disease worldwide. In addition, it can cause neurological post-infectious sequels, such as Guillain-Barré syndrome (GBS). Humoral immune response to C. jejuni was monitored in patients with C. jejuni enterocolitis, GBS patients and healthy persons, by ELISA. Statistical significance between patients with enterocolitis and healthy persons, as well as among GBS patients and healthy controls, was proven. Statistical sign...

  9. Single Amino Acid Modification of Adeno-Associated Virus Capsid Changes Transduction and Humoral Immune Profiles

    OpenAIRE

    Li, Chengwen; DiPrimio, Nina; Bowles, Dawn E.; Hirsch, Matthew L.; Monahan, Paul E.; Asokan, Aravind; Rabinowitz, Joseph; Agbandje-McKenna, Mavis; Samulski, R. Jude

    2012-01-01

    Adeno-associated virus (AAV) vectors have the potential to promote long-term gene expression. Unfortunately, humoral immunity restricts patient treatment and in addition provides an obstacle to the potential option of vector readministration. In this study, we describe a comprehensive characterization of the neutralizing antibody (NAb) response to AAV type 1 (AAV1) through AAV5 both in vitro and in vivo. These results demonstrated that NAbs generated from one AAV type are unable to neutralize...

  10. Augmentation of humoral and cell mediated immune responses by Thujone.

    Science.gov (United States)

    Siveen, K S; Kuttan, Girija

    2011-12-01

    Thujone, a naturally occurring monoterpene, was found to enhance the total WBC count, bone marrow cellularity, number of α-esterase positive cells, number of plaque forming cells in spleen and circulating antibody titer in Balb/c mice (1mg/kg body weight, intraperitoneally for 5 days). Thujone treatment enhanced proliferation of splenocytes and thymocytes, both in the presence and absence of specific mitogens. Administration of Thujone was found to stimulate the cell-mediated immunological response in normal and tumor bearing Balb/c mice. A significant enhancement in natural killer (NK) cell mediated cytotoxicity, antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent complement mediated cytotoxicity (ACC) in both normal as well as tumor-bearing animals was observed after the administration of Thujone. Production of cytokines such as IL-2 and IFN-γ was significantly enhanced by the administration of Thujone. The stimulatory effect of Thujone on cytotoxic T lymphocyte (CTL) generation was determined by Winn's neutralization assay using CTL sensitive EL4 thymoma cells. Thujone treatment showed a significant increase in CTL production in both the in vivo and in vitro models, as indicated by a significant increase in the life span of tumor bearing animals. All these results indicate that administration of Thujone could enhance the immune response of mice. There was a significant reduction in solid tumor development, mediated by the presence of alert immune responses during Thujone administration. Copyright © 2011 Elsevier B.V. All rights reserved.

  11. Cellular and humoral immunity of virus-induced asthma

    Directory of Open Access Journals (Sweden)

    Yoshimichi eOkayama

    2013-08-01

    Full Text Available Asthma inception is associated with respiratory viral infection, especially infection with respiratory syncytial virus (RSV and/or human rhinovirus (HRV, in the vast majority of cases. However, the reason why RSV and HRV induce the majority of bronchiolitis cases during early childhood and why only a small percentage of children with RSV- and HRV-induced bronchiolitis later develop asthma remains unclear. A genetic association study has revealed the important interaction between viral illness and genetic variants in patients with asthma. Severe RSV- and HRV-induced bronchiolitis may be associated with a deficiency in the innate immune response to RSV and HRV. RSV and HRV infections in infants with deficient innate immune response and the dysfunction of regulatory T cells are considered to be a risk factor for the development of asthma. Sensitization to aeroallergens, beginning in the first year of life, consistently predisposes children to HRV-induced wheezing illnesses, but the converse is not true. Some evidence of virus specificity exists, in that allergic sensitization specifically increased the risk of wheezing in individuals infected with HRV, but not RSV. Administration of Palivizumab, a humanized monoclonal antibody that targets the A antigenic site of the Fusion-protein of RSV, decreases the risk of hospitalization in high-risk infants and the risk of recurrent of wheezing. However, palivizumab did not have any effect on subsequent recurrent wheezing in children with a family history of atopy. These findings suggest that infection with RSV and infection with HRV might predispose individuals to recurrent wheezing through an atopy-independent and an atopy-dependent mechanism, respectively. Respiratory virus-induced wheezing illnesses may encompass multiple sub-phenotypes that relate to asthma in different ways.

  12. Humoral and cellular immune responses after influenza vaccination in patients with chronic fatigue syndrome

    Directory of Open Access Journals (Sweden)

    Prinsen Hetty

    2012-12-01

    Full Text Available Abstract Background Chronic fatigue syndrome (CFS is a clinical condition characterized by severe and disabling fatigue that is medically unexplained and lasts longer than 6 months. Although it is possible to effectively treat CFS, the nature of the underlying physiology remains unclear. Various studies have sought evidence for an underlying disturbance in immunity. The aim of this study was to compare the humoral and cellular immune responses upon influenza vaccination in CFS patients and healthy controls. Results Identical antibody titers were observed in CFS patients and healthy controls. Patients and controls demonstrated similar seroprotection rates against all three virus-strains of the influenza vaccine, both pre- and post-vaccination. Functional T cell reactivity was observed in both CFS patients and healthy controls. CFS patients showed a non-significant, numerically lower cellular proliferation at baseline compared to controls. Vaccination induced a significant increase in cellular proliferation in CFS patients, but not in healthy controls. Cytokine production and the number of regulatory T cells were comparable in patients and controls. Conclusions The humoral and cellular immune responses upon influenza vaccination were comparable in CFS patients and healthy controls. Putative aberrations in immune responses in CFS patients were not evident for immunity towards influenza. Standard seasonal influenza vaccination is thus justified and, when indicated, should be recommended for patients suffering from CFS.

  13. Nonredundant Roles of IL-10 and TGF-β in Suppression of Immune Responses to Hepatic AAV-Factor IX Gene Transfer

    OpenAIRE

    Hoffman, Brad E.; Martino, Ashley T.; Sack, Brandon K; Cao, Ou; Liao, Gongxian; Terhorst, Cox; Herzog, Roland W.

    2011-01-01

    Hepatic gene transfer using adeno-associated viral (AAV) vectors has been shown to efficiently induce immunological tolerance to a variety of proteins. Regulatory T-cells (Treg) induced by this route suppress humoral and cellular immune responses against the transgene product. In this study, we examined the roles of immune suppressive cytokines interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) in the development of tolerance to human coagulation factor IX (hF.IX). Interestingly,...

  14. Swiprosin-1/EFhd2 limits germinal center responses and humoral type 2 immunity.

    Science.gov (United States)

    Brachs, Sebastian; Turqueti-Neves, Adriana; Stein, Merle; Reimer, Dorothea; Brachvogel, Bent; Bösl, Michael; Winkler, Thomas; Voehringer, David; Jäck, Hans-Martin; Mielenz, Dirk

    2014-11-01

    Activated B cells are selected for in germinal centers by regulation of their apoptosis. The Ca2+ -binding cytoskeletal adaptor protein Swiprosin-1/EFhd2 (EFhd2) can promote apoptosis in activated B cells. We therefore hypothesized that EFhd2 might limit humoral immunity by repressing both the germinal center reaction and the expected enhancement of immune responses in the absence of EFhd2. Here, we established EFhd2(-/-) mice on a C57BL/6 background, which revealed normal B- and T-cell development, basal Ab levels, and T-cell independent type 1, and T-cell independent type 2 responses. However, T cell-dependent immunization with sheep red blood cells and infection with the helminth Nippostrongylus brasiliensis (N.b) increased production of antibodies of multiple isotypes, as well as germinal center formation in EFhd2(-/-) mice. In addition, serum IgE levels and numbers of IgE+ plasma cells were strongly increased in EFhd2(-/-) mice, both after primary as well as after secondary N.b infection. Finally, mixed bone marrow chimeras unraveled an EFhd2-dependent B cell-intrinsic contribution to increased IgE plasma cell numbers in N.b-infected mice. Hence, we established a role for EFhd2 as a negative regulator of germinal center-dependent humoral type 2 immunity, with implications for the generation of IgE. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. The Hepatitis C Virus Glycan Shield and Evasion of the Humoral Immune Response

    Directory of Open Access Journals (Sweden)

    Jean Dubuisson

    2011-10-01

    Full Text Available Despite the induction of effective immune responses, 80% of hepatitis C virus (HCV-infected individuals progress from acute to chronic hepatitis. In contrast to the cellular immune response, the role of the humoral immune response in HCV clearance is still subject to debate. Indeed, HCV escapes neutralizing antibodies in chronically infected patients and reinfection has been described in human and chimpanzee. Studies of antibody-mediated HCV neutralization have long been hampered by the lack of cell-culture-derived virus and the absence of a small animal model. However, the development of surrogate models and recent progress in HCV propagation in vitro now enable robust neutralization assays to be performed. These advances are beginning to shed some light on the mechanisms of HCV neutralization. This review summarizes the current state of knowledge of the viral targets of anti-HCV-neutralizing antibodies and the mechanisms that enable HCV to evade the humoral immune response. The recent description of the HCV glycan shield that reduces the immunogenicity of envelope proteins and masks conserved neutralizing epitopes at their surface constitutes the major focus of this review.

  16. The Hepatitis C Virus Glycan Shield and Evasion of the Humoral Immune Response

    Science.gov (United States)

    Helle, François; Duverlie, Gilles; Dubuisson, Jean

    2011-01-01

    Despite the induction of effective immune responses, 80% of hepatitis C virus (HCV)-infected individuals progress from acute to chronic hepatitis. In contrast to the cellular immune response, the role of the humoral immune response in HCV clearance is still subject to debate. Indeed, HCV escapes neutralizing antibodies in chronically infected patients and reinfection has been described in human and chimpanzee. Studies of antibody-mediated HCV neutralization have long been hampered by the lack of cell-culture-derived virus and the absence of a small animal model. However, the development of surrogate models and recent progress in HCV propagation in vitro now enable robust neutralization assays to be performed. These advances are beginning to shed some light on the mechanisms of HCV neutralization. This review summarizes the current state of knowledge of the viral targets of anti-HCV-neutralizing antibodies and the mechanisms that enable HCV to evade the humoral immune response. The recent description of the HCV glycan shield that reduces the immunogenicity of envelope proteins and masks conserved neutralizing epitopes at their surface constitutes the major focus of this review. PMID:22069522

  17. Interference of the humoral immune response against resident and non-resident intestinal commensal strains in weaning pigs

    NARCIS (Netherlands)

    Casini, L.; Konstantinov, S.R.; Coloretti, F.; Filippi, de S.; Mazzoni, M.; Trevisi, P.; Bosi, P.

    2007-01-01

    Not nocuous bacteria are important for the maturation and the modulating activity of the gut immune system. However, the humoral immune response against commensal and probiotic bacteria is less documented, particularly in farmhouse animals. Blood serum and saliva were collected in two trials where

  18. Effect of response to backtest and housing condition on cell-mediated and humoral immunity in adult pigs

    NARCIS (Netherlands)

    Geverink, N.A.; Parmentier, H.K.; Vries Reilingh, de G.; Schouten, W.G.P.; Gort, G.; Wiegant, V.M.

    2004-01-01

    Several recent studies in juvenile pigs demonstrated a relationship between the degree of resistance displayed early in life in a so-called "backtest" and parameters of cell-mediated and humoral immunity. Some of the immune characteristics were reported to depend on the interaction between backtest

  19. Difference in the presence of cell-mediated and humoral immunity in patients with endometriosis compared with healthy women

    Directory of Open Access Journals (Sweden)

    Nina Slabe

    2011-08-01

    Conclusions: We have not fully confirmed the hypothesis that women with endomeriosis have alterations in the immune response. However, the present study supports and adds important infomation to the views that immune abnormality plays an important role in the etiopathogenesis of endometriosis. On the humoral level, we showed the presence of antiendothelial antibodies reacting with vascular endothelium.

  20. Analysis of the humoral immune response to Chlamydia outer membrane protein 2

    DEFF Research Database (Denmark)

    Mygind, P; Christiansen, Gunna; Persson, K

    1998-01-01

    The humoral immune response to Chlamydia outer membrane protein 2 (Omp2) was studied. Omp2 is a highly genus-conserved structural protein of all Chlamydia species, containing a variable N-terminal fragment. To analyze where the immunogenic parts were localized, seven highly purified truncated...... fusion proteins constituting different regions of the protein were produced (Chlamydia pneumoniae-Omp2aa23-aa93, Chlamydia psittaci-Omp2aa23-aa94, and Chlamydia trachomatis-Omp2aa23-aa84, aa87-aa547, aa23-aa182, aa167-aa434, aa420-aa547). By an enzyme-linked immunosorbent assay with serologically defined...

  1. AAV-mediated delivery of optogenetic constructs to the macaque brain triggers humoral immune responses.

    Science.gov (United States)

    Mendoza, Skyler D; El-Shamayleh, Yasmine; Horwitz, Gregory D

    2017-05-01

    Gene delivery to the primate central nervous system via recombinant adeno-associated viral vectors (AAV) allows neurophysiologists to control and observe neural activity precisely. A current limitation of this approach is variability in vector transduction efficiency. Low levels of transduction can foil experimental manipulations, prompting vector readministration. The ability to make multiple vector injections into the same animal, even in cases where successful vector transduction has already been achieved, is also desirable. However, vector readministration has consequences for humoral immunity and gene delivery that depend on vector dosage and route of administration in complex ways. As part of optogenetic experiments in rhesus monkeys, we analyzed blood sera collected before and after AAV injections into the brain and quantified neutralizing antibodies to AAV using an in vitro assay. We found that injections of AAV1 and AAV9 vectors elevated neutralizing antibody titers consistently. These immune responses were specific to the serotype injected and were long lasting. These results demonstrate that optogenetic manipulations in monkeys trigger immune responses to AAV capsids, suggesting that vector readministration may have a higher likelihood of success by avoiding serotypes injected previously.NEW & NOTEWORTHY Adeno-associated viral vector (AAV)-mediated gene delivery is a valuable tool for neurophysiology, but variability in transduction efficiency remains a bottleneck for experimental success. Repeated vector injections can help overcome this limitation but affect humoral immune state and transgene expression in ways that are poorly understood. We show that AAV vector injections into the primate central nervous system trigger long-lasting and serotype-specific immune responses, raising the possibility that switching serotypes may promote successful vector readministration. Copyright © 2017 the American Physiological Society.

  2. Protection and humoral immune responses against Bordetella pertussis infection in mice immunized with acellular or cellular pertussis immunogens.

    Science.gov (United States)

    van den Berg, B M; David, S; Beekhuizen, H; Mooi, F R; van Furth, R

    2000-12-08

    In the present study, protection against Bordetella pertussis infection and humoral immunological responses in mice has been assessed upon immunization with custom-made acellular pertussis vaccines (ACVs) and whole-cell pertussis vaccine (WCV). Mice were immunized, next intranasally infected with B. pertussis and during 14 days the number of bacteria in the trachea and lungs and the level of serum antibodies were determined. ACV contained five immunogens, filamentous hemagglutinin, pertactin, fimbriae serotypes 2 and 3, and chemically detoxified pertussis toxin (PMC-5), or three immunogens, filamentous hemagglutinin, pertactin, and genetically detoxified (BC-3) or chemically detoxified pertussis toxin (SKB-3). Immunization with a high or low dose of ACV or WCV resulted in significant protection against B. pertussis, with differences in the degree of protection between the vaccines. The lowest protection was found with a low dose of SKB-3 and WCV. The pattern of cytokine production by spleen cells of immunized, non-infected, mice indicated that T-helper 1 cells are activated by vaccination with WCV, and T-helper 1 and T-helper 2 cells are involved in the immune response upon vaccination with ACVs. Each vaccine stimulated the production of IgG, but not IgA, antibodies. In mice immunized with ACV, elimination of B. pertussis from trachea and lungs correlated significantly with the titre of IgG1, but not IgG2a, antibodies.

  3. Humoral Immune Response Induced by PLGA Micro Particle Coupled Newcastle Disease Virus Vaccine in Chickens

    Directory of Open Access Journals (Sweden)

    Sanganagouda K

    2014-02-01

    Full Text Available This experiment was conducted for evaluating the humoral immune responses induced by Poly Lactide-co-Glycolide Acid (PLGA microspheres coupled inactivated Newcastle Disease Virus (NDV vaccine in comparison to an ‘in-house’ prepared inactivated and a live commercial vaccine. PLG microparticles containing inactivated NDV were prepared by a double emulsion technique based on solvent evaporation method. The size of the NDV coupled PLG microparticles was determined by Electron Microscopy. NDV coupled PLG microparticles were spherical having smooth surface, hollow core inside with no pores on the surface. The experiment was conducted in four groups of chickens (n=15. The encapsulation efficiency of NDV coupled PLG microparticles was determined by protein estimation and HA activity in elute. The mean (± SE size of PLG microspheres was found to be 2.409 ± 0.65 µm. The mean percent of encapsulation efficiency of PLG microspheres coupled to NDV was assessed based on the total protein content and HA activity in elute was found to be 8.03 ± 0.50 and 12.5 ± 0.00, respectively. In conclusion, the results of the experiment showed that PLGA coupled NDV vaccine elicited stronger and prolonged humoral immune response in chickens, in comparison to the other tested vaccines, as assessed by haemagglutination inhibition and enzyme linked immuno sorbent asaay titers.

  4. Humoral and cell mediated immune responses against Schistosoma spindale in BALB/c mice.

    Science.gov (United States)

    Prechatangkit, B; Dhaliwal, J S; Ambu, S

    1994-03-01

    (BALB/c mice were infected with cercariae of Schistosoma spindale by tail immersion technique and by dropping some cercariae from a pipet onto the outer surface of the pinna of the ears. Groups of mice were removed on Days 10, 20 and 30 and tested for humoral and cell mediated immune responses using either adult worm or cercarial antigen. On Day 50 the mice were sacrificed and the worm burden was determined for each mouse. This method resulted in an infectivity rate of 89.7%. There was a significant increase in antibody titer to the adult worm antigen while no significant increase was observed for cercarial antigen over the period of the study. Results obtained for cell mediated immunity were more dramatic. There was a significant increase in foot pad swelling for adult worm antigen compared to a significant decrease for cercarial antigen during the course of the infection.

  5. Effect of dietary probiotic on performance and humoral immune response in layer hens.

    Science.gov (United States)

    Balevi, T; Uçan, U S; Coşkun, B; Kurtoglu, V; Cetingül, I S

    2001-09-01

    1. The effects of dietary supplementation of a commercial probiotic (Protexin) on daily feed consumption, egg yield, egg weight, food conversion ratio and humoral immune response in layer hens were investigated. In 7 replicates, a total of 280 40-week-old layers were given diets containing either 0, 250, 500 or 750 parts per million (ppm) for 90 d. 2. When compared with the controls, the food consumption, food conversion ratio and the proportions of damaged eggs were lower in the group consuming 500 ppm probiotic (P<0.05). 3. There was no significant difference between the controls and the groups receiving 250 and 750 ppm probiotic in food consumption, food conversion ratio and proportion of damaged eggs. Similarly, the egg yield, egg weight, specific gravity, and peripheral immune response showed no statistically significant differences between the groups.

  6. Effects of the endoparasitoid Cotesia chilonis (Hymenoptera: Braconidae) parasitism, venom, and calyx fluid on cellular and humoral immunity of its host Chilo suppressalis (Lepidoptera: Crambidae) larvae.

    Science.gov (United States)

    Teng, Zi-Wen; Xu, Gang; Gan, Shi-Yu; Chen, Xuan; Fang, Qi; Ye, Gong-Yin

    2016-02-01

    The larval endoparasitoid Cotesia chilonis injects venom and bracoviruses into its host Chilo suppressalis during oviposition. Here we study the effects of the polydnavirus (PDV)-carrying endoparasitoid C. chilonis (Hymenoptera: Braconidae) parasitism, venom and calyx fluid on host cellular and humoral immunity, specifically hemocyte composition, cellular spreading, encapsulation and melanization. Total hemocyte counts (THCs) were higher in parasitized larvae than in unparasitized larvae in the late stages following parasitization. While both plasmatocyte and granulocyte fractions and hemocyte mortality did not differ between parasitized and unparasitized hosts, in vitro spreading behavior of hemocytes was inhibited significantly by parasitism throughout the course of parasitoid development. C. chilonis parasitism suppressed the encapsulation response and melanization in the early stages. Venom alone did not alter cellular immune responses, including effects on THCs, mortality, hemocyte composition, cell spreading and encapsulation, but venom did inhibit humoral immunity by reducing melanization within 6h after injection. In contrast to venom, calyx fluid had a significant effect on cell spreading, encapsulation and melanization from 6h after injection. Dose-response injection studies indicated the effects of venom and calyx fluid synergized, showing a stronger and more persistent reduction in immune system responses than the effect of either injected alone. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. Combination of Protein and Viral Vaccines Induces Potent Cellular and Humoral Immune Responses and Enhanced Protection from Murine Malaria Challenge▿

    OpenAIRE

    Hutchings, Claire L.; Birkett, Ashley J.; Moore, Anne C.; Hill, Adrian V. S.

    2007-01-01

    The search for an efficacious vaccine against malaria is ongoing, and it is now widely believed that to confer protection a vaccine must induce very strong cellular and humoral immunity concurrently. We studied the immune response in mice immunized with the recombinant viral vaccines fowlpox strain FP9 and modified virus Ankara (MVA), a protein vaccine (CV-1866), or a combination of the two; all vaccines express parts of the same preerythrocytic malaria antigen, the Plasmodium berghei circums...

  8. Preparation of ESAT-6 Nanoparticles and Evaluation of Humoral Immunity after Intranasal Administration

    Directory of Open Access Journals (Sweden)

    H Najminezhad

    2013-01-01

    Full Text Available Introduction: Among several tuberculosis vaccine candidates for replacement of BCG, ESAT-6 protein has a special role. Since mycobacterium tuberculosis infection most often attacks the lungs, intranasal rout can be regarded as appropriate methods for tuberculosis vaccines and drug delivery. One of the appropriate systems for intranasal vaccine delivery is using biodegradable nanoparticles. Among biodegradable polymers, chitosan polymer has great features to increase the response of immunity system. This study aimed to investigate the specific humoral immune response of mice model after encapsulation of recombinant ESAT-6 antigen in chitosan nanoparticles. Methods: The chitosan nanoparticles containing ESAT-6 antigen were synthesized by ionic gelation. Nanoparticle properties including morphology, particle size, zeta potential, encapsulation rates, and protein release were measured in vitro. The immunization was performed through the nose for 3 times on days 0 and 14 and 28. 2 weeks after last administration, blood samples were collected and specific IgG titers were measured by indirect ELISA. Results: The nanoparticles synthesized had appropriate properties. The mean size of resulting nanoparticles was 242.8 nm by excellent antigen loading capacity (95.23 %. The vitro release of antigen from nanoparticles after 200 hours was detected as 67.5%. The Level of IgG antibody showed significant increase in the group that had received chitosan nanoparticles containing ESAT-6 compared with other groups. Conclusion: ESAT-6 protein was encapsulated in chitosan nanoparticles successfully. Administration of chitosan nanoparticles can be a suitable method for administration of humoral immunity antigens of Mycobacterium tuberculosis through intranasal rout.

  9. A Study on the Humoral and Complement Immune System of Patients with Organic Acidemia.

    Science.gov (United States)

    Alizadeh Najjarbashi, Faegheh; Mesdaghi, Mehrnaz; Alaei, Mohammadreza; Shakiba, Marjan; Jami, Aliakbar; Ghadimi, Farah

    2015-12-01

    Patients with organic acidemia are prone to different infections, which lead to acidosis episodes. Some studies have evaluated the status of immune system in acidotic phase in these patients, but to the best of our knowledge no study has evaluated the immune system in non-acidotic phase of the disease. In this study, thirty-one patients with organic acidemia were enrolled. For evaluation of humoral immunity, serum IgA, IgG, IgE, IgM, isohemaggltuinin titer, anti tetanus and anti diphtheria IgG were measured. For screening of complement deficiencies, serum C3, C4, and CH50 were assessed. Eleven patients had Maple Syrup Urine Disease (MSUD), 10 had methylmalonic acidemia, 5 had isovaleric acidemia, 4 had glutaric aciduria, and 1 had propionic acidemia. Serum IgM level was less than normal in 2 patients. Serum isohemagglutinin titer was less than 1:8 in 2 other patients. IgA, IgE, and IgG were within normal range for all patients. Anti tetanus and anti diphtheria IgG levels were low in two patients with MSUD. No significant relationship was found between any of the measured parameters and history of recurrent admissions, recurrent infections and the type of their diseases. Five patients had high C3 level, 4 had high C4 level, and 5 had high CH50 percentage. Totally, 10 patients had high complement level, but no remarkable connection was noted between the type of the disease and complement level. Minor insignificant deficiencies in humoral immunity in non-acidotic phase of organic acidemia were found. Some components of complement system showed increase in some patients, which might be due to decreased pH in extracellular fluid.

  10. Humoral immune responses in chickens and turkeys after infection with Toxoplasma gondii by using recombinant antigens.

    Science.gov (United States)

    Hotop, Andrea; Buschtöns, Susanne; Bangoura, Berit; Zöller, Birte; Koethe, Martin; Spekker-Bosker, Katrin; Hotop, Sven-Kevin; Tenter, Astrid M; Däubener, Walter; Straubinger, Reinhard K; Groß, Uwe

    2014-04-01

    Toxoplasma gondii is a parasite which can be transmitted to humans via the consumption of contaminated meat products derived from different animal species, e.g., poultry. In Europe, the consumption rate of poultry meat is high and may pose a risk for humans. However, little is known about the prevalence and immune response against T. gondii in these animals. Based on these circumstances, we experimentally infected 18 turkeys and 16 chickens with the parasite. Turkeys were infected either with tachyzoites on different routes or with various amounts of oocysts. In contrast, chickens were only infected with different doses of oocysts. The immunoglobulin (Ig) Y humoral immune responses of these animals were investigated in a lineblot assay against the recombinant T. gondii antigens rGRA1, rGRA6, rGRA9, rSAG1, and rSUB1. By using the recombinant antigens rGRA6, rGRA9, and rSUB1 in the lineblot assay, we found a correlation between the humoral immune response and the parasite stage in turkeys. Thereby, an infection with oocysts induced a stronger, permanent long-lasting antibody response compared to tachyzoite-infected animals. Only a minor relation between the oocyst infection dose and the manifestation of the immune response in chickens was found 7 days post infection (dpi) by using rGRA1 and rGRA9. However, an inconstant detection of antigen-specific IgY antibodies in the lineblot assay seems not to be a sufficient method for the identification of a Toxoplasma infection in chickens. In contrast, the detection of anti-rGRA6, anti-rGRA9, and anti-rSUB1 IgY antibodies showed potential for the identification of an infection in turkeys.

  11. Effect of nanovaccine chemistry on humoral immune response kinetics and maturation

    Science.gov (United States)

    Haughney, Shannon L.; Ross, Kathleen A.; Boggiatto, Paola M.; Wannemuehler, Michael J.; Narasimhan, Balaji

    2014-10-01

    Acute respiratory infections represent a significant portion of global morbidity and mortality annually. There is a critical need for efficacious vaccines against respiratory pathogens. To vaccinate against respiratory disease, pulmonary delivery is an attractive route because it mimics the route of natural infection and can confer both mucosal and systemic immunity. We have previously demonstrated that a single dose, intranasal vaccine based on polyanhydride nanoparticles elicited a protective immune response against Yersinia pestis for at least 40 weeks after immunization with F1-V. Herein, we investigate the effect of nanoparticle chemistry and its attributes on the kinetics and maturation of the antigen-specific serum antibody response. We demonstrate that manipulation of polyanhydride nanoparticle chemistry facilitated differential kinetics of development of antibody titers, avidity, and epitope specificity. The results provide new insights into the underlying role(s) of nanoparticle chemistry in providing long-lived humoral immunity and aid in the rational design of nanovaccine formulations to induce long-lasting and mature antibody responses.Acute respiratory infections represent a significant portion of global morbidity and mortality annually. There is a critical need for efficacious vaccines against respiratory pathogens. To vaccinate against respiratory disease, pulmonary delivery is an attractive route because it mimics the route of natural infection and can confer both mucosal and systemic immunity. We have previously demonstrated that a single dose, intranasal vaccine based on polyanhydride nanoparticles elicited a protective immune response against Yersinia pestis for at least 40 weeks after immunization with F1-V. Herein, we investigate the effect of nanoparticle chemistry and its attributes on the kinetics and maturation of the antigen-specific serum antibody response. We demonstrate that manipulation of polyanhydride nanoparticle chemistry

  12. Combination of protein and viral vaccines induces potent cellular and humoral immune responses and enhanced protection from murine malaria challenge.

    Science.gov (United States)

    Hutchings, Claire L; Birkett, Ashley J; Moore, Anne C; Hill, Adrian V S

    2007-12-01

    The search for an efficacious vaccine against malaria is ongoing, and it is now widely believed that to confer protection a vaccine must induce very strong cellular and humoral immunity concurrently. We studied the immune response in mice immunized with the recombinant viral vaccines fowlpox strain FP9 and modified virus Ankara (MVA), a protein vaccine (CV-1866), or a combination of the two; all vaccines express parts of the same preerythrocytic malaria antigen, the Plasmodium berghei circumsporozoite protein (CSP). Mice were then challenged with P. berghei sporozoites to determine the protective efficacies of different vaccine regimens. Two immunizations with the protein vaccine CV-1866, based on the hepatitis B core antigen particle, induced strong humoral immunity to the repeat region of CSP that was weakly protective against sporozoite challenge. Prime-boost with the viral vector vaccines, FP9 followed by MVA, induced strong T-cell immunity to the CD8+ epitope Pb9 and partially protected animals from challenge. Physically mixing CV-1866 with FP9 or MVA and then immunizing with the resultant combinations in a prime-boost regimen induced both cellular and humoral immunity and afforded substantially higher levels of protection (combination, 90%) than either vaccine alone (CV-1866, 12%; FP9/MVA, 37%). For diseases such as malaria in which different potent immune responses are required to protect against different stages, using combinations of partially effective vaccines may offer a more rapid route to achieving deployable levels of efficacy than individual vaccine strategies.

  13. Assessment of humoral immunity to Eimeria tenella sporozoites in chickens by ELISA

    Directory of Open Access Journals (Sweden)

    S. Saravanan

    2014-07-01

    Full Text Available Aim: To assess the humoral immune response of Eimeria tenella sporozoites in broiler chickens by a developed enzyme linked immunosorbent assay (ELISA and the efficacy in terms of bodyweight, lesion score and oocysts excretion in immunized broilers. Materials and Methods: Purified live E. tenella sporozoites were administered subcutaneously in neck region of broiler chickens in the early life (first week at different concentrations. The potency of the sporozoite vaccine as assessed by IgG levels and the performance in immunized broilers as assessed by body weight, lesion score and oocysts excretion in faeces after challenge with 10, 000 live E. tenella oocysts at 49 days of age were evaluated. Results: The chickens of group (T4 immunized with 20 µg of antigen on day 6 showed an increase in IgG levels (0.161±0.004 two weeks post immunization (PI peaking (0.399± 0.016 at 5 weeks PI. The mean weekly weight gain (g after challenge, at 56 days of age was high in T4 (148±4.751 g with a low mean lesion score (2.5±0.22 and mean oocyst output (x103 oocytes per gram (OPG in faeces (100.3± 45.72 when compared to unimmunised infected controls. Conclusion: An early but partial immune response against caecal coccidiosis could be achieved by immunization with E. tenella specific sporozoites in chickens of less than a week old. Moreover, the performance of immunized chickens as indicated by weight gain, lesion score and oocyst output was found to be superior to the unimmunized infected controls.

  14. Bilateral Lung Transplantation in a Patient with Humoral Immune Deficiency: A Case Report with Review of the Literature

    Directory of Open Access Journals (Sweden)

    Jocelyn R. Farmer

    2014-01-01

    Full Text Available Humoral immune deficiencies have been associated with noninfectious disease complications including autoimmune cytopenias and pulmonary disease. Herein we present a patient who underwent splenectomy for autoimmune cytopenias and subsequently was diagnosed with humoral immune deficiency in the context of recurrent infections. Immunoglobulin analysis prior to initiation of intravenous immunoglobulin (IVIG therapy was notable for low age-matched serum levels of IgA (11 mg/dL, IgG2 (14 mg/L, and IgG4 (5 mg/L with a preserved total level of IgG. Flow cytometry was remarkable for B cell maturation arrest at the IgM+/IgD+ stage. Selective screening for known primary immune deficiency-causing genetic defects was negative. The disease course was uniquely complicated by the development of pulmonary arteriovenous malformations (AVMs, ultimately requiring bilateral lung transplantation in 2012. This is a patient with humoral immune deficiency that became apparent only after splenectomy, which argues for routine immunologic evaluation prior to vaccination and splenectomy. Lung transplantation is a rare therapeutic endpoint and to our knowledge has never before been described in a patient with humoral immune deficiency for the indication of pulmonary AVMs.

  15. Cellular and humoral immunity elicited by influenza vaccines in pediatric hematopoietic-stem cell transplantation.

    Science.gov (United States)

    Guérin-El Khourouj, Valérie; Duchamp, Marie; Krivine, Anne; Pédron, Béatrice; Ouachée-Chardin, Marie; Yakouben, Karima; Frémond, Marie-Louise; Baruchel, André; Dalle, Jean-Hugues; Sterkers, Ghislaine

    2012-09-01

    Immunity induced by influenza vaccines following hematopoietic stem-cell transplantation (HSCT) is poorly understood. Here, 14 pediatric recipients (mean age: 6 years) received H1N1 (n=9) or H1N1/H3N2 (n=5) vaccines at a median of 5.7 months post-HSCT (HLA-identical related bone-marrow graft: 10/14). Fourteen clinically-matched non-vaccinated recipients were included as controls. Cellular response to vaccination was assessed by a T-cell proliferation assay. Humoral response was assessed by H1N1-specific antibody titration. IL2 and IFNγ responses to influenza were also evaluated by an intracellular cytokine accumulation method for some of the recipients. Higher proliferative responses to H1N1 (p=0.0001) and higher H1N1-specific antibody titers (p<0.02) were observed in vaccines opposed to non-vaccinated recipients. In some cases, proliferative responses to H1N1 developed while at the same time antibody titers did not reach protective (≥1:40) levels. Most recipients vaccinated with only the H1N1 strain had proliferative responses to both H1N1 and H3N2 (median stimulation index H1N1: 96, H3N2: 126 in responders). Finally, IL2 responses predominated over IFNγ responses (p<0.02) to influenza viruses in responders. In conclusion, H1N1 vaccination induced substantial cell-mediated immunity, and to a lesser extent, humoral immunity at early times post-HSCT. H1N1/H3N2 T-cell cross-reactivity and protective (IL2) rather than effector (IFNγ) cytokinic profiles were elicited. Copyright © 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  16. Alteration of antioxidant defense status precedes humoral immune response abnormalities in macrosomia

    Science.gov (United States)

    Haddouche, Mustapha; Aribi, Mourad; Moulessehoul, Soraya; Smahi, Mohammed Chems-Eddine Ismet; Lammani, Mohammed; Benyoucef, Mohammed

    2011-01-01

    Summary Background This study aimed to investigate whether the anomalies affecting the antioxidant and humoral immune defenses could start at birth and to check whether the decrease in antioxidant defenses may precede the immune abnormalities in macrosomic newborns. Material/Methods Thirty macrosomic and 30 sex-matched control newborns were recruited for a retrospective case-control study at the Maghnia Maternity Hospital of Tlemcen Department (Algeria). Results The serum IgG levels were similar in both groups. However, plasma ORAC, albumin, vitamin E, SOD, CAT and GSH-Px levels were significantly decreased in macrosomic as compared to control newborns, yet no difference was observed after adjustment for weight. Additionally, serum concentrations of complement C3, MDA and XO were significantly higher in macrosomic as compared to controls before adjustment for weight. Moreover, macrosomia was significantly associated with high levels of complement C3 (OR=8, p=0.002); whereas no association with those of IgG was observed (OR0.05). Furthermore, macrosomia was significantly associated with low levels of ORAC (OR=4.96, p=0.027), vitamin E (OR=4.5, p=0.018), SOD (OR=6.88, p=0.020) and CAT (OR=5.67, p=0.017), and with high levels of MDA (OR=10.29, p=0.005). Conclusions Abnormalities of the humoral defense system in excessive weight could be preceded by alterations of the anti-oxidative defense and by inflammatory response and activation of innate immunity at birth. Additionally, excessive weight could be a potential factor contributing to decreased anti-oxidative capacity and increased oxidative stress. PMID:22037745

  17. A Major Cell Surface Antigen of Coccidioides immitis Which Elicits Both Humoral and Cellular Immune Responses

    Science.gov (United States)

    Hung, Chiung-Yu; Ampel, Neil M.; Christian, Lara; Seshan, Kalpathi R.; Cole, Garry T.

    2000-01-01

    Multinucleate parasitic cells (spherules) of Coccidioides immitis isolates produce a membranous outer wall component (SOW) in vitro which has been reported to be reactive with antibody from patients with coccidioidal infection, elicits a potent proliferative response of murine immune T cells, and has immunoprotective capacity in a murine model of coccidioidomycosis. To identify the antigenic components of SOW, the crude wall material was first subjected to Triton X-114 extraction, and a water-soluble fraction derived from this treatment was examined for protein composition and reactivity in humoral and cellular immunoassays. Protein electrophoresis revealed that the aqueous fraction of three different isolates of C. immitis each contained one or two major glycoproteins (SOWgps), distinguished by their molecular sizes, which ranged from 58 to 82 kDa. The SOWgps, however, showed identical N-terminal amino acid sequences, and each was recognized by sera from patients with C. immitis infection. Antibody raised against the purified 58-kDa glycoprotein (SOWgp58) of the Silveira isolate was used for Western blot and immunolocalization analyses. Expression of SOWgp was shown to be parasitic phase specific, and the antigen was localized to the membranous SOW. The water-soluble fraction of SOW and the purified SOWgp58 were tested for the ability to stimulate proliferation of human peripheral monocytic cells (PBMC). The latter were obtained from healthy volunteers with positive skin test reaction to spherulin, a parasitic-phase antigen of C. immitis, and from volunteers who showed no skin test reaction to the same antigen. The SOW preparations stimulated proliferation of PBMC from skin test-positive but not skin test-negative donors, and the activated cells secreted gamma interferon, which is indicative of a T helper 1 pathway of immune response. Results of this study suggest that SOWgp is a major parasitic cell surface-expressed antigen that elicits both humoral and cellular

  18. Camellia sinensis Mediated Enhancement of Humoral Immunity to Particulate and Non-particulate Antigens.

    Science.gov (United States)

    Khan, Adnan; Ali, Nafisa Hassan; Santercole, Viviana; Paglietti, Bianca; Rubino, Salvatore; Kazmi, Shahana Urooj; Farooqui, Amber

    2016-01-01

    The most common drinking beverage in large portion of the world is Camellia sinensis (green tea). In the present study, we evaluated the adjuvant effect of green tea and tea polyphenols to particulate and non-particulate antigens. BALB/c mice were immunized with particulate and non-particulate antigens. Modulation of immunoglobulin-secreting splenocytes, IgG-mediated and IgM-mediated immunity, was evaluated by hemolytic plaque assay and enzyme-linked immunosorbent assay, respectively. Dose-dependent response of tea polyphenols was also assayed. Phenolic content was measured in crude preparations of green tea. We observed a stimulatory effect of green tea preparations on humoral immune response mediated by the increased number of antibody-secreted cells in spleen. A significant increase in IgM-mediated and IgG-mediated immune response to non-particulate antigen was also observed in green tea-treated animals. A dose-dependent adjuvant effect was seen in the case of tea polyphenols for a longer period of time compared with crude tea preparations. This study indicates polyphenols as major constituents responsible for the enhanced and sustained adjuvant activity of green tea. We suggest that tea polyphenols might be considered for real-life evaluation during adjuvant-mediated vaccination trial programs. Copyright © 2015 John Wiley & Sons, Ltd.

  19. Prenatal androgen exposure modulates cellular and humoral immune function of black-headed gull chicks

    NARCIS (Netherlands)

    Mueller, Wendt; Groothuis, TGG; Kasprzik, A; Dijkstra, C; Alatalo, RV; Siitari, H

    2005-01-01

    Avian eggs contain considerable amounts of maternal yolk androgens, which have been shown to beneficially influence the physiology and behaviour of the chick. As androgens may suppress immune functions, they may also entail costs for the chick. This is particularly relevant for colonial species,

  20. Adjuvant effect of green propolis on humoral immune response of bovines immunized with bovine herpesvirus type 5.

    Science.gov (United States)

    Fischer, Geferson; Cleff, Marlete Brum; Dummer, Luana Alves; Paulino, Niraldo; Paulino, Amarílis Scremin; de Oliveira Vilela, Camila; Campos, Fabrício Souza; Storch, Tiago; D'Avila Vargas, Gilberto; de Oliveira Hübner, Silvia; Vidor, Telmo

    2007-03-15

    Despite recent technological advances in vaccine production, most vaccines depend on the association with adjuvant substances. In this study, propolis, which has been attracting the attention of researchers due to its bioactive properties, was evaluated as an immunological adjuvant. The association of 40mg/dose of an ethanolic extract of green propolis with an inactivated oil vaccine against bovine herpesvirus type 5 (BoHV-5), resulted in a significant increase (Ppropolis. Besides, propolis increased the percentage of animals with high antibody titers (above 32). Phenolic compounds such as artepillin C (3,5-diprenyl-4-hydroxycinnamic acid) and the derivatives of cinnamic acid besides other flavonoid substances were abundant in the propolis extract used, and they could be the main substances with adjuvant action. The effect of the green propolis extract on the humoral immune response can be exploited in the development of new vaccines.

  1. Cellular and humoral immune responses in a population from the Baringo District, Kenya to Leishmania promastigote lipophosphoglycan

    DEFF Research Database (Denmark)

    Kurtzhals, J A; Hey, A S; Theander, T G

    1992-01-01

    In a cross-sectional house-to-house study in a leishmaniasis-endemic area in Kenya, the cellular and humoral immune response to Leishmania lipophosphoglycan (LPG) was determined. Clinical data, peripheral blood mononuclear cells, and plasma were obtained from 50 individuals over the age of eight...

  2. Humoral immune response to campylobacter jejuni in patients with enterocolitis and Guillain-Barré syndrome

    Directory of Open Access Journals (Sweden)

    Ristić Ljiljana

    2012-01-01

    Full Text Available Campylobacter jejuni is one of the most important causes of diarrheal disease worldwide. In addition, it can cause neurological post-infectious sequels, such as Guillain-Barré syndrome (GBS. Humoral immune response to C. jejuni was monitored in patients with C. jejuni enterocolitis, GBS patients and healthy persons, by ELISA. Statistical significance between patients with enterocolitis and healthy persons, as well as among GBS patients and healthy controls, was proven. Statistical significance in IgA among the examined groups was also noticed. The highest values of IgM were found in the patients with GBS, while the highest values of IgG were found in those with enterocolitis. C. jejuni is a significant cause of antecedent infection in GBS. ELISA techniques can be considered a reliable method in determining the presence of serum antibodies in patients with enterocolitis caused by C. jejuni, as well as in patients with GBS.

  3. Investigation on the humoral immune response in patients with gastro-intestinal cancer.

    Science.gov (United States)

    Quintiliani, L; Iudicone, P; Di Girolamo, M; Buzzonetti, A; Giuliani, E; Guglielmetti, M; Scocchera, R; Severi, L; Martini, F; Van Axel, I

    1990-06-01

    The humoral immune reactivity was studied in patients affected by gastro-intestinal cancer. The number of peripheral B lymphocytes, the concentration of serum immunoglobulins (Ig) and of C3 complement factor and the frequency of circulating immuno complexes (CIC) did not significantly differ between patients and age-matched controls, while the C4 factor level was significantly increased. The frequency of serum monoclonal components (M-components) was higher in the patients than in the elderly subjects. Moreover the results concerning the "in vitro" functional response of patient B lymphocytes showed a significant decrease of the proliferative responses to Staphylococcus Aureus Cowan I (SAC) and a significant increase of the IgG and IgM synthesis by peripheral blood mononuclear cells (PBMC) in unstimulated and pokeweed mitogen (PWM) stimulated cultures. The meaning of these results, taken together with those reported by others, is discussed.

  4. Features of Cellular and Humoral Immunity Functioning in Patients with Juvenile Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    H.A. Pavlyshyn

    2016-02-01

    Full Text Available The objective was to examine the state of cellular and humoral immunity in children with juvenile rheumatoid arthritis. The study involved 48 patients with juvenile rheumatoid arthritis, 24 patients with reactive arthritis and 22 apparently healthy children. It was found that juvenile rheumatoid arthritis is associated with a likely decrease of CD3+-, CD4+-, CD8+-, CD16+-lymphocytes levels in peripheral blood, high levels of IgA, IgE, TNF-α, IL-4, ­IL-8 and the unchanged parameters of IgM and IgG, which is associated with chronization of rheumatoid process. The need for close monitoring and long-term treatment of patients in remission causes CD8+-lymphocytes deficiency and high rates of CD4+/CD8+, CD3+/CD16+, IgЕ, IL-4. The course of reactive arthritis is accompanied by low content of CD3+-cells and unchanged immunoglobulin levels in peripheral blood.

  5. In Vivo Delivery of Antigens by Adenovirus Dodecahedron Induces Cellular and Humoral Immune Responses to Elicit Antitumor Immunity

    Science.gov (United States)

    Villegas-Mendez, Ana; Garin, Marina I; Pineda-Molina, Estela; Veratti, Eugenia; Bueren, Juan A; Fender, Pascal; Lenormand, Jean-Luc

    2010-01-01

    Cancer vaccines based on virus-like particles (VLPs) vectors may offer many advantages over other antigen-delivery systems and represent an alternative to the ex vivo cell therapy approach. In this study, we describe the use of penton-dodecahedron (Pt-Dd) VLPs from human adenovirus type 3 (Ad3) as cancer vaccine vehicle for specific antigens, based on its unique cellular internalization properties. WW domains from the ubiquitin ligase Nedd4 serve as an adapter to bind the antigen to Pt-Dd. By engineering fusion partners of WW with the model antigen ovalbumin (OVA), Pt-Dd can efficiently deliver WW-OVA in vitro and the Pt-Dd/WW complex can be readily internalized by dendritic cells (DCs). Immunization with WW-OVA/Pt-Dd results in 90% protection against B16-OVA melanoma implantation in syngeneic mice. This high level of protection correlates with the development of OVA-specific CD8+ T cells. Moreover, vaccination with WW-OVA Pt-Dd induces robust humoral responses in mice as shown by the high levels of anti-OVA antibodies (Abs) detected in serum. Importantly, treatment of mice bearing B16-OVA tumors with WW-OVA/Pt-Dd results in complete tumor regression in 100% of cases. Thus, our data supports a dual role of Pt-Dd as antigen-delivery vector and natural adjuvant, able to generate integrated cellular and humoral responses of broad immunogenic complexity to elicit specific antitumor immunity. Antigen delivery by Pt-Dd vector is a promising novel strategy for development of cancer vaccines with important clinical applications. PMID:20179681

  6. Humoral Immune Response in Japanese Acute Hepatitis Patients with Hepatitis C Virus Infection

    Directory of Open Access Journals (Sweden)

    N Yamaguchi

    2000-01-01

    Full Text Available The humoral immune response to acute infection by hepatitis C virus (HCV is not yet perfectly clear in terms of immunoglobulin (Ig response, diversity of HCV antigen, and the relation with hepatitis severity and antibody response.  Serum IgM and IgG anti-HCV levels in patients with HCV and either acute hepatitis (AH or fulminant hepatitis (FH were investigated; the diversity of HCV antigen was investigated by RIBA test III.  Of 22 AH patients, 12 (54.5% were positive for IgM anti-HCV, mainly reacting to HCV core protein. The mean interval until the appearance of IgM anti-HCV after onset was 24.1±26.2 days. IgG anti-HCV mainly reacted to both core and NS-3 antigen, appearing 42.6±42.1 days after onset.  From a serial study of 15 AH patients, it was considered that in seven AH patients (46.7%, the IgM response would precede the IgG response. In another two AH patients, IgM anti-HCV was not detected during the acute disease phase. Of 48 chronic hepatitis patients with HCV-RNA, 40 patients were positive for IgM anti-HCV.  Therefore, IgM anti-HCV was useful for diagnosis in some of the AH patients, but it was difficult to use for distinguishing between acute and chronic infection. All four FH patients with HCV-RNA were positive for both IgM and IgG antibody to HCV at onset. Their antibody titres were higher than those of AH patients. These results suggested that, as in FH due to HBV, FH due to HCV could induce strong and rapid humoral immunity.

  7. Dynamics of the humoral immune response of calves infected and re-infected with Cooperia punctata.

    Science.gov (United States)

    Yatsuda, A P; Vieira-Bressan, M C

    2000-02-01

    The dynamics of the humoral immune response of calves were analysed after primary infection and re-infection with the intestinal nematode Cooperia punctata. 12 male 5 month-old Holstein-Friesian calves were randomly divided into two groups A and B. At the beginning of the experiment Group A animals were each infected experimentally with a single oral dose of 130,000 infective third stage larvae (L3) of C. punctata. The animals of Group B were kept as non-infected controls. The two calves from Group A with the highest infections died of cooperiosis at 32 and 44 days after infection (DAI), respectively. On DAI 100 the calves were treated with the recommended dose of oxfendazole. On DAI 180 the remaining four calves of Group A and three animals of Group B (B1) were infected with 260,000 L3 of C. punctata, while the other three calves of Group B (B2) served as non-infected controls. Monitoring of the humoral immune response predominantly demonstrated an IgG1 response against both adult and L3 antigen of C. punctata. Moreover, re-infections increased the levels of these immunoglobulins. IgA levels were less increased than IgG1 and no significant increase was observed in IgG2 and IgM levels. Immunoblotting analysis showed that total IgG present in the serum of the primary infected animals mainly reacted against adult proteins of 12-14 and 17-20 kDa and against L3 proteins of 33 and 43 kDa. After re-infection total IgG reacted with the same adult proteins but also with an adult 29 kDa protein.

  8. The Effect of Pistacia khynjuk on Humoral Immune System of Wistar Rats

    Directory of Open Access Journals (Sweden)

    A Hadinia

    2011-01-01

    Full Text Available Introduction & Objective: Plants from the genus Pistacia family such as Pistacia atlantica, Pistacia vera and Pistacia khynjuk are considered as herbal medicines. Antibacterial and anti-inflammatory effects of these plants have been confirmed. The aim of the current study was to find the effect of Pistacia khynjuk on humoral immune system of Wistar rats. Materials & Methods: This is an experimental study which was conducted at Yasuj University of Medical Sciences in 2009. Forty male Wistar rats were randomly allocated into four groups of ten animals and orally received 10 mg/kg of the extract of nucleus, cutin and fruit of Pistacia khynjuk respectively, every day for two weeks. The control group received only placebo. Immuno-reactivity was induced using BCG vaccine (IP with Freund‘s complete adjuvant (CFA. The titer of IgG and IgM were measured after the treatment using ELISA method. Moreover, the cervical lymph nodes and spleen of animals were excised and the volume and density of the primary and secondary follicle was evaluated by steriology. The collected data were analyzed by the SPSS using one-way ANOVA. Results: The differences in the mean level of IgG and IgM between the treated and the control animals were not significant (p>.05. Also, the mean volume of the spleen and cervical lymph nodes of the first three groups in comparison with the control animals were not significant (p>.05. Conclusion: Findings of this study showed that the Pistacia khynjuk did not have any direct effect on the activity of humoral immune system and the increasing of antibody level among Wistar rats.

  9. Conditional immune-gene suppression of honeybees parasitized by Varroa mites

    Science.gov (United States)

    Gregory, Pamela G.; Evans, Jay D.; Rinderer, Thomas; de Guzman, Lilia

    2005-01-01

    The ectoparasitic mite, Varroa destructor, is the most destructive parasite of managed honeybee colonies worldwide. Since V. destructor transfers pathogens to honeybees, it may be adaptive for bees to respond to mite infestation by upregulating their immune responses. Mites, however, may overcome the host's immune responses by suppressing them, which could facilitate the mite's ability to feed on hemolymph. A humoral immune response of bees parasitized by V. destructor may be detected by studying the expression levels of antibacterial peptides, such as abaecin and defensin, known to be immune-responsive. Expression levels for these two antibacterial peptides changed non-linearly with respect to the number of mites parasitizing honeybee pupae. Bees exposed to low or moderate number of mites had fewer immune-related transcripts than pupae that were never parasitized or pupae with high mite loads. Although many of the pupae tested indicated the presence of bacteria, no correlation with mite numbers or immune-response levels existed. All bees tested negative for acute paralysis and Kashmir bee viruses known to be vectored by V. destructor. PMID:16299597

  10. Vaccination with Salmonella Typhi recombinant outer membrane protein 28 induces humoral but non-protective immune response in rabbit

    Directory of Open Access Journals (Sweden)

    Anjani Saxena

    2017-08-01

    Full Text Available Aim: Typhoid is one of the most important food and water borne disease causing millions of deaths over the world. Presently, there is no cost effective vaccine available in India. The outer-membrane proteins (Omps of Salmonella have been exhibited as a potential candidate for development of subunit vaccine against typhoid. The objective of the present study was to evaluate the use of recombinant Omp 28 protein for immunization of rabbit to elucidate its protection against virulent Salmonella Typhi. Materials and Methods: Immune potential of recombinant Omp28 was tested in New Zealand Rabbits. Rabbits were divided into two groups, i.e., control and test group. Control group was injected with phosphate buffer saline with adjuvant while test group were injected with recombinant Omp28 along with adjuvant. Rabbits were bleed and serum was collected from each rabbit. Serum was tested by Enzyme-linked immunosorbent assay (ELISA for humoral response. Rabbits were challenged with virulent culture to test the protective immunity. Results: Humoral response was provoked at 15th day and maintained till 30th day. The mean ELISA titer at 15th day was 1 : 28000 (mean titer log 10 : 4.4472 and on the 30th day was 1 : 25866 (mean titer log 10 : 4.4127. Protective immune potential of Omp 28 was assessed by challenge studies in rabbits for which vaccinated and control rabbits were challenged with 109 cells of virulent culture of S. Typhi. In control group, out of six, no rabbit could survive after 48 days while in vaccinated group, three out of six rabbit were survived. Conclusion: Immunization of rabbit with recombinant Omp 28 induced a strong humoral response which was exhibited by high antibody titer in ELISA. Subsequently, intraperitoneal homologous challenge of the immunized New Zealand rabbit resulted in lack of significant protection. These findings indicate that Omp 28 though provoked the humoral immunity but could not provide the protective immunity in

  11. His-tag ELISA for the detection of humoral tumor-specific immunity

    Directory of Open Access Journals (Sweden)

    Disis Mary L

    2008-05-01

    Full Text Available Abstract Background The application of high throughput molecular techniques such as SEREX are resulting in the identification of a multitude of tumor associated antigens. As newly identified antigens are incorporated into a variety of clinical trials, standardization of immunologic monitoring methods becomes increasingly important. We questioned whether mammalian cell expression of a histadine-linked human protein could be used to produce antigen suitable for detecting tumor-specific humoral immunity and whether such an assay could be amenable to standardization for clinical use. Methods We designed a his-tagged capture ELISA based on lysate from genetically engineered CHO cells for detection of antibodies to insulin-like growth factor binding protein 2, a novel tumor antigen. We performed technical and preliminary clinical validation studies, including comparison to a standard indirect ELISA based on commercially prepared recombinant antigen. Results The his-tagged capture ELISA could be standardized. Precision experiments resulted in CVs 2 values of 0.99. In comparison to Western blot analysis, his-tag and indirect ELISA accurately identified 88% and 93% of samples, respectively. Sample concordance between capture and indirect assays was highly significant (p = 0.003. Furthermore, significantly greater levels of IGFBP-2 antibody immunity were found in cancer patients compared to normal controls (p = 0.008. Conclusion A genetically engineered cell lysate based ELISA can be amenable to standardization and can detect increased levels of antibody immunity to tumor-associated antigen in cancer patients compared to non tumor-bearing healthy controls.

  12. Characterization of naturally-occurring humoral immunity to AAV in sheep.

    Science.gov (United States)

    Tellez, Joseph; Van Vliet, Kim; Tseng, Yu-Shan; Finn, Jonathan D; Tschernia, Nick; Almeida-Porada, Graça; Arruda, Valder R; Agbandje-McKenna, Mavis; Porada, Christopher D

    2013-01-01

    AAV vectors have shown great promise for clinical gene therapy (GT), but pre-existing human immunity against the AAV capsid often limits transduction. Thus, testing promising AAV-based GT approaches in an animal model with similar pre-existing immunity could better predict clinical outcome. Sheep have long been used for basic biological and preclinical studies. Moreover, we have re-established a line of sheep with severe hemophilia A (HA). Given the impetus to use AAV-based GT to treat hemophilia, we characterized the pre-existing ovine humoral immunity to AAV. ELISA revealed naturally-occurring antibodies to AAV1, AAV2, AAV5, AAV6, AAV8, and AAV9. For AAV2, AAV8, and AAV9 these inhibit transduction in a luciferase-based neutralization assay. Epitope mapping identified peptides that were common to the capsids of all AAV serotypes tested (AAV2, AAV5, AAV8 and AAV9), with each animal harboring antibodies to unique and common capsid epitopes. Mapping using X-ray crystallographic AAV capsid structures demonstrated that these antibodies recognized both surface epitopes and epitopes located within regions of the capsid that are internal or buried in the capsid structure. These results suggest that sheep harbor endogenous AAV, which induces immunity to both intact capsid and to capsid epitopes presented following proteolysis during the course of infection. In conclusion, their clinically relevant physiology and the presence of naturally-occurring antibodies to multiple AAV serotypes collectively make sheep a unique model in which to study GT for HA, and other diseases, and develop strategies to circumvent the clinically important barrier of pre-existing AAV immunity.

  13. Characterization of naturally-occurring humoral immunity to AAV in sheep.

    Directory of Open Access Journals (Sweden)

    Joseph Tellez

    Full Text Available AAV vectors have shown great promise for clinical gene therapy (GT, but pre-existing human immunity against the AAV capsid often limits transduction. Thus, testing promising AAV-based GT approaches in an animal model with similar pre-existing immunity could better predict clinical outcome. Sheep have long been used for basic biological and preclinical studies. Moreover, we have re-established a line of sheep with severe hemophilia A (HA. Given the impetus to use AAV-based GT to treat hemophilia, we characterized the pre-existing ovine humoral immunity to AAV. ELISA revealed naturally-occurring antibodies to AAV1, AAV2, AAV5, AAV6, AAV8, and AAV9. For AAV2, AAV8, and AAV9 these inhibit transduction in a luciferase-based neutralization assay. Epitope mapping identified peptides that were common to the capsids of all AAV serotypes tested (AAV2, AAV5, AAV8 and AAV9, with each animal harboring antibodies to unique and common capsid epitopes. Mapping using X-ray crystallographic AAV capsid structures demonstrated that these antibodies recognized both surface epitopes and epitopes located within regions of the capsid that are internal or buried in the capsid structure. These results suggest that sheep harbor endogenous AAV, which induces immunity to both intact capsid and to capsid epitopes presented following proteolysis during the course of infection. In conclusion, their clinically relevant physiology and the presence of naturally-occurring antibodies to multiple AAV serotypes collectively make sheep a unique model in which to study GT for HA, and other diseases, and develop strategies to circumvent the clinically important barrier of pre-existing AAV immunity.

  14. The relationship between undernutrition and humoral immune status in children with pneumonia in Papua New Guinea.

    Science.gov (United States)

    Cripps, Allan W; Otczyk, Diana C; Barker, Jane; Lehmann, Deborah; Alpers, Michael P

    2008-01-01

    Malnutrition is a significant risk factor for childhood infectious diseases in developing countries, including Papua New Guinea (PNG). Whilst the mechanisms are not fully understood there is little doubt that impairment of immune function is a major contributing factor in enhancing disease susceptibility in malnourished children. This susceptibility has been clearly shown for pneumonia in PNG. The aim of this study was to examine the effect of undernutrition on the humoral immune profile in children less than 60 months of age with pneumonia. The study was cross-sectional with measurements of nutritional status and parameters of the immune response being assessed simultaneously. The children were grouped according to age for the purpose of comparative analysis. The children were from the Goroka region of the Eastern Highlands Province of PNG and had been admitted to hospital with moderate-severe pneumonia. They were classified as undernourished (less than 80% weight for age) or nourished (greater than or equal to 80% weight for age). Serum albumin, IgG, IgA and IgM and salivary albumin and IgA were measured. Antibodies to nontypeable Haemophilus influenzae outer membrane protein and Escherichia coli O antigen were also determined in serum and saliva. Undernourished children aged less than 49 months had lower levels of serum albumin than nourished children throughout this age range. Lower values of salivary IgA were observed in infants (less than 13 months of age) than in older children, with a larger proportion of younger children having no detectable IgA. The age-related immunological profile was similar in undernourished and nourished children. At different age intervals the concentration of immunoglobulins in serum and saliva from undernourished children was generally found to be less than or the same as that from nourished children. In most cases undernourished children had lower levels of specific antibodies than nourished children but for some antibodies in

  15. Adult Drosophila melanogaster evolved for antibacterial defense invest in infection-induced expression of both humoral and cellular immunity genes

    Directory of Open Access Journals (Sweden)

    McGraw Elizabeth A

    2011-08-01

    Full Text Available Abstract Background While the transcription of innate immunity genes in response to bacterial infection has been well-characterised in the Drosophila model, we recently demonstrated the capacity for such transcription to evolve in flies selected for improved antibacterial defense. Here we use this experimental system to examine how insects invest in constitutive versus infection-induced transcription of immunity genes. These two strategies carry with them different consequences with respect to energetic and pleiotropic costs and may be more or less effective in improving defense depending on whether the genes contribute to humoral or cellular aspects of immunity. Findings Contrary to expectation we show that selection preferentially increased the infection-induced expression of both cellular and humoral immunity genes. Given their functional roles, infection induced increases in expression were expected for the humoral genes, while increases in constitutive expression were expected for the cellular genes. We also report a restricted ability to improve transcription of immunity genes that is on the order of 2-3 fold regardless of total transcription level of the gene. Conclusions The evolved increases in infection-induced expression of the cellular genes may result from specific cross talk with humoral pathways or from generalised strategies for enhancing immunity gene transcription. A failure to see improvements in constitutive expression of the cellular genes suggests either that increases might come at too great a cost or that patterns of expression in adults are decoupled from the larval phase where increases would be most effective. The similarity in fold change increase across all immunity genes may suggest a shared mechanism for the evolution of increased transcription in small, discrete units such as duplication of cis-regulatory elements.

  16. Overexpression of Interleukin-7 Extends the Humoral Immune Response Induced by Rabies Vaccination.

    Science.gov (United States)

    Li, Yingying; Zhou, Ming; Luo, Zhaochen; Zhang, Yachun; Cui, Min; Chen, Huanchun; Fu, Zhen F; Zhao, Ling

    2017-04-01

    Rabies continues to present a public health threat in most countries of the world. The most efficient way to prevent and control rabies is to implement vaccination programs for domestic animals. However, traditional inactivated vaccines used in animals are costly and have relatively low efficiency, which impedes their extensive use in developing countries. There is, therefore, an urgent need to develop single-dose and long-lasting rabies vaccines. However, little information is available regarding the mechanisms underlying immunological memory, which can broaden humoral responses following rabies vaccination. In this study, a recombinant rabies virus (RABV) that expressed murine interleukin-7 (IL-7), referred to here as rLBNSE-IL-7, was constructed, and its effectiveness was evaluated in a mouse model. rLBNSE-IL-7 induced higher rates of T follicular helper (Tfh) cells and germinal center (GC) B cells from draining lymph nodes (LNs) than the parent virus rLBNSE. Interestingly, rLBNSE-IL-7 improved the percentages of long-lived memory B cells (Bmem) in the draining LNs and plasma cells (PCs) in the bone marrow (BM) for up to 360 days postimmunization (dpi). As a result of the presence of the long-lived PCs, it also generated prolonged virus-neutralizing antibodies (VNAs), resulting in better protection against a lethal challenge than that seen with rLBNSE. Moreover, consistent with the increased numbers of Bmem and PCs after a boost with rLBNSE, rLBNSE-IL-7-immunized mice promptly produced a more potent secondary anti-RABV neutralizing antibody response than rLBNSE-immunized mice. Overall, our data suggest that overexpressing IL-7 improved the induction of long-lasting primary and secondary antibody responses post-RABV immunization.IMPORTANCE Extending humoral immune responses using adjuvants is an important method to develop long-lasting and efficient vaccines against rabies. However, little information is currently available regarding prolonged immunological

  17. Yeast product supplementation modulated humoral and mucosal immunity and uterine inflammatory signals in transition dairy cows.

    Science.gov (United States)

    Yuan, K; Mendonça, L G D; Hulbert, L E; Mamedova, L K; Muckey, M B; Shen, Y; Elrod, C C; Bradford, B J

    2015-05-01

    The transition from late gestation to early lactation is characterized by substantial metabolic stress and altered immune function. The objective of this study was to assess the effects of supplementing a yeast product derived from Saccharomyces cerevisiae on immunity and uterine inflammation in transition cows. Forty multiparous Holstein cows were blocked by expected parturition date and randomly assigned within block to 1 of 4 treatments (n=10) from 21d before expected parturition to 42d postpartum. Rations were top-dressed with a product containing yeast culture plus enzymatically hydrolyzed yeast (YC-EHY; Celmanax, Vi-COR, Mason City, IA) at the rate of 0, 30, 60, or 90g/d throughout the experiment. Cows were injected subcutaneously with ovalbumin on d -21, -7, and 14 to assess their humoral response. Data were analyzed using mixed models with repeated measures over time. Concentrations of colostrum IgG were unaffected by treatments. A treatment × week interaction was observed for somatic cell linear score, reflecting a tendency for a quadratic dose effect on wk 1 (2.34, 2.85, 1.47, and 4.06±0.59 for 0, 30, 60, and 90g/d, respectively) and a quadratic dose effect on wk 5 (1.36, -0.15, -1.07, and 0.35±0.64 for 0, 30, 60, and 90g/d, respectively). Platelet count was increased by YC-EHY. Increasing YC-EHY dose linearly increased plasma anti-ovalbumin IgG levels following 3 ovalbumin challenges, suggesting that treatments enhanced humoral immunity. Increasing YC-EHY dose also quadratically increased fecal IgA concentrations in early lactation, suggesting that 30 and 60g/d doses enhanced mucosal immunity. Uterine neutrophil populations were much greater in samples collected on d 7 compared with those on d 42 (32.1 vs. 7.6±3.5% of cells), reflecting neutrophil infiltration immediately after calving, but no treatment effect was detected. Significant day effects were detected for mRNA of IL-6, IL-8, neutrophil myeloperoxidase (MPO), and neutrophil elastase (ELANE

  18. Vaccination with dengue virus-like particles induces humoral and cellular immune responses in mice

    Directory of Open Access Journals (Sweden)

    Zhang Quanfu

    2011-06-01

    Full Text Available Abstract Background The incidence of dengue, an infectious disease caused by dengue virus (DENV, has dramatically increased around the world in recent decades and is becoming a severe public health threat. However, there is currently no specific treatment for dengue fever, and licensed vaccine against dengue is not available. Vaccination with virus-like particles (VLPs has shown considerable promise for many viral diseases, but the effect of DENV VLPs to induce specific immune responses has not been adequately investigated. Results By optimizing the expression plasmids, recombinant VLPs of four antigenically different DENV serotypes DENV1-4 were successfully produced in 293T cells. The vaccination effect of dengue VLPs in mice showed that monovalent VLPs of each serotype stimulated specific IgG responses and potent neutralizing antibodies against homotypic virus. Tetravalent VLPs efficiently enhanced specific IgG and neutralizing antibodies against all four serotypes of DENV. Moreover, vaccination with monovalent or tetravalent VLPs resulted in the induction of specific cytotoxic T cell responses. Conclusions Mammalian cell expressed dengue VLPs are capable to induce VLP-specific humoral and cellular immune responses in mice, and being a promising subunit vaccine candidate for prevention of dengue virus infection.

  19. Humoral Immune Pressure Selects for HIV-1 CXC-chemokine Receptor 4-using Variants.

    Science.gov (United States)

    Lin, Nina; Gonzalez, Oscar A; Registre, Ludy; Becerril, Carlos; Etemad, Behzad; Lu, Hong; Wu, Xueling; Lockman, Shahin; Essex, Myron; Moyo, Sikhulile; Kuritzkes, Daniel R; Sagar, Manish

    2016-06-01

    Although both C-C chemokine receptor 5 (CCR5)- and CXC chemokine receptor 4 (CXCR4)-using HIV-1 strains cause AIDS, the emergence of CXCR4-utilizing variants is associated with an accelerated decline in CD4+ T cells. It remains uncertain if CXCR4-using viruses hasten disease or if these variants only emerge after profound immunological damage. We show that exclusively CXCR4- as compared to cocirculating CCR5-utilizing variants are less sensitive to neutralization by both contemporaneous autologous plasma and plasma pools from individuals that harbor only CCR5-using HIV-1. The CXCR4-utilizing variants, however, do not have a global antigenic change because they remain equivalently susceptible to antibodies that do not target coreceptor binding domains. Studies with envelope V3 loop directed antibodies and chimeric envelopes suggest that the neutralization susceptibility differences are potentially influenced by the V3 loop. In vitro passage of a neutralization sensitive CCR5-using virus in the presence of autologous plasma and activated CD4+ T cells led to the emergence of a CXCR4-utilizing virus in 1 of 3 cases. These results suggest that in some but not necessarily all HIV-1 infected individuals humoral immune pressure against the autologous virus selects for CXCR4-using variants, which potentially accelerates disease progression. Our observations have implications for using antibodies for HIV-1 immune therapy. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  20. The miaoyao fanggan sachets regulate humoral immunity and cellular immunity in mice.

    Science.gov (United States)

    Zhang, Quan; Wang, Hui; Cheng, Ming Liang; Jin, Mingchang; Meng, Qing Zhi; Duan, Liang; Chen, Yun

    2015-03-01

    Although some studies in the southeast part of Guizhou Province have suggested that Miaoyao Fanggan sachets (MFS) prevent influenza, little is known about its influence on immune systems. Influenza virus mainly infects immune-compromised individuals. The effects of MFS have mainly been recognized in clinical practice. However, there have been relatively few studies on its biological mechanism. Here we investigated whether MFS was able to affect the mucosal immunization and the activation of alveolar macrophages (AM), CD4+and CD8+ T-cells in vivo. Eighty Kunming male mice were treated with MFS continuously or intermittently with Yu-Ping-Feng powder (YPF-P) (positive control group) or with normal saline (NS) (control group) for 4 weeks, respectively. Mice treated with MFS were further divided into the continuous inhalation group (12 h daily/4 weeks) and the discontinuous inhalation group (1 h, three times a day for 4 weeks). Mice in both groups were placed under 0.5 m3 masks which had four ventilation holes (10×15 cm) containing 40 g MFS. Positive control mice were orally treated with YPF-P 0.2 mg/10 g/day once a day for 4 weeks. Control mice were orally treated with equal volumes of NS once a day for 4 weeks. MFS was replaced every 6 days. Administration of YPF-P was used as a positive control since it has been used as an established Traditional Chinese Medicine (TCM) treatment before. After 4 weeks, mice in all experimental groups were sacrificed. IgA and IgG1 in lung and blood serum were detected by Western blot and enzyme-linked immuno sorbent assay (ELISA). The expression of alveolar macrophages (AM) in mice was analyzed by immunochemistry test based on CD68+staining. Blood samples were collected in which CD4+and CD8+T-cells were analyzed by flow cytometry. Mice continuously and intermittently inhaling MFS showed a moderate increase in IgA and IgG1 protein levels compared with mice in the control groups. There was also a slightly significant increase in the

  1. Study of humoral immune response in mammals immunized with Plasmodium falciparum antigenic preparations

    Directory of Open Access Journals (Sweden)

    Antonio B. Cruz Cubas

    1992-01-01

    Full Text Available Six Plasmodium falciparum protein fractions, isolated under reducing conditions, were used to immunize mice, rabbits and the squirrel monkey Saimiri sciureus. Five or seven subcutaneous injections of each antigenic preparation, in conjunction with Freund's complete or incomplete adjuvants, were administered. This led to the development of specific antibodies detected by IFAT, ELISA or immunobloting which inhibited merozoite reinvasion in in vitro P. falciparum cultures. This activity seems to be associated with rhoptry proteins contained in fractions Pf F2 and Pf F4.

  2. Stress response and humoral immune system alterations related to chronic hypergravity in mice.

    Science.gov (United States)

    Guéguinou, Nathan; Bojados, Mickaël; Jamon, Marc; Derradji, Hanane; Baatout, Sarah; Tschirhart, Eric; Frippiat, Jean-Pol; Legrand-Frossi, Christine

    2012-01-01

    Spaceflights are known to induce stress and immune dysregulation. Centrifugation, as hindlimb unloading, is a good ground based-model to simulate altered gravity which occurs during space missions. The aim of this study was to investigate the consequences of a long-term exposure to different levels of hypergravity on the stress response and the humoral immunity in a mouse model. For this purpose, adult C57Bl/6J male mice were subjected for 21 days either to control conditions or to 2G or 3G acceleration gravity forces. Corticosterone level and anxiety behavior revealed a stress response which was associated with a decrease of body weight, after 21-day of centrifugation at 3G but not at 2G. Spleen lymphocyte lipopolysaccharide (LPS) responsiveness was diminished by 40% in the 2G group only, whereas a decrease was noted when cells were stimulated with concanavalin A for both 2G and 3G groups (about 25% and 20%, respectively) compared to controls. Pro-inflammatory chemokines (MCP-1 and IP-10) and Th1 cytokines (IFNγ and IL2) were slightly decreased in the 2G group and strongly decreased in the 3G mouse group. Regarding Th2 cytokines (IL4, IL5) no further significant modification was observed, whereas the immunosuppressive cytokine IL10 was slightly increased in the 3G mice. Finally, serum IgG concentration was twice higher whereas IgA concentration was slightly increased (about 30%) and IgM were unchanged in 2G mice compared to controls. No difference was observed in the 3G group with these isotypes. Consequently, functional immune dysregulations and stress responses were dependent of the gravity level. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. Single amino acid modification of adeno-associated virus capsid changes transduction and humoral immune profiles.

    Science.gov (United States)

    Li, Chengwen; Diprimio, Nina; Bowles, Dawn E; Hirsch, Matthew L; Monahan, Paul E; Asokan, Aravind; Rabinowitz, Joseph; Agbandje-McKenna, Mavis; Samulski, R Jude

    2012-08-01

    Adeno-associated virus (AAV) vectors have the potential to promote long-term gene expression. Unfortunately, humoral immunity restricts patient treatment and in addition provides an obstacle to the potential option of vector readministration. In this study, we describe a comprehensive characterization of the neutralizing antibody (NAb) response to AAV type 1 (AAV1) through AAV5 both in vitro and in vivo. These results demonstrated that NAbs generated from one AAV type are unable to neutralize the transduction of other types. We extended this observation by demonstrating that a rationally engineered, muscle-tropic AAV2 mutant containing 5 amino acid substitutions from AAV1 displayed a NAb profile different from those of parental AAV2 and AAV1. Here we found that a single insertion of Thr from AAV1 into AAV2 capsid at residue 265 preserved high muscle transduction, while also changing the immune profile. To better understand the role of Thr insertion at position 265, we replaced all 20 amino acids and evaluated both muscle transduction and the NAb response. Of these variants, 8 mutants induced higher muscle transduction than AAV2. Additionally, three classes of capsid NAb immune profile were defined based on the ability to inhibit transduction from AAV2 or mutants. While no relationship was found between transduction, amino acid properties, and NAb titer or its cross-reactivity, these studies map a critical capsid motif involved in all steps of AAV infectivity. Our results suggest that AAV types can be utilized not only as templates to generate mutants with enhanced transduction efficiency but also as substrates for repeat administration.

  4. Suppression of immune surveillance in melanoma [Immunotherapy of metastatic melanoma by reversal of immune suppression

    Energy Technology Data Exchange (ETDEWEB)

    Biggs, M. W. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Eiselein, J. E. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2001-06-01

    In this paper we develop the hypothesis that a significant fraction of patients with advanced melanoma can be successfully treated with immunotherapy. Reversal of antigen-specific immune suppression to melanoma polypeptide antigens is an essential, first step. We postulate the key regulation of CTL responses resides within the CD4+ T-lymphocytes and macrophage/dendritic cells. There is a pluri-potential cell within this regulatory arm that functions either as a Th1 cell or as a suppressor T-cell, Ths, depending on how antigen is presented. We have shown that poliovirus 1 Sabin will lyse human melanoma cells in tissue culture, and a special "vaccine" prepared from this lysis actively stimulates Ths cell function. The Ths arm of the regulatory system can be down-regulated with cyclophosphamide given 24 hours after the vaccine. The capacity to generate a CTL response is retained. The summary conclusion is that a phase 1 clinical trial in advanced melanoma using the special viral-tumor-lysate followed by cyclophosphamide, plus expanded autologous dendritic cells sensitized with the polypeptide epitopes captained in the viral-lysate will produce beneficial results.

  5. Honey bee drones maintain humoral immune competence throughout all life stages in the absence of vitellogenin production.

    Science.gov (United States)

    Gätschenberger, Heike; Gimple, Olaf; Tautz, Jürgen; Beier, Hildburg

    2012-04-15

    Drones are haploid male individuals whose major social function in honey bee colonies is to produce sperm and mate with a queen. In spite of their limited tasks, the vitality of drones is of utmost importance for the next generation. The immune competence of drones - as compared to worker bees - is largely unexplored. Hence, we studied humoral and cellular immune reactions of in vitro reared drone larvae and adult drones of different age upon artificial bacterial infection. Haemolymph samples were collected after aseptic and septic injury and subsequently employed for (1) the identification of immune-responsive peptides and/or proteins by qualitative proteomic analyses in combination with mass spectrometry and (2) the detection of antimicrobial activity by inhibition-zone assays. Drone larvae and adult drones responded with a strong humoral immune reaction upon bacterial challenge, as validated by the expression of small antimicrobial peptides. Young adult drones exhibited a broader spectrum of defence reactions than drone larvae. Distinct polypeptides including peptidoglycan recognition protein-S2 and lysozyme 2 were upregulated in immunized adult drones. Moreover, a pronounced nodulation reaction was observed in young drones upon bacterial challenge. Prophenoloxidase zymogen is present at an almost constant level in non-infected adult drones throughout the entire lifespan. All observed immune reactions in drones were expressed in the absence of significant amounts of vitellogenin. We conclude that drones - like worker bees - have the potential to activate multiple elements of the innate immune response.

  6. Effect of response to backtest and housing condition on cell-mediated and humoral immunity in adult pigs.

    Science.gov (United States)

    Geverink, N A; Parmentier, H K; de Vries Reilingh, G; Schouten, W G P; Gort, G; Wiegant, V M

    2004-01-01

    Several recent studies in juvenile pigs demonstrated a relationship between the degree of resistance displayed early in life in a so-called "backtest" and parameters of cell-mediated and humoral immunity. Some of the immune characteristics were reported to depend on the interaction between backtest classification and housing system. In the present study, the effects of backtest classification and housing condition on immune reactivity in adult gilts were examined. At 10 and 17 days of age, female piglets were subjected to the backtest. In this test, each piglet is restrained on its back for 1 min and the number of escape attempts is scored. Pigs classified as high resisting (HR) or low resisting (LR) were selected and housed in groups of six gilts. At 7 months of age, half of the gilts were housed in individual stalls. At 12 months of age, gilts were challenged by immunization with DNP-KLH. Control gilts were treated similarly with a placebo. Blood samples were drawn prior to immunization (Day 0) and weekly thereafter until Day 28. No significant effects of backtest type on cellular and humoral responses against KLH were found. Furthermore, being housed in stalls as compared to groups had no consequences for the immune response and did not induce differences between HR and LR gilts. Differences in behavior and physiology found previously between HR and LR gilts, particularly in gilts in stall housing, may thus be of relatively little importance for immune-related health.

  7. Humoral Immune Response Kinetics in Philander opossum and Didelphis marsupialis Infected and Immunized by Trypanosoma cruzi Employing an Immunofluorescence Antibody Test

    Directory of Open Access Journals (Sweden)

    Ana Paula Legey

    1999-05-01

    Full Text Available Philander opossum and Didelphis marsupialis considered the most ancient mammals and an evolutionary success, maintain parasitism by Trypanosoma cruzi without developing any apparent disease or important tissue lesion. In order to elucidate this well-balanced interaction, we decided to compare the humoral immune response kinetics of the two didelphids naturally and experimentally infected with T. cruzi and immunized by different schedules of parasite antigens, employing an indirect fluorescence antibody test (IFAT. Both didelphids responded with high serological titers to different immunization routes, while the earliest response occurred with the intradermic route. Serological titers of naturally infected P. opossum showed a significant individual variation, while those of D. marsupialis remained stable during the entire follow-up period. The serological titers of the experimentally infected animals varied according to the inoculated strain. Our data suggest that (1 IFAT was sensitive for follow-up of P. opossum in natural and experimental T. cruzi infections; (2 both P. opossum and D. marsupialis are able to mount an efficient humoral immune response as compared to placental mammals; (3 experimentally infected P. opossum and D. marsupialis present distinct patterns of infection, depending on the subpopulation of T. cruzi, (4 the differences observed in the humoral immune responses between P. opossum and D. marsupialis, probably, reflect distinct strategies selected by these animals during their coevolution with T. cruzi.

  8. The suppression of immune system disorders by passive attrition.

    Directory of Open Access Journals (Sweden)

    Sean P Stromberg

    Full Text Available Exposure to infectious diseases has an unexpected benefit of inhibiting autoimmune diseases and allergies. This is one of many fundamental fitness tradeoffs associated with immune system architecture. The immune system attacks pathogens, but also may (inappropriately attack the host. Exposure to pathogens can suppress the deleterious response, at the price of illness and the decay of immunity to previous diseases. This "hygiene hypothesis" has been associated with several possible underlying biological mechanisms. This study focuses on physiological constraints that lead to competition for survival between immune system cell types. Competition maintains a relatively constant total number of cells within each niche. The constraint implies that adding cells conferring new immunity requires loss (passive attrition of some cells conferring previous immunities. We consider passive attrition as a mechanism to prevent the initial proliferation of autoreactive cells, thus preventing autoimmune disease. We see that this protection is a general property of homeostatic regulation and we look specifically at both the IL-15 and IL-7 regulated niches to make quantitative predictions using a mathematical model. This mathematical model yields insight into the dynamics of the "Hygiene Hypothesis," and makes quantitative predictions for experiments testing the ability of passive attrition to suppress immune system disorders. The model also makes a prediction of an anti-correlation between prevalence of immune system disorders and passive attrition rates.

  9. Effects of carotenoids, immune activation and immune suppression on the intensity of chronic coccidiosis in greenfinches.

    Science.gov (United States)

    Sepp, Tuul; Karu, Ulvi; Sild, Elin; Männiste, Marju; Hõrak, Peeter

    2011-03-01

    Allocation trade-offs of carotenoids between their use in the immune system and production of integumentary colouration have been suggested as a proximate mechanism maintaining honesty of signal traits. We tested how dietary carotenoid supplementation, immune activation and immune suppression affect intensity of coccidian infection in captive greenfinches Carduelis chloris, a passerine with carotenoid-based plumage. Immune activation with phytohaemagglutinin (PHA) decreased body mass among birds not supplemented with lutein, while among the carotenoid-fed birds, PHA had no effect on mass dynamics. Immune suppression with dexamethasone (DEX) induced loss of body mass and reduced the swelling response to PHA. DEX and PHA increased the concentration of circulating heterophils. Lutein supplementation increased plasma carotenoid levels but had no effect on the swelling response induced by PHA. PHA and DEX treatments did not affect plasma carotenoids. Immune stimulation by PHA suppressed the infection, but only among carotenoid-supplemented birds. Priming of the immune system can thus aid in suppressing chronic infection but only when sufficient amount of carotenoids is available. Our experiment shows the importance of carotenoids in immune response, but also the complicated nature of this impact, which could be the reason for inconsistent results in studies investigating the immunomodulatory effects of carotenoids. The findings about involvement of carotenoids in modulation of an immune response against coccidiosis suggest that carotenoid-based ornaments may honestly signal individuals' ability to manage chronic infections. Copyright © 2010 Elsevier Inc. All rights reserved.

  10. Comparison of Effects of Smoking and Smokeless Tobacco “Maras Powder” Use on Humoral Immune System Parameters

    Directory of Open Access Journals (Sweden)

    2006-01-01

    Full Text Available Background. The aim of this study is to assess the impacts of “Maras powder” and cigarette smoking on the parameters of the humoral immune system. Material and Methods. One hundred seventy seven subjects were included in the study. The IgA, IgG, IgM, C3 and C4 levels were detected via nephelometric method. Results. In 1.4 % of the control group IgM levels were below normal where it was 10.8 % and 18.6 % in Maras powder group and in cigarette smoking group respectively. The IgM levels of both groups were significantly lower compared to the control group (PConclusion. Effects of Maras powder on humoral immune response were found to be similar to that of smoking.

  11. Alphavirus replicon particles expressing TRP-2 provide potent therapeutic effect on melanoma through activation of humoral and cellular immunity.

    Directory of Open Access Journals (Sweden)

    Francesca Avogadri

    2010-09-01

    Full Text Available Malignant melanoma is the deadliest form of skin cancer and is refractory to conventional chemotherapy and radiotherapy. Therefore alternative approaches to treat this disease, such as immunotherapy, are needed. Melanoma vaccine design has mainly focused on targeting CD8+ T cells. Activation of effector CD8+ T cells has been achieved in patients, but provided limited clinical benefit, due to immune-escape mechanisms established by advanced tumors. We have previously shown that alphavirus-based virus-like replicon particles (VRP simultaneously activate strong cellular and humoral immunity against the weakly immunogenic melanoma differentiation antigen (MDA tyrosinase. Here we further investigate the antitumor effect and the immune mechanisms of VRP encoding different MDAs.VRP encoding different MDAs were screened for their ability to prevent the growth of the B16 mouse transplantable melanoma. The immunologic mechanisms of efficacy were investigated for the most effective vaccine identified, focusing on CD8+ T cells and humoral responses. To this end, ex vivo immune assays and transgenic mice lacking specific immune effector functions were used. The studies identified a potent therapeutic VRP vaccine, encoding tyrosinase related protein 2 (TRP-2, which provided a durable anti-tumor effect. The efficacy of VRP-TRP2 relies on a novel immune mechanism of action requiring the activation of both IgG and CD8+ T cell effector responses, and depends on signaling through activating Fcγ receptors.This study identifies a VRP-based vaccine able to elicit humoral immunity against TRP-2, which plays a role in melanoma immunotherapy and synergizes with tumor-specific CD8+ T cell responses. These findings will aid in the rational design of future immunotherapy clinical trials.

  12. Alphavirus replicon particles expressing TRP-2 provide potent therapeutic effect on melanoma through activation of humoral and cellular immunity.

    Science.gov (United States)

    Avogadri, Francesca; Merghoub, Taha; Maughan, Maureen F; Hirschhorn-Cymerman, Daniel; Morris, John; Ritter, Erika; Olmsted, Robert; Houghton, Alan N; Wolchok, Jedd D

    2010-09-10

    Malignant melanoma is the deadliest form of skin cancer and is refractory to conventional chemotherapy and radiotherapy. Therefore alternative approaches to treat this disease, such as immunotherapy, are needed. Melanoma vaccine design has mainly focused on targeting CD8+ T cells. Activation of effector CD8+ T cells has been achieved in patients, but provided limited clinical benefit, due to immune-escape mechanisms established by advanced tumors. We have previously shown that alphavirus-based virus-like replicon particles (VRP) simultaneously activate strong cellular and humoral immunity against the weakly immunogenic melanoma differentiation antigen (MDA) tyrosinase. Here we further investigate the antitumor effect and the immune mechanisms of VRP encoding different MDAs. VRP encoding different MDAs were screened for their ability to prevent the growth of the B16 mouse transplantable melanoma. The immunologic mechanisms of efficacy were investigated for the most effective vaccine identified, focusing on CD8+ T cells and humoral responses. To this end, ex vivo immune assays and transgenic mice lacking specific immune effector functions were used. The studies identified a potent therapeutic VRP vaccine, encoding tyrosinase related protein 2 (TRP-2), which provided a durable anti-tumor effect. The efficacy of VRP-TRP2 relies on a novel immune mechanism of action requiring the activation of both IgG and CD8+ T cell effector responses, and depends on signaling through activating Fcγ receptors. This study identifies a VRP-based vaccine able to elicit humoral immunity against TRP-2, which plays a role in melanoma immunotherapy and synergizes with tumor-specific CD8+ T cell responses. These findings will aid in the rational design of future immunotherapy clinical trials.

  13. Protective Humoral Immunity in the Central Nervous System Requires Peripheral CD19-Dependent Germinal Center Formation following Coronavirus Encephalomyelitis.

    Science.gov (United States)

    Atkinson, Jeffrey R; Bergmann, Cornelia C

    2017-12-01

    B cell subsets with phenotypes characteristic of naive, non-isotype-switched, memory (Bmem) cells and antibody-secreting cells (ASC) accumulate in various models of central nervous system (CNS) inflammation, including viral encephalomyelitis. During neurotropic coronavirus JHMV infection, infiltration of protective ASC occurs after T cell-mediated viral control and is preceded by accumulation of non-isotype-switched IgD+ and IgM+ B cells. However, the contribution of peripheral activation events in cervical lymph nodes (CLN) to driving humoral immune responses in the infected CNS is poorly defined. CD19, a signaling component of the B cell receptor complex, is one of multiple regulators driving B cell differentiation and germinal center (GC) formation by lowering the threshold of antigen-driven activation. JHMV-infected CD19-/- mice were thus used to determine how CD19 affects CNS recruitment of B cell subsets. Early polyclonal ASC expansion, GC formation, and virus-specific ASC were all significantly impaired in CLN of CD19-/- mice compared to wild-type (WT) mice, consistent with lower and unsustained virus-specific serum antibody (Ab). ASC were also significantly reduced in the CNS, resulting in increased infectious virus during persistence. Nevertheless, CD19 deficiency did not affect early CNS IgD+ B cell accumulation. The results support the notion that CD19-independent factors drive early B cell mobilization and recruitment to the infected CNS, while delayed accumulation of virus-specific, isotype-switched ASC requires CD19-dependent GC formation in CLN. CD19 is thus essential for both sustained serum Ab and protective local Ab within the CNS following JHMV encephalomyelitis.IMPORTANCE CD19 activation is known to promote GC formation and to sustain serum Ab responses following antigen immunization and viral infections. However, the contribution of CD19 in the context of CNS infections has not been evaluated. This study demonstrates that antiviral protective

  14. Synergistic immunostimulatory effect of pidotimod and red ginseng acidic polysaccharide on humoral immunity of immunosuppressed mice.

    Science.gov (United States)

    Du Xiao, Fei; Jiang, Cheng Zhe; Wu, Chun Fu; Won, Eun Kyung; Choung, Se Young

    2008-12-01

    We investigated the synergistic effect of pidotimod and red ginseng acidic polysaccharide (RGAP) from Panax ginseng C.A. Meyer on humoral immune response challenged by lipopolysaccharide (LPS) and sheep red blood cells (SRBC) in immunosuppressed mice. Combined treatment with pidotimod and RGAP significantly increased the number of plaque-forming cells in the spleen in response to both LPS and SRBC, while treatment with either pidotimod or RGAP individually had no such effect. IgG levels in serum were augmented for secondary responses to SRBC in co-treated mice, but not in mice treated with either drug alone. Microscopic studies revealed that architecture of the spleen, thymus, and lymph nodes was conserved. GPT and creatinine in serum as indicators of hepatic and renal functions showed no difference compared to the control group. These results indicate that combined treatment with pidotimod and RGAP has an immunostimulatory effect in a synergistic manner on antibody response to challenge with LPS and SRBC without toxic changes.

  15. Humoral immunity to AAV-6, 8, and 9 in normal and dystrophic dogs.

    Science.gov (United States)

    Shin, Jin-Hong; Yue, Yongping; Smith, Bruce; Duan, Dongsheng

    2012-03-01

    Adeno-associated virus (AAV)-6, 8, and 9 are promising gene-delivery vectors for testing novel Duchenne muscular dystrophy gene therapy in the canine model. Humoral immunity greatly influences in vivo AAV transduction. However, neutralizing antibodies to AAV-6, 8, and 9 have not been systemically examined in normal and dystrophic dogs. To gain information on the seroprevalence of antibodies to AAV-6, 8, and 9, we measured neutralizing antibody titers using an in vitro transduction inhibition assay. We examined 72 naive serum samples and 26 serum samples obtained from dogs that had received AAV gene transfer. Our data demonstrated that AAV-6 neutralizing antibody was the most prevalent antibody in dogs irrespective of age, gender, disease status (dystrophic or not), and prior parvovirus vaccination history. Surprisingly, high-level anti-AAV-6 antibody was detected at birth in newborn puppies. Further, a robust antibody response was induced in affected, but not normal newborn dogs following systemic AAV gene transfer. Taken together, our data have provided an important baseline on the seroprevalence of AAV-6, 8, and 9 neutralizing antibodies in normal and Duchenne muscular dystrophy dogs. These results will help guide translational AAV gene-therapy studies in dog models of muscular dystrophy.

  16. Lateral flow assay for simultaneous detection of cellular- and humoral immune responses.

    Science.gov (United States)

    Corstjens, Paul L A M; de Dood, Claudia J; van der Ploeg-van Schip, Jolien J; Wiesmeijer, Karien C; Riuttamäki, Terhi; van Meijgaarden, Krista E; Spencer, John S; Tanke, Hans J; Ottenhoff, Tom H M; Geluk, Annemieke

    2011-10-01

    The development of a cytokine detection assay suitable for detection of multiple biomarkers for improved diagnosis of mycobacterial diseases. A lateral flow (LF) assay to detect IL-10 was developed utilizing the up-converting phosphor (UCP) reporter-technology. The assay was evaluated using blood samples of leprosy patients. Multiplex applications were explored targeting: 1) IL-10 and IFN-γ in assay buffer; 2) IL-10 and anti-phenolic glycolipid (PGL-I) antibodies in serum from leprosy patients. Detection of IL-10 below the targeted level of 100pg/mL in serum was shown. Comparison with ELISA showed a quantitative correlation with R(2) value of 0.92. Multiplexing of cytokines and simultaneous detection of cytokine and antibody was demonstrated. The UCP-LF IL-10 assay is a user-friendly, rapid alternative for IL-10 ELISAs, suitable for multiplex detection of different cytokines and can be merged with antibody-detection assays to simultaneously detect cellular- and humoral immunity. Copyright © 2011 Elsevier B.V. All rights reserved.

  17. Investigation of the temporal humoral immune response in a murine model of actinomycetoma.

    Science.gov (United States)

    Rodríguez, M del C; Torres, J A; Zlotnik, H

    1996-06-01

    The murine model of actinomycetoma offers the potential of studying many unknown aspects of this infection. In this work, the model was used to investigate the temporal humoral immune response to actinomycetoma agents. Groups of 7- to 9-week-old female BALB/c mice were inoculated in one of the hind footpads with one of four different Nocardia strains. To mimic the constant exposure of infected humans to the virulent soil inhabiting agents, a second injection consisting of live nocardiae in incomplete Freund's adjuvant was administered five months after the first one. Murine serum samples were collected throughout the study and their IgM and IgM titers were determined by ELISA and the Western blot assay. The results obtained indicate that the ELISA titers increased as the infection progressed and this correlated with a greater number of antigen bands being recognized in the blots. Overall, however, the ELISA titers were lower for the N. brasiliensis infected mice than those of the N. asteroides ones. This observation may be indicative of an immunosuppressive state and is worthy of further investigation.

  18. Humoral Immunity to Primary Smallpox Vaccination: Impact of Childhood versus Adult Immunization on Vaccinia Vector Vaccine Development in Military Populations.

    Science.gov (United States)

    Slike, Bonnie M; Creegan, Matthew; Marovich, Mary; Ngauy, Viseth

    2017-01-01

    Modified Vaccinia virus has been shown to be a safe and immunogenic vector platform for delivery of HIV vaccines. Use of this vector is of particular importance to the military, with the implementation of a large scale smallpox vaccination campaign in 2002 in active duty and key civilian personnel in response to potential bioterrorist activities. Humoral immunity to smallpox vaccination was previously shown to be long lasting (up to 75 years) and protective. However, using vaccinia-vectored vaccine delivery for other diseases on a background of anti-vector antibodies (i.e. pre-existing immunity) may limit their use as a vaccine platform, especially in the military. In this pilot study, we examined the durability of vaccinia antibody responses in adult primary vaccinees in a healthy military population using a standard ELISA assay and a novel dendritic cell neutralization assay. We found binding and neutralizing antibody (NAb) responses to vaccinia waned after 5-10 years in a group of 475 active duty military, born after 1972, who were vaccinated as adults with Dryvax®. These responses decreased from a geometric mean titer (GMT) of 250 to baseline (vaccination. This contrasted with a comparator group of adults, ages 35-49, who were vaccinated with Dryvax® as children. In the childhood vaccinees, titers persisted for >30 years with a GMT of 210 (range 112-3234). This data suggests limited durability of antibody responses in adult vaccinees compared to those vaccinated in childhood and further that adult vaccinia recipients may benefit similarly from receipt of a vaccinia based vaccine as those who are vaccinia naïve. Our findings may have implications for the smallpox vaccination schedule and support the ongoing development of this promising viral vector in a military vaccination program.

  19. Humoral Immunity to Primary Smallpox Vaccination: Impact of Childhood versus Adult Immunization on Vaccinia Vector Vaccine Development in Military Populations.

    Directory of Open Access Journals (Sweden)

    Bonnie M Slike

    Full Text Available Modified Vaccinia virus has been shown to be a safe and immunogenic vector platform for delivery of HIV vaccines. Use of this vector is of particular importance to the military, with the implementation of a large scale smallpox vaccination campaign in 2002 in active duty and key civilian personnel in response to potential bioterrorist activities. Humoral immunity to smallpox vaccination was previously shown to be long lasting (up to 75 years and protective. However, using vaccinia-vectored vaccine delivery for other diseases on a background of anti-vector antibodies (i.e. pre-existing immunity may limit their use as a vaccine platform, especially in the military. In this pilot study, we examined the durability of vaccinia antibody responses in adult primary vaccinees in a healthy military population using a standard ELISA assay and a novel dendritic cell neutralization assay. We found binding and neutralizing antibody (NAb responses to vaccinia waned after 5-10 years in a group of 475 active duty military, born after 1972, who were vaccinated as adults with Dryvax®. These responses decreased from a geometric mean titer (GMT of 250 to baseline (30 years with a GMT of 210 (range 112-3234. This data suggests limited durability of antibody responses in adult vaccinees compared to those vaccinated in childhood and further that adult vaccinia recipients may benefit similarly from receipt of a vaccinia based vaccine as those who are vaccinia naïve. Our findings may have implications for the smallpox vaccination schedule and support the ongoing development of this promising viral vector in a military vaccination program.

  20. Novel protein and poxvirus-based vaccine combinations for simultaneous induction of humoral and cell-mediated immunity.

    Science.gov (United States)

    Hutchings, Claire L; Gilbert, Sarah C; Hill, Adrian V S; Moore, Anne C

    2005-07-01

    The presence of both cell-mediated and humoral immunity is important in protection from and clearance of a number of infectious pathogens. We describe novel vaccine regimens using combinations of plasmid DNA, poxvirus and protein to induce strong Ag-specific T cell and Ab responses simultaneously in a murine model. Intramuscular (i.m.) immunization with plasmid DNA encoding the middle Ag of hepatitis B (DNA) concurrently with a commercial hepatitis B virus (HBV) vaccine (Engerix-B) followed by boosting immunizations with both modified vaccinia virus Ankara (MVA) encoding the middle Ag of HBV and Engerix-B induced high levels of CD4(+) and CD8(+) T cells and high titer Ab responses to hepatitis B surface Ag (HbsAg). Substitution of Engerix-B with adjuvant-free rHBsAg induced similar T cell responses and greatly enhanced Ab levels. Repeated immunizations with recombinant or nonrecombinant MVA mixed with Ag induced higher titers of Abs compared with immunization with either Ag or Engerix-B further demonstrating this novel adjuvant effect of MVA. The poxviruses NYVAC, fowlpox (FP9) and ALVAC, and to a lesser extent, adenovirus, also displayed similar adjuvant properties when used in combination with rHBsAg. The use of poxviruses as an adjuvant for protein to concurrently induce Ag-specific T cells and Abs could be applied to the development of vaccines for many diseases, including HIV and malaria, where both cell mediated and humoral immunity may be important for protection.

  1. Pathogen-mimicking vaccine delivery system designed with a bioactive polymer (inulin acetate) for robust humoral and cellular immune responses.

    Science.gov (United States)

    Kumar, Sunny; Kesharwani, Siddharth S; Kuppast, Bhimanna; Bakkari, Mohammed Ali; Tummala, Hemachand

    2017-09-10

    New and improved vaccines are needed against challenging diseases such as malaria, tuberculosis, Ebola, influenza, AIDS, and cancer. The majority of existing vaccine adjuvants lack the ability to significantly stimulate the cellular immune response, which is required to prevent the aforementioned diseases. This study designed a novel particulate based pathogen-mimicking vaccine delivery system (PMVDS) to target antigen-presenting-cells (APCs) such as dendritic cells. The uniqueness of PMVDS is that the polymer used to prepare the delivery system, Inulin Acetate (InAc), activates the innate immune system. InAc was synthesized from the plant polysaccharide, inulin. PMVDS provided improved and persistent antigen delivery to APCs as an efficient vaccine delivery system, and simultaneously, activated Toll-Like Receptor-4 (TLR-4) on APCs to release chemokine's/cytokines as an immune-adjuvant. Through this dual mechanism, PMVDS robustly stimulated both the humoral (>32 times of IgG1 levels vs alum) and the cell-mediated immune responses against the encapsulated antigen (ovalbumin) in mice. More importantly, PMVDS stimulated both cytotoxic T cells and natural killer cells of cell-mediated immunity to provide tumor (B16-ova-Melanoma) protection in around 40% of vaccinated mice and significantly delayed tumor progression in rest of the mice. PMVDS is a unique bio-active vaccine delivery technology with broader applications for vaccines against cancer and several intracellular pathogens, where both humoral and cellular immune responses are desired. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Measles immune suppression: lessons from the macaque model.

    Directory of Open Access Journals (Sweden)

    Rory D de Vries

    Full Text Available Measles remains a significant childhood disease, and is associated with a transient immune suppression. Paradoxically, measles virus (MV infection also induces robust MV-specific immune responses. Current hypotheses for the mechanism underlying measles immune suppression focus on functional impairment of lymphocytes or antigen-presenting cells, caused by infection with or exposure to MV. We have generated stable recombinant MVs that express enhanced green fluorescent protein, and remain virulent in non-human primates. By performing a comprehensive study of virological, immunological, hematological and histopathological observations made in animals euthanized at different time points after MV infection, we developed a model explaining measles immune suppression which fits with the "measles paradox". Here we show that MV preferentially infects CD45RA(- memory T-lymphocytes and follicular B-lymphocytes, resulting in high infection levels in these populations. After the peak of viremia MV-infected lymphocytes were cleared within days, followed by immune activation and lymph node enlargement. During this period tuberculin-specific T-lymphocyte responses disappeared, whilst strong MV-specific T-lymphocyte responses emerged. Histopathological analysis of lymphoid tissues showed lymphocyte depletion in the B- and T-cell areas in the absence of apoptotic cells, paralleled by infiltration of T-lymphocytes into B-cell follicles and reappearance of proliferating cells. Our findings indicate an immune-mediated clearance of MV-infected CD45RA(- memory T-lymphocytes and follicular B-lymphocytes, which causes temporary immunological amnesia. The rapid oligoclonal expansion of MV-specific lymphocytes and bystander cells masks this depletion, explaining the short duration of measles lymphopenia yet long duration of immune suppression.

  3. Effect of Zinc on Humoral and Cell-Mediated Immunity of Broilers Vaccinated Against Coccidiosis

    Directory of Open Access Journals (Sweden)

    Milad Moazeni

    2013-09-01

    Full Text Available Background: The aim of the present study was the comparison of humoral and cell-mediated immunity in ‎broilers fed with different levels of zinc during a coccidiosis challenge.‎Methods: One hundred and forty-‎four one-day-old broiler chicks were used with three ‎dietary zinc ‎(40, 120 and 200 mg/kg. At 14 d of age, all birds were inoculated orally with 5×103 sporulated oocysts of E. Tenella. ‎At ‎2, 22, 32, 42 ‎days of age, the blood serums were tested for ‎antibody titer against‎ Newcas­tle disease vaccine, using ‎the standard HI test. On day 42 the sum of nitrite ‎and nitrate based on the reduction of nitrate ‎to nitrite by cadmium ‎and white blood cell count (WBC using a hemocytometer were measured.Results: At 42 d, levels of ‎120 and 200 mg significantly (P< 0.05 increased the antibody titer in compare with the control. The peak response of CBH was observed at the level of 200 mg Zn/kg diet. Also both level of 120 and 200 mg Zn/kg diet increased WBC count and sum of nitrite and nitrate‎ in serum compared with the control.Conclusion: The levels of 120 and 200 mg Zn/kg diet could be considered as a non-pharmacologic booster of immunity in broilers chicks infected with E. Tenella.

  4. Tyrosine kinase inhibitor therapy-induced changes in humoral immunity in patients with chronic myeloid leukemia.

    Science.gov (United States)

    Rajala, Hanna L M; Missiry, Mohamed El; Ruusila, Anniina; Koskenvesa, Perttu; Brümmendorf, Tim H; Gjertsen, Bjorn T; Janssen, Jeroen; Lotfi, Kourosh; Markevärn, Berit; Olsson-Strömberg, Ulla; Stenke, Leif; Stentoft, Jesper; Richter, Johan; Hjorth-Hansen, Henrik; Kreutzman, Anna; Mustjoki, Satu

    2017-08-01

    Tyrosine kinase inhibitors (TKIs) have well-characterized immunomodulatory effects on T and NK cells, but the effects on the humoral immunity are less well known. In this project, we studied TKI-induced changes in B cell-mediated immunity. We collected peripheral blood (PB) and bone marrow (BM) samples from chronic myeloid leukemia (CML) patients before and during first-line imatinib (n = 20), dasatinib (n = 16), nilotinib (n = 8), and bosutinib (n = 12) treatment. Plasma immunoglobulin levels were measured, and different B cell populations in PB and BM were analyzed with flow cytometry. Imatinib treatment decreased plasma IgA and IgG levels, while dasatinib reduced IgM levels. At diagnosis, the proportion of patients with IgA, IgG, and IgM levels below the lower limit of normal (LLN) was 0, 11, and 6% of all CML patients, respectively, whereas at 12 months timepoint the proportions were 6% (p = 0.13), 31% (p = 0.042) and 28% (p = 0.0078). Lower initial Ig levels predisposed to the development of hypogammaglobulinemia during TKI therapy. Decreased Ig levels in imatinib-treated patients were associated with higher percentages of immature BM B cells. The patients, who had low Ig levels during the TKI therapy, had significantly more frequent minor infections during the follow-up compared with the patients with normal Ig values (33% vs. 3%, p = 0.0016). No severe infections were reported, except recurrent upper respiratory tract infections in one imatinib-treated patient, who developed severe hypogammaglobulinemia. TKI treatment decreases plasma Ig levels, which should be measured in patients with recurrent infections.

  5. [Changes in serum YKL-40 level and humoral immune function and their significance in children with recurrent pneumonia].

    Science.gov (United States)

    Ma, Wei-Yin; Peng, Shao; Zhang, Ting

    2017-04-01

    To investigate the changes in serum YKL-40 level and humoral immune function and their significance in children with recurrent pneumonia. Blood samples were collected from 30 children with recurrent pneumonia (recurrent pneumonia group), 30 children with acute pneumonia (acute pneumonia group), and 30 healthy children (control group). Serum YKL-40 levels were measured by enzyme-linked immunosorbent assay. The correlation between serum YKL-40 level and laboratory indices related to humoral immune function was analyzed. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of serum YKL-40 level for recurrent pneumonia. The recurrent pneumonia group had a significantly higher serum YKL-40 level than the acute pneumonia and control groups (Ppneumonia group had a significantly higher serum YKL-40 level than the control group (Ppneumonia group were significantly lower than in the acute pneumonia group (Ppneumonia was 0.958 (95%CI: 0.921-0.994). Humoral immune function is low in children with recurrent pneumonia. Serum YKL-40 may be involved in the occurrence of recurrent pneumonia and can be used as a reference index for diagnosing recurrent pneumonia.

  6. Effect of humoral immunity on HIV-1 dynamics with virus-to-target and infected-to-target infections

    Science.gov (United States)

    Elaiw, A. M.; Raezah, A. A.; Alofi, A. S.

    2016-08-01

    We consider an HIV-1 dynamics model by incorporating (i) two routes of infection via, respectively, binding of a virus to a receptor on the surface of a target cell to start genetic reactions (virus-to-target infection), and the direct transmission from infected cells to uninfected cells through the concept of virological synapse in vivo (infected-to-target infection); (ii) two types of distributed-time delays to describe the time between the virus or infected cell contacts an uninfected CD4+ T cell and the emission of new active viruses; (iii) humoral immune response, where the HIV-1 particles are attacked by the antibodies that are produced from the B lymphocytes. The existence and stability of all steady states are completely established by two bifurcation parameters, R 0 (the basic reproduction number) and R 1 (the viral reproduction number at the chronic-infection steady state without humoral immune response). By constructing Lyapunov functionals and using LaSalle's invariance principle, we have proven that, if R 0 ≤ 1 , then the infection-free steady state is globally asymptotically stable, if R 1 ≤ 1 1 , then the chronic-infection steady state with humoral immune response is globally asymptotically stable. We have performed numerical simulations to confirm our theoretical results.

  7. Characterization of Cellular and Humoral Immune Responses After IBV Infection in Chicken Lines Differing in MBL Serum Concentration

    DEFF Research Database (Denmark)

    Kjærup, Rikke Munkholm; Dalgaard, Tina Sørensen; Norup, Liselotte Rothmann

    2014-01-01

    Chickens from two inbred lines selected for high (L10H) or low (L10L) mannose-binding lectin (MBL) serum concentrations were infected with infectious bronchitis virus (IBV), and innate as well as adaptive immunological parameters were measured throughout the experimental period. Chickens with high...... L10H chickens than in the infected and noninfected L10L chickens. Thus, these results indicate that MBL is produced locally and may be involved in the regulation of the cellular immune response after an IBV infection. However, MBL did not appear to influence the humoral immune response after IBV...

  8. Porphyromonas gingivalis suppresses adaptive immunity in periodontitis, atherosclerosis, and Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Ingar Olsen

    2016-11-01

    Full Text Available Porphyromonas gingivalis, a keystone pathogen in chronic periodontitis, has been found to associate with remote body organ inflammatory pathologies, including atherosclerosis and Alzheimer’s disease (AD. Although P. gingivalis has a plethora of virulence factors, much of its pathogenicity is surprisingly related to the overall immunosuppression of the host. This review focuses on P. gingivalis aiding suppression of the host’s adaptive immune system involving manipulation of cellular immunological responses, specifically T cells and B cells in periodontitis and related conditions. In periodontitis, this bacterium inhibits the synthesis of IL-2 and increases humoral responses. This reduces the inflammatory responses related to T- and B-cell activation, and subsequent IFN-γ secretion by a subset of T cells. The T cells further suppress upregulation of programmed cell death-1 (PD-1-receptor on CD+cells and its ligand PD-L1 on CD11b+-subset of T cells. IL-2 downregulates genes regulated by immune response and induces a cytokine pattern in which the Th17 lineage is favored, thereby modulating the Th17/T-regulatory cell (Treg imbalance. The suppression of IFN-γ-stimulated release of interferon-inducible protein-10 (IP-10 chemokine ligands [ITAC (CXCL11 and Mig (CXCL9] by P. gingivalis capsular serotypes triggers distinct T cell responses and contributes to local immune evasion by release of its outer membrane vesicles. In atherosclerosis, P. gingivalis reduces Tregs, transforms growth factor beta-1 (TGFβ-1, and causes imbalance in the Th17 lineage of the Treg population. In AD, P. gingivalis may affect the blood–brain barrier permeability and inhibit local IFN-γ response by preventing entry of immune cells into the brain. The scarcity of adaptive immune cells in AD neuropathology implies P. gingivalis infection of the brain likely causing impaired clearance of insoluble amyloid and inducing immunosuppression. By the effective manipulation of

  9. Correspondence of Neutralizing Humoral Immunity and CD4 T Cell Responses in Long Recovered Sudan Virus Survivors.

    Science.gov (United States)

    Sobarzo, Ariel; Stonier, Spencer W; Herbert, Andrew S; Ochayon, David E; Kuehne, Ana I; Eskira, Yael; Fedida-Metula, Shlomit; Tali, Neta; Lewis, Eli C; Egesa, Moses; Cose, Stephen; Lutwama, Julius Julian; Yavelsky, Victoria; Dye, John M; Lobel, Leslie

    2016-05-11

    Robust humoral and cellular immunity are critical for survival in humans during an ebolavirus infection. However, the interplay between these two arms of immunity is poorly understood. To address this, we examined residual immune responses in survivors of the Sudan virus (SUDV) outbreak in Gulu, Uganda (2000-2001). Cytokine and chemokine expression levels in SUDV stimulated whole blood cultures were assessed by multiplex ELISA and flow cytometry. Antibody and corresponding neutralization titers were also determined. Flow cytometry and multiplex ELISA results demonstrated significantly higher levels of cytokine and chemokine responses in survivors with serological neutralizing activity. This correspondence was not detected in survivors with serum reactivity to SUDV but without neutralization activity. This previously undefined relationship between memory CD4 T cell responses and serological neutralizing capacity in SUDV survivors is key for understanding long lasting immunity in survivors of filovirus infections.

  10. Correspondence of Neutralizing Humoral Immunity and CD4 T Cell Responses in Long Recovered Sudan Virus Survivors

    Directory of Open Access Journals (Sweden)

    Ariel Sobarzo

    2016-05-01

    Full Text Available Robust humoral and cellular immunity are critical for survival in humans during an ebolavirus infection. However, the interplay between these two arms of immunity is poorly understood. To address this, we examined residual immune responses in survivors of the Sudan virus (SUDV outbreak in Gulu, Uganda (2000–2001. Cytokine and chemokine expression levels in SUDV stimulated whole blood cultures were assessed by multiplex ELISA and flow cytometry. Antibody and corresponding neutralization titers were also determined. Flow cytometry and multiplex ELISA results demonstrated significantly higher levels of cytokine and chemokine responses in survivors with serological neutralizing activity. This correspondence was not detected in survivors with serum reactivity to SUDV but without neutralization activity. This previously undefined relationship between memory CD4 T cell responses and serological neutralizing capacity in SUDV survivors is key for understanding long lasting immunity in survivors of filovirus infections.

  11. Humoral Immunity to West Nile Virus Is Long-Lasting and Protective in the House Sparrow (Passer domesticus)

    Science.gov (United States)

    Nemeth, Nicole M.; Oesterle, Paul T.; Bowen, Richard A.

    2009-01-01

    The house sparrow (Passer domesticus) is a common and abundant amplifying host of West Nile virus (WNV) and many survive infection and develop humoral immunity. We experimentally inoculated house sparrows with WNV and monitored duration and protection of resulting antibodies. Neutralizing antibody titers remained relatively constant for ≥ 36 months (N = 42) and provided sterilizing immunity for up to 36 months post-inoculation in 98.6% of individuals (N = 72). These results imply that immune house sparrows are protected from WNV infection for multiple transmission seasons. Additionally, individuals experiencing WNV-associated mortality reached significantly higher peak viremia titers than survivors, and mortality during acute infection was significantly higher in caged versus free-flight sparrows. A better understanding of the long-term immunity and mortality rates in birds is valuable in interpreting serosurveillance and diagnostic data and modeling transmission and disease dynamics. PMID:19407139

  12. Humoral immune responses against the Mycobacterium tuberculosis 38-kilodalton, MTB48, and CFP-10/ESAT-6 antigens in tuberculosis.

    Science.gov (United States)

    Wu, Xueqiong; Yang, Yourong; Zhang, Junxian; Li, Bangying; Liang, Yan; Zhang, Chuiying; Dong, Mei; Cheng, Hongbing; He, Jufang

    2010-03-01

    The diagnosis of smear-negative and culture-negative patients with active tuberculosis (TB) is challenging. The detection of Mycobacterium tuberculosis-specific antibodies in human sera has been an important diagnostic aid. However, detection of antibody responses to a single antigen usually has a low sensitivity for diagnosis of TB. In this study, humoral immune responses against recombinant M. tuberculosis 38-kDa, MTB48, and CFP-10/ESAT-6 (culture filtrate protein 10/6-kDa early secreted antigen target of M. tuberculosis) antigens in 250 Chinese TB patients and 260 healthy subjects were evaluated by an enzyme-linked immunosorbent assay (ELISA). The levels of antibodies against those antigens in TB patients, even in bacterium-negative ones, were significantly higher than those in healthy subjects (P CFP-10/ESAT-6 antigens, in TB patients were 73.6%, 73.2%, and 60.4%, respectively, with specificities of 85.4%, 77.7%, and 73.8%, respectively. Importantly, the sensitivity to positively detect humoral responses to one of the antigens increased further. Our data suggest that the humoral immune responses to M. tuberculosis antigens in TB patients are heterogeneous. The 38-kDa, MTB48, and CFP-10/ESAT-6 antigens can be used as the cocktail antigens in the serodiagnosis of active TB, especially for smear- or culture-negative TB cases.

  13. Evaluation of the humoral immune response to human leukocyte antigens in Brazilian renal transplant candidates.

    Directory of Open Access Journals (Sweden)

    Patricia Keiko Saito

    Full Text Available Pre-transplant sensitization to human leukocyte antigens (HLA is a risk factor for graft failure. Studies of the immunological profile related to anti-HLA antibodies in Brazilian renal transplant candidates are few. In this study, we evaluated the humoral immune response to HLA antigens in 269 renal transplant candidates, in Paraná State, Brazil. The HLA typing was performed by the polymerase chain reaction sequence-specific oligonucleotide method (PCR-SSO combined with Luminex technology, using an SSO-LABType commercial kit (One Lambda, Inc., Canoga Park, CA, USA. The percentages of panel-reactive antibodies (PRA and the specificity of anti-HLA antibodies were determined using the LS1PRA and LS2PRA commercial kits (One Lambda, Inc.. The PRA-positive group consisted of 182 (67.7% patients, and the PRA-negative group of 87 (32.3% patients. The two groups differed significantly only with respect to gender. Females were the most sensitized. Among the 182 patients with PRA- positive, 62 (34.1% were positive for class I and negative for class II, 39 (21.4% were negative for class I and positive for class II, and 81 (44.5% were positive for both classes I and II. The HLA-A*02, A*24, A*01, B*44, B*35, B*15, DRB1*11, DRB1*04 and DRB1*03 allele groups were the most frequent. The specificities of anti-HLA antibodies were more frequent: A34, B57, Cw15, Cw16, DR51, DQ8 and DP14. This study documented the profile of anti-HLA antibodies in patients with chronic renal failure who were on waiting lists for an organ in Paraná, and found high sensitization to HLA antigens in the samples.

  14. Humoral immune reaction of newborn calves congenitally infected with Neospora caninum and experimentally treated with toltrazuril.

    Science.gov (United States)

    Haerdi, Corinne; Haessig, Michael; Sager, Heinz; Greif, Gisela; Staubli, Daniela; Gottstein, Bruno

    2006-10-01

    Neospora caninum is widely recognized as one of the most important infectious organisms causing abortion and stillbirth in cattle. This parasite causes severe economical losses worldwide. Infection is mostly passed vertically from mother to calf during pregnancy. Under certain circumstances, an infection can lead to abortion, but in most cases it results in a chronically infected calf, which itself will represent the next endogenously infectious generation. So far, no reliable therapeutic or metaphylactic tool has been developed. One possibility to control the problem may consist of treating newborn calves that became vertically infected by a persistently infected mother. This may allow parasite-free offspring. The aim of the present study was to address the questions: (1) can serology be used to assess efficiency of treatment in toltrazuril-medicated animals? and (2) is a strategic prevention measure possible by means of producing N. caninum-free calves from positive cows? Calves from Neospora-seropositive cows and heifers were randomly split into two different medication groups: 36 calves were medicated with toltrazuril and 36 calves obtained a placebo. Medication (20 mg toltrazuril per kg bw) was administered three times, every second day, within the 7 days post natum. Three months after medication, there was no difference in antibody reactivity between the two groups. At later time points (4-6 months), however, significant differences were found, as explained by a strong humoral immunity after chemotherapeutical affection of parasites, while the placebo-treated animals only responded weakly to the persistent infection. In summary, we concluded that (1) serology was not an entirely appropriate tool to answer our initial question and (2) toltrazuril has the potential to eliminate N. caninum in newborn calves. As a consequence, we plan to follow up toltrazuril-medicated calves clinically and serologically over a longer period and investigate if they give birth to

  15. Humoral immune response to measles and varicella vaccination in former very low birth weight preterm infants

    Directory of Open Access Journals (Sweden)

    Carolina Schlindwein Mariano Ferreira

    2018-01-01

    Conclusions: Humoral responses to measles and varicella were similar between infants born prematurely and full-term infants. Measles antibody levels were negatively associated with antenatal corticosteroid use; varicella antibodies were positively associated with prolonged breastfeeding.

  16. Polymorphisms in HLA-DPB1 are associated with differences in rubella virus-specific humoral immunity after vaccination.

    Science.gov (United States)

    Lambert, Nathaniel D; Haralambieva, Iana H; Kennedy, Richard B; Ovsyannikova, Inna G; Pankratz, Vernon Shane; Poland, Gregory A

    2015-03-15

    Vaccination with live attenuated rubella virus induces a strong immune response in most individuals. However, small numbers of subjects never reach or maintain protective antibody levels, and there is a high degree of variability in immune response. We have previously described genetic polymorphisms in HLA and other candidate genes that are associated with interindividual differences in humoral immunity to rubella virus. To expand our previous work, we performed a genome-wide association study (GWAS) to discover single-nucleotide polymorphisms (SNPs) associated with rubella virus-specific neutralizing antibodies. We identified rs2064479 in the HLA-DPB1 genetic region as being significantly associated with humoral immune response variations after rubella vaccination (P = 8.62 × 10(-8)). All other significant SNPs in this GWAS were located near the HLA-DPB1 gene (P ≤ 1 × 10(-7)). These findings demonstrate that polymorphisms in HLA-DPB1 are strongly associated with interindividual differences in neutralizing antibody levels to rubella vaccination and represent a validation of our previous HLA work. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  17. Humor: an antidote for stress.

    Science.gov (United States)

    Wooten, P

    1996-01-01

    Humor and laughter can be effective self-care tools to cope with stress. An ability to find humor gives us a sense of perspective on our problems. Laughter provides a physical release for accumulated tension. The article reviews research on the effect of humor and laughter on our immune function and resilience to stress. Resources for finding humor are included.

  18. Regulatory T cells in γ irradiation-induced immune suppression.

    Directory of Open Access Journals (Sweden)

    Hugh I McFarland

    Full Text Available Sublethal total body γ irradiation (TBI of mammals causes generalized immunosuppression, in part by induction of lymphocyte apoptosis. Here, we provide evidence that a part of this immune suppression may be attributable to dysfunction of immune regulation. We investigated the effects of sublethal TBI on T cell memory responses to gain insight into the potential for loss of vaccine immunity following such exposure. We show that in mice primed to an MHC class I alloantigen, the accelerated graft rejection T memory response is specifically lost several weeks following TBI, whereas identically treated naïve mice at the same time point had completely recovered normal rejection kinetics. Depletion in vivo with anti-CD4 or anti-CD25 showed that the mechanism involved cells consistent with a regulatory T cell (T reg phenotype. The loss of the T memory response following TBI was associated with a relative increase of CD4+CD25+ Foxp3+ expressing T regs, as compared to the CD8+ T effector cells requisite for skin graft rejection. The radiation-induced T memory suppression was shown to be antigen-specific in that a third party ipsilateral graft rejected with normal kinetics. Remarkably, following the eventual rejection of the first MHC class I disparate skin graft, the suppressive environment was maintained, with markedly prolonged survival of a second identical allograft. These findings have potential importance as regards the immunologic status of T memory responses in victims of ionizing radiation exposure and apoptosis-inducing therapies.

  19. CD4+ levels control the odds of induction of humoral immune responses to tracer doses of therapeutic antibodies.

    Science.gov (United States)

    Srinivasula, Sharat; Gabriel, Erin; Kim, Insook; DeGrange, Paula; St Claire, Alexis; Mallow, Candace; Donahue, Robert E; Paik, Chang; Lane, H C; Di Mascio, Michele

    2017-01-01

    Rapidly increasing number of therapeutic antibodies are being repurposed to imaging probes for noninvasive diagnosis, as well as monitoring during treatment or disease recurrence. Though antibody-based imaging involves tracer doses (~3 log lower than therapeutic doses), and immune responses are severely reduced in patients with impaired immunity, formation of anti-tracer antibodies (ATA) has been observed hampering further diagnostic monitoring. Here, we explored the potential to develop humoral responses to intravenously administered tracer dose of a monoclonal antibody F(ab΄)2 fragment, and associated with host related immune measures in 49 rhesus macaques categorized into healthy (uninfected controls), SIV-progressors, SIV non-progressors, or total body irradiated (TBI). Antibody fragment administered in tracer amount (~100μg) induced immune responses with significantly lower odds in SIV-progressors or TBI macaques (P<0.005) as compared to healthy animals. Peripheral blood (PB) CD4+ cell counts, but not CD20+ cell levels, were associated with significantly higher risk of developing a humoral response (P<0.001). Doubling the PB CD4+ counts is associated with an odds ratio of developing an immune response of 1.73. Among SIV-infected animals, CD4+ cell count was a stronger predictor of immune response than plasma SIV-RNA levels. Both SIV-progressors and TBI macaques showed higher odds of responses with increasing CD4+ counts, however when compared to healthy or SIV non-progressors with similar CD4+ count, they were still functionally incompetent in generating a response (P<0.01). Moreover, presence of ATA in systemic circulation altered the in vivo biodistribution by increasing hepatic uptake and decreasing plasma radiotracer clearance, with minimal to no binding detected in targeted tissues.

  20. Heat killed multi-serotype Shigella immunogens induced humoral immunity and protection against heterologous challenge in rabbit model.

    Science.gov (United States)

    Nag, Dhrubajyoti; Sinha, Ritam; Mitra, Soma; Barman, Soumik; Takeda, Yoshifumi; Shinoda, Sumio; Chakrabarti, M K; Koley, Hemanta

    2015-11-01

    Recently we have shown the homologous protective efficacy of heat killed multi-serotype Shigella (HKMS) immunogens in a guinea pig colitis model. In our present study, we have advanced our research by immunizing rabbits with a reduced number of oral doses and evaluating the host's adaptive immune responses. The duration of immunogenicity and subsequently protective efficacy was determined against wild type heterologous Shigella strains in a rabbit luminal model. After three successive oral immunizations with HKMS immunogens, serum and lymphocyte supernatant antibody titer against the heterologous shigellae were reciprocally increased and remained at an elevated level up to 180 days. Serogroup and serotype specific O-antigen of lipopolysaccharide and immunogenic proteins of heterologous challenge strains were detected by immunoblot assay. Up-regulation of IL-12p35, IFN-γ and IL-10 mRNA expression was detected in immunized rabbit peripheral blood mononuclear cells (PBMC) after stimulation with HKMS in vitro. HKMS-specific plasma cell response was confirmed by production of a relatively higher level of HKMS-specific IgG in immunized PBMC supernatant compared to control group. Furthermore, the immunized groups of rabbits exhibited complete protection against wild type heterologous shigellae challenge. Thus HKMS immunogens induced humoral and Th1-mediated adaptive immunity and provided complete protection in a rabbit model. These immunogens could be a broad spectrum non-living vaccine candidate for human use in the near future. Copyright © 2015 Elsevier GmbH. All rights reserved.

  1. Isocitrate dehydrogenase of Helicobacter pylori potentially induces humoral immune response in subjects with peptic ulcer disease and gastritis.

    Directory of Open Access Journals (Sweden)

    M Abid Hussain

    Full Text Available BACKGROUND: H. pylori causes gastritis and peptic ulcers and is a risk factor for the development of gastric carcinoma. Many of the proteins such as urease, porins, flagellins and toxins such as lipo-polysaccharides have been identified as potential virulence factors which induce proinflammatory reaction. We report immunogenic potentials of isocitrate dehydrogenase (ICD, an important house keeping protein of H. pylori. METHODOLOGY/PRINCIPAL FINDINGS: Amino acid sequences of H. pylori ICD were subjected to in silico analysis for regions with predictably high antigenic indexes. Also, computational modelling of the H. pylori ICD as juxtaposed to the E. coli ICD was carried out to determine levels of structure similarity and the availability of surface exposed motifs, if any. The icd gene was cloned, expressed and purified to a very high homogeneity. Humoral response directed against H. pylori ICD was detected through an enzyme linked immunosorbent assay (ELISA in 82 human subjects comprising of 58 patients with H. pylori associated gastritis or ulcer disease and 24 asymptomatic healthy controls. The H. pylori ICD elicited potentially high humoral immune response and revealed high antibody titers in sera corresponding to endoscopically-confirmed gastritis and ulcer disease subjects. However, urea-breath-test negative healthy control samples and asymptomatic control samples did not reveal any detectable immune responses. The ELISA for proinflammatory cytokine IL-8 did not exhibit any significant proinflammatory activity of ICD. CONCLUSIONS/SIGNIFICANCE: ICD of H. pylori is an immunogen which interacts with the host immune system subsequent to a possible autolytic-release and thereby significantly elicits humoral responses in individuals with invasive H. pylori infection. However, ICD could not significantly stimulate IL8 induction in a cultured macrophage cell line (THP1 and therefore, may not be a notable proinflammatory agent.

  2. Humoral immune responses to Pneumocystis jirovecii antigens in HIV-infected and uninfected young children with pneumocystis pneumonia.

    Directory of Open Access Journals (Sweden)

    Kpandja Djawe

    Full Text Available Humoral immune responses in human immunodeficiency virus (HIV-infected and uninfected children with Pneumocystis pneumonia (PcP are poorly understood.Consecutive children hospitalized with acute pneumonia, tachypnea, and hypoxia in South Africa were investigated for PcP, which was diagnosed by real-time polymerase chain reaction on lower respiratory tract specimens. Serum antibody responses to recombinant fragments of the carboxyl terminus of Pneumocystis jirovecii major surface glycoprotein (MsgC were analyzed.149 children were enrolled of whom 96 (64% were HIV-infected. PcP occurred in 69 (72% of HIV-infected and 14 (26% of HIV-uninfected children. HIV-infected children with PcP had significantly decreased IgG antibodies to MsgC compared to HIV-infected patients without PcP, but had similar IgM antibodies. In contrast, HIV-uninfected children with PcP showed no change in IgG antibodies to MsgC, but had significantly increased IgM antibodies compared to HIV-uninfected children without PCP. Age was an independent predictor of high IgG antibodies, whereas PcP was a predictor of low IgG antibodies and high IgM antibodies. IgG and IgM antibody levels to the most closely related MsgC fragments were predictors of survival from PcP.Young HIV-infected children with PcP have significantly impaired humoral immune responses to MsgC, whereas HIV-uninfected children with PcP can develop active humoral immune responses. The children also exhibit a complex relationship between specific host factors and antibody levels to MsgC fragments that may be related to survival from PcP.

  3. 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.

  4. The humoral pattern recognition molecule PTX3 is a key component of innate immunity against urinary tract infection.

    Science.gov (United States)

    Jaillon, Sébastien; Moalli, Federica; Ragnarsdottir, Bryndis; Bonavita, Eduardo; Puthia, Manoj; Riva, Federica; Barbati, Elisa; Nebuloni, Manuela; Cvetko Krajinovic, Lidija; Markotic, Alemka; Valentino, Sonia; Doni, Andrea; Tartari, Silvia; Graziani, Giorgio; Montanelli, Alessandro; Delneste, Yves; Svanborg, Catharina; Garlanda, Cecilia; Mantovani, Alberto

    2014-04-17

    Immunity in the urinary tract has distinct and poorly understood pathophysiological characteristics and urinary tract infections (UTIs) are important causes of morbidity and mortality. We investigated the role of the soluble pattern recognition molecule pentraxin 3 (PTX3), a key component of the humoral arm of innate immunity, in UTIs. PTX3-deficient mice showed defective control of UTIs and exacerbated inflammation. Expression of PTX3 was induced in uroepithelial cells by uropathogenic Escherichia coli (UPEC) in a Toll-like receptor 4 (TLR4)- and MyD88-dependent manner. PTX3 enhanced UPEC phagocytosis and phagosome maturation by neutrophils. PTX3 was detected in urine of UTI patients and amounts correlated with disease severity. In cohorts of UTI-prone patients, PTX3 gene polymorphisms correlated with susceptibility to acute pyelonephritis and cystitis. These results suggest that PTX3 is an essential component of innate resistance against UTIs. Thus, the cellular and humoral arms of innate immunity exert complementary functions in mediating resistance against UTIs. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Humoral and cellular capsid-specific immune responses to adeno-associated virus type 1 in randomized healthy donors.

    Science.gov (United States)

    Veron, Philippe; Leborgne, Christian; Monteilhet, Virginie; Boutin, Sylvie; Martin, Samia; Moullier, Philippe; Masurier, Carole

    2012-06-15

    A major impediment to the use of adeno-associated virus (AAV)-mediated gene delivery to muscle in clinical applications is the pre-existing immune responses against the vector. Pre-existing humoral response to different AAV serotypes is now well documented. In contrast, cellular responses to AAV capsid have not been analyzed in a systematic manner, despite the risk of T cell reactivation upon gene transfer. AAV1 has been widely used in humans to target muscle. In this study, we analyzed PBMCs and sera of healthy donors for the presence of AAV1 capsid-specific T cell responses and AAV1 neutralizing factors. Approximately 30% of donors presented AAV1 capsid-specific T cells, mainly effector memory CD8(+) cells. IFN-γ-producing cells were also observed among effector memory CD4(+) cells for two of these donors. Moreover, to our knowledge, this study shows for the first time on a large cohort that there was no correlation between AAV1-specific T cell and humoral responses. Indeed, most donors presenting specific Ig and neutralizing factors were negative for cellular response (and vice versa). These new data raise the question of prescreening patients not only for the humoral response, but also for the cellular response. Clearly, a better understanding of the natural immunology of AAV serotypes will allow us to improve AAV gene therapy and make it an efficient treatment for genetic disease.

  6. LEI0258 microsatellite variability and its association with humoral and cell mediated immune responses in broiler chickens.

    Science.gov (United States)

    Esmailnejad, Atefeh; Nikbakht Brujeni, Gholamreza; Badavam, Maryam

    2017-10-01

    Major histocompatibility complex (MHC) has a profound influence on disease resistance or susceptibility, productivity and important economic traits in chicken. Association of the MHC with a wide range of immune responses makes it a valuable predictive factor for the disease pathogenesis and outcome. The tandem repeat LEI0258 is a genetic marker which is located within the B locus of chicken MHC and strongly associated with serologically defined haplotypes. LEI0258 microsatellite marker was applied to investigate the MHC polymorphism in Ross 308 broiler chicken (N=104). Association of LEI0258 alleles with humoral and cell mediated immune responses to Newcastle disease (ND), Infectious bursal disease (IBD) and Avian influenza (AI) vaccines were also examined. LEI0258 polymorphism was determined by PCR-based fragment analysis, and association of LEI0258 alleles with immune responses were evaluated using multivariate regression analysis and GLM procedures. A total of seven alleles ranging from 195 to 448bp were found, including two novel alleles (263 and 362bp) that were unique in Ross 308 broiler population. Association study revealed a significant influence of MHC alleles on humoral and cellular immune responses in Ross population (Pimmune responses to Infectious bursal disease vaccine, and allele 263bp was significantly correlated with elevated antibody titer against Newcastle disease vaccine. Results obtained from this study confirmed the important role of MHC as a candidate gene marker for immune responses that could be used in genetic improvement of disease-resistant traits and resource conservation in broiler population. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. The GATA factor Serpent is required for the onset of the humoral immune response in Drosophila embryos

    Science.gov (United States)

    Tingvall, Tove Önfelt; Roos, Erik; Engström, Ylva

    2001-01-01

    Innate immunity in Drosophila is characterized by the inducible expression of antimicrobial peptides. We have investigated the development and regulation of immune responsiveness in Drosophila embryos after infection. Immune competence, as monitored by the induction of Cecropin A1-lacZ constructs, was observed first in the embryonic yolk. This observation suggests that the yolk plays an important role in the humoral immune response of the developing embryo by synthesizing antimicrobial peptides. Around midembryogenesis, the response in the yolk was diminished. Simultaneously, Cecropin expression became inducible in a large number of cells in the epidermis, demonstrating that late-stage embryos can synthesize their own antibiotics in the epidermis. This production likely serves to provide the hatching larva with an active antimicrobial barrier and protection against systemic infections. Cecropin expression in the yolk required the presence of a GATA site in the promoter as well as the involvement of the GATA-binding transcription factor Serpent (dGATAb). In contrast, neither the GATA site nor Serpent were necessary for Cecropin expression in the epidermis. Thus, the inducible immune responses in the yolk and in the epidermis can be uncoupled and call for distinct sets of transcription factors. Our data suggest that Serpent is involved in the distinction between a systemic response in the yolk/fat body and a local immune response in epithelial cells. In addition, the present study shows that signal transduction pathways controlling innate and epithelial defense reactions can be dissected genetically in Drosophila embryos. PMID:11274409

  8. Impaired humoral immunity and tolerance in K14-VEGFR-3-Ig mice that lack dermal lymphatic drainage.

    Science.gov (United States)

    Thomas, Susan N; Rutkowski, Joseph M; Pasquier, Miriella; Kuan, Emma L; Alitalo, Kari; Randolph, Gwendalyn J; Swartz, Melody A

    2012-09-01

    Lymphatic vessels transport interstitial fluid, soluble Ag, and immune cells from peripheral tissues to lymph nodes (LNs), yet the contribution of peripheral lymphatic drainage to adaptive immunity remains poorly understood. We examined immune responses to dermal vaccination and contact hypersensitivity (CHS) challenge in K14-VEGFR-3-Ig mice, which lack dermal lymphatic capillaries and experience markedly depressed transport of solutes and dendritic cells from the skin to draining LNs. In response to dermal immunization, K14-VEGFR-3-Ig mice produced lower Ab titers. In contrast, although delayed, T cell responses were robust after 21 d, including high levels of Ag-specific CD8+ T cells and production of IFN-γ, IL-4, and IL-10 upon restimulation. T cell-mediated CHS responses were strong in K14-VEGFR-3-Ig mice, but importantly, their ability to induce CHS tolerance in the skin was impaired. In addition, 1-y-old mice displayed multiple signs of autoimmunity. These data suggest that lymphatic drainage plays more important roles in regulating humoral immunity and peripheral tolerance than in effector T cell immunity.

  9. Humoral immune responses against gonadotropin releasing hormone elicited by immunization with phage-peptide constructs obtained via phage display.

    Science.gov (United States)

    Samoylov, Alexandre; Cochran, Anna; Schemera, Bettina; Kutzler, Michelle; Donovan, Caitlin; Petrenko, Valery; Bartol, Frank; Samoylova, Tatiana

    2015-12-20

    Phage display is based on genetic engineering of phage coat proteins resulting in fusion peptides displayed on the surface of phage particles. The technology is widely used for generation of phages with novel characteristics for numerous applications in biomedicine and far beyond. The focus of this study was on development of phage-peptide constructs that stimulate production of antibodies against gonadotropin releasing hormone (GnRH). Phage-peptide constructs that elicit production of neutralizing GnRH antibodies can be used for anti-fertility and anti-cancer applications. Phage-GnRH constructs were generated via selection from a phage display library using several types of GnRH antibodies as selection targets. Such phage constructs were characterized for sequence similarities to GnRH peptide and frequency of their occurrence in the selection rounds. Five of the constructs with suitable characteristics were tested in mice as a single dose 5×10(11) virions (vir) vaccine and were found to be able to stimulate production of GnRH-specific antibodies, but not to suppress testosterone (indirect indicator of GnRH antibody neutralizing properties). Next, one of the constructs was tested at a higher dose of 2×10(12) vir per mouse in combination with a poly(lactide-co-glycolide) (PLGA)-based adjuvant. This resulted in multifold increase in GnRH antibody production and significant reduction of serum testosterone, indicating that antibodies produced in response to the phage-GnRH immunization possess neutralizing properties. To achieve optimal immune responses for desired applications, phage-GnRH constructs can be modified with respect to flanking sequences of GnRH-like peptides displayed on phage. Anticipated therapeutic effects also might be attained using optimized phage doses, a combination of several constructs in a single treatment, or application of adjuvants and advanced phage delivery systems. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Immunosuppressive activity of a polychlorinated biphenyl preparation on the humoral immune response in guinea pigs

    NARCIS (Netherlands)

    Vos, J.G.; Roij, Th. de

    Three groups of 12 female albino guinea pigs were fed 0, 10 and 50 ppm Aroclor 1260 (PCB) for 8 wk. In half of the animals a function test of the immunological system was carried out: tetanus toxoid injection was used to study the humoral response. At the end of the experiment cellulose acetate

  11. Targeting Localized Immune Suppression Within the Tumor Through Repeat Cycles of Immune Cell-oncolytic Virus Combination Therapy

    OpenAIRE

    Thorne, Stephen H; Liang, Wenchun; Sampath, Padma; Schmidt, Tobi; Sikorski, Rachel; Beilhack, Andreas; Contag, Christopher H.

    2010-01-01

    A major limitation to the use of immunotherapy in the treatment of cancer has been the localized immune suppressive environment within the tumor. Although there is evidence that tumor-selective (oncolytic) viruses may help to overcome this immune suppression, a primary limitation to their use has been limited systemic delivery potential, especially in the face of antiviral immunity. We recently demonstrated that tumor-trafficking immune cells can efficiently deliver oncolytic viral therapies ...

  12. The Effect of Dietary Supplementation of Prebiotic and Probiotic on Performance, Humoral Immunity Responses and Egg Hatchability in Broiler Breeders

    Directory of Open Access Journals (Sweden)

    Hajati H

    2014-01-01

    Full Text Available In this experiment, the influence of prebiotic and probiotic supplementation in the broiler breeder diets on body weight, mortality, feed intake, egg production, hatchability and humoral immunity response was investigated. A total number of 13140 female and 1260 male breeders (Cobb 500 with 26 wks of age were allocated to three treatments with six replicates (800 birds each replicate. Breeders were fed control basal diet, basal diet supplemented with prebiotic (mannan oligosaccharide or probiotic (Protexin® for 17 weeks. Body weight, feed intake and egg production were measured weekly during 26-40 wks of age. The hatchability of eggs was recorded on weeks 38, 39, and 40. Antibody production was recorded after 8 wks of prebiotic and probiotic supplementation. Prebiotic supplementation did not affect feed intake, the percentages of egg production and settable eggs percents. Prebiotic increased egg hatchability and reduced the percentages of infertile eggs, as well as dead embryo-in-shells. Antibody titers against influenza and reovirus were higher in prebiotic fed group, but there were no significant differences among the other blood antibody titers. Probiotic had no significant effect on the considered parameters. In conclusion, findings of present study showed that prebiotic improved egg hatchability and humoral immunity of broiler breeders.

  13. Dissection of SAP-dependent and SAP-independent SLAM family signaling in NKT cell development and humoral immunity.

    Science.gov (United States)

    Chen, Shasha; Cai, Chenxu; Li, Zehua; Liu, Guangao; Wang, Yuande; Blonska, Marzenna; Li, Dan; Du, Juan; Lin, Xin; Yang, Meixiang; Dong, Zhongjun

    2017-02-01

    Signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) mutations in X-linked lymphoproliferative disease (XLP) lead to defective NKT cell development and impaired humoral immunity. Because of the redundancy of SLAM family receptors (SFRs) and the complexity of SAP actions, how SFRs and SAP mediate these processes remains elusive. Here, we examined NKT cell development and humoral immunity in mice completely deficient in SFR. We found that SFR deficiency severely impaired NKT cell development. In contrast to SAP deficiency, SFR deficiency caused no apparent defect in follicular helper T (TFH) cell differentiation. Intriguingly, the deletion of SFRs completely rescued the severe defect in TFH cell generation caused by SAP deficiency, whereas SFR deletion had a minimal effect on the defective NKT cell development in SAP-deficient mice. These findings suggest that SAP-dependent activating SFR signaling is essential for NKT cell selection; however, SFR signaling is inhibitory in SAP-deficient TFH cells. Thus, our current study revises our understanding of the mechanisms underlying T cell defects in patients with XLP. © 2017 Chen et al.

  14. Efficiency of recombinant bacille Calmette-Guérin in inducing humoral and cell mediated immunities against human immunodeficiency virus type 1 third variable domain in immunized mice.

    Science.gov (United States)

    Kim, Young Jae

    2011-01-01

    The third variable (V3) loop of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein has been intensively studied for AIDS vaccine development. Bacille Calmette-Guérin (BCG) is widely used to immunize against tuberculosis and has many advantages as a vaccine vehicle, such as low toxicity, adjuvant potential, low cost, and long-lasting immune-inducing capacity. This work was initiated to investigate the immunogenicity of recombinant BCG (rBCG-mV3) designed to express trimeric HIV-1 V3 loop (mV3) in rBCG-mV3-immunized animals. HIV-1 V3-concatamer was cloned into pMV261, a BCG-expression vector, and then rBCG-mV3 was constructed by introducing the recombinant plasmid (pMV-V3). The recombinant BCG was examined with regard to its expression of V3-concatamer and the genetic stability in vivo and in vitro. The immune responses induced by recombinant BCG were tested in immunized mice and guinea pigs. The rBCG-mV3 expressed detectable amounts of V3-concatamer when induced by single heat-shock. The recombinant BCG was genetically stable and maintained the introduced mV3 gene for several weeks. V3-specific antibodies were clearly detected 6 weeks after inoculation. The antibody titer rapidly increased after immunization up to 10 weeks, and then maintained for over 4 weeks. IgG2a was prevalent in the V3-specific antiserum. The recombinant BCG was also effective in inducing delayed-type hypersensitivity responses in the immunized guinea pigs. rBCG-immunized mice retained substantial amounts of V3-specific T cells in the spleen, even 5 months after the first immunization. Recombinant BCG-mV3 is very efficient in inducing humoral and long-lasting cell-mediated immunity against HIV-1 V3 in the immunized animals.

  15. The new normal: immunomodulatory agents against sepsis immune suppression.

    Science.gov (United States)

    Hutchins, Noelle A; Unsinger, Jacqueline; Hotchkiss, Richard S; Ayala, Alfred

    2014-04-01

    Sepsis is the leading cause of death among critically ill patients in intensive care units, and treatment options are limited. Therapies developed against the proinflammatory stage have failed clinically; therefore, new approaches that target the host immune response in sepsis are necessary. Increasing evidence suggests that a major pathophysiological event in sepsis is immune suppression, often resulting in secondary fungal, bacterial, or viral infections. Recent studies from animal sepsis models and patient samples suggest that cytokines such as interleukin-7 (IL-7), IL-15, granulocyte macrophage colony-stimulating factor (GM-CSF), as well as co-inhibitory molecule blockade, such as anti-programmed cell death receptor-1 (anti-PD-1) and anti-B and T lymphocyte attenuator (anti-BTLA), may have utility in alleviating the clinical morbidity associated with sustained sepsis. This review discusses some of these novel immunomodulatory agents and evaluates their potential use as therapeutics. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. PLGA, PLGA-TMC and TMC-TPP nanoparticles differentially modulate the outcome of nasal vaccination by inducing tolerance or enhancing humoral immunity.

    Science.gov (United States)

    Keijzer, Chantal; Slütter, Bram; van der Zee, Ruurd; Jiskoot, Wim; van Eden, Willem; Broere, Femke

    2011-01-01

    Development of vaccines in autoimmune diseases has received wide attention over the last decade. However, many vaccines showed limited clinical efficacy. To enhance vaccine efficacy in infectious diseases, biocompatible and biodegradable polymeric nanoparticles have gained interest as antigen delivery systems. We investigated in mice whether antigen-encapsulated PLGA (poly-lactic-co-glycolic acid), PLGA-TMC (N-trimethyl chitosan) or TMC-TPP (tri-polyphosphate) nanoparticles can also be used to modulate the immunological outcome after nasal vaccination. These three nanoparticles enhanced the antigen presentation by dendritic cells, as shown by increased in vitro and in vivo CD4(+) T-cell proliferation. However, only nasal PLGA nanoparticles were found to induce an immunoregulatory response as shown by enhanced Foxp3 expression in the nasopharynx associated lymphoid tissue and cervical lymph nodes. Nasal administration of OVA-containing PLGA particle resulted in functional suppression of an OVA-specific Th-1 mediated delayed-type hypersensitivity reaction, while TMC-TPP nanoparticles induced humoral immunity, which coincided with the enhanced generation of OVA-specific B-cells in the cervical lymph nodes. Intranasal treatment with Hsp70-mB29a peptide-loaded PLGA nanoparticles suppressed proteoglycan-induced arthritis, leading to a significant reduction of disease. We have uncovered a role for PLGA nanoparticles to enhance CD4(+) T-cell mediated immunomodulation after nasal application. The exploitation of this differential regulation of nanoparticles to modulate nasal immune responses can lead to innovative vaccine development for prophylactic or therapeutic vaccination in infectious or autoimmune diseases.

  17. Intranasal immunization with plasmid DNA encoding spike protein of SARS-coronavirus/polyethylenimine nanoparticles elicits antigen-specific humoral and cellular immune responses

    Directory of Open Access Journals (Sweden)

    Yang Moon-Sik

    2010-12-01

    Full Text Available Abstract Background Immunization with the spike protein (S of severe acute respiratory syndrome (SARS-coronavirus (CoV in mice is known to produce neutralizing antibodies and to prevent the infection caused by SARS-CoV. Polyethylenimine 25K (PEI is a cationic polymer which effectively delivers the plasmid DNA. Results In the present study, the immune responses of BALB/c mice immunized via intranasal (i.n. route with SARS DNA vaccine (pci-S in a PEI/pci-S complex form have been examined. The size of the PEI/pci-S nanoparticles appeared to be around 194.7 ± 99.3 nm, and the expression of the S mRNA and protein was confirmed in vitro. The mice immunized with i.n. PEI/pci-S nanoparticles produced significantly (P + cells found in PEI/pci-S vaccinated mice was elevated. Co-stimulatory molecules (CD80 and CD86 and class II major histocompatibility complex molecules (I-Ad were increased on CD11c+ dendritic cells in cervical lymph node from the mice after PEI/pci-S vaccination. The percentage of IFN-γ-, TNF-α- and IL-2-producing cells were higher in PEI/pci-S vaccinated mice than in control mice. Conclusion These results showed that intranasal immunization with PEI/pci-S nanoparticles induce antigen specific humoral and cellular immune responses.

  18. Enhancement of humoral immunity in mice by coupling pUCpGs10 and aluminium to the HCV recombinant immunogen

    Directory of Open Access Journals (Sweden)

    Zhan Na

    2011-11-01

    Full Text Available Abstract Aim To investigate the enhancement of humoral immunity when CpG ODN (cytidine phosphate guanosine oligodeoxynucleotides and aluminium adjuvants are complexed with the HCV (Hepatitis C virus recombinant immunogen in mice. Methods After immunizing Balb/c mice with the recombination HCV antigen adjuvanted with pUCpGs10 and/or aluminium(antigen+CpG+alum, antigen+CpG, antigen+alum, antigen+PBS, enzyme-linked immunosorbent assay (ELISA was used to measure the specific serum antibody titers of IgG, to determine the neutralization response to various peptide genotypes, and to determine the concentration of IL-6 and IL-10 in supernatants of in vitro cultured splenic lymphocytes. Enzyme-linked immunospot assay (ELISPOT was used to quantify the non-specific and specific splenic antibody-secreting cells (ASCs, and flow cytometry (FCM determined the ratio of different splenic lymphocytes. The serum of rabbits immunized with the recombinant pBVGST/HVR1 antigen immunoprecipitated the HCV isolated from 12 patients' serum. Results The sera antibody titers were 1:51200, 1:9051, 1:18102, 1:6400 respectively after the final immunization and demonstrated good neutralization responses to the six gene peptide containing 1a, 1b, 2a, 3a, 4a and 6a. The aluminum adjuvant increased the population of both specific ASCs (P +CD27+ (P +CD38+ splenic lymphocytes with the aluminum and pUCpGs10 adjuvant present compared to the control group(P Conclusions 1. The aluminum adjuvant induces a potent Th2-biased immune response by increasing both the populations of specific and total ASCs and the ratio of CD19+CD27+ cells. 2. The pUCpGs10 complexed with the aluminum adjuvant boosts the population of plasma cells and increase the efficiency of the immune response. 3. The two adjuvants have synergistic effects on humoral immunity. 4. The recombinant HVR1 protein has the possibility of generating broadly reactive anti-HVR1 antibody.

  19. Evaluation of specific humoral immune response in pigs vaccinated with cell culture adapted classical swine fever vaccine

    Directory of Open Access Journals (Sweden)

    Mrinal K. Nath

    2016-03-01

    Full Text Available Aim: To determine an efficient vaccination schedule on the basis of the humoral immune response of cell culture adapted live classical swine fever virus (CSFV vaccinated pigs and maternally derived antibody (MDA in piglets of vaccinated sows. Materials and Methods: A cell culture adapted live CSFV vaccine was subjected to different vaccination schedule in the present study. Serum samples were collected before vaccination (day 0 and 7, 14, 28, 42, 56, 180, 194, 208, 270, 284 and 298 days after vaccination and were analyzed by liquid phase blocking enzyme-linked immunosorbent assay. Moreover, MDA titre was detected in the serum of piglets at 21 and 42 days of age after farrowing of the vaccinated sows. Results: On 28 days after vaccination, serum samples of 83.33% vaccinated pigs showed the desirable level of antibody titer (log10 1.50 at 1:32 dilution, whereas 100% animals showed log10 1.50 at 1:32 dilution after 42 days of vaccination. Animals received a booster dose at 28 and 180 days post vaccination showed stable high-level antibody titre till the end of the study period. Further, piglets born from pigs vaccinated 1 month after conception showed the desirable level of MDA up to 42 days of age. Conclusion: CSF causes major losses in pig industry. Lapinised vaccines against CSFV are used routinely in endemic countries. In the present study, a cell culture adapted live attenuated vaccine has been evaluated. Based on the level of humoral immune response of vaccinated pigs and MDA titer in piglets born from immunized sows, it may be concluded that the more effective vaccination schedule for prevention of CSF is primary vaccination at 2 months of age followed by booster vaccination at 28 and 180 days post primary vaccination and at 1 month of gestation.

  20. Humoral immune response against native or {sup 60}Co irradiated venom and mucus from stingray Paratrygon aiereba

    Energy Technology Data Exchange (ETDEWEB)

    Thomazi, Gabriela Ortega Coelho; Alves, Glaucie Jussilane; Aires, Raquel da Silva; Turibio, Thompson de Oliveira; Rocha, Andre Moreira; Spencer, Patrick Jack; Nascimento, Nanci do, E-mail: 0916@prof.itpacporto.com.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Seibert, Carla Simone, E-mail: carlaseibert@yahoo.com [Universidade Federal do Tocantins (UFT), Porto Nacional, TO (Brazil)

    2015-07-01

    Poisonings and traumas caused by poisonous freshwater fish such as rays are considered a major public health problem and draw attention because of accidents involving these animals cause serious local symptoms and are disabling, keeping the victim away from work. The therapy of these cases is based only on the symptoms of patients, which implies in its low efficiency, causing suffering for the victims. This study aims to evaluate and compare the humoral immune response in animals inoculated with native or {sup 60}Co irradiated Paratrygon aiereba venom and mucus. Ionizing radiation has proven to be an excellent tool to decrease the toxicity of venoms and isolated toxins. The mucus and venom samples of P. aiereba were irradiated using gamma rays from a {sup 60}Co source. Animals models were immunized with the native or irradiated mucus or venom. The assays were conducted to assess the production of antibodies by the immunized animals using enzyme immunoassay and western blotting. Preliminary results show the production of antibodies by the immunized animals. The resulting sera were also checked for antigenic cross- reactivity between venom and mucus, demonstrating the potential of mucus as an antigen for serum production for the specific treatment for accidents by stingrays. However, it is essential to carry out further tests in order to verify the neutralization of the toxin by antibodies formed by animals. (author)

  1. Critical role of SAP in progression and reactivation but not maintenance of T cell-dependent humoral immunity.

    Science.gov (United States)

    Zhong, Ming-Chao; Veillette, André

    2013-03-01

    Signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) is a small adaptor molecule mutated in X-linked lymphoproliferative disease, a human immunodeficiency. SAP plays a critical role in the initiation of T cell-dependent B cell responses leading to germinal center reaction, the production of high-affinity antibodies, and B cell memory. However, whether SAP has a role in these responses beyond their initiation is not known. It is important to address this matter not only for mechanistic reasons but also because blockade of the SAP pathway is being contemplated as a means to treat autoimmune diseases in humans. Using an inducibly SAP deficient mouse, we found that SAP was required not only for the initiation but also for the progression of primary T cell-driven B cell responses to haptens. It was also necessary for the reactivation of T cell-dependent B cell immunity during secondary immune responses. These activities consistently correlated with the requirement of SAP for full expression of the lineage commitment factor Bcl-6 in follicular T helper (T(FH)) cells. However, once memory B cells and long-lived antibody-secreting cells were established, SAP became dispensable for maintaining T cell-dependent B cell responses. Thus, SAP is pivotal for nearly all phases, but not for maintenance, of T cell-driven B cell humoral immunity. These findings may have implications for the treatment of immune disorders by targeting the SAP pathway.

  2. Loss of Humoral and Cellular Immunity to Invasive Nontyphoidal Salmonella during Current or Convalescent Plasmodium falciparum Infection in Malawian Children.

    Science.gov (United States)

    Nyirenda, Tonney S; Nyirenda, James T; Tembo, Dumizulu L; Storm, Janet; Dube, Queen; Msefula, Chisomo L; Jambo, Kondwani C; Mwandumba, Henry C; Heyderman, Robert S; Gordon, Melita A; Mandala, Wilson L

    2017-07-01

    Invasive nontyphoidal Salmonella (iNTS) infections are commonly associated with Plasmodium falciparum infections, but the immunologic basis for this linkage is poorly understood. We hypothesized that P. falciparum infection compromises the humoral and cellular immunity of the host to NTS, which increases the susceptibility of the host to iNTS infection. We prospectively recruited children aged between 6 and 60 months at a Community Health Centre in Blantyre, Malawi, and allocated them to the following groups; febrile with uncomplicated malaria, febrile malaria negative, and nonfebrile malaria negative. Levels of Salmonella enterica serovar Typhimurium-specific serum bactericidal activity (SBA) and whole-blood bactericidal activity (WBBA), complement C3 deposition, and neutrophil respiratory burst activity (NRBA) were measured. Levels of SBA with respect to S Typhimurium were reduced in febrile P. falciparum-infected children (median, -0.20 log10 [interquartile range {IQR}, -1.85, 0.32]) compared to nonfebrile malaria-negative children (median, -1.42 log10 [IQR, -2.0, -0.47], P = 0.052). In relation to SBA, C3 deposition on S Typhimurium was significantly reduced in febrile P. falciparum-infected children (median, 7.5% [IQR, 4.1, 15.0]) compared to nonfebrile malaria-negative children (median, 29% [IQR, 11.8, 48.0], P = 0.048). WBBA with respect to S Typhimurium was significantly reduced in febrile P. falciparum-infected children (median, 0.25 log10 [IQR, -0.73, 1.13], P = 0.0001) compared to nonfebrile malaria-negative children (median, -1.0 log10 [IQR, -1.68, -0.16]). In relation to WBBA, S Typhimurium-specific NRBA was reduced in febrile P. falciparum-infected children (median, 8.8% [IQR, 3.7, 20], P = 0.0001) compared to nonfebrile malaria-negative children (median, 40.5% [IQR, 33, 65.8]). P. falciparum infection impairs humoral and cellular immunity to S Typhimurium in children during malaria episodes, which may explain the increased risk of iNTS observed in

  3. Galleria mellonella larvae are capable of sensing the extent of priming agent and mounting proportionatal cellular and humoral immune responses.

    Science.gov (United States)

    Wu, Gongqing; Xu, Li; Yi, Yunhong

    2016-06-01

    Larvae of Galleria mellonella are useful models for studying the innate immunity of invertebrates or for evaluating the virulence of microbial pathogens. In this work, we demonstrated that prior exposure of G. mellonella larvae to high doses (1×10(4), 1×10(5) or 1×10(6) cells/larva) of heat-killed Photorhabdus luminescens TT01 increases the resistance of larvae to a lethal dose (50 cells/larva) of viable P. luminescens TT01 infection administered 48h later. We also found that the changes in immune protection level were highly correlated to the changes in levels of cellular and humoral immune parameters when priming the larvae with different doses of heat-killed P. luminescens TT01. Priming the larvae with high doses of heat-killed P. luminescens TT01 resulted in significant increases in the hemocytes activities of phagocytosis and encapsulation. High doses of heat-killed P. luminescens TT01 also induced an increase in total hemocyte count and a reduction in bacterial density within the larval hemocoel. Quantitative real-time PCR analysis showed that genes coding for cecropin and gallerimycin and galiomycin increased in expression after priming G. mellonella with heat-killed P. luminescens TT01. All the immune parameters changed in a dose-dependent manner. These results indicate that the insect immune system is capable of sensing the extent of priming agent and mounting a proportionate immune response. Copyright © 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  4. Nonredundant roles of IL-10 and TGF-β in suppression of immune responses to hepatic AAV-factor IX gene transfer.

    Science.gov (United States)

    Hoffman, Brad E; Martino, Ashley T; Sack, Brandon K; Cao, Ou; Liao, Gongxian; Terhorst, Cox; Herzog, Roland W

    2011-07-01

    Hepatic gene transfer using adeno-associated viral (AAV) vectors has been shown to efficiently induce immunological tolerance to a variety of proteins. Regulatory T-cells (Treg) induced by this route suppress humoral and cellular immune responses against the transgene product. In this study, we examined the roles of immune suppressive cytokines interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) in the development of tolerance to human coagulation factor IX (hF.IX). Interestingly, IL-10 deficient C57BL/6 mice receiving gene transfer remained tolerant to hF.IX and generated Treg that suppressed anti-hF.IX formation. Effects of TGF-β blockade were also minor in this strain. In contrast, in C3H/HeJ mice, a strain known to have stronger T-cell responses against hF.IX, IL-10 was specifically required for the suppression of CD8(+) T-cell infiltration of the liver. Furthermore, TGF-β was critical for tipping the balance toward an regulatory immune response. TGF-β was required for CD4(+)CD25(+)FoxP3(+) Treg induction, which was necessary for suppression of effector CD4(+) and CD8(+) T-cell responses as well as antibody formation. These results demonstrate the crucial, nonredundant roles of IL-10 and TGF-β in prevention of immune responses against AAV-F.IX-transduced hepatocytes.

  5. The influence of Maloprim chemoprophylaxis on cellular and humoral immune responses to Plasmodium falciparum asexual blood stage antigens in schoolchildren living in a malaria endemic area of Mozambique

    DEFF Research Database (Denmark)

    Hogh, B; Thompson, R; Lobo, V

    1994-01-01

    We examined the impact of chemoprophylaxis on the cellular and humoral immune responses to polypeptides of the asexual Plasmodium falciparum blood stage antigens, the glutamate rich protein GLURP and Pf155/RESA, both of which in previous field studies have been identified as potentially protectiv...

  6. Humoral immune response against proteins E6 and E7 in cervical carcinoma patients positive for human papilloma virus type 16 during treatment and follow-up

    NARCIS (Netherlands)

    Baay, MFD; Duk, JM; Burger, MPM; de Bruijn, HWA; Stolz, E; Herbrink, P

    To investigate the humoral immune response to transforming proteins E6 and E7 of human papillomavirus type 16 before and after treatment and during follow-up, consecutive serum samples from 36 cervical cancer patients whose tumours were found to contain human papillomavirus type 16 DNA by use of the

  7. The in vivo effects of neutralizing antibodies against IFN-γ, IL-4, or IL-10 on the humoral immune response in young and aged mice

    NARCIS (Netherlands)

    Dobber, R.; Tielemans, M.; Nagelkerken, L.

    1995-01-01

    In the present study we investigated whether age-related changes in the composition and functional properties of murine CD4+ T cells are reflected in vivo by a changed humoral response to influenza vaccine in aged mice. After the primary immunization, the titers of influenza-specific IgM, IgG1,

  8. Humoral Immune Responses of White-tailed Deer (Odocoileus virginianus) to Mycobacterium bovis BCG Vaccination and Experimental Challenge with M. bovis

    Science.gov (United States)

    Monitoring serum antibody production kinetics to multiple mycobacterial antigens can be useful as a diagnostic tool for the detection of Mycobacterium bovis infection as well as for the characterization of disease progression and efficacy of intervention strategies in several species. Humoral immun...

  9. Discordance of epstein-barr virus (ebv) specific humoral and cellular immunity in patients with malignant lymphomas : Elevated antibody titers and lowered invitro lymphocyte-reactivity

    NARCIS (Netherlands)

    ten Napel, C. H. H.; The, T. Hauw; van Egten-Bijker, J; de Gast, G. C.; Halie, M. R.; Langenhuysen, M. M. A. C.

    1978-01-01

    The relationship between specific viral cellular and humoral immunity to the Epstein–Barr Virus (EBV) was investigated in thirty-one untreated patients with malignant lymphoma (ML) and sex- and age-matched controls. In vitro reactivity of peripheral blood lymphocytes to heatinactivated purified EBV,

  10. Capture of influenza by medullary dendritic cells via SIGN-R1 is essential for humoral immunity in draining lymph nodes

    DEFF Research Database (Denmark)

    Gonzalez, Santiago F.; Lukacs-Kornek, Veronika; Kuligowski, Michael P.

    2010-01-01

    A major pathway for B cell acquisition of lymph-borne particulate antigens relies on antigen capture by subcapsular sinus macrophages of the lymph node. Here we tested whether this mechanism is also important for humoral immunity to inactivated influenza virus. By multiple approaches, including m...

  11. The Mycoplasma hominis P120 membrane protein contains a 216 amino acid hypervariable domain that is recognized by the human humoral immune response

    DEFF Research Database (Denmark)

    Nyvold, Charlotte Guldborg; Birkelund, Svend; Christiansen, Gunna

    1997-01-01

    domain. Based on restriction endonuclease cleavage patterns of the hypervariable domain the 18 isolates could be divided into four cases. Reactivity with both mAb 26.7D and pAb 121 confirmed these classes. The hypervariable, but not the constant, part of P120 was recognized by the human humoral immune...

  12. PTIP chromatin regulator controls development and activation of B cell subsets to license humoral immunity in mice

    DEFF Research Database (Denmark)

    Su, Dan; Vanhee, Stijn; Soria, Rebeca

    2017-01-01

    of follicular B cells during germinal center formation, and normal signaling through the classical NF-κB pathway. Together with the previously identified role for PTIP in promoting sterile transcription at the Igh locus, the present results establish PTIP as a licensing factor for humoral immunity that acts......B cell receptor signaling and downstream NF-κB activity are crucial for the maturation and functionality of all major B cell subsets, yet the molecular players in these signaling events are not fully understood. Here we use several genetically modified mouse models to demonstrate that expression...... of the multifunctional BRCT (BRCA1 C-terminal) domain-containing PTIP (Pax transactivation domain-interacting protein) chromatin regulator is controlled by B cell activation and potentiates steady-state and postimmune antibody production in vivo. By examining the effects of PTIP deficiency in mice at various ages during...

  13. The effect of arginine dietary supplementation in broiler breeder hens on offspring humoral and cell-mediated immune responses

    Directory of Open Access Journals (Sweden)

    AE Murakami

    2014-06-01

    Full Text Available The influence of supplementing the diet of broiler breeder hens with arginine (Arg on their offspring's humoral and cell-mediated immune response was evaluated in two experiments. In experiments I and II, breeder hens were fed diets containing graded levels of Arg (0.943, 1.093, 1.243, 1.393 and 1.543% digestible Arg. In experiment I, the offspring was randomly grouped according to the treatment received by the breeder hens, with five levels of Arg in the maternal diet and six replicates, giving a total 30 experimental units. In experiment II, the offspring were grouped in accordance with the treatment received by the breeder hens; however, Arg was added to the starter diet (1.300, 1.450, 1.600, 1.750 and 1.900% digestible Arg and also the growing diet (1.150, 1.300, 1.450, 1.600 and 1.750% digestible Arg. Supplementation of the broiler breeder hen diet did not influence (p > 0.05 the development of the lymphoid organs (cloacal bursa, thymus and spleen of the offspring, whether their diet were supplemented or not. Nevertheless, greater weight and dimensions cloacal bursa were found in the supplemented offspring in comparison with the nonsupplemented offspring. Macrophage phagocytic activity was found to be unaffected (p > 0.05, independently of the Arg supplementation. The offspring fed with supplemented diets showed a linear reduction in the antibody titer against Newcastle Disease (p 0.05 by the breeder hen diet. This study concluded that supplementing the breeder hen diet with arginine is insufficient to improve the humoral and cellular immune response, requiring supplementation of the offspring diet.

  14. Humoral immune response to Plasmodium falciparum vaccine candidate GMZ2 and its components in populations naturally exposed to seasonal malaria in Ethiopia

    OpenAIRE

    Mamo, Hassen; Esen, Meral; Ajua, Anthony; Theisen, Michael; Mordm?ller, Benjamin; Petros, Beyene

    2013-01-01

    Background In Ethiopia, the general population is vulnerable to unpredictable epidemics of Plasmodium falciparum malaria. However, there is little information on the anti-malaria immune profile of the population in the endemic regions of the country. Methods The study was designed to investigate the nature of humoral immune response to malaria in two ethnic groups in two endemic localities: Shewa Robit in north, and Boditi in south Ethiopia which are characterized by varying levels of malaria...

  15. A multi-ingredient containing, proteins, carbohydrate and creatine does not attenuate humoral immune response or performance decrease compared to carbohydrate during resistance training

    OpenAIRE

    Ashrafi, Nadia; Seijo, Marcos; Pullen, Frank; Birthe V. Nielsen; Smith, Joshua; Wilkinson, Christian; Fu, Yue; Miller, Jack; Larumbe-Zabala, Eneko; Naclerio, Fernando

    2015-01-01

    Background: Nowadays, only carbohydrate has shown to be an effective countermeasure to exercise-induced immune dysfunction while the effect of protein remains controversial. The purpose of this study was to investigate the acute effects of a commercially available multi-nutrient supplement on performance and salivary markers of humoral immunity, following a bout of circuit resistance training in young athletes.\\ud \\ud Methods: Twelve recreationally resistance-trained males (age: 22 ± 1.4 year...

  16. Profiling of Measles-Specific Humoral Immunity in Individuals Following Two Doses of MMR Vaccine Using Proteome Microarrays

    Directory of Open Access Journals (Sweden)

    Iana H. Haralambieva

    2015-03-01

    Full Text Available Introduction: Comprehensive evaluation of measles-specific humoral immunity after vaccination is important for determining new and/or additional correlates of vaccine immunogenicity and efficacy. Methods: We used a novel proteome microarray technology and statistical modeling to identify factors and models associated with measles-specific functional protective immunity in 150 measles vaccine recipients representing the extremes of neutralizing antibody response after two vaccine doses. Results: Our findings demonstrate a high seroprevalence of antibodies directed to the measles virus (MV phosphoprotein (P, nucleoprotein (N, as well as antibodies to the large polymerase (L protein (fragment 1234 to 1900 AA. Antibodies to these proteins, in addition to anti-F antibodies (and, to a lesser extent, anti-H antibodies, were correlated with neutralizing antibody titer and/or were associated with and predictive of neutralizing antibody response. Conclusion: Our results identify antibodies to specific measles virus proteins and statistical models for monitoring and assessment of measles-specific functional protective immunity in vaccinated individuals.

  17. Effect of different levels of dietary sweet orange (Citrus sinensis) peel extract on humoral immune system responses in broiler chickens.

    Science.gov (United States)

    Pourhossein, Zohreh; Qotbi, Ali Ahmad Alaw; Seidavi, Alireza; Laudadio, Vito; Centoducati, Gerardo; Tufarelli, Vincenzo

    2015-01-01

    This experiment was conducted to evaluate the effects of different levels of sweet orange (Citrus sinensis) peel extract (SOPE) on humoral immune system responses in broiler chickens. Three hundred 1-day broilers (Ross-308) were randomly allocated to treatments varying in supplemental SOPE added in the drinking water. The experimental groups consisted of three treatments fed for 42 days as follows: a control treatment without feed extract, a treatment containing 1000 ppm of SOPE and a treatment containing 1250 ppm of SOPE. All treatments were isocaloric and isonitrogenous. Broilers were vaccinated with Newcastle disease virus (NDV), avian influenza (AI), infectious bursal disease (IBD) and infectious bronchitis virus (IBV) vaccines. Antibody titer response to sheep red blood cells (SRBC) was higher in the group fed 1250 ppm of SOPE (P < 0.05) as well as for immunoglobulin G (IgG) and IgM. Similarly, antibody titer responses to all vaccines were constantly elevated (P < 0.05) by SOPE enrichment in a dose-dependent manner. Relative weights of spleen and bursa of Fabricius were unaffected by treatments. Dietary SOPE supplementation may improve the immune response and diseases resistance, indicating that it can constitute a useful additive in broiler feeding. Thus, supplying SOPE in rations may help to improve relative immune response in broiler chickens. © 2014 Japanese Society of Animal Science.

  18. 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 ...

  19. 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

    2015-01-01

    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

  20. Humoral immunity through immunoglobulin M protects mice from an experimental actinomycetoma infection by Nocardia brasiliensis.

    Science.gov (United States)

    Salinas-Carmona, Mario C; Pérez-Rivera, Isabel

    2004-10-01

    An experimental model of infection with Nocardia brasiliensis, used as an example of a facultative intracellular pathogen, was tested. N. brasiliensis was injected into the rear foot pads of BALB/c mice to establish an infection. Within 30 days, infected animals developed a chronic actinomycetoma infection. Batch cultures of N. brasiliensis were used to purify P61, P38, and P24 antigens; P61 is a catalase, and P38 is a protease with strong caseinolytic activity. Active and passive immunizations of BALB/c mice with these three purified soluble antigens were studied. Protection was demonstrated for actively immunized mice. However, immunity lasted only 30 days. Other groups of immunized mice were bled at different times, and their sera were passively transferred to naive recipients that were then infected with N. brasiliensis. Sera collected 5, 6, and 7 days after donor immunization conferred complete, long-lasting protection. The protective effect of passive immunity decreased when sera were collected 2 weeks after donor immunization. However, neither the early sera (1-, 2-, and 3-day sera) nor the later sera (30- or 45-day sera) prevented the infection. Hyperimmune sera with the highest levels of immunoglobulin G (IgG) to N. brasiliensis antigens did not protect at all. The antigens tested induced two IgM peaks. The first peak was present 3 days after immunization but was not antigen specific and did not transfer protection. The second peak was evident 7 days after immunization, was an IgM response, was antigen specific, and conferred protection. This results clearly demonstrate that IgM antibodies protect the host against a facultative intracellular bacterium.

  1. Limited ability of humoral immune responses in control of viremia during infection with SIVsmmD215 strain

    Energy Technology Data Exchange (ETDEWEB)

    Ribiero, Ruy M [Los Alamos National Laboratory

    2009-01-01

    To investigate the impact of humoral immunity on SIV replication, 11 rhesus macaques (RMs) were inoculated with the neutralization-sensitive strain SIVsmmD215. Seven RMs were treated every three weeks, with 50 mglkg of an anti-CD20 antibody (Rituxan, gift from Genentech) starting from day -7 p.i., as follows: four RMs were treated for two months, and three were treated for five months. The remaining four RMs were used as controls. Three RMs were completely depleted of CD20 cells. Four RMs only partially depleted CD20 cells in the LNs and intestine. The efficacy of tissue CD20 depletion predicted the ablation of antibody production, with SIVsmm seroconversion being delayed in the animals with complete tissue CD20 depletion, and neutralizing antibody production being significantly delayed and at low levels in all CD20-depleted RMs. There was no significant difference in acute or chronic VLs between CD20-depleted RMs and control monkeys, with a tendency for lower set-point VLs in CD20-depleted RMs. At 6 weeks p.i., cellular immune responses were significantly stronger in CD20 depleted RMs than in controls. After two years p.i., there was no significant difference in survival between CD20-depleted and control RMs. We concluded that CD20 depletion plays no significant role in the control of SIV replication or disease progression in SIVsmmD215-infected RMs.

  2. Humoral immunity in tuberculin skin test anergy and its role in high-risk persons exposed to active tuberculosis

    Science.gov (United States)

    Encinales, Liliana; Zuñiga, Joaquin; Yunis, Maria; Granados-Montiel, Julio; Granados, Julio; Almeciga, Ingrid; Clavijo, Olga; Awad, Carlos; Collazos, Vilma; Vargas-Rojas, María Inés; Bañales-Mendez, José Luis; Vazquez-Castañeda, Lilia; Stern, Joel N.; Romero, Viviana; Frindkis-Hareli, Masha; Terreros, Daniel; Fernandez-Viña, Marcelo; Yunis, Edmond J.

    2009-01-01

    The most common test to identify latent tuberculosis is the Tuberculin skin test that detects T cell responses of delayed type hypersensitivity type IV. Since it produces false negative reactions in active tuberculosis or in high-risk persons exposed to tuberculosis patients as shown in this report, we studied antibody profiles to explain the anergy of such responses in high-risk individuals without active infection. Our results showed that humoral immunity against Tuberculin, regardless of the result of the Tuberculin skin test is important for protection from active tuberculosis and that the presence of high antibody titers is a more reliable indicator of infection latency suggesting that latency can be based on the levels of antibodies together with in vitro proliferation of peripheral blood mononuclear cells in the presence of the purified protein derivative. Importantly, anti-Tuberculin IgG antibody levels mediate the anergy described herein, which could also prevent reactivation of disease in high-risk individuals with high antibody titers. Such IgG Tuberculin antibodies were also found associated with blocking and/or stimulation of in vitro cultures of PBMC with Tuberculin. In this regard, future studies need to establish if immune responses to Mycobacterium tuberculosis can generate a broad spectrum of reactions either toward Th1 responses favoring stimulation by cytokines or by antibodies and those toward diminished responses by Th2 cytokines or blocking by antibodies; possibly involving mechanisms of antibody dependent protection from Mtb by different subclasses of IgG. PMID:20004475

  3. Humoral immunity 10 years after booster immunization with an adolescent and adult formulation combined tetanus, diphtheria, and 5-component acellular pertussis vaccine.

    Science.gov (United States)

    Tomovici, A; Barreto, L; Zickler, P; Meekison, W; Noya, F; Voloshen, T; Lavigne, P

    2012-03-30

    Persistence of antibodies after a single dose of Tdap vaccine (tetanus, diphtheria, and 5-component acellular pertussis vaccine) was evaluated in a follow-up study of adolescents (N=324) and adults (N=644) who had received Tdap in earlier clinical trials. Outcome measures were seroprotection (tetanus and diphtheria) or seropositivity (pertussis) and geometric mean concentrations. Humoral immune responses to all antigens were robust 1 month after initial immunization, decreased at subsequent measurements, but continued to exceed pre-immunization levels 1, 3, 5, and 10 years later. Protective levels of diphtheria and tetanus antitoxin persisted in 99.3% of adolescents 10 years after a booster dose of Tdap. Seropositivity to 1 or more pertussis antigens also persisted in most adolescents for 10 years. Although tetanus antitoxin responses were similar in adults to those observed in adolescents, diphtheria antitoxin titers were lower, reflecting the fact that a smaller proportion of adults had received diphtheria toxoid in the previous 10 years compared to adolescents. These data will contribute to the selection of the optimal interval for repeat doses of Tdap. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. The role of metalloproteinase ADAM17 in regulating ICOS ligand-mediated humoral immune responses.

    Science.gov (United States)

    Marczynska, Joanna; Ozga, Aleksandra; Wlodarczyk, Agnieszka; Majchrzak-Gorecka, Monika; Kulig, Paulina; Banas, Magdalena; Michalczyk-Wetula, Dominika; Majewski, Pawel; Hutloff, Andreas; Schwarz, Jeanette; Chalaris, Athena; Scheller, Jürgen; Rose-John, Stefan; Cichy, Joanna

    2014-09-15

    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 cells. Shedding is largely attributed to a family of a disintegrin and metalloprotease domain (ADAM) metalloproteases, including ADAM17. Although ADAM17 is well known to contribute to the innate immune response, mainly by releasing TNF-α, much less is known about whether/how this metalloprotease regulates adaptive immunity. To determine whether ADAM17 contributes to regulating adaptive immune responses, we took advantage of ADAM17 hypomorphic (ADAM17(ex/ex)) mice, in which ADAM17 expression is reduced by 90-95% compared with wild-type littermates. In this study, we show that that ADAM17 deficiency results in spleen and lymph node enlargement, as well as increased levels of Ag-specific class-switched Ig production following immunization with OVA together with anti-CD40 mAbs and polyinosinic-polycytidylic acid. Moreover, we demonstrate that the costimulatory ligand ICOS ligand (ICOSL) is selectively downregulated on the surface of B cells in an ADAM17-specific manner, although it is not proteolitically processed by recombinant ADAM17 in vitro. Finally, we show that higher cell surface levels of ICOSL in ADAM17(ex/ex) mice may contribute to the development of excessive Ab responses. Therefore, our data suggest a functional link between ADAM17 and ICOSL in controlling adaptive immune responses. Copyright © 2014 by The American Association of Immunologists, Inc.

  5. Immune activation alters cellular and humoral responses to yellow fever 17D vaccine.

    Science.gov (United States)

    Muyanja, Enoch; Ssemaganda, Aloysius; Ngauv, Pearline; Cubas, Rafael; Perrin, Helene; Srinivasan, Divya; Canderan, Glenda; Lawson, Benton; Kopycinski, Jakub; Graham, Amanda S; Rowe, Dawne K; Smith, Michaela J; Isern, Sharon; Michael, Scott; Silvestri, Guido; Vanderford, Thomas H; Castro, Erika; Pantaleo, Giuseppe; Singer, Joel; Gillmour, Jill; Kiwanuka, Noah; Nanvubya, Annet; Schmidt, Claudia; Birungi, Josephine; Cox, Josephine; Haddad, Elias K; Kaleebu, Pontiano; Fast, Patricia; Sekaly, Rafick-Pierre; Trautmann, Lydie; Gaucher, Denis

    2014-07-01

    Defining the parameters that modulate vaccine responses in African populations will be imperative to design effective vaccines for protection against HIV, malaria, tuberculosis, and dengue virus infections. This study aimed to evaluate the contribution of the patient-specific immune microenvironment to the response to the licensed yellow fever vaccine 17D (YF-17D) in an African cohort. We compared responses to YF-17D in 50 volunteers in Entebbe, Uganda, and 50 volunteers in Lausanne, Switzerland. We measured the CD8+ T cell and B cell responses induced by YF-17D and correlated them with immune parameters analyzed by flow cytometry prior to vaccination. We showed that YF-17D-induced CD8+ T cell and B cell responses were substantially lower in immunized individuals from Entebbe compared with immunized individuals from Lausanne. The impaired vaccine response in the Entebbe cohort associated with reduced YF-17D replication. Prior to vaccination, we observed higher frequencies of exhausted and activated NK cells, differentiated T and B cell subsets and proinflammatory monocytes, suggesting an activated immune microenvironment in the Entebbe volunteers. Interestingly, activation of CD8+ T cells and B cells as well as proinflammatory monocytes at baseline negatively correlated with YF-17D-neutralizing antibody titers after vaccination. Additionally, memory T and B cell responses in preimmunized volunteers exhibited reduced persistence in the Entebbe cohort but were boosted by a second vaccination. Together, these results demonstrate that an activated immune microenvironment prior to vaccination impedes efficacy of the YF-17D vaccine in an African cohort and suggest that vaccine regimens may need to be boosted in African populations to achieve efficient immunity. Registration is not required for observational studies. This study was funded by Canada's Global Health Research Initiative, Defense Threat Reduction Agency, National Institute of Allergy and Infectious Diseases

  6. Cell-mediated and humoral immune responses to chlamydial antigens in guinea pigs infected ocularly with the agent of guinea pig inclusion conjunctivitis.

    OpenAIRE

    Senyk, G; Kerlan, R; Stites, D P; Schanzlin, D.J.; Ostler, H. B.; Hanna, L; Keshishyan, H; Jawetz, E.

    1981-01-01

    Cell-mediated immune response and humoral response to chlamydial antigens were investigated in guinea pigs infected with the agent of guinea pig inclusion conjunctivitis (GPIC). Pronounced cell-mediated immune response to the homologous antigen, as well as to two other chlamydial antigens, 6BC (Chlamydia psittaci) and LB-1 (C. trachomatis), occurred in all infected animals. Cell-mediated immune response to GPIC, and to a lesser extent to 6BC and LB-1 as well, was enhanced with time after infe...

  7. Humoral immune response of Galleria mellonella after repeated infection with Bacillus thuringiensis.

    Science.gov (United States)

    Taszłow, Paulina; Vertyporokh, Lidiia; Wojda, Iwona

    2017-10-01

    The insect immune system relies on innate mechanisms only. However, there is an increasing number of data reporting that previous immune challenge with microbial elicitors or a low number of microorganisms can modulate susceptibility after subsequent lethal infection with the same or different pathogen. This phenomenon is called immune priming. Its biochemical and molecular mechanisms remain unravelled. Here we present that Galleria mellonella larvae that survived infection induced by intrahemocelic injection of a low dose of Bacillus thuringiensis were more resistant to re-injection of a lethal dose of the same bacteria but not other bacteria and fungi tested. This correlated with enhanced activity detected in full hemolymph as well as in separated hemolymph polypeptides. In addition, we observed differences in the hemolymph protein pattern between primed and non-primed larvae after infection with the lethal dose of B. thuringiensis. Expression of genes encoding inducible defence molecules was not enhanced in the primed larvae after the infection with the lethal dose of B. thuringiensis. It is likely that priming affects the turnover of immune related hemolymph proteins; hence, upon repeated contact, the immune response may be more ergonomic. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Oestrogen-induced suppression of collagen arthritis. II. Treatment of rats suppresses development of arthritis but does not affect the anti-type II collagen humoral response.

    Science.gov (United States)

    Larsson, P; Holmdahl, R

    1987-11-01

    Immunization of female Lewis rats with bovine type II collagen induces a severe polyarthritis with an incomplete penetration. Castration of the rats increased the incidence to 94% compared with 50% among sham-operated controls. When castrated female rats were implanted with silicone capsules containing beta-oestradiol they developed arthritis with a delayed onset and a decreased severity compared with castrated rats implanted with empty Silastic capsules. The levels of anti-type II collagen auto-antibodies were not affected by castration or oestrogen treatment. These findings show that oestrogen suppresses the development of collagen arthritis in rats and that this effect is mediated by mechanisms other than anti-type II collagen auto-antibodies.

  9. Humoral immunity of pregnant bitches, vaccinated with inactivated vaccine against parvoviral infections in dogs

    Directory of Open Access Journals (Sweden)

    Bacić Dragan

    2002-01-01

    Full Text Available Parvoviral infections are a big medical and economic problem, in particular in large dog-breeding facilities. Having in mind the manner in which this infection is spread (fecal-oral pathways, and the strong resistence of parvoviruses to the outer environment, general and immunoprophylaxis have a significant role in the control of this dangerous disease. This work examines the humoral immunological response of pregnant bitches, vaccinated with an inactivated vaccine against parvoviral infection in dogs. An experiment was performed on 10 pregnant bitches which were vaccinated on the 42nd day of gravidity with an inactivated vaccine, and an IHA test proved the lowest titer of antibodies was 1:1280, and the highest 1:20480. The titer of pregnant bitches before vaccination ranged from 1:80 to 1:320. These investigations indicate that puppies of vaccinated bitches receive the corresponding level of immunoglobulin through colostrum, and are protected from parvoviral infection in the first 6-7 weeks of life.

  10. Influence of chemotherapy for lymphoma in canine parvovirus DNA distribution and specific humoral immunity.

    Science.gov (United States)

    Elias, M A; Duarte, A; Nunes, T; Lourenço, A M; Braz, B S; Vicente, G; Henriques, J; Tavares, L

    2014-12-01

    In man, the combination of cancer and its treatment increases patients' susceptibility to opportunistic infections, due to immune system impairment. In veterinary medicine little information is available concerning this issue. In order to evaluate if a similar dysfunction is induced in small animals undergoing chemotherapy, we assessed the complete blood count, leukocytic, plasma and fecal canine parvovirus (CPV) viral load, and anti-CPV protective antibody titers, in dogs with lymphoma treated with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) protocol, before and during chemotherapy. There was no evidence of decreased immune response, either at admission or after two chemotherapy cycles, indicating that the previously established immunity against CPV was not significantly impaired, supporting the idea that immunosuppression as a result of hematopoietic neoplasms and their treatment in dogs requires further investigation and conclusions cannot be extrapolated from human literature. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. 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

    2011-01-01

    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

  12. UVB-induced immune suppression and infection with Schistosoma mansoni

    Energy Technology Data Exchange (ETDEWEB)

    Noonan, F.P.; Lewis, F.A. [George Washington Univ., Washington, DC (United States). School of Medicine]|[Biomedical Research Inst., Rockville, MD (United States)

    1995-01-01

    Irradiation with ultraviolet B (UVB, 290-320 nm) causes a systematic immunosuppression of cell-mediated immunity. The question of whether UV immunosuppression modulates the course of infectious diseases is important because UVB levels in sunlight are sufficient to predict significant UV-induced immunosuppression at most latitudes. We have investigated the effect of immunosuppressive doses of UVB on the disease caused by the helminth parasite Schistosoma mansoni. C57BL/6 mice were irradiated once or three times weekly over 60-80 days with UV from a bank of FS40 sunlamps. Each UV treatment consisted of an immunosuppressive UV dose, as determined by suppression of contact hypersensitivity to trinitrochlorobenzene, corresponding to about 15-30 min of noonday tropical sunlight exposure under ideal clear sky conditions. Cumulative UV doses were between 80 and 170 kJ/m{sup 2}. Worm and egg burdens, liver granuloma diameters and liver fibrosis showed minimal changes (< 20%) compared with parameters in unirradiated animals. Ultraviolet irradiation (a total of 55 kJ/m{sup 2} administered in six treatments) did not impair the resistance to rechallenge conferred by vaccination with {sup 60}Co-irradiated cercariae. We have observed a dichotomy between UV immnosuppression and both disease and vaccination in this helminth infection, in contrast to the effects of UVB shown in other infectious diseases. (author).

  13. Mechanisms of humoral immune response against Pseudomonas aeruginosa biofilm infection in cystic fibrosis

    DEFF Research Database (Denmark)

    Mauch, Renan Marrichi; Jensen, Peter Østrup; Moser, Claus

    2017-01-01

    P. aeruginosa chronic lung infection is the major cause of morbidity and mortality in patients with cystic fibrosis (CF), and is characterized by a biofilm mode of growth, increased levels of specific IgG antibodies and immune complex formation. However, despite being designed to combat...

  14. Efficient evaluation of humoral immune responses by the use of serum pools.

    Science.gov (United States)

    Sternbæk, Louise; Draborg, Anette H; Nielsen, Christoffer T; Jacobsen, Søren; Iversen, Line V; Troelsen, Lone; Theander, Elke; Houen, Gunnar

    2017-04-01

    Collection and testing of individual serum samples are often used in research to gain knowledge about e.g. the humoral response against bacteria or virus. This is a valid but time-consuming method and might be a waste of valuable serum samples for inefficient research. So far, no study has considered using serum pools as a quick and efficient screening method to confirm or deny hypotheses. We created serum pools from four different patient groups (systemic lupus erythematosus n=85, rheumatoid arthritis n=77, Sjögren's syndrome n=91, systemic sclerosis n=66) and one healthy control group (n=67). Each serum pool was analyzed using three well-known immunoassays: enzyme-linked immunosorbent assay (ELISA), line blot, and immunofluorescence microscopy (anti-nuclear antibody (ANA) screening). The presence of Epstein-Barr virus (EBV) EA/D-, EBNA-1-, VCA p23-, and gp350-directed antibodies was used to validate serum pools as an efficient tool for further investigations by comparison to previous findings in this area. The presence of EBV EA/D-, EBNA-1-, VCA p23-, and gp350-directed antibodies in each pool was consistent within the obtained ELISA and line blot results, as increased titers of IgG against the four antigens were found in all patient serum pools and also in individual sera regarding gp350. These results correspond to previous findings on individual samples from patients with these diseases. The presence of ANAs was observed in all four patient serum pools and not in the HC pool by both line blots and immunofluorescence microscopy, which corresponds with the expectations and further corroborate the application of serum pools for screenings. We developed and validated the use of serum pools that reliably and rapidly can confirm or deny hypotheses, which enables a more efficient research concentrating on the most evident factors. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Melatonin mediates photoperiod control of endocrine adaptations and humoral immunity in male Siberian hamsters.

    Science.gov (United States)

    Yellon, Steven M

    2007-09-01

    Effects of photoperiod are mediated by the pineal gland in male Siberian hamsters. The hypothesis that the pineal hormone melatonin mediates the effects of short days (SD) to blunt select humoral and endocrine functions was tested. In the first study, regressed testes were found in pineal-intact controls transferred from long days (LD) to SDs (16 hr to 8 hr light/day); the rise in antigen-induced serum immunoglobulin (Ig) M was blunted and serum cortisol concentrations elevated compared with long-day controls. These effects of short-day were blocked in pinealectomized males moved from long to SDs, but restored by melatonin treatments. In a second study, males in LD were exposed to constant light (LL) to abolish the nighttime melatonin rhythm. In hamsters in LL, melatonin induced testicular regression as in males in SDs. Large testes were present in vehicle-treated controls in LL and in males that remained in LDs. Antigen-induced increases in serum IgM in vehicle and melatonin treatment males in LL were intermediate between concentrations in long- or short-day controls and not significantly different from each other. However, serum cortisol was again elevated in hamsters in SDs or in LL when treated with melatonin compared with males in LL or LDs. These findings indicate that melatonin treatments mimicked the effects of SDs to regulate adaptive physiologic functions in hamsters lacking the nocturnal melatonin rhythm. Thus, the photoneuroendocrine mechanism regulating reproductive responses to photoperiod also mediates short-day effects on T cell-dependent B-cell antibody production and processes that regulate cortisol in circulation.

  16. STAT3-blocked whole-cell hepatoma vaccine induces cellular and humoral immune response against HCC

    Directory of Open Access Journals (Sweden)

    Qiuju Han

    2017-11-01

    Full Text Available Abstract Background Whole-cell tumor vaccines have shown much promise; however, only limited success has been achieved for the goal of eliciting robust tumor-specific T-cell responses. Methods Hepatocellular carcinoma (HCC cells, H22 and Hepa1–6, were modified by blocking the STAT3 signaling pathway with a STAT3 decoy oligodeoxynucleotide, and the immunogenicity and possibility of using these cell lysates as a vaccine were evaluated. Results STAT3-blocked whole HCC cell lysates inhibited tumor growth and tumorigenesis, and prolonged the survival of tumor-bearing mice. In addition, STAT3-blocked whole HCC cell lysates stimulated the activation of T cells and natural killer (NK cells, and enhanced the infiltration of cytotoxic CD8+ T cells in the tumor tissues. In addition, the maturation of dendritic cells (DCs was enhanced, which promoted the generation of immunological memory against HCC. Furthermore, secondary immune responses could be primed as soon as these immunized mice were challenged with HCC cells, accompanied by T cell and NK cell activation and infiltration. Additionally, immunization with this vaccine decreased the generation of Tregs and the production of TGF-β and IL-10. Importantly, STAT3-blocked whole HCC cell lysates prevented HCC-mediated exhaustion of T cells and NK cells, showing low expression of checkpoint molecules such as PD-1 and TIGIT on T cells and NK cells in the immunized mice. Conclusions The newly generated STAT3-blocked whole-cell HCC vaccine has potential for cancer cell vaccination.

  17. Comparative analysis of the humoral immunity of skin mucus from several marine teleost fish.

    Science.gov (United States)

    Guardiola, Francisco A; Cuesta, Alberto; Abellán, Emilia; Meseguer, José; Esteban, María A

    2014-09-01

    Fish skin mucus contains several immune substances that provide the first line of defence against a broad spectrum of pathogens although they are poorly studied to date. Terminal carbohydrate composition and levels of total IgM antibodies, several immune-related enzymes (lysozyme, peroxidase, alkaline phosphatase, esterases, proteases and antiproteases) as well as the bactericidal activity (against fish pathogenic Vibrio harveyi, Vibrio angillarum, Photobacterium damselae and non-pathogenic bacteria Escherichia coli, Bacillus subtilis, Shewanella putrefaciens) were identified and measured in the skin mucus of five marine teleosts: gilthead seabream (Sparus aurata), European sea bass (Dicentrarchus labrax), shi drum (Umbrina cirrosa), common dentex (Dentex dentex) and dusky grouper (Epinephelus marginatus). First, lectin binding results suggests that skin mucus contain, in order of abundance, N-acetylneuraminic acid, glucose, N-acetyl-glucosamine, N-acetyl-galactosamine, galactose and fucose residues. Second, results showed that while some immune activities were very similar in the studied fish (e.g. IgM and lysozyme activity) other such as protease, antiprotease, alkaline phosphatase, esterase and peroxidase activities varied depending on the fish species. High levels of peroxidase and protease activity were found in U. cirrosa respect to the values obtained in the other species while E. marginatus and S. aurata showed the highest levels of alkaline phosphatase and esterase activities, respectively. Moreover, skin mucus of S. aurata revealed higher bactericidal activity against pathogenic bacteria, contrarily, to what happened with non-pathogenic bacteria (E. coli, B. subtilis). Thus, study of the variations in the carbohydrate profile and immune-related components of the fish skin mucus could help to understand the fish resistance as well as the presence and distribution of pathogens and magnitude of infections, aspects that are of major importance for the

  18. Immunoblot detection of class-specific humoral immune response to outer membrane proteins isolated from Salmonella typhi in humans with typhoid fever.

    OpenAIRE

    ORTIZ,V; Isibasi, A.; García-Ortigoza, E; Kumate, J.

    1989-01-01

    The studies reported here were undertaken to assess the ability of the outer membrane proteins (OMPs) of Salmonella typhi to induce a humoral immune response in humans with typhoid fever. OMPs were isolated with the nonionic detergent Triton X-100 and were found to be contaminated with approximately 4% lipopolysaccharide. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis patterns showed protein bands with molecular size ranges from 17 to 70 kilodaltons; the major groups of proteins we...

  19. Cell-mediated and humoral immune responses to chlamydial antigens in guinea pigs infected ocularly with the agent of guinea pig inclusion conjunctivitis.

    Science.gov (United States)

    Senyk, G; Kerlan, R; Stites, D P; Schanzlin, D J; Ostler, H B; Hanna, L; Keshishyan, H; Jawetz, E

    1981-04-01

    Cell-mediated immune response and humoral response to chlamydial antigens were investigated in guinea pigs infected with the agent of guinea pig inclusion conjunctivitis (GPIC). Pronounced cell-mediated immune response to the homologous antigen, as well as to two other chlamydial antigens, 6BC (Chlamydia psittaci) and LB-1 (C. trachomatis), occurred in all infected animals. Cell-mediated immune response to GPIC, and to a lesser extent to 6BC and LB-1 as well, was enhanced with time after infection even without the re-inoculation of the infectious agent. Extensive cross-reactions among the three chlamydial antigens during the cell-mediated immune response appeared to be due to shared species-specific and group-reactive antigens. Serum antibody response was pronounced and uniform to GPIC; it was less marked to 6BC and LB-1, with fewer cross-reactions than seen in tests for cell-mediated immunity.

  20. Bifidobacterium bifidum OLB6378 Simultaneously Enhances Systemic and Mucosal Humoral Immunity in Low Birth Weight Infants: A Non-Randomized Study

    Directory of Open Access Journals (Sweden)

    Katsunori Tanaka

    2017-02-01

    Full Text Available Probiotic supplementation has been part of the discussion on methods to enhance humoral immunity. Administration of Bifidobacterium bifidum OLB6378 (OLB6378 reduced the incidence of late-onset sepsis in infants. In this non-randomized study, we aimed to determine the effect of administration of live OLB6378 on infants’ humoral immunity. Secondly, we tried to elucidate whether similar effects would be observed with administration of non-live OLB6378. Low birth weight (LBW infants weighing 1500–2500 g were divided into three groups: Group N (no intervention, Group L (administered live OLB6378 concentrate, and Group H (administered non-live OLB6378 concentrate. The interventions were started within 48 h after birth and continued until six months of age. Serum immunoglobulin G (IgG levels (IgG at one month/IgG at birth were significantly higher in Group L than in Group N (p < 0.01. Group H exhibited significantly higher serum IgG levels (p < 0.01 at one month of age and significantly higher intestinal secretory immunoglobulin A (SIgA levels (p < 0.05 at one and two months of age than Group N. No difference was observed in the mortality or morbidity between groups. Thus, OLB6378 administration in LBW infants enhanced humoral immunity, and non-live OLB6378, which is more useful as a food ingredient, showed a more marked effect than the viable bacteria.

  1. Autologous neutralizing humoral immunity and evolution of the viral envelope in the course of subtype B human immunodeficiency virus type 1 infection.

    Science.gov (United States)

    Bunnik, Evelien M; Pisas, Linaida; van Nuenen, Ad C; Schuitemaker, Hanneke

    2008-08-01

    Most human immunodeficiency virus type 1 (HIV-1)-infected individuals develop an HIV-specific neutralizing antibody (NAb) response that selects for escape variants of the virus. Here, we studied autologous NAb responses in five typical CCR5-using progressors in relation to viral NAb escape and molecular changes in the viral envelope (Env) in the period from seroconversion until after AIDS diagnosis. In sera from three patients, high-titer neutralizing activity was observed against the earliest autologous virus variants, followed by declining humoral immune responses against subsequent viral escape variants. Autologous neutralizing activity was undetectable in sera from two patients. Patients with high-titer neutralizing activity in serum showed the strongest positive selection pressure on Env early in infection. In the initial phase of infection, gp160 length and the number of potential N-linked glycosylation sites (PNGS) increased in viruses from all patients. Over the course of infection, positive selection pressure declined as the NAb response subsided, coinciding with reversions of changes in gp160 length and the number of PNGS. A number of identical amino acid changes were observed over the course of infection in the viral quasispecies of different patients. Our results indicate that although neutralizing autologous humoral immunity may have a limited effect on the disease course, it is an important selection pressure in virus evolution early in infection, while declining HIV-specific humoral immunity in later stages may coincide with reversion of NAb-driven changes in Env.

  2. Single-Dose Hepatitis A Immunization: 7.5-Year Observational Pilot Study in Nicaraguan Children to Assess Protective Effectiveness and Humoral Immune Memory Response.

    Science.gov (United States)

    Mayorga, Orlando; Bühler, Silja; Jaeger, Veronika K; Bally, Seraina; Hatz, Christoph; Frösner, Gert; Protzer, Ulrike; Van Damme, Pierre; Egger, Matthias; Herzog, Christian

    2016-11-15

     Universal 2-dose hepatitis A virus (HAV) vaccination of toddlers effectively controls hepatitis A. High vaccine costs, however, impede implementation in endemic countries. To test single-dose vaccination as a possible alternative, we initiated an observational, longitudinal study in Nicaragua, to assess protective effectiveness and-through challenge vaccination-humoral immune memory response.  After a 2003 serosurvey, 130 originally seronegative children received one dose of virosomal HAV vaccine in 2005, followed by yearly serological and clinical assessments until 2012. After 7.5 years, a vaccine booster was administered. Concurrent antibody screening of patients presenting with hepatitis symptoms documented persistent HAV circulation in the communities studied.  Between serosurvey and vaccination, 25 children contracted hepatitis A subclinically (>8000 mIU/mL anti-HAV). In the remaining 105 children, immunization resulted in anti-HAV levels of 17-572 mIU/mL. Based on the ≥15% annual infection risk, an estimated 60% of children were exposed to HAV encounters during follow-up. No child presented with hepatitis symptoms. Serological breakthrough infection (7106 mIU/mL) was documented in 1 child, representing an estimated protective effectiveness of 98.3% (95% confidence interval, 87.9-99.8). Boosting elicited an average 29.7-fold increase of anti-HAV levels.  In children living in hyperendemic settings, a single dose of virosomal HAV vaccine is sufficient to activate immune memory and may provide long-term protection. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  3. Probiotics and colostrum/milk differentially affect neonatal humoral immune responses to oral rotavirus vaccine.

    Science.gov (United States)

    Chattha, Kuldeep S; Vlasova, Anastasia N; Kandasamy, Sukumar; Esseili, Malak A; Siegismund, Christine; Rajashekara, Gireesh; Saif, Linda J

    2013-04-08

    Breast milk (colostrum [col]/milk) components and gut commensals play important roles in neonatal immune maturation, establishment of gut homeostasis and immune responses to enteric pathogens and oral vaccines. We investigated the impact of colonization by probiotics, Lactobacillus rhamnosus GG (LGG) and Bifidobacterium lactis Bb12 (Bb12) with/without col/milk (mimicking breast/formula fed infants) on B lymphocyte responses to an attenuated (Att) human rotavirus (HRV) Wa strain vaccine in a neonatal gnotobiotic pig model. Col/milk did not affect probiotic colonization in AttHRV vaccinated pigs. However, unvaccinated pigs fed col/milk shed higher numbers of probiotic bacteria in feces than non-col/milk fed colonized controls. In AttHRV vaccinated pigs, col/milk feeding with probiotic treatment resulted in higher mean serum IgA HRV antibody titers and intestinal IgA antibody secreting cell (ASC) numbers compared to col/milk fed, non-colonized vaccinated pigs. In vaccinated pigs without col/milk, probiotic colonization did not affect IgA HRV antibody titers, but serum IgG HRV antibody titers and gut IgG ASC numbers were lower, suggesting that certain probiotics differentially impact HRV vaccine responses. Our findings suggest that col/milk components (soluble mediators) affect initial probiotic colonization, and together, they modulate neonatal antibody responses to oral AttHRV vaccine in complex ways. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Effective humoral immunity against diphtheria and tetanus in patients with systemic lupus erythematosus or myasthenia gravis.

    Science.gov (United States)

    Csuka, Dorottya; Czirják, László; Hóbor, Renáta; Illes, Zsolt; Bánáti, Miklós; Rajczy, Katalin; Tordai, Attila; Füst, George

    2013-07-01

    Controversy exists about the effectiveness of vaccine-induced immune response in patients with immunoregulatory disorders. Our aim was to determine the antibody titers to diphtheria and tetanus in patients with either of two autoimmune diseases. 279 patients with SLE (205 females, aged 45.0 ± 13.8 years), 158 patients with myasthenia gravis (MG) (101 females, aged 55 ± 18.7 years) and 208 healthy subjects (122 females, aged 48 ± 14.6 years) were enrolled. Serum concentrations of diphtheria-antitoxin-IgG (A-DIPHTH) and tetanus-antitoxoid-IgG (A-TET) were determined with ELISA. Equal proportions of healthy subjects, as well as patients with SLE or MG exhibited proper antibody responses and immune protection against diphtheria and tetanus. In all three test groups, serum concentration of A-DIPHTH decreased significantly (p60-years-old) subjects. There were no significant differences among the groups in the age-related changes of A-TET and A-DIPHTH except that in diphtheria and tetanus infections in patients with SLE or MG is comparable to the healthy population. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. A recombinant varicella vaccine harboring a respiratory syncytial virus gene induces humoral immunity.

    Science.gov (United States)

    Murakami, Kouki; Matsuura, Masaaki; Ota, Megumi; Gomi, Yasuyuki; Yamanishi, Koichi; Mori, Yasuko

    2015-11-09

    The varicella-zoster virus (VZV) Oka vaccine strain (vOka) is highly efficient and causes few adverse events; therefore, it is used worldwide. We previously constructed recombinant vOka (rvOka) harboring the mumps virus gene. Immunizing guinea pigs with rvOka induced the production of neutralizing antibodies against the mumps virus and VZV. Here, we constructed recombinant vOka viruses containing either the respiratory syncytial virus (RSV) subgroup A fusion glycoprotein (RSV A-F) gene or RSV subgroup B fusion glycoprotein (RSV B-F) gene (rvOka-RSV A-F or rvOka-RSV B-F). Indirect immunofluorescence and Western blot analyses confirmed the expression of each recombinant RSV protein in virus-infected cells. Immunizing guinea pigs with rvOka-RSV A-F or rvOka-RSV B-F led to the induction of antibodies against RSV proteins. These results suggest that the current varicella vaccine genome can be used to generate custom-made vaccine vectors to develop the next generation of live vaccines. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Plasma-mediated immune suppression : a neonatal perspective

    NARCIS (Netherlands)

    Belderbos, Mirjam E.; Levy, Ofer; Meyaard, Linde; Bont, Louis

    Plasma is a rich mixture of immune regulatory factors that shape immune cell function. This immunomodulatory role of plasma is especially important in neonates. To maintain in utero feto-maternal tolerance and to allow for microbial colonization after birth, the neonatal immune system is biased

  7. Evaluation of Humoral Immunity, Cellular Immunity and Phagocytosis in Peripheral Blood of Major Thalassemia Patients Refered to Ahvaz Shafa Hospital

    Directory of Open Access Journals (Sweden)

    M. Ghafourian Boroujerdnia

    2011-10-01

    Full Text Available Introduction & Objective: Thalassemia is the most common genetic disorders in the world. These disorders are common in the Middle Estern countries containing Iran. It seems that factors like splenectomy, iron overload, frequent contacts with antigens during blood transfusion & using chelating agents cause severe disturbances to immune system. This study is done to evaluate the immune status in thalasemic patients refered to Ahvaz Shafa Hospital. Materials & Methods: This case- control study was done on 40 major thalassemic patients who had not the history of frequent bacterial and viral infections, splenectomy, using immunosuppressive drugs& patients with hepatitis, diabetes or other chronic diseases. Control group contained 31 healthy persons. Peripheral blood samples were collected from all participants. The last CBC and serum ferritin was taken from patient files. NBT test, evaluation of CD4, CD8, CD5 , CD20 markers with flowcytometry, and assessment of IgG, IgM, and IgA levels with nephlometry method carried out on peripheral blood samples of patient and control groups. Results: The percent of CD4, CD8 and CD5 markers and CD4/CD8 ratio had no significant difference between case & control groups. The percent of CD20 marker, and IgG , IgM & IgA levels were significantly higher in case group in comparison with control group. NBT test in all case and control groups were normal. There was no significant difference in serum ferritin, WBC count and percentage of lymphocytes and neutrophils among two groups. Conclusion: In major thalassemia patients, cellular immunity and phagocytosis are similar to normal individuals. CD4, CD8 and CD5 positive lymphocytes and CD4/CD8 ratio showed no difference between patients and normal groups. CD20 positive lymphocytes and IgM, IgG & IgA levels in patient group were significantly higher than normal control group. This can’t be due to viral or recurrent infections, because these patients were excluded from our

  8. 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.

  9. Lactoferrin accelerates reconstitution of the humoral and cellular immune response during chemotherapy-induced immunosuppression and bone marrow transplant in mice.

    Science.gov (United States)

    Artym, J; Zimecki, M; Kuryszko, J; Kruzel, M L

    2005-10-01

    Experimental evidence from previous studies supports the conclusion that orally administered lactoferrin (LF) restores the immune response in mice treated with a sublethal dose of cyclophosphamide (CP). The aim of this study was to elucidate potential benefit of LF in mice undergoing chemotherapy with busulfan (BU) and CP, followed by intravenous (i.v.) injection of bone marrow cells. CBA mice were treated orally with busulfan (4 mg/kg) for 4 consecutive days, followed by two daily doses of CP delivered intraperitoneally (i.p.) at a dose of 100 mg/kg and reconstituted next day with i.v. injection of 10(7) syngeneic bone marrow cells. One group of these mice was given LF in drinking water (0.5% solution). After treatment, mice were immunized with ovalbumin (OVA) to subsequently measure delayed type hypersensitivity responsiveness and with sheep red blood cells to determine humoral immunity by evaluation of splenic antibody-forming cells. As expected, both humoral and cellular immune responses of mice that were treated with these chemotherapeutic agents was markedly impaired. Here we report that this impairment was remarkably attenuated by oral administration of LF. Humoral immunity fell to levels that were 66-88% lower than that of untreated animals. Humoral immunity of LF-treated animals was equivalent to that of untreated mice within 1 month. Cellular immune responses were inhibited by chemotherapy treatment to a lesser degree, reaching levels that were approximately 50% lower than those of untreated animals. Again, LF mitigated this decrease, resulting in responses that were only slightly lower than those observed in untreated animals. Furthermore, when mice were given a lethal dose of BU (4 x 25 mg daily doses, i.p.) followed by a bone marrow transplant, LF caused enhanced lympho-, erythro-, and myelopoiesis in the bone marrow and appearance of transforming splenic lymphoblasts, similar to effects caused by administration of recombinant human granulocyte

  10. Cerebrospinal fluid humoral immunity in the differential diagnosis of multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Evanthia Bernitsas

    Full Text Available The diagnostic accuracy of cerebrospinal fluid oligoclonal bands (CSF-OCB detected by isoelectric focusing (IEF in patients with multiple sclerosis (MS was evaluated in our study.Three hundred and twenty-one patients with MS and other central nervous system (CNS immune mediated disorders were assessed (CIMD. Cerebrospinal fluid and matched serum samples were examined for the presence of OCB by IEF-IB (isoelectric focusing with immunoblotting.Isolated oligoclonal bands (ISO-OCB were the only predictor of MS diagnosis independent of age, gender and CSF-OCB. ISO-OCB ≥ 3.5 detected by IEF yielded a sensitivity of 98% and specificity of 87% in distinguishing MS from MS mimickers.For the neurologist, a score of ≥ 4 ISO-OCB supports the diagnosis of MS. On the other hand, ISO-OCB ≤3 favors CIMD. Further studies with larger population samples are warranted to confirm these findings.

  11. Role of Natural Immunomodulator (Aloe Vera in Cellular and Humoral Immune Responses

    Directory of Open Access Journals (Sweden)

    Ening Wiedosari

    2007-12-01

    Full Text Available Aloe vera belongs to a group of Liliaceae family plant and cultivated worldwide. It possesses acemannan (acetylated mannan, which has a significant pharmacological property. The acemannan has an immunomodulatory activity when administered to animals. The major immunomodulating effect includes the activation of immune effector cells, such as lymphocytes and macrophages, resulting in the production of cytokines, interleukin (IL-1, IL-6, IL-12 and tumor necrosis factor alpha (TNFα. In particular, this extract can modulate the differentiation capacity of CD4+T cells to mature into Th1 subsets and enhance the innate cytokine response. As a consequence, this extract will have a profound effect in controlling disease, caused by intracellular infectious agents (bacteria and viruses. However, further studies are needed to determine the immunomodulating effects of Aloe vera in multi-component extracts equivalent to what are being used commonly in traditional medicine.

  12. Intranasal Immunization with Pressure Inactivated Avian Influenza Elicits Cellular and Humoral Responses in Mice.

    Science.gov (United States)

    Barroso, Shana P C; Nico, Dirlei; Nascimento, Danielle; Santos, Ana Clara V; Couceiro, José Nelson S S; Bozza, Fernando A; Ferreira, Ana M A; Ferreira, Davis F; Palatnik-de-Sousa, Clarisa B; Souza, Thiago Moreno L; Gomes, Andre M O; Silva, Jerson L; Oliveira, Andréa C

    2015-01-01

    Influenza viruses pose a serious global health threat, particularly in light of newly emerging strains, such as the avian influenza H5N1 and H7N9 viruses. Vaccination remains the primary method for preventing acquiring influenza or for avoiding developing serious complications related to the disease. Vaccinations based on inactivated split virus vaccines or on chemically inactivated whole virus have some important drawbacks, including changes in the immunogenic properties of the virus. To induce a greater mucosal immune response, intranasally administered vaccines are highly desired as they not only prevent disease but can also block the infection at its primary site. To avoid these drawbacks, hydrostatic pressure has been used as a potential method for viral inactivation and vaccine production. In this study, we show that hydrostatic pressure inactivates the avian influenza A H3N8 virus, while still maintaining hemagglutinin and neuraminidase functionalities. Challenged vaccinated animals showed no disease signs (ruffled fur, lethargy, weight loss, and huddling). Similarly, these animals showed less Evans Blue dye leakage and lower cell counts in their bronchoalveolar lavage fluid compared with the challenged non-vaccinated group. We found that the whole inactivated particles were capable of generating a neutralizing antibody response in serum, and IgA was also found in nasal mucosa and feces. After the vaccination and challenge we observed Th1/Th2 cytokine secretion with a prevalence of IFN-γ. Our data indicate that the animals present a satisfactory immune response after vaccination and are protected against infection. Our results may pave the way for the development of a novel pressure-based vaccine against influenza virus.

  13. Intracellular B Lymphocyte Signalling and the Regulation of Humoral Immunity and Autoimmunity.

    Science.gov (United States)

    Taher, Taher E; Bystrom, Jonas; Ong, Voon H; Isenberg, David A; Renaudineau, Yves; Abraham, David J; Mageed, Rizgar A

    2017-04-29

    B lymphocytes are critical for effective immunity; they produce antibodies and cytokines, present antigens to T lymphocytes and regulate immune responses. However, because of the inherent randomness in the process of generating their vast repertoire of antigen-specific receptors, B cells can also cause diseases through recognizing and reacting to self. Therefore, B lymphocyte selection and responses require tight regulation at multiple levels and at all stages of their development and activation to avoid diseases. Indeed, newly generated B lymphocytes undergo rigorous tolerance mechanisms in the bone marrow and, subsequently, in the periphery after their migration. Furthermore, activation of mature B cells is regulated through controlled expression of co-stimulatory receptors and intracellular signalling thresholds. All these regulatory events determine whether and how B lymphocytes respond to antigens, by undergoing apoptosis or proliferation. However, defects that alter regulated co-stimulatory receptor expression or intracellular signalling thresholds can lead to diseases. For example, autoimmune diseases can result from altered regulation of B cell responses leading to the emergence of high-affinity autoreactive B cells, autoantibody production and tissue damage. The exact cause(s) of defective B cell responses in autoimmune diseases remains unknown. However, there is evidence that defects or mutations in genes that encode individual intracellular signalling proteins lead to autoimmune diseases, thus confirming that defects in intracellular pathways mediate autoimmune diseases. This review provides a synopsis of current knowledge of signalling proteins and pathways that regulate B lymphocyte responses and how defects in these could promote autoimmune diseases. Most of the evidence comes from studies of mouse models of disease and from genetically engineered mice. Some, however, also come from studying B lymphocytes from patients and from genome-wide association

  14. Intranasal Immunization with Pressure Inactivated Avian Influenza Elicits Cellular and Humoral Responses in Mice.

    Directory of Open Access Journals (Sweden)

    Shana P C Barroso

    Full Text Available Influenza viruses pose a serious global health threat, particularly in light of newly emerging strains, such as the avian influenza H5N1 and H7N9 viruses. Vaccination remains the primary method for preventing acquiring influenza or for avoiding developing serious complications related to the disease. Vaccinations based on inactivated split virus vaccines or on chemically inactivated whole virus have some important drawbacks, including changes in the immunogenic properties of the virus. To induce a greater mucosal immune response, intranasally administered vaccines are highly desired as they not only prevent disease but can also block the infection at its primary site. To avoid these drawbacks, hydrostatic pressure has been used as a potential method for viral inactivation and vaccine production. In this study, we show that hydrostatic pressure inactivates the avian influenza A H3N8 virus, while still maintaining hemagglutinin and neuraminidase functionalities. Challenged vaccinated animals showed no disease signs (ruffled fur, lethargy, weight loss, and huddling. Similarly, these animals showed less Evans Blue dye leakage and lower cell counts in their bronchoalveolar lavage fluid compared with the challenged non-vaccinated group. We found that the whole inactivated particles were capable of generating a neutralizing antibody response in serum, and IgA was also found in nasal mucosa and feces. After the vaccination and challenge we observed Th1/Th2 cytokine secretion with a prevalence of IFN-γ. Our data indicate that the animals present a satisfactory immune response after vaccination and are protected against infection. Our results may pave the way for the development of a novel pressure-based vaccine against influenza virus.

  15. Effects of two-stage weaning with nose flap devices applied to calves on cow body condition, calf performance, and calf humoral immune response.

    Science.gov (United States)

    Lippolis, K D; Ahola, J K; Mayo, C E; Fischer, M C; Callan, R J

    2016-02-01

    The effects of nose flap devices in calves before dam separation on cow BCS, pre- and postseparation calf performance, and humoral immune response were compared with traditional weaning. Primiparous and multiparous Angus and Hereford cows ( = 113) and their Angus, Hereford, and Angus × Hereford calves (179.4 ± 3.92 kg and 161 ± 22.7 d of age) were used. Cow-calf pairs were allocated to 1 of 2 treatments in a completely randomized design: 1) nose flap for 21 d before separation from the dam (NF) or 2) no nose flap for 21 d before separation from the dam (CON). Calves were separated from dams on d 0, and calves were placed in group feed-yard pens for 28 d. A subset ( = 75) of weaned calves were placed into 1 of 8 pens to evaluate DMI. Cow BCS was measured on d -21 and 56, and calves were given modified live vaccinations (d -21 and 1), challenged with ovalbumin (OVA; d 1), and weighed (d -21, 1, 7, 14, 21, and 28). In addition, blood samples were collected (d -21, 1, 14, and 28) to measure primary humoral immune response. Control calves tended to have greater BW on d 14 ( = 0.09) and 21 ( = 0.07) than NF calves, and CON calves had greater ( Serum neutralization tests for bovine viral diarrhea virus type 1 (BVDV-1) and bovine herpesvirus type 1 (BHV-1) were used to measure humoral response to a viral vaccination. Serum antibody titers to BVDV-1 for CON calves tended ( = 0.08) to be greater on d 1 and were greater ( Serum antibody titers for BHV-1 were greater ( serum BVDV-1 and BHV-1 titers, and humoral immune response to OVA were decreased in calves that received the nose flap treatment.

  16. Enhancement of humoral and cellular immune responses by monophosphoryl lipid A (MPLA) as an adjuvant to the rabies vaccine in BALB/c mice.

    Science.gov (United States)

    Hu, Xiaobo; Liu, Rui; Zhu, Naishuo

    2013-12-01

    The development of effective vaccines against the rabies virus could prevent infection with this fatal virus. However, the current rabies vaccine fails to provide a full range of protection because of its limited ability to elicit a cellular immune response and the requirement for repeat vaccination. Monophosphoryl lipid A (MPLA) is well known as a potent adjuvant to enhance immune responses against virus infection. Here we investigated the efficacy of MPLA as an adjuvant to improve the humoral and cellular immune responses to the rabies vaccine in BALB/c mice. Supplementation of the rabies vaccine with MPLA significantly accelerated the production of specific antibodies by 10 days compared to the original vaccines. Furthermore, MPLA promoted the induction of stronger cellular immune responses by the rabies vaccine, including the production of IL-4, IFN-γ and the activation of CD4⁺/CD8⁺ T cells, than those elicited without MPLA. Collectively, our findings indicated that MPLA enhances humoral and cellular immunity and is a promising adjuvant for the development of more effective rabies vaccines. Copyright © 2013 Elsevier GmbH. All rights reserved.

  17. Ascaridia galli infection influences the development of both humoral and cell-mediated immunity after Newcastle Disease vaccination in chickens.

    Science.gov (United States)

    Pleidrup, Janne; Dalgaard, Tina S; Norup, Liselotte R; Permin, Anders; Schou, Torben W; Skovgaard, Kerstin; Vadekær, Dorte F; Jungersen, Gregers; Sørensen, Poul; Juul-Madsen, Helle R

    2014-01-09

    Potent vaccine efficiency is crucial for disease control in both human and livestock vaccination programmes. Free range chickens and chickens with access to outdoor areas have a high risk of infection with parasites including Ascaridia galli, a gastrointestinal nematode with a potential influence on the immunological response to vaccination against other infectious diseases. The purpose of this study was to investigate whether A. galli infection influences vaccine-induced immunity to Newcastle Disease (ND) in chickens from an MHC-characterized inbred line. Chickens were experimentally infected with A. galli at 4 weeks of age or left as non-parasitized controls. At 10 and 13 weeks of age half of the chickens were ND-vaccinated and at 16 weeks of age, all chickens were challenged with a lentogenic strain of Newcastle disease virus (NDV). A. galli infection influenced both humoral and cell-mediated immune responses after ND vaccination. Thus, significantly lower NDV serum titres were found in the A. galli-infected group as compared to the non-parasitized group early after vaccination. In addition, the A. galli-infected chickens showed significantly lower frequencies of NDV-specific T cells in peripheral blood three weeks after the first ND vaccination as compared to non-parasitized chickens. Finally, A. galli significantly increased local mRNA expression of IL-4 and IL-13 and significantly decreased TGF-ß4 expression in the jejunum two weeks after infection with A. galli. At the time of vaccination (six and nine weeks after A. galli infection) the local expression in the jejunum of both IFN-? and IL-10 was significantly decreased in A. galli-infected chickens. Upon challenge with the NDV LaSota strain, viral genomes persisted in the oral cavity for a slightly longer period of time in A. galli-infected vaccinees as compared to non-parasitized vaccinees. However, more work is needed in order to determine if vaccine-induced protective immunity is impaired in A. galli

  18. Humor's healing potential.

    Science.gov (United States)

    Seaward, B L

    1992-04-01

    In the past three decades the medical world has begun to take more serious notice of the healing power of humor and the positive emotions associated with it. Humor and laughter are currently being employed by psychotherapists and other care givers as tools to promote and maintain health, as well as intervention and rehabilitation tools for a host of maladies and illnesses related to stress and life-style. Although this empirical medical approach is relatively new, the study of humor has revealed a complex psychological phenomenon. Senses of humor have been categorized in types associated with personality. Humor has many styles and can be found in almost any situation, on any occasion. Theories of humor include the superiority theory, the incongruity theory, the release/relief theory, and the divinity theory. Laughter has many clinical benefits, promoting beneficial physiological changes and an overall sense of well-being. Humor even has long-term effects that strengthen the effectiveness of the immune system. In healthcare, humor therapy can help relieve stress associated with disease and illness. It serves as a diversionary tactic, a therapeutic tool for disorders such as depression, and a coping mechanism. It also is a natural healing component for care givers trying to cope with the stress and personal demands of their occupations.

  19. Chronic Schistosome Infection Leads to Modulation of Granuloma Formation and Systemic Immune Suppression

    Directory of Open Access Journals (Sweden)

    Steven K. Lundy

    2013-02-01

    Full Text Available Schistosome worms have been infecting humans for millennia, but it is only in the last half century that we have begun to understand the complexities of this inter-relationship. As our sophistication about the inner workings of every aspect of the immune system has increased, it has also become obvious that schistosome infections have broad ranging effects on nearly all of the innate and adaptive immune response mechanisms. Selective pressures on both the worms and their hosts, has no doubt led to co-evolution of protective mechanisms, particularly those that favor granuloma formation around schistosome eggs and immune suppression during chronic infection. The immune modulatory effects that chronic schistosome infection and egg deposition elicit have been intensely studied, not only because of their major implications to public health issues, but also due to the emerging evidence that schistosome infection may protect humans from severe allergies and autoimmunity. Mouse models of schistosome infection have been extremely valuable for studying immune modulation and regulation, and in the discovery of novel aspects of immunity. A progression of immune reactions occurs during granuloma formation ranging from innate inflammation, to activation of each branch of adaptive immune response, and culminating in systemic immune suppression and granuloma fibrosis. Although molecular factors from schistosome eggs have been identified as mediators of immune modulation and suppressive functions of T and B cells, much work is still needed to define the mechanisms of the immune alteration and determine whether therapies for asthma or autoimmunity could be developed from these pathways.

  20. Novel Bivalent Viral-Vectored Vaccines Induce Potent Humoral and Cellular Immune Responses Conferring Protection against Stringent Influenza A Virus Challenge.

    Science.gov (United States)

    Tully, Claire M; Chinnakannan, Senthil; Mullarkey, Caitlin E; Ulaszewska, Marta; Ferrara, Francesca; Temperton, Nigel; Gilbert, Sarah C; Lambe, Teresa

    2017-07-19

    Seasonal influenza viruses are a common cause of acute respiratory illness worldwide and generate a significant socioeconomic burden. Influenza viruses mutate rapidly, necessitating annual vaccine reformulation because traditional vaccines do not typically induce broad-spectrum immunity. In addition to seasonal infections, emerging pandemic influenza viruses present a continued threat to global public health. Pandemic influenza viruses have consistently higher attack rates and are typically associated with greater mortality compared with seasonal strains. Ongoing strategies to improve vaccine efficacy typically focus on providing broad-spectrum immunity; although B and T cells can mediate heterosubtypic responses, typical vaccine development will augment either humoral or cellular immunity. However, multipronged approaches that target several Ags may limit the generation of viral escape mutants. There are few vaccine platforms that can deliver multiple Ags and generate robust cellular and humoral immunity. In this article, we describe a novel vaccination strategy, tested preclinically in mice, for the delivery of novel bivalent viral-vectored vaccines. We show this strategy elicits potent T cell responses toward highly conserved internal Ags while simultaneously inducing high levels of Abs toward hemagglutinin. Importantly, these humoral responses generate long-lived plasma cells and generate Abs capable of neutralizing variant hemagglutinin-expressing pseudotyped lentiviruses. Significantly, these novel viral-vectored vaccines induce strong immune responses capable of conferring protection in a stringent influenza A virus challenge. Thus, this vaccination regimen induces lasting efficacy toward influenza. Importantly, the simultaneous delivery of dual Ags may alleviate the selective pressure that is thought to potentiate antigenic diversity in avian influenza viruses. Copyright © 2017 by The American Association of Immunologists, Inc.

  1. DHA Supplementation during Pregnancy and Lactation Affects Infants' Cellular but Not Humoral Immune Response

    Directory of Open Access Journals (Sweden)

    Esther Granot

    2011-01-01

    Full Text Available Background. It is currently recommended that diet of pregnant mothers contain 200–300 mg DHA/day. Aim. To determine whether DHA supplementation during pregnancy and lactation affects infants' immune response. Methods. 60 women in ≥3rd pregnancy studied; 30 randomly assigned to receive DHA 400 mg/day from 12th week gestation until 4 months postpartum. From breast-fed infants, blood obtained for anti-HBs antibodies, immunoglobulins, lymphocyte subset phenotyping, and intracellular cytokine production. Results. CD4+ lymphocytes did not differ between groups, but CD4CD45RA/CD4 (naïve cells significantly higher in infants in DHA+ group. Proportion of CD4 and CD8 cells producing IFNγ significantly lower in DHA+ group, with no differences in proportion of IL4-producing cells. Immunoglobulins and anti-HBs levels did not differ between groups. Conclusions. In infants of mothers receiving DHA supplementation, a higher percentage of CD4 naïve cells and decreased CD4 and CD8 IFNγ production is compatible with attenuation of a proinflammatory response.

  2. A study of the localized humoral immune response to implicated microorganisms in juvenile periodontitis

    Energy Technology Data Exchange (ETDEWEB)

    Hall, E.R.

    1988-01-01

    A study was undertaken using an in vitro explant culture system to determine the presence of immunoglobulins (IgG, IgA, and IgM) in the supernatant fluids (SF) of disease gingival tissue explant cultures. Studies were also undertaken to determine if the de novo biosynthesis of {sup 14}C-immunoglobulins could be observed in the explant cultures of diseased tissues from juvenile periodontitis (JP) patients. Radiolabeled proteins were detected in the SF and immunodiffusion studies using goat antihuman gamma, alpha or mu chain serum revealed the presence of IgG and IgA but no IgM present in the SF of the JP gingival tissue explant cultures. Immunodiffusion studies using goat anti-human gamma chain serum with Staph protein A isolated IgG fractions of the SF, followed by autoradiography of the IgG precipitation lines demonstrated the biosynthesis of IgG by the JP gingival tissue explant cultures. The serological studies suggested that local immune response in JP was to a polymicrobic infection. The SF of JP showed significantly higher levels of antibody reactivity to B. intermedius, C. ochracea, E. nodatum and P. micros as compared to healthy tissues. The local antibody response to the microorganisms tested differed from that observed in the sera of the patients.

  3. Insight on cellular and humoral components of innate immunity in Squilla mantis (Crustacea, Stomatopoda).

    Science.gov (United States)

    Gallo, Chiara; Schiavon, Filippo; Ballarin, Loriano

    2011-09-01

    For deeper insights into the function of crustacean haemocytes in immune responses, we studied the morphology and enzyme content of circulating cells of the mantis shrimp Squilla mantis from the North Adriatic Sea, together with their ability to phagocytose foreign cells. We also assayed the enzyme content and the agglutinating and haemolytic activities of cell-free haemolymph. Three haemocyte types, i.e., hyalinocytes, semigranulocytes and granulocytes, can be distinguished, according to cell and nuclear morphology and the presence of cytoplasmic granules. All of them share the same patterns of enzyme activities and are recognised by the same lectins. Spreading cells (hyalinocytes and semigranulocytes) can ingest foreign cells; granules of semigranular and granular cells have similar cytochemical properties. Injection of Micrococcus luteus into the heart sinus results in an increase in the frequency of hyaline cells and a decrease in the frequency of granulocytes. After 24 h from the injection, a decrease in the number of phagocytosing hyalinocytes, and a general decrease in the frequency of acid phosphatase-positive cells was reported. Our data match previous results and suggest the existence of a single differentiation pathway for Squilla haemocytes with the three haemocyte morphs as different stages of cell differentiation. Results also indicate that Squilla haemolymph performs immunosurveillance, through rapid changes in haemocyte distribution, increase of antimicrobial and antioxidant enzymes and secretion of lectins stimulating agglutination, phagocytosis and encapsulation. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. Interbilayer-crosslinked multilamellar vesicles as synthetic vaccines for potent humoral and cellular immune responses

    Science.gov (United States)

    Moon, James J.; Suh, Heikyung; Bershteyn, Anna; Stephan, Matthias T.; Liu, Haipeng; Huang, Bonnie; Sohail, Mashaal; Luo, Samantha; Ho Um, Soong; Khant, Htet; Goodwin, Jessica T.; Ramos, Jenelyn; Chiu, Wah; Irvine, Darrell J.

    2011-03-01

    Vaccines based on recombinant proteins avoid the toxicity and antivector immunity associated with live vaccine (for example, viral) vectors, but their immunogenicity is poor, particularly for CD8+ T-cell responses. Synthetic particles carrying antigens and adjuvant molecules have been developed to enhance subunit vaccines, but in general these materials have failed to elicit CD8+ T-cell responses comparable to those for live vectors in preclinical animal models. Here, we describe interbilayer-crosslinked multilamellar vesicles formed by crosslinking headgroups of adjacent lipid bilayers within multilamellar vesicles. Interbilayer-crosslinked vesicles stably entrapped protein antigens in the vesicle core and lipid-based immunostimulatory molecules in the vesicle walls under extracellular conditions, but exhibited rapid release in the presence of endolysosomal lipases. We found that these antigen/adjuvant-carrying vesicles form an extremely potent whole-protein vaccine, eliciting endogenous T-cell and antibody responses comparable to those for the strongest vaccine vectors. These materials should enable a range of subunit vaccines and provide new possibilities for therapeutic protein delivery.

  5. Antiretroviral therapy, immune suppression and renal impairment in HIV-positive persons

    DEFF Research Database (Denmark)

    Nielsen, Lene Ryom; Mocroft, Amanda; Lundgren, Jens D

    2014-01-01

    The purpose of this article is to review recent literature on antiretroviral treatment (ART) and immune suppression as risk factors for renal impairment in HIV-positive persons, and to discuss pending research questions within this field.......The purpose of this article is to review recent literature on antiretroviral treatment (ART) and immune suppression as risk factors for renal impairment in HIV-positive persons, and to discuss pending research questions within this field....

  6. Mechanisms of Immune Suppression Utilized by Canine Adipose and Bone Marrow-Derived Mesenchymal Stem Cells.

    Science.gov (United States)

    Chow, Lyndah; Johnson, Valerie; Coy, Jonathan; Regan, Dan; Dow, Steven

    2017-03-01

    Mesenchymal stem cells (MSCs) from rodents and humans have been shown to suppress T cells by distinct primary pathways, with nitric oxide (NO)-dependent pathways dominating in rodents and indoleamine 2,3-deoxygenase (IDO)-dependent pathways dominating in humans. However, the immune suppressive pathways utilized by canine MSC have not been thoroughly studied, nor have bone marrow-derived MSC (BM-MSC) and adipose-derived MSC (Ad-MSC) been directly compared for their immune modulatory potency or pathway utilization. Therefore, canine BM-MSC and Ad-MSC were generated in vitro and their potency in suppressing T cell proliferation and cytokine production was compared, and differential gene expression. Mechanisms of T cells suppression were also investigated for both MSC types. We found that BM-MSC and Ad-MSC were roughly equivalent in terms of their ability to suppress T cell activation. However, the two MSC types used both shared and distinct biochemical pathways to suppress T cell activation. Ad-MSC utilized TGF-β signaling pathways and adenosine signaling to suppress T cell activation, whereas BM-MSC used cyclooxygenase, TGF-β and adenosine signaling pathways to suppress T cell activation. These results indicate that canine MSC are distinct from human and rodent MSC terms of their immune suppressive pathways, relying primarily on cyclooxygenase and TGF-β pathways for T cell suppression, rather than on NO or IDO-mediated pathways.

  7. Induction of humoral immune response in piglets after perinatal or post-weaning immunization against porcine circovirus type-2 or keyhole limpet hemocyanin.

    Science.gov (United States)

    Law, Jessica; McCorkell, Robert; Muench, Greg; Wynne-Edwards, Katherine; Schaetzl, Hermann M; Solis, Cristina; Nourozieh, Narges; Waeckerlin, Regula; Eschbaumer, Michael; Horsman, Shawn; Czub, Markus

    2017-01-01

    The objective of this study was to test the hypothesis that porcine circovirus type-2 (PCV2) vaccination is efficacious when administered in the first week of life. Three groups of pigs were vaccinated with Circumvent either early (at the end of week 1), late (at the end of week 4), or not at all. All 3 groups were later challenged intranasally with PCV2 (at the end of week 5). Two other groups were immunized with keyhole limpet hemocyanin (KLH) as a novel antigen at the end of either week 1 or week 4. Weight, PCV2 genome copy number in serum and saliva, anti-KLH antibody titer, and serum PCV2-neutralizing antibodies were measured weekly. Early PCV2 vaccination or KLH antigen exposure resulted in earlier humoral responses that were slower to develop than in older piglets, yet converged with the responses to later vaccination within 5 wk. Both groups of vaccinated piglets had periods of higher PCV2-neutralizing antibody titers and lower viral levels shortly after weaning and PCV2 challenge, thus supporting the recent labelling of 1 Canadian PCV2 vaccine for use in week 1 and suggesting that early PCV2 vaccination can reduce piglet handling without compromising vaccine efficacy.

  8. Short-term energy restriction during late gestation of beef cows decreases postweaning calf humoral immune response to vaccination.

    Science.gov (United States)

    Moriel, P; Piccolo, M B; Artioli, L F A; Marques, R S; Poore, M H; Cooke, R F

    2016-06-01

    Our objectives were to evaluate the pre- and postweaning growth and measurements of innate and humoral immune response of beef calves born to cows fed 70 or 100% of NEm requirements during the last 40 d of gestation. On d 0 (approximately 40 d before calving), 30 multiparous Angus cows pregnant to embryo transfer (BW = 631 ± 15 kg; age = 5.2 ± 0.98 yr; BCS = 6.3 ± 0.12) were randomly allocated into 1 of 10 drylot pens (3 cows/pen). Treatments were randomly assigned to pens (5 pens/treatment) and consisted of cows limit-fed (d 0 to calving) isonitrogenous, total-mixed diets formulated to provide 100 (CTRL) or 70% (REST) of daily NEm requirements of a 630-kg beef cow at 8 mo of gestation. Immediately after calving, all cow-calf pairs were combined into a single management group and rotationally grazed on tall fescue pastures (6 pastures; 22 ha/pasture) until weaning (d 266). All calves were assigned to a 40-d preconditioning period in a drylot from d 266 to 306 and vaccinated against infectious bovine rhinotracheitis, bovine viral diarrhea virus (BVDV), , and spp. on d 273 and 287. Blood samples from jugular vein were collected from cows on d 0, 17, and 35 and from calves within 12 h of birth and on d 266, 273, 274, 276, 279, and 287. By design, REST cows consumed less ( ≤ 0.002) total DMI, TDN, and NEm but had similar CP intake ( = 0.67), which tended ( = 0.06) to increase BW loss from d 0 to calving, than CTRL cows (-1.09 vs. -0.70 ± 0.14 kg/d, respectively). However, gestational NEm intake did not affect ( ≥ 0.30) plasma concentrations of cortisol, insulin, and glucose during gestation and BCS at calving as well as postcalving pregnancy rate, BW, and BCS change of cows. Calf serum IgG concentrations and plasma concentrations of haptoglobin and cortisol at birth as well as calf pre- and postweaning BW and ADG did not differ ( ≥ 0.15) between calves born to REST and CTRL cows. However, calf postweaning overall plasma concentrations of cortisol; plasma

  9. Epitope-based vaccines with the Anaplasma marginale MSP1a functional motif induce a balanced humoral and cellular immune response in mice.

    Directory of Open Access Journals (Sweden)

    Paula S Santos

    Full Text Available Bovine anaplasmosis is a hemoparasitic disease that causes considerable economic loss to the dairy and beef industries. Cattle immunized with the Anaplasma marginale MSP1 outer membrane protein complex presents a protective humoral immune response; however, its efficacy is variable. Immunodominant epitopes seem to be a key-limiting factor for the adaptive immunity. We have successfully demonstrated that critical motifs of the MSP1a functional epitope are essential for antibody recognition of infected animal sera, but its protective immunity is yet to be tested. We have evaluated two synthetic vaccine formulations against A. marginale, using epitope-based approach in mice. Mice infection with bovine anaplasmosis was demonstrated by qPCR analysis of erythrocytes after 15-day exposure. A proof-of-concept was obtained in this murine model, in which peptides conjugated to bovine serum albumin were used for immunization in three 15-day intervals by intraperitoneal injections before challenging with live bacteria. Blood samples were analyzed for the presence of specific IgG2a and IgG1 antibodies, as well as for the rickettsemia analysis. A panel containing the cytokines' transcriptional profile for innate and adaptive immune responses was carried out through qPCR. Immunized BALB/c mice challenged with A. marginale presented stable body weight, reduced number of infected erythrocytes, and no mortality; and among control groups mortality rates ranged from 15% to 29%. Additionally, vaccines have significantly induced higher IgG2a than IgG1 response, followed by increased expression of pro-inflammatory cytokines. This is a successful demonstration of epitope-based vaccines, and protection against anaplasmosis may be associated with elicitation of effector functions of humoral and cellular immune responses in murine model.

  10. Enhancing versus Suppressive Effects of Stress on Immune Function: Implications for Immunoprotection versus Immunopathology

    Directory of Open Access Journals (Sweden)

    Dhabhar Firdaus S

    2008-03-01

    Full Text Available It is widely believed that stress suppresses immune function and increases susceptibility to infections and cancer. Paradoxically, stress is also known to exacerbate allergic, autoimmune, and inflammatory diseases. These observations suggest that stress may have bidirectional effects on immune function, being immunosuppressive in some instances and immunoenhancing in others. It has recently been shown that in contrast to chronic stress that suppresses or dysregulates immune function, acute stress can be immunoenhancing. Acute stress enhances dendritic cell, neutrophil, macrophage, and lymphocyte trafficking, maturation, and function and has been shown to augment innate and adaptive immune responses. Acute stress experienced prior to novel antigen exposure enhances innate immunity and memory T-cell formation and results in a significant and long-lasting immunoenhancement. Acute stress experienced during antigen reexposure enhances secondary/adaptive immune responses. Therefore, depending on the conditions of immune activation and the immunizing antigen, acute stress may enhance the acquisition and expression of immunoprotection or immunopathology. In contrast, chronic stress dysregulates innate and adaptive immune responses by changing the type 1-type 2 cytokine balance and suppresses immunity by decreasing leukocyte numbers, trafficking, and function. Chronic stress also increases susceptibility to skin cancer by suppressing type 1 cytokines and protective T cells while increasing suppressor T-cell function. We have suggested that the adaptive purpose of a physiologic stress response may be to promote survival, with stress hormones and neurotransmitters serving as beacons that prepare the immune system for potential challenges (eg, wounding or infection perceived by the brain (eg, detection of an attacker. However, this system may exacerbate immunopathology if the enhanced immune response is directed against innocuous or self-antigens or

  11. Immune-suppressive properties of the tumor microenvironment

    DEFF Research Database (Denmark)

    Becker, Jürgen C; Andersen, Mads Hald; Schrama, David

    2013-01-01

    framework. The stroma can be divided into the extracellular matrix consisting of proteoglycans, hyaluronic acid, and fibrous proteins, as well as stromal cells including mesenchymal and immune cells; moreover, it contains various peptide factors and metabolites. Here, we will focus on immune...

  12. Influence of HLA-DR polymorphism and allergic sensitization on humoral immune responses to intact pneumococcus in a transgenic mouse model.

    Science.gov (United States)

    Sheen, Y H; Rajagopalan, G; Snapper, C M; Kita, H; Wi, C-I; Umaretiya, P J; Juhn, Y J

    2016-07-01

    Asthma is independently associated with HLA-DR3 and increased risks of pneumococcal diseases. We aimed to determine whether HLA-DR polymorphism (HLA-DRB1*03), sensitization to house dust mite (HDM), or their interaction affects humoral immune responses to pneumococcal polysaccharide and protein antigens of intact pneumococci. Induction of serum titers of anti-pneumococcal polysaccharide and anti-surface protein IgM and IgG in response to immunization with intact pneumococci (Pn) serotype 14 was determined using humanized HLA-DR3 and DR2 transgenic mice. Transgenic mice were sensitized by injecting HDM and challenged with intranasal HDM. Mice were subsequently immunized with heat-killed Pn14 at day 24. Serum titers of anti-phosphorylcholine (PC) IgM and IgG, anti-pneumococcal polysaccharide, capsular type 14 (PPS14) IgM and IgG, and anti-pneumococcal surface protein A (PspA) IgG were measured. We included a total of 44 mice (22 DR3 and 22 DR2 mice) and half of mice in each group were sensitized with HDM (i.e. 22 HDM-sensitized and 22 control mice). HDM-sensitized mice, irrespective of HLA-DR polymorphism, had significantly lower humoral immune responses. HLA-DR3 mice, irrespective of HDM sensitization, elicited a significantly lower anti-PC IgG response. In contrast, the anti-PspA IgG response was higher in DR3 relative to DR2 mice. The effect of HDM sensitization on lowering humoral immune responses to Pn14 was observed in DR3 mice regardless of the nature of the antigen, whereas such decreases were observed only for the anti-PPS14 IgG and anti-PC IgM responses in DR2 mice. HDM sensitization lowered humoral immune responses to intact pneumococcus and this effect was significantly modified by the HLA-DR polymorphism. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Elicitation of both anti HIV-1 Env humoral and cellular immunities by replicating vaccinia prime Sendai virus boost regimen and boosting by CD40Lm.

    Directory of Open Access Journals (Sweden)

    Xianfeng Zhang

    Full Text Available For protection from HIV-1 infection, a vaccine should elicit both humoral and cell-mediated immune responses. A novel vaccine regimen and adjuvant that induce high levels of HIV-1 Env-specific T cell and antibody (Ab responses was developed in this study. The prime-boost regimen that used combinations of replication-competent vaccinia LC16m8Δ (m8Δ and Sendai virus (SeV vectors expressing HIV-1 Env efficiently produced both Env-specific CD8(+ T cells and anti-Env antibodies, including neutralizing antibodies (nAbs. These results sharply contrast with vaccine regimens that prime with an Env expressing plasmid and boost with the m8Δ or SeV vector that mainly elicited cellular immunities. Moreover, co-priming with combinations of m8Δs expressing Env or a membrane-bound human CD40 ligand mutant (CD40Lm enhanced Env-specific CD8(+ T cell production, but not anti-Env antibody production. In contrast, priming with an m8Δ that coexpresses CD40Lm and Env elicited more anti-Env Abs with higher avidity, but did not promote T cell responses. These results suggest that the m8Δ prime/SeV boost regimen in conjunction with CD40Lm expression could be used as an immunization platform for driving both potent cellular and humoral immunities against pathogens such as HIV-1.

  14. Specific and Non-Specific Factors of Humoral Immunity as Markers for Pregnancy Loss in Women with Cytomegalovirus Infection

    Directory of Open Access Journals (Sweden)

    Irina A. Andrievskaya

    2015-12-01

    Full Text Available The aim of this study was to estimate the changes in humoral immunity and their association with complications of pregnancy (spontaneous abortions, threatened miscarriage, premature birth depending on the gestational age and recurrence of cytomegalovirus infection (CMVI. A direct relationship between the frequency of detection of an anti-CMV IgG antibody titer of 1:1600 and the prevalence of acute respiratory disease during pregnancy has been identified. We found an imbalance in the production of the non-specific antibodies (an increase in the blood levels of total IgM and a decrease in IgA and IgG levels in the subgroup of women with relapsed CMVI at 6 to 8 weeks of gestation and spontaneous abortion, as well as in the subgroup of women with relapsed CMVI at 15 to 21 weeks of gestation and the risk of the late miscarriage, compared to those with relapsed CMVI at 9 to 14 weeks and 22 to 32 weeks of gestation. An increase in blood levels of total IgM and IgG and a decrease in IgA level was identified in the subgroup of women with relapsed CMVI at 9 to14 weeks of gestation and a threatened abortion, as well as in the subgroup of women with relapsed CMVI at 22 to 32 weeks of gestation and preterm birth. The obtained data of the imbalance in the primary and secondary immune response in CMV- seropositive pregnant women during relapsed CMVI indicate disturbances in the systemic and local intercellular interactions of immunocompetent cells, which lead to an imbalance in the production of antibodies involved in the elimination of viral agents and to the development of a systemic inflammatory response that complicates the course of pregnancy. CMVI relapse at 7 to 8 weeks of gestation is associated with reproductive losses; a risk for threatened miscarriage, threatened premature labor, and retrochorial hematoma increases significantly with CMVI relapse in the more remote gestational age.

  15. Oct2 and Obf1 as facilitators of B:T cell collaboration during a humoral immune response

    Directory of Open Access Journals (Sweden)

    Lynn M Corcoran

    2014-03-01

    Full Text Available The Oct2 protein, encoded by the Pou2f2 gene, was originally predicted to act as a DNA binding transcriptional activator of immunoglobulin (Ig in B lineage cells. This prediction flowed from the earlier observation that an 8 bp sequence, the octamer motif, was a highly conserved component of most Ig gene promoters and enhancers, and evidence from over-expression and reporter assays confirmed Oct2-mediated, octamer-dependent gene expression. Complexity was added to the story when Oct1, an independently encoded protein, ubiquitously expressed from the Pou2f 1 gene, was characterised and found to bind to the octamer motif with almost identical specificity, and later, when the co-activator Obf1 (OCA-B, Bob.1, encoded by the Pou2af1 gene, was cloned. Obf1 joins Oct2 (and Oct1 on the DNA of a subset of octamer motifs to enhance their transactivation strength. While these proteins variously carried the mantle of determinants of Ig gene expression in B cells for many years, such a role has not been borne out for them by characterisation of mice lacking functional copies of the genes, either as single or as compound mutants. Instead, we and others have shown that Oct2 and Obf1 are required for B cells to mature fully in vivo, for B cells to respond to the T cell cytokines IL5 and IL4, and for B cells to produce IL6 normally during a T cell dependent immune response. We show here that Oct2 affects Syk gene expression, thus influencing B cell receptor signalling, and that Oct2 loss blocks Slamf1 expression in vivo as a result of incomplete B cell maturation. Upon IL4 signalling, Stat6 up-regulates Obf1, indirectly via Xbp1, to enable plasma cell differentiation. Thus, Oct2 and Obf1 enable B cells to respond normally to antigen receptor signals, to express surface receptors that mediate physical interaction with T cells, or to produce and respond to cytokines that are critical drivers of B cell and T cell differentiation during a humoral immune response.

  16. Induction of innate immune signatures following polyepitope protein-glycoprotein B-TLR4&9 agonist immunization generates multifunctional CMV-specific cellular and humoral immunity.

    Science.gov (United States)

    Dasari, Vijayendra; Smith, Corey; Schuessler, Andrea; Zhong, Jie; Khanna, Rajiv

    2014-01-01

    Recent studies have suggested that a successful subunit human cytomegalovirus (CMV) vaccine requires improved formulation to generate broad-based anti-viral immunity following immunization. Here we report the development of a non-live protein-based vaccine strategy for CMV based on a polyepitope protein and CMV glycoprotein B (gB) adjuvanted with TLR4 and/or TLR9 agonists. The polyepitope protein includes contiguous multiple MHC class I-restricted epitopes with an aim to induce CD8(+) T cell immunity, while gB is an important target for CD4(+) T cell immunity and neutralizing antibodies. Optimal immunogenicity of this bivalent non-live protein vaccine formulation was dependent upon the co-administration of both the TLR4 and TLR9 agonist, which was associated with the activation of innate immune signatures and the influx of different DC subsets including plasmacytoid DCs and migratory CD8-DEC205+CD103-CD326- langerin-negative dermal DCs into the draining lymph nodes. Furthermore these professional antigen presenting cells also expressed IL-6, IL-12p70, TNFα, and IFNα which play a crucial role in the activation of adaptive immunity. In summary, this study provides a novel platform technology in which broad-based anti-CMV immune responses upon vaccination can be maximised by co-delivery of viral antigens and TLR4 and 9 agonists which induce activation of innate immune signatures and promote potent antigen acquisition and cross-presentation by multiple DC subsets.

  17. Immune activation suppresses initiation of lytic Epstein-Barr virus infection.

    Science.gov (United States)

    Ladell, Kristin; Dorner, Marcus; Zauner, Ludwig; Berger, Christoph; Zucol, Franziska; Bernasconi, Michele; Niggli, Felix K; Speck, Roberto F; Nadal, David

    2007-08-01

    Primary infection with Epstein-Barr virus (EBV) is asymptomatic in children with immature immune systems but may manifest as infectious mononucleosis, a vigorous immune activation, in adolescents or adults with mature immune systems. Infectious mononucleosis and chronic immune activation are linked to increased risk for EBV-associated lymphoma. Here we show that EBV initiates progressive lytic infection by expression of BZLF-1 and the late lytic genes gp85 and gp350/220 in cord blood mononuclear cells (CBMC) but not in peripheral blood mononuclear cells (PBMC) from EBV-naive adults after EBV infection ex vivo. Lower levels of proinflammatory cytokines in CBMC, used to model a state of minimal immune activation and immature immunity, than in PBMC were associated with lytic EBV infection. Triggering the innate immunity specifically via Toll-like receptor-9 of B cells substantially suppressed BZLF-1 mRNA expression in acute EBV infection ex vivo and in anti-IgG-stimulated chronically latently EBV-infected Akata Burkitt lymphoma cells. This was mediated in part by IL-12 and IFN-gamma. These results identify immune activation as critical factor for the suppression of initiation of lytic EBV infection. We hypothesize that immune activation contributes to EBV-associated lymphomagenesis by suppressing lytic EBV and in turn promotes latent EBV with transformation potential.

  18. The impact of immunosenescence on humoral immune response variation after influenza A/H1N1 vaccination in older subjects.

    Directory of Open Access Journals (Sweden)

    Iana H Haralambieva

    Full Text Available Although influenza causes significant morbidity and mortality in the elderly, the factors underlying the reduced vaccine immunogenicity and efficacy in this age group are not completely understood. Age and immunosenescence factors, and their impact on humoral immunity after influenza vaccination, are of growing interest for the development of better vaccines for the elderly.We assessed associations between age and immunosenescence markers (T cell receptor rearrangement excision circles - TREC content, peripheral white blood cell telomerase - TERT expression and CD28 expression on T cells and influenza A/H1N1 vaccine-induced measures of humoral immunity in 106 older subjects at baseline and three timepoints post-vaccination.TERT activity (TERT mRNA expression was significantly positively correlated with the observed increase in the influenza-specific memory B cell ELISPOT response at Day 28 compared to baseline (p-value=0.025. TREC levels were positively correlated with the baseline and early (Day 3 influenza A/H1N1-specific memory B cell ELISPOT response (p-value=0.042 and p-value=0.035, respectively. The expression and/or expression change of CD28 on CD4+ and/or CD8+ T cells at baseline and Day 3 was positively correlated with the influenza A/H1N1-specific memory B cell ELISPOT response at baseline, Day 28 and Day 75 post-vaccination. In a multivariable analysis, the peak antibody response (HAI and/or VNA at Day 28 was negatively associated with age, the percentage of CD8+CD28 low T cells, IgD+CD27- naïve B cells, and percentage overall CD20- B cells and plasmablasts, measured at Day 3 post-vaccination. The early change in influenza-specific memory B cell ELISPOT response was positively correlated with the observed increase in influenza A/H1N1-specific HAI antibodies at Day 28 and Day 75 relative to baseline (p-value=0.007 and p-value=0.005, respectively.Our data suggest that influenza-specific humoral immunity is significantly influenced by

  19. Autophagy suppresses host adaptive immune responses toward Borrelia burgdorferi

    NARCIS (Netherlands)

    Buffen, Kathrin; Oosting, Marije; Li, Yang; Kanneganti, Thirumala-Devi; Netea, Mihai G.; Joosten, Leo A. B.

    Inhibition of autophagy increases the severity of murine Lyme arthritis and human adaptive immune responses against B. burgdorferi. We have previously demonstrated that inhibition of autophagy increased the Borrelia burgdorferi induced innate cytokine production in vitro, but little is known

  20. Anti-inflammatory triterpenoid blocks immune suppressive function of myeloid-derived suppressor cells and improves immune response in cancer

    Science.gov (United States)

    Nagaraj, Srinivas; Youn, Je-In; Weber, Hannah; Iclozan, Cristina; Lu, Lily; Cotter, Matthew J.; Meyer, Colin; Becerra, Carlos R.; Fishman, Mayer; Antonia, Scott; Sporn, Michael B.; Liby, Karen T.; Rawal, Bhupendra; Lee, Ji-Hyun; Gabrilovich, Dmitry I.

    2010-01-01

    Purpose Myeloid-derived suppressor cells (MDSC) are one of the major factors responsible for immune suppression in cancer. Therefore it would be important to identify effective therapeutic means to modulate these cells. Experimental Design We evaluated the effect of the synthetic triterpenoid C-28 methyl ester of 2-cyano-3,12-dioxooleana-1,9,-dien-28-oic acid (CDDO-Me; bardoxolone methyl) in MC38 colon carcinoma, Lewis lung carcinoma, and EL-4 thymoma mouse tumor models as well as blood samples from patients with renal cell cancer and soft tissue sarcoma. Samples were also analyzed from patients with pancreatic cancer treated with CDDO-Me in combination with gemcitabine. Results CDDO-Me at concentrations of 25-100 nM completely abrogated immune suppressive activity of MDSC in vitro. CDDO-Me reduced reactive oxygen species in MDSC but did not affect their viability or the levels of nitric oxide and arginase. Treatment of tumor-bearing mice with CDDO-Me did not affect the proportion of MDSC in the spleens but eliminated their suppressive activity. This effect was independent of antitumor activity. CDDO-Me treatment decreased tumor growth in mice. Experiments with immune-deficient SCID-beige mice indicated that this effect was largely mediated by the immune system. CDDO-Me substantially enhanced the antitumor effect of a cancer vaccines. Treatment of pancreatic cancer patients with CDDO-Me did not affect the number of MDSC in peripheral blood but significantly improved the immune response. Conclusions CDDO-Me abrogated the immune suppressive effect of MDSC and improved immune responses in tumor-bearing mice and cancer patients. It may represent an attractive therapeutic option by enhancing the effect of cancer immunotherapy. PMID:20215551

  1. Augmentation of humoral and cellular immunity in response to Tetanus and Diphtheria toxoids by supercritical carbon dioxide extracts of Hippophae rhamnoides L. leaves.

    Science.gov (United States)

    Jayashankar, Bindhya; Singh, Divya; Tanwar, Himanshi; Mishra, K P; Murthy, Swetha; Chanda, Sudipta; Mishra, Jigni; Tulswani, R; Misra, K; Singh, S B; Ganju, Lilly

    2017-03-01

    Hippophae rhamnoides L. commonly known as Seabuckthorn (SBT), a wild shrub of family Elaegnacea, has extensively used for treating various ailments like skin diseases, jaundice, asthma, lung troubles. SBT leaves have been reported to possess several pharmacological properties including immunomodulatory, antioxidant, anti-inflammatory, antimicrobial and tissue regeneration etc. The present study was undertaken to evaluate the adjuvant property of supercritical carbon dioxide extracts (SCEs 300ET and 350ET) of SBT leaves in balb/c mice immunized with Tetanus and Diphtheria toxoids. The dynamic changes in the immune response were measured in terms of humoral and cell-mediated immune responses. We have seen the effect of SCEs on immunoglobulin subtypes and secondary immune response generation. In addition, the effect of SCEs on antigen specific cellular immunity was evaluated. Our results show that SCEs 300ET and 350ET significantly enhanced antibody titers in response to both TT and DT antigens. The secondary immune response generated was significantly increased in case of TT immunized animals. SCEs also enhanced cytokine levels (IFN-γ, IL-4, TNF-α and IL-1β) and increased lymphoproliferation. Besides, both SCEs did not show any toxic effects. Therefore, the study suggests that SCEs are safe and have potent immunostimulatory activity and hence, seems to be a promising balanced Th1 and Th2 directing immunological adjuvant for various veterinary as well as human vaccines. Copyright © 2017. Published by Elsevier B.V.

  2. Mycobacterium tuberculosis Zinc Metalloprotease-1 Elicits Tuberculosis-specific Humoral Immune Response Independent of Mycobacterial Load in Pulmonary and Extra-Pulmonary Tuberculosis Patients

    Directory of Open Access Journals (Sweden)

    Mani Harika eVemula

    2016-03-01

    Full Text Available Conventionally, facultative intracellular pathogen, Mycobacterium tuberculosis (M.tb, the tuberculosis (TB causing bacilli in human is cleared by cell-mediated immunity (CMI with CD4+ T cells playing instrumental role in protective immunity, while antibody-mediated immunity (AMI is considered non-protective. This longstanding convention has been challenged with recent evidences of increased susceptibility of hosts with compromised AMI and monoclonal antibodies conferring passive protection against TB and other intracellular pathogens. Therefore, novel approaches towards vaccine development include strategies aiming at induction of humoral response along with CMI. This necessitates the identification of mycobacterial proteins with properties of immunomodulation and strong immunogenicity. In this study, we determined the immunogenic potential of M.tb Zinc metalloprotease-1 (Zmp1, a secretory protein essential for intracellular survival and pathogenesis of M.tb. We observed that Zmp1 was secreted by in vitro grown M.tb under granuloma-like stress conditions (acidic, oxidative, iron deficiency and nutrient deprivation and generated Th2 cytokine microenvironment upon exogenous treatment of Peripheral Blood Mononulear Cells (PBMCs with recombinant Zmp1 (rZmp1. This was supported by recording specific and robust humoral response in TB patients in a cohort of 295. The anti-Zmp1 titers were significantly higher in TB patients (n=121 as against healthy control (n=62, household contacts (n=89 and non-specific infection controls (n=23. A significant observation of the study is the presence of equally high titers of anti-Zmp1 antibodies in a range of patients with high bacilli load (sputum bacilli load of 300+ per mL to paucibacillary smear-negative pulmonary tuberculosis (PTB cases. This clearly indicated the potential of Zmp1 to evoke an effective humoral response independent of mycobacterial load. Such mycobacterial proteins can be explored as antigen

  3. Rapid escape from preserved cross-reactive neutralizing humoral immunity without loss of viral fitness in HIV-1-infected progressors and long-term nonprogressors.

    Science.gov (United States)

    van Gils, Marit J; Bunnik, Evelien M; Burger, Judith A; Jacob, Yodit; Schweighardt, Becky; Wrin, Terri; Schuitemaker, Hanneke

    2010-04-01

    A substantial proportion of human immunodeficiency virus type 1 (HIV-1)-infected individuals has cross-reactive neutralizing activity in serum, with a similar prevalence in progressors and long-term nonprogressors (LTNP). We studied whether disease progression in the face of cross-reactive neutralizing serum activity is due to fading neutralizing humoral immunity over time or to viral escape. In three LTNP and three progressors, high-titer cross-reactive HIV-1-specific neutralizing activity in serum against a multiclade pseudovirus panel was preserved during the entire clinical course of infection, even after AIDS diagnosis in progressors. However, while early HIV-1 variants from all six individuals could be neutralized by autologous serum, the autologous neutralizing activity declined during chronic infection. This could be attributed to viral escape and the apparent inability of the host to elicit neutralizing antibodies to the newly emerging viral escape variants. Escape from autologous neutralizing activity was not associated with a reduction in the viral replication rate in vitro. Escape from autologous serum with cross-reactive neutralizing activity coincided with an increase in the length of the variable loops and in the number of potential N-linked glycosylation sites in the viral envelope. Positive selection pressure was observed in the variable regions in envelope, suggesting that, at least in these individuals, these regions are targeted by humoral immunity with cross-reactive potential. Our results may imply that the ability of HIV-1 to rapidly escape cross-reactive autologous neutralizing antibody responses without the loss of viral fitness is the underlying explanation for the absent effect of potent cross-reactive neutralizing humoral immunity on the clinical course of infection.

  4. CpG oligodeoxynucleotide-enhanced humoral immune response and production of antibodies to prion protein PrPSc in mice immunized with 139A scrapie-associated fibrils.

    Science.gov (United States)

    Spinner, Daryl S; Kascsak, Regina B; Lafauci, Giuseppe; Meeker, Harry C; Ye, Xuemin; Flory, Michael J; Kim, Jae Il; Schuller-Levis, Georgia B; Levis, William R; Wisniewski, Thomas; Carp, Richard I; Kascsak, Richard J

    2007-06-01

    Prion diseases are characterized by conversion of the cellular prion protein (PrP(C)) to a protease-resistant conformer, the srapie form of PrP (PrP(Sc)). Humoral immune responses to nondenatured forms of PrP(Sc) have never been fully characterized. We investigated whether production of antibodies to PrP(Sc) could occur in PrP null (Prnp(-/-)) mice and further, whether innate immune stimulation with the TLR9 agonist CpG oligodeoxynucleotide (ODN) 1826 could enhance this process. Whether such stimulation could raise anti-PrP(Sc) antibody levels in wild-type (Prnp(+/+)) mice was also investigated. Prnp(-/-) and Prnp(+/+) mice were immunized with nondenatured 139A scrapie-associated fibrils (SAF), with or without ODN 1826, and were tested for titers of PrP-specific antibodies. In Prnp(-/-) mice, inclusion of ODN 1826 in the immunization regime increased anti-PrP titers more than 13-fold after two immunizations and induced, among others, antibodies to an N-terminal epitope, which were only present in the immune repertoire of mice receiving ODN 1826. mAb 6D11, derived from such a mouse, reacts with the N-terminal epitope QWNK in native and denatured forms of PrP(Sc) and recombinant PrP and exhibits a K(d) in the 10(-)(11) M range. In Prnp(+/+) mice, ODN 1826 increased anti-PrP levels as much as 84% after a single immunization. Thus, ODN 1826 potentiates adaptive immune responses to PrP(Sc) in 139A SAF-immunized mice. These results represent the first characterization of humoral immune responses to nondenatured, infectious PrP(Sc) and suggest methods for optimizing the generation of mAbs to PrP(Sc), many of which could be used for diagnosis and treatment of prion diseases.

  5. Integration of Immune Cell Populations, mRNA-Seq, and CpG Methylation to Better Predict Humoral Immunity to Influenza Vaccination: Dependence of mRNA-Seq/CpG Methylation on Immune Cell Populations

    Directory of Open Access Journals (Sweden)

    Gregory A. Poland

    2017-04-01

    Full Text Available The development of a humoral immune response to influenza vaccines occurs on a multisystems level. Due to the orchestration required for robust immune responses when multiple genes and their regulatory components across multiple cell types are involved, we examined an influenza vaccination cohort using multiple high-throughput technologies. In this study, we sought a more thorough understanding of how immune cell composition and gene expression relate to each other and contribute to interindividual variation in response to influenza vaccination. We first hypothesized that many of the differentially expressed (DE genes observed after influenza vaccination result from changes in the composition of participants’ peripheral blood mononuclear cells (PBMCs, which were assessed using flow cytometry. We demonstrated that DE genes in our study are correlated with changes in PBMC composition. We gathered DE genes from 128 other publically available PBMC-based vaccine studies and identified that an average of 57% correlated with specific cell subset levels in our study (permutation used to control false discovery, suggesting that the associations we have identified are likely general features of PBMC-based transcriptomics. Second, we hypothesized that more robust models of vaccine response could be generated by accounting for the interplay between PBMC composition, gene expression, and gene regulation. We employed machine learning to generate predictive models of B-cell ELISPOT response outcomes and hemagglutination inhibition (HAI antibody titers. The top HAI and B-cell ELISPOT model achieved an area under the receiver operating curve (AUC of 0.64 and 0.79, respectively, with linear model coefficients of determination of 0.08 and 0.28. For the B-cell ELISPOT outcomes, CpG methylation had the greatest predictive ability, highlighting potentially novel regulatory features important for immune response. B-cell ELISOT models using only PBMC composition had

  6. Humoral immune response to Plasmodium falciparum vaccine candidate GMZ2 and its components in populations naturally exposed to seasonal malaria in Ethiopia

    DEFF Research Database (Denmark)

    Mamo, Hassen; Esen, Meral; Ajua, Anthony

    2013-01-01

    to investigate the nature of humoral immune response to malaria in two ethnic groups in two endemic localities: Shewa Robit in north, and Boditi in south Ethiopia which are characterized by varying levels of malaria transmission and altitude. In a cross-sectional study, the study participants were diagnosed...... for malaria infection microscopically and by the rapid diagnostic test (RDT). Sera were tested by using enzyme-linked immunosorbent assay (ELISA) for total immunoglobulin (Ig) G against P. falciparum blood-stage vaccine candidate GMZ2 and its subunits (Glutamate-rich protein (GLURP-R0), merozoite surface...

  7. HIVIS-DNA or HIVISopt-DNA priming followed by CMDR vaccinia-based boosts induce both humoral and cellular murine immune responses to HIV

    Directory of Open Access Journals (Sweden)

    J Hinkula

    2017-06-01

    Conclusions: HIVIS-DNA was modified to obtain HIVISopt-DNA that had fewer plasmids, and additional epitopes. Even with one DNA prime followed by two MVA-CMDR boosts, humoral and cell-mediated immune responses were readily induced by priming with either DNA construct composition. Priming by HIV-DNA augmented neutralizing antibody responses revealed by boosting with the vaccinia-based heterologous sequences. Cellular and antibody responses covered selected strains representing HIV-1 subtypes A, B, C and CRF01_AE. We assume this is related to the inclusion of heterologous full genes in the vaccine schedule.

  8. In vivo blockade of gamma interferon affects the influenza virus-induced humoral and the local cellular immune response in lung tissue.

    OpenAIRE

    Baumgarth, N.; Kelso, A

    1996-01-01

    Influenza virus infection induces the local production of gamma interferon (IFN-gamma) by T cells and non-T cells in the respiratory tract. To elucidate the possible functions of this cytokine, the humoral and local cellular immune responses to influenza virus were studied in BALB/c mice with or without in vivo neutralization of IFN-gamma by using monoclonal antibodies. Neutralization of IFN-gamma led to a significant reduction in virus-specific titers of immunoglobulins G2a and G3 in serum b...

  9. Tumor-Derived Exosomes and Their Role in Tumor-Induced Immune Suppression

    Directory of Open Access Journals (Sweden)

    Theresa L. Whiteside

    2016-10-01

    Full Text Available Tumor-derived exosomes (TEX are emerging as critical components of an intercellular information network between the tumor and the host. The tumor escapes from the host immune system by using a variety of mechanisms designed to impair or eliminate anti-tumor immunity. TEX carrying a cargo of immunoinhibitory molecules and factors represent one such mechanism. TEX, which are present in all body fluids of cancer patients, deliver negative molecular or genetic signals to immune cells re-programming their functions. Although TEX can also stimulate immune activity, in the microenvironments dominated by the tumor, TEX tend to mediate immune suppression thus promoting tumor progression. The TEX content, in part resembling that of the parent cell, may serve as a source of cancer biomarkers. TEX also interfere with immune therapies. A better understanding of TEX and their contribution to cancer progression and cancer patients’ response to immune therapies represents a challenging new field of investigation.

  10. Perillyl alcohol suppresses antigen-induced immune responses in the lung

    Energy Technology Data Exchange (ETDEWEB)

    Imamura, Mitsuru; Sasaki, Oh; Okunishi, Katsuhide; Nakagome, Kazuyuki; Harada, Hiroaki; Kawahata, Kimito; Tanaka, Ryoichi; Yamamoto, Kazuhiko [Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo (Japan); Dohi, Makoto, E-mail: mdohi-tky@umin.ac.jp [Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo (Japan); Institute of Respiratory Immunology, Shibuya Clinic for Respiratory Diseases and Allergology, Tokyo (Japan)

    2014-01-03

    Highlights: •Perillyl alcohol (POH) is an isoprenoid which inhibits the mevalonate pathway. •We examined whether POH suppresses immune responses with a mouse model of asthma. •POH treatment during sensitization suppressed Ag-induced priming of CD4{sup +} T cells. •POH suppressed airway eosinophila and cytokine production in thoracic lymph nodes. -- Abstract: Perillyl alcohol (POH) is an isoprenoid which inhibits farnesyl transferase and geranylgeranyl transferase, key enzymes that induce conformational and functional changes in small G proteins to conduct signal production for cell proliferation. Thus, it has been tried for the treatment of cancers. However, although it affects the proliferation of immunocytes, its influence on immune responses has been examined in only a few studies. Notably, its effect on antigen-induced immune responses has not been studied. In this study, we examined whether POH suppresses Ag-induced immune responses with a mouse model of allergic airway inflammation. POH treatment of sensitized mice suppressed proliferation and cytokine production in Ag-stimulated spleen cells or CD4{sup +} T cells. Further, sensitized mice received aerosolized OVA to induce allergic airway inflammation, and some mice received POH treatment. POH significantly suppressed indicators of allergic airway inflammation such as airway eosinophilia. Cytokine production in thoracic lymph nodes was also significantly suppressed. These results demonstrate that POH suppresses antigen-induced immune responses in the lung. Considering that it exists naturally, POH could be a novel preventive or therapeutic option for immunologic lung disorders such as asthma with minimal side effects.

  11. Humoral immune response of horses experimentally infected with Trypanosoma evansi/ Resposta imune humoral de eqüinos infectados experimentalmente com Trypanosoma evansi

    Directory of Open Access Journals (Sweden)

    Lúcia Padilha Cury Thomaz de Aquino

    2001-05-01

    Full Text Available Six adult horses were experimentally infected with Trypanosoma evansi (106 parasites. Three other adult horses served as negative control. Serum samples of the experimentally infected horses with T. evansi and non-infected controls horses were obtained before inoculation, and daily thereafter until 14 days post infection (DPI. After that time the serum samples were obtained weekly. Sera of the infected and non-infected control horses was tested by indirect fluorescent antibody test (IFAT and enzyme-linked immunosorbent assay (ELISA for the detection of antibodies against T. evansi. Both ELISA and IFAT detected trypanosomal antibodies shortly after infection and showed progressive increases in antibodies levels during early stages of infection. The responses started on the eighth and eleventh DPI. Maximum IFAT and ELISA values were reached after four weeks of infection and were maintained at this level until the end of the period of study.Seis eqüinos foram inoculados com 106 tripomastigota sangüícolas de Trypanosoma evansi. Três outros animais foram mantidos como testemunhas. Amostras de soro sangüíneo foram obtidas de todos os animais, antes da inoculação, e diariamente até o 14º dia pós inoculação (DPI; após este período uma vez por semana. Pesquisa de anticorpos anti- T. evansi, foram realizadas através da reação de imunofluorescência indireta (RIFI e do ensaio de imunoabsorção enzimática (ELISA. A resposta imune humoral, detectada através da RIFI e do ELISA, iniciou-se, em média, a partir do oitavo DPI, alcançando títulos máximos após quatro semanas de evolução, e os titulos de anticorpos anti- T. evansi mantiveram-se elevadas até o término das observações.

  12. Analysis of the humoral immune responses among cynomolgus macaque naturally infected with Reston virus during the 1996 outbreak in the Philippines

    Directory of Open Access Journals (Sweden)

    Taniguchi Satoshi

    2012-10-01

    Full Text Available Abstract Background Ebolaviruses induce lethal viral hemorrhagic fevers (VHFs in humans and non-human primates, with the exceptions of Reston virus (RESTV, which is not pathogenic for humans. In human VHF cases, extensive analyses of the humoral immune responses in survivors and non-survivors have shown that the IgG responses to nucleoprotein (NP and other viral proteins are associated with asymptomatic and survival outcomes, and that the neutralizing antibody responses targeting ebolaviruses glycoprotein (GP1,2 are the major indicator of protective immunity. On the other hand, the immune responses in non-human primates, especially naturally infected ones, have not yet been elucidated in detail, and the significance of the antibody responses against NP and GP1,2 in RESTV-infected cynomolgus macaques is still unclear. In this study, we analyzed the humoral immune responses of cynomolgus macaque by using serum specimens obtained from the RESTV epizootic in 1996 in the Philippines to expand our knowledge on the immune responses in naturally RESTV-infected non-human primates. Results The antibody responses were analyzed using IgG-ELISA, an indirect immunofluorescent antibody assay (IFA, and a pseudotyped VSV-based neutralizing (NT assay. Antigen-capture (Ag-ELISA was also performed to detect viral antigens in the serum specimens. We found that the anti-GP1,2 responses, but not the anti-NP responses, closely were correlated with the neutralization responses, as well as the clearance of viremia in the sera of the RESTV-infected cynomolgus macaques. Additionally, by analyzing the cytokine/chemokine concentrations of these serum specimens, we found high concentrations of proinflammatory cytokines/chemokines, such as IFNγ, IL8, IL-12, and MIP1α, in the convalescent phase sera. Conclusions These results imply that both the antibody response to GP1,2 and the proinflammatory innate responses play significant roles in the recovery from RESTV infection in

  13. Immunity in Chagas’ Disease.

    Science.gov (United States)

    This is the final report on the immunity in Chagas ’ disease contract and it summarizes the results of a diversity of studies directed toward...antibody test for Chagas ’ disease . Also mentioned are the facts that the cell membranes of live trypomastigotes are not immunoreactive with the...humoral immune response of an infected host and that suppression of parasitemias in chronic Chagas ’ disease is probably a function of the cell immune system of the host. (Author)

  14. Effect of cesium radioisotope on humoral immune status in Ukrainian children with clinical symptoms of irritable bowel syndrome related to Chernobyl disaster.

    Science.gov (United States)

    Sheikh Sajjadieh, M R; Kuznetsova, L V; Bojenko, V B

    2011-02-01

    The aim of this study is to determine humoral immune status in Ukrainian children with clinical symptoms of irritable bowel syndrome 23 years after the Chernobyl disaster. The test population consisted of 95 participants: 75 rural patients aged 4-18, who lived in a contaminated area exposed to natural environmental radiation (falling under three groups) and 20 healthy urban participants from Kiev aged 5-15 as a control group. Internal radiation activity has been measured by gamma-ray spectrometry. B-lymphocytes population was analyzed with monoclonal antibody against antigen CD22(+). Serum immunoglobulins were evaluated by enzyme-linked immunosorbent assay (ELISA) method. p < 0.05 was considered significant. The percentage of CD22(+) in study groups is increased significantly in comparison to control group at p < 0.05. Reduced serum immunoglobulins levels have developed in the majority of the participants. Humoral immune status of study groups with clinical symptom of irritable bowel syndrome residing in a contaminated area has changed.

  15. Effects of dietary yeast autolysate (Saccharomyces cerevisiae) on performance, egg traits, egg cholesterol content, egg yolk fatty acid composition and humoral immune response of laying hens.

    Science.gov (United States)

    Yalçin, Sakine; Yalçin, Suzan; Cakin, Kemal; Eltan, Onder; Dağaşan, Levent

    2010-08-15

    The objective of this study was to determine the effects of dietary yeast autolysate on performance, egg traits, egg cholesterol content, egg yolk fatty acid composition, lipid oxidation of egg yolk, some blood parameters and humoral immune response of laying hens during a 16 week period. A total of 225 Hyline Brown laying hens, 22 weeks of age, were allocated equally to one control group and four treatment groups. Yeast autolysate (Saccharomyces cerevisiae, InteWall) was used at levels of 1, 2, 3 and 4 g kg(-1) in the diets of the first, second, third and fourth treatment groups respectively. Dietary treatments did not significantly affect body weight, feed intake and egg traits. Yeast autolysate supplementation increased egg production (P Yeast autolysate at levels of 2, 3 and 4 g kg(-1) decreased egg yolk cholesterol level as mg g(-1) yolk (P yeast autolysate supplementation. Dietary yeast autolysate at levels of 2, 3 and 4 g kg(-1) had beneficial effects on performance, egg cholesterol content and humoral immune response. It is concluded that 2 g kg(-1) yeast autolysate will be enough to have beneficial effects in laying hens. Copyright (c) 2010 Society of Chemical Industry.

  16. Mechanisms of protective immunity against Schistosoma mansoni infection in mice vaccinated with irradiated cercariae. V. Anamnestic cellular and humoral responses following challenge infection

    Energy Technology Data Exchange (ETDEWEB)

    Correa-Oliveira, R.; Sher, A.; James, S.L.

    1984-03-01

    Mice vaccinated with radiation-attenuated cercariae display low levels of cellular and humoral immune responses toward schistosomulum antigens, as measured in vitro by lymphocyte blastogenesis and quantitation of anti-larval antibodies by indirect immunofluorescence. Both responses wane with time after vaccination. However subsequent challenge infection provokes immune responses of classical anamnestic character, being both more rapid in appearance and of greater magnitude. Antigen responsive cells appear in lymph nodes draining the challenge site within 24 hours after infection. Both circulating anti-schistosomulum surface antibodies as well as cytophilic IgE anti-worm antigen antibodies increase substantially by 1 week after challenge. All of the anamnestic circulating antibodies belong to the IgG class. Those findings support the concept that vaccine-induced resistance to Schistosoma mansoni infection involves sensitized T and B lymphocytes, and point to the possible role of post-challenge anamnestic responses in the effector mechanism of parasite killing in this model.

  17. The new normal: immuno-modulatory agents against sepsis immune suppression

    OpenAIRE

    Hutchins, Noelle A.; Unsinger, Jacqueline; Hotchkiss, Richard S.; Ayala, Alfred

    2014-01-01

    Sepsis is the leading cause of death amongst critically ill patients in intensive care units, and treatment options are limited. Therapies developed against the pro-inflammatory stage have failed clinically; therefore new approaches that target the host immune response in sepsis are necessary. Increasing evidence suggests that a major pathophysiological event in sepsis is immune suppression, often resulting in secondary fungal, bacterial, or viral infections. Recent studies from animal sepsis...

  18. Cross-suppression of specific immune responses after oral tolerance

    Directory of Open Access Journals (Sweden)

    Nelson M. Vaz

    1981-03-01

    Full Text Available Adult normal inbred mice rendered tolerant to OVA by previous oral exposure do not respond to intraperitonela immunization with DNP-OVA in adjuvant. These tolerant mice also form less DNP-specific antibodies to DNP-KLH when immunized with mixtures of DNP-KLH and DNP-OVA, or less HGG-specific antibodies when immunized with cross-linked conjugates of OVA and HGG. These same procedures increased DNP-specific or HGG-specific responses in non-tolerant control mice. The cross-supperssion was ineffective, however, to inhibit already ongoing antibody responses.Camundongos adultos normais tornados imunologicamente tolerantes a ovoalbumina (OVA por exposição oral não formam anticorpos antidinitrofenil (anti-DNP quando imunizados com DNP-OVA, mas respondem normalmente à DNP-hemocianina (DNO-KLH. Entretanto, a adição de DNP-OVA à injeção de DNP-KLH reduz a formação de anticorpos anti-DNP em animais tolerantes a OVA, mas não em animais normais. Similarmente animais tolerantes à OVA formam menos anticorpos antiglobulina humana (HGG quando imunizados com agregados (por glutaraldeído de OVA e HGG. A tolerância oral e, portanto, capaz de inibir a indução de respostas imunes por um esquema de supressão-cruzada. Esse esquema, no entanto, não foi capaz de inibir respostas imunes já iniciadas.

  19. Emergence of monoclonal antibody b12-resistant human immunodeficiency virus type 1 variants during natural infection in the absence of humoral or cellular immune pressure.

    Science.gov (United States)

    Bunnik, Evelien M; van Gils, Marit J; Lobbrecht, Marilie S D; Pisas, Linaida; Nanlohy, Nening M; van Baarle, Debbie; van Nuenen, Ad C; Hessell, Ann J; Schuitemaker, Hanneke

    2010-05-01

    Human immunodeficiency virus type 1 (HIV-1) resistance to broadly neutralizing antibodies such as b12, which targets the highly conserved CD4-binding site, raises a significant hurdle for the development of a neutralizing antibody-based vaccine. Here, 15 individuals were studied of whom seven developed b12-resistant viruses late in infection. The study investigated whether immune pressure may be involved in the selection of these viruses in vivo. Although four out of seven patients showed HIV-1-specific broadly neutralizing activity in serum, none of these patients had CD4-binding site-directed antibodies, indicating that strong humoral immunity is not a prerequisite for the outgrowth of b12-resistant viruses. In virus variants from one patient, who showed extremely weak heterologous and autologous neutralizing activity in serum, mutations were identified in the envelope that coincided with changes in b12 neutralization sensitivity. Lack of cytotoxic T-cell activity against epitopes with and without these mutations excluded a role for host cellular immunity in the selection of b12-resistant mutant viruses in this patient. However, b12 resistance correlated well with increased virus replication kinetics, indicating that selection for enhanced infectivity, possibly driven by the low availability of target cells in the later stages of disease, may coincide with increased resistance to CD4-binding site-directed agents, such as b12. These results showed that b12-resistant HIV-1 variants can emerge during the course of natural infection in the absence of both humoral and cellular immune pressure, suggestive of other mechanisms playing a role in the selective outgrowth of b12-resistant viruses.

  20. Heat dissipation does not suppress an immune response in laboratory mice divergently selected for basal metabolic rate (BMR).

    Science.gov (United States)

    Książek, Aneta; Konarzewski, Marek

    2016-05-15

    The capacity for heat dissipation is considered to be one of the most important constraints on rates of energy expenditure in mammals. To date, the significance of this constraint has been tested exclusively under peak metabolic demands, such as during lactation. Here, we used a different set of metabolic stressors, which do not induce maximum energy expenditures and yet are likely to expose the potential constraining effect of heat dissipation. We compared the physiological responses of mice divergently selected for high (H-BMR) and low basal metabolic rate (L-BMR) to simultaneous exposure to the keyhole limpet haemocyanin (KLH) antigen and high ambient temperature (Ta). At 34°C (and at 23°C, used as a control), KLH challenge resulted in a transient increase in core body temperature (Tb) in mice of both line types (by approximately 0.4°C). Warm exposure did not produce line-type-dependent differences in Tb (which was consistently higher by ca. 0.6°C in H-BMR mice across both Ta values), nor did it result in the suppression of antibody synthesis. These findings were also supported by the lack of between-line-type differences in the mass of the thymus, spleen or lymph nodes. Warm exposure induced the downsizing of heat-generating internal organs (small intestine, liver and kidneys) and an increase in intrascapular brown adipose tissue mass. However, these changes were similar in scope in both line types. Mounting a humoral immune response in selected mice was therefore not affected by ambient temperature. Thus, a combined metabolic challenge of high Ta and an immune response did not appreciably compromise the capacity to dissipate heat, even in the H-BMR mice. © 2016. Published by The Company of Biologists Ltd.

  1. The skin microbiome: Is it affected by UV-induced immune suppression?

    Directory of Open Access Journals (Sweden)

    Vijaykumar Patra

    2016-08-01

    Full Text Available Human skin apart from functioning as a physical barricade to stop the entry of pathogens, also hosts innumerable commensal organisms. The skin cells and the immune system constantly interact with microbes, to maintain cutaneous homeostasis, despite the challenges offered by various environmental factors. A major environmental factor affecting the skin is ultraviolet radiation UV-R from sunlight. UV-R is well known to modulate the immune system, which can be both beneficial and deleterious. By targeting the cells and molecules within skin, UV-R can trigger the production and release of antimicrobial peptides (AMPs, affect the innate immune system and ultimately suppress the adaptive cellular immune response. This can contribute to skin carcinogenesis and the promotion of infectious agents such as herpes simplex virus and possibly others. On the other hand, a UV-established immunosuppressive environment may protect against the induction of immunologically mediated skin diseases including some of photodermatoses such as polymorphic light eruption. In this article, we share our perspective about the possibility that UV-induced immune suppression may alter the landscape of the skin's microbiome and its components. Alternatively, or in concert with this, direct UV-induced DNA and membrane damage to the microbiome may result in pathogen associated molecular patterns (PAMPs that interfere with UV-induced immune suppression.

  2. Cord blood in regenerative medicine: do we need immune suppression?

    Directory of Open Access Journals (Sweden)

    Marleau Annette M

    2007-01-01

    Full Text Available Abstract Cord blood is currently used as an alternative to bone marrow as a source of stem cells for hematopoietic reconstitution after ablation. It is also under intense preclinical investigation for a variety of indications ranging from stroke, to limb ischemia, to myocardial regeneration. A major drawback in the current use of cord blood is that substantial morbidity and mortality are associated with pre-transplant ablation of the recipient hematopoietic system. Here we raise the possibility that due to unique immunological properties of both the stem cell and non-stem cell components of cord blood, it may be possible to utilize allogeneic cells for regenerative applications without needing to fully compromise the recipient immune system. Issues raised will include: graft versus host potential, the immunogeneicity of the cord blood graft, and the parallels between cord blood transplantation and fetal to maternal trafficking. The previous use of unmatched cord blood in absence of any immune ablation, as well as potential steps for widespread clinical implementation of allogeneic cord blood grafts will also be discussed.

  3. Clemastine causes immune suppression through inhibition of extracellular signal-regulated kinase-dependent proinflammatory cytokines.

    Science.gov (United States)

    Johansen, Pål; Weiss, Andreas; Bünter, Antonia; Waeckerle-Men, Ying; Fettelschoss, Antonia; Odermatt, Bernhard; Kündig, Thomas M

    2011-12-01

    Antihistamines are considered safe and used worldwide against allergy, pruritus, nausea, and cough and as sleeping aids. Nonetheless, a growing number of reports suggest that antihistamines also have immunoregulatory functions. We examined the extent and by what potential mechanisms histamine-1-receptor (H1R) antagonists exert immune suppressive effects. Immune suppression by antihistamines and immunosuppressants was tested in mice infected with Listeria monocytogenes. Potential modes of action were studied in vitro by using murine and human cells. We also tested whether injection of clemastine in healthy volunteers affected the activation of peripheral macrophages and monocytes. Finally, therapeutic application of clemastine-mediated immune suppression was tested in a murine model of sepsis. Clemastine and desloratadine strongly reduced innate responses to Listeria monocytogenes in mice as did dexamethasone. The immune suppression was MyD88 independent and characterized by inhibition of the mitogen-activated protein kinase-extracellular signal-regulated kinase signaling pathway, leading to overall impaired innate immunity with reduced TNF-α and IL-6 production. Surprisingly, the observed effects were H1R independent as demonstrated in H1R-deficient mice. Moreover, in a double-blind placebo-controlled clinical trial, 1 intravenous administration of clemastine reduced the TNF-α secretion potential of peripheral blood macrophages and monocytes. This inhibition could be exploited to treat sepsis in mice. The safety profile of antihistamines may need to be revisited. However, antihistamine-mediated immune suppression may also be exploited and find applications in the treatment of inflammatory diseases. Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  4. Human cellular and humoral immune responses to Phlebotomus papatasi salivary gland antigens in endemic areas differing in prevalence of Leishmania major infection.

    Directory of Open Access Journals (Sweden)

    Wafa Kammoun-Rebai

    2017-10-01

    Full Text Available Sand fly saliva compounds are able to elicit specific immune responses that have a significant role in Leishmania parasite establishment and disease outcome. Characterizing anti-saliva immune responses in individuals living in well defined leishmaniasis endemic areas would provide valuable insights regarding their effect on parasite transmission and establishment in humans.We explored the cellular and humoral immune responses to Phlebotomus (P. papatasi salivary gland extracts (SGE in individuals living in cutaneous leishmaniasis (CL old or emerging foci (OF, EF. OF was characterized by a higher infection prevalence as assessed by higher proportions of leishmanin skin test (LST positive individuals compared to EF. Subjects were further subdivided into healed, asymptomatic or naïve groups. We showed anti-SGE proliferation in less than 30% of the individuals, regardless of the immune status, in both foci. IFN-γ production was higher in OF and only observed in immune individuals from OF and naïve subjects from EF. Although IL-10 was not detected, addition of anti-human IL-10 antibodies revealed an increase in proliferation and IFN-γ production only in individuals from OF. The percentage of seropositive individuals was similar in immune and naïves groups but was significantly higher in OF. No correlation was observed between anti-saliva immune responses and LST response. High anti-SGE-IgG responses were associated with an increased risk of developing ZCL. No differences were observed for anti-SGE humoral or cellular responses among naïve individuals who converted or not their LST response or developed or not ZCL after the transmission season.These data suggest that individuals living in an old focus characterized by a frequent exposure to sand fly bites and a high prevalence of infection, develop higher anti-saliva IgG responses and IFN-γ levels and a skew towards a Th2-type cellular response, probably in favor of parasite establishment

  5. The effects of humoral, cellular and non-specific immunity on intracerebral Bordetella pertussis infections in mice.

    Science.gov (United States)

    Dolby, J. M.; Dolby, D. E.; Bronne-Shanbury, C. J.

    1975-01-01

    suppressive effect. Lymphocytes from fully protected once-vaccinated mice, transferred 2-3 weeks after intraperitoneal vaccination, were able to confer some protection when injected intraperitoneally or intracerebrally into recipient mice infected 2 weeks after transfer. Homologous, non-concentrated antiserum from once-vaccinated mice, injected intraperitoneally 1 hr. before infection sometimes augmented the transferred immunity, whereas alone it was inactive. Images Figs. 1-2 PMID:163275

  6. The historical association between measles and pertussis: A case of immune suppression?

    Directory of Open Access Journals (Sweden)

    Stephen Coleman

    2015-12-01

    Full Text Available Objectives: According to historical medical reports, many children with measles subsequently contracted pertussis, often with fatal results. The likelihood of a child contracting pertussis after a measles infection is increased by its immune-suppressing effects. This research aims to verify the historical reports. Methods: The analysis examines statistically the historical relationship between average measles and pertussis incidence rates in the United States from 1938 to 1954 at the state level and in average weekly rates. Analysis of incidence rates is cross-sectional at the state level using public health data. Results: The results show that, on average and over time, states with higher measles rates have higher pertussis rates, and the peaks and nadirs of average weekly incidence rates of pertussis lag measles by a delay of about 3–4 weeks, well within the duration of immune suppression. Measles and pertussis have similar geographical distributions. Conclusion: The research tentatively supports the hypothesis that because of its immune-suppressing effects, measles causes an increase in pertussis, but other factors may be involved. Epidemic models should give more attention to the possibility of immune suppression for diseases such as measles where that might be a risk factor. The findings reemphasize the importance of measles vaccination for the prevention of other diseases.

  7. The historical association between measles and pertussis: A case of immune suppression?

    Science.gov (United States)

    Coleman, Stephen

    2015-01-01

    Objectives: According to historical medical reports, many children with measles subsequently contracted pertussis, often with fatal results. The likelihood of a child contracting pertussis after a measles infection is increased by its immune-suppressing effects. This research aims to verify the historical reports. Methods: The analysis examines statistically the historical relationship between average measles and pertussis incidence rates in the United States from 1938 to 1954 at the state level and in average weekly rates. Analysis of incidence rates is cross-sectional at the state level using public health data. Results: The results show that, on average and over time, states with higher measles rates have higher pertussis rates, and the peaks and nadirs of average weekly incidence rates of pertussis lag measles by a delay of about 3–4 weeks, well within the duration of immune suppression. Measles and pertussis have similar geographical distributions. Conclusion: The research tentatively supports the hypothesis that because of its immune-suppressing effects, measles causes an increase in pertussis, but other factors may be involved. Epidemic models should give more attention to the possibility of immune suppression for diseases such as measles where that might be a risk factor. The findings reemphasize the importance of measles vaccination for the prevention of other diseases. PMID:27092263

  8. Immune suppression of challenged vaccinates as a rigorous assessment of sterile protection by lentiviral vaccines.

    Science.gov (United States)

    Craigo, Jodi K; Durkin, Shannon; Sturgeon, Timothy J; Tagmyer, Tara; Cook, Sheila J; Issel, Charles J; Montelaro, Ronald C

    2007-01-15

    We previously reported that an experimental live-attenuated equine infectious anemia virus (EIAV) vaccine, containing a mutated S2 accessory gene, provided protection from disease and detectable infection after virulent virus (EIAV(PV)) challenge [Li F, Craigo JK, Howe L, Steckbeck JD, Cook S, Issel C, et al. A live-attenuated equine infectious anemia virus proviral vaccine with a modified S2 gene provides protection from detectable infection by intravenous virulent virus challenge of experimentally inoculated horses. J Virol 2003;77(13):7244-53; Craigo JK, Li F, Steckbeck JD, Durkin S, Howe L, Cook SJ, et al. Discerning an effective balance between equine infectious anemia virus attenuation and vaccine efficacy. J Virol 2005;79(5):2666-77]. To determine if attenuated EIAV vaccines actually prevent persistent infection by challenge virus, we employed a 14-day dexamethasone treatment of vaccinated horses post-challenge to suppress host immunity and amplify replication levels of any infecting EIAV. At 2 months post-challenge the horses were all protected from virulent-virus challenge, evidenced by a lack of EIA signs and detectable challenge plasma viral RNA. Upon immune suppression, 6/12 horses displayed clinical EIA. Post-immune suppression characterizations demonstrated that the attenuated vaccine evidently prevented detectable challenge virus infection in 50% of horses. These data highlight the utility of post-challenge immune suppression for evaluating persistent viral vaccine protective efficacy.

  9. Signaling Circuits and Regulation of Immune Suppression by Ovarian Tumor-Associated Macrophages

    Directory of Open Access Journals (Sweden)

    Martin J. Cannon

    2015-05-01

    Full Text Available The barriers presented by immune suppression in the ovarian tumor microenvironment present one of the biggest challenges to development of successful tumor vaccine strategies for prevention of disease recurrence and progression following primary surgery and chemotherapy. New insights gained over the last decade have revealed multiple mechanisms of immune regulation, with ovarian tumor-associated macrophages/DC likely to fulfill a central role in creating a highly immunosuppressive milieu that supports disease progression and blocks anti-tumor immunity. This review provides an appraisal of some of the key signaling pathways that may contribute to immune suppression in ovarian cancer, with a particular focus on the potential involvement of the c-KIT/PI3K/AKT, wnt/β-catenin, IL-6/STAT3 and AhR signaling pathways in regulation of indoleamine 2,3-dioxygenase expression in tumor-associated macrophages. Knowledge of intercellular and intracellular circuits that shape immune suppression may afford insights for development of adjuvant treatments that alleviate immunosuppression in the tumor microenvironment and enhance the clinical efficacy of ovarian tumor vaccines.

  10. Immune-suppressive activity of punicalagin via inhibition of NFAT activation.

    Science.gov (United States)

    Lee, Sang-Ik; Kim, Byoung-Soo; Kim, Kyoung-Shin; Lee, Samkeun; Shin, Kwang-Soo; Lim, Jong-Soon

    2008-07-11

    Since T cell activation is central to the development of autoimmune diseases, we screened a natural product library comprising 1400 samples of medicinal herbal extracts, to identify compounds that suppress T cell activity. Punicalagin (PCG) isolated from the fruit of Punica granatum was identified as a potent immune suppressant, based on its inhibitory action on the activation of the nuclear factor of activated T cells (NFAT). PCG downregulated the mRNA and soluble protein expression of interleukin-2 from anti-CD3/anti-CD28-stimulated murine splenic CD4+ T cells and suppressed mixed leukocytes reaction (MLR) without exhibiting cytotoxicity to the cells. In vivo, the PCG treatment inhibited phorbol 12-myristate 13-acetate (PMA)-induced chronic ear edema in mice and decreased CD3+ T cell infiltration of the inflamed tissue. These results suggest that PCG could be a potential candidate for the therapeutics of various immune pathologies.

  11. The suppression of innate immune response by human rhinovirus C.

    Science.gov (United States)

    Pang, Li-Li; Yuan, Xin-Hui; Shao, Chang-Sheng; Li, Mao-Zhong; Wang, Ying; Wang, Hui-Min; Xie, Guang-Cheng; Xie, Zhi-Ping; Yuan, Yue; Zhou, Dong-Mei; Sun, Xiao-Man; Zhang, Qing; Xin, Yan; Li, Dan-di; Duan, Zhao-Jun

    2017-08-12

    Rhinovirus C (RV-C), a newly identified group of human rhinoviruses (RVs), is associated with exacerbation of severe asthma. The type I interferon (IFN) response induced by this virus and the mechanisms of evasion of IFN-mediated innate immunity for RV-C remain unclear. In this study, we constructed a full-length cDNA clone of RV-C (LZ651) from a clinical sample. IFN-β mRNA and protein levels were not elevated in differentiated Human bronchial epithelial (HBE) cells at the air-liquid interface infected with RV-C, except in the early stage of infection. The ability to attenuate IFN-β activation was ascribed to 3C(pro) of RV-C, and the 40-His site of 3C(pro) played an important role. Furthermore, RIG-I was degraded by 3C(pro) in a caspase-dependent manner and 3C(pro) cleaved MAVS at 148 Q/A, which inhibited IFN signaling. Taken together, our results demonstrate the mechanism by which RV-C circumvents the production of type I IFN in infected cells. Copyright © 2017. Published by Elsevier Inc.

  12. Equine influenza: evaluation of the humoral immune response through the hemagglutination inhibition and single radial haemolysis, in vaccinated horses with commercial and experimental vaccines

    Directory of Open Access Journals (Sweden)

    Dalva Assunção Portari Mancini

    1996-03-01

    Full Text Available Equine Influenza: evaluation of the humoral immune response through the hemagglutination inhibition and single radial haemolysis, in horses vaccinated with commercial and experimental vaccines. From 4 equine groups, the antibody protection levels against influenza were evaluted through the hemagglutination inhibition and single radial haemolysis. One group of these animals received immunization from 2 doses of influenza vaccine, of experimental preparation, at the Butantan Institute, São Paulo, Brasil (IB. Two other horse groups, regularly vaccinated received the annual booster dose from both commercial and experimental vaccines (IB. A control group remained without vaccination. Differences were observed among the antibody level medians of the serum samples harvested prior and post immunization of those vaccinated animals. No evident differences were detected among the antibody level medians from animals that received annual booster doses, due to the persistence of the protective antibody level, 12 months after the regular immunization. In the control group, the animals showed low antibody levels, for both serum samples. In fact these results suggested the good serologic response of both vaccines, the commercial and the experimental, tested preparations.

  13. Effect of supplementation of different levels of selenium as nanoparticles/sodium selenite on blood biochemical profile and humoral immunity in male Wistar rats

    Directory of Open Access Journals (Sweden)

    S. J. Bunglavan

    2014-12-01

    Full Text Available Aim: To study the effect of supplementation of different levels of selenium as nanoparticles/sodium selenite on blood biochemical profile and humoral immunity in male Wistar rats. Materials and Methods: The experimental research was conducted at Division of Animal Nutrition, Indian Veterinary Research Institute, Izatnagar. 63 male Wistar rats were divided into 9 equal groups on the basis of their mean body weight (BW (124.3±3.1 g BW following completely randomized design. Experimental feeding was similar in all the groups except for the source and level of selenium (Se in the diet. While Group 1 (control was fed a basal diet with no Se supplementation, in Groups 2 and 3, 150 ppb Se was supplemented either as sodium selenite or Se nanoparticles, respectively. In Groups 4, 5, 6 and 7, Se was supplemented as its nanoparticles at 50%, 25%, 12.5% and 6.25% levels respectively i.e. at 75 ppb, 37.5 ppb, 18.75 ppb and 9.375 ppb levels respectively. In Groups 8 and 9, 300 ppb Se was supplemented either as Se nanoparticles or sodium selenite, respectively. Experimental feeding was conducted for a period of 91 days. At the end of the experimental trial, blood samples were collected to analyze the blood serum biochemical profile (serum glucose, serum total protein (TP, serum albumin, serum globulin, serum albumin: globulin ratio [A:G ratio], serum total cholesterol and humoral immunity. Results: The levels of serum glucose, serum TP and serum albumin were comparable (p>0.05 among the nine groups of male Wistar rats. The mean serum total cholesterol was significantly (p<0.001 lowered in all the Se supplemented Wistar rats compared to the control group. The mean serum globulin level was significantly (p<0.05 higher and A:G ratio was significantly (p<0.05 lowered in Group 3 (supplemented with 150 ppb selenium nanoparticles followed by Groups 2, 4, 5, 6, 8, and 9 as compared to the control group. The mean serum antibody titer was significantly (p<0.001 higher

  14. Stress effect on humoral and cell mediated immune response: Indispensable part of corticosterone and cytokine in neutrophil function

    Directory of Open Access Journals (Sweden)

    Sakthivel Srinivasan

    2016-01-01

    Conclusion: This result further concludes that prior immunization of SRBC in animal’s act as a vaccination, which helps to prevent noise stress induced impairment in immune system. Orally administered I. tinctoria prevented noise altered immune system. These results also concluded that I. tinctoria supplementation could act as an immunomodulators and suggesting its therapeutic efficacy as an antistressor.

  15. Protein A Suppresses Immune Responses during Staphylococcus aureus Bloodstream Infection in Guinea Pigs

    Science.gov (United States)

    Kim, Hwan Keun; Falugi, Fabiana; Thomer, Lena; Missiakas, Dominique M.

    2015-01-01

    ABSTRACT   Staphylococcus aureus infection is not associated with the development of protective immunity, and disease relapses occur frequently. We hypothesize that protein A, a factor that binds immunoglobulin Fcγ and cross-links VH3 clan B cell receptors (IgM), is the staphylococcal determinant for host immune suppression. To test this, vertebrate IgM was examined for protein A cross-linking. High VH3 binding activity occurred with human and guinea immunoglobulin, whereas mouse and rabbit immunoglobulins displayed little and no binding, respectively. Establishing a guinea pig model of S. aureus bloodstream infection, we show that protein A functions as a virulence determinant and suppresses host B cell responses. Immunization with SpAKKAA, which cannot bind immunoglobulin, elicits neutralizing antibodies that enable guinea pigs to develop protective immunity. Importance  Staphylococcus aureus is the leading cause of soft tissue and bloodstream infections; however, a vaccine with clinical efficacy is not available. Using mice to model staphylococcal infection, earlier work identified protective antigens; however, corresponding human clinical trials did not reach their endpoints. We show that B cell receptor (IgM) cross-linking by protein A is an important immune evasion strategy of S. aureus that can be monitored in a guinea pig model of bloodstream infection. Further, immunization with nontoxigenic protein A enables infected guinea pigs to elicit antibody responses that are protective against S. aureus. Thus, the guinea pig model may support preclinical development of staphylococcal vaccines. PMID:25564466

  16. Induction of regulatory T cells by high-dose gp96 suppresses murine liver immune hyperactivation.

    Directory of Open Access Journals (Sweden)

    Xinghui Li

    Full Text Available Immunization with high-dose heat shock protein gp96, an endoplasmic reticulum counterpart of the Hsp90 family, significantly enhances regulatory T cell (Treg frequency and suppressive function. Here, we examined the potential role and mechanism of gp96 in regulating immune-mediated hepatic injury in mice. High-dose gp96 immunization elicited rapid and long-lasting protection of mice against concanavalin A (Con A-and anti-CD137-induced liver injury, as evidenced by decreased alanine aminotransaminase (ALT levels, hepatic necrosis, serum pro-inflammatory cytokines (IFN-γ, TNF-α, and IL-6, and number of IFN-γ (+ CD4(+ and IFN-γ (+ CD8(+ T cells in the spleen and liver. In contrast, CD4(+CD25(+Foxp3(+ Treg frequency and suppressive function were both increased, and the protective effect of gp96 could be generated by adoptive transfer of Treg cells from gp96-immunized mice. In vitro co-culture experiments demonstrated that gp96 stimulation enhanced Treg proliferation and suppressive function, and up-regulation of Foxp3, IL-10, and TGF-β1 induced by gp96 was dependent on TLR2- and TLR4-mediated NF-κB activation. Our work shows that activation of Tregs by high-dose gp96 immunization protects against Con A- and anti-CD137-induced T cell-hepatitis and provides therapeutic potential for the development of a gp96-based anti-immune hyperactivation vaccine against immune-mediated liver destruction.

  17. Induction of humoral and cellular immune response to hepatitis B virus (HBV) vaccine can be upregulated by CpG oligonucleotides complexed with Dectin-1 ligand.

    Science.gov (United States)

    Ito, H; Ando, T; Nakamura, M; Ishida, H; Kanbe, A; Kobiyama, K; Yamamoto, T; Ishii, K J; Hara, A; Seishima, M; Ishikawa, T

    2017-02-01

    A persistent hepatitis B virus (HBV) infection is characterized by a lack of or a weak immune response to HBV, which may be reflective of tolerance to HBV. Efficient induction of HBV-specific immune response leads to the clearance of HBV in patients with a chronic HBV infection. CpG oligodeoxynucleotides (ODN) has a powerful adjuvant effect in HBV vaccination. A recent report demonstrated that the immunization by B/K CpG ODN (K3) wrapped by the nonagonistic Dectin-1 ligand, schizophyllan (SPG), namely K3-SPG, was more effective in the induction of antigen-specific immune response than that by K3. In this study, we examined the efficacy of K3-SPG as a HBV vaccine adjuvant. Wild-type (WT) mice and HBV transgenic (HBV-Tg) mice were subcutaneously immunized with hepatitis B surface antigen (HBsAg) alone, HBsAg and K3, or HBsAg and K3-SPG. The vaccination with HBsAg and K3-SPG significantly enhanced humoral and cellular immune response to HBV antigen compared to the other vaccinations in WT and HBV-Tg mice. K3-SPG induced the accumulation of dendritic cells (DCs) into draining lymph node and the activation of DCs. The expression of cytokines and chemokines related to Th1 and Th2 responses was upregulated after the vaccination including with K3-SPG. In conclusion, these results indicated that the vaccination using K3-SPG may overcome tolerance even in patients with chronic HBV infection. © 2016 John Wiley & Sons Ltd.

  18. Cellular and humoral immune responses to a tetanus toxoid booster in perinatally HIV-1-infected children and adolescents receiving highly active antiretroviral therapy (HAART).

    Science.gov (United States)

    Ching, Natascha; Deville, Jaime G; Nielsen, Karin A; Ank, Bonnie; Wei, Lian S; Sim, Myung Shin; Wolinsky, Steven M; Bryson, Yvonne J

    2007-01-01

    Human immunodeficiency virus type 1 (HIV-1) infected children treated with highly active antiretroviral therapy (HAART) may develop a significant reduction of plasma viremia associated with an increase in CD4+ T-cell counts. Functional capacity of this reconstituted immune system in response to recall antigens is important to maintain protective immunity to vaccine-preventable diseases. We therefore determined cellular and humoral immune responses to tetanus toxoid (TT) booster in perinatally HIV-1-infected children and adolescents receiving HAART. Immune responses were prospectively evaluated pre- and post-tetanus booster using lymphocyte proliferation assay (LPA) stimulation index (SI > or = 3.0) and tetanus antibody (TAb > or = 0.15) in 15 patients. The median interval from primary tetanus immunization series was 6 years (range 2-12 years). We compared patients by their virological response to HAART (complete responders, CR, n=7; incomplete responders, ICR, n=8). There were no significant differences in median age 12.6 years (CR: 12.9; ICR: 10.6) or median CD4 T-cell pre-booster (CR: 35%/819; ICR: 26%/429) between groups. Tetanus LPA responses were observed in one patient prior to booster and in seven patients post-booster. In contrast, 38% of patients had protective TAb pre-booster, but 92% developed protective TAb post-booster. All of the CR and 5/6 ICR patients developed protective TAb. HIV-1-infected children and adolescents had modest LPA responses to tetanus following booster, similar to HIV-1-infected adults. However, the majority of patients developed protective TAb levels after booster and maintained the response. Shorter intervals may need to be considered for TT immunization boosters in HIV-1-infected pediatric patients, as only 38% had protective TAb at baseline.

  19. Abnormal humoral immune response to influenza vaccination in pediatric type-1 human immunodeficiency virus infected patients receiving highly active antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Carlos J Montoya

    2007-06-01

    Full Text Available Given that highly active antiretroviral therapy (HAART has been demonstrated useful to restore immune competence in type-1 human immunodeficiency virus (HIV-1-infected subjects, we evaluated the specific antibody response to influenza vaccine in a cohort of HIV-1-infected children on HAART so as to analyze the quality of this immune response in patients under antiretroviral therapy. Sixteen HIV-1-infected children and 10 HIV-1 seronegative controls were immunized with a commercially available trivalent inactivated influenza vaccine containing the strains A/H1N1, A/H3N2, and B. Serum hemagglutinin inhibition (HI antibody titers were determined for the three viral strains at the time of vaccination and 1 month later. Immunization induced a significantly increased humoral response against the three influenza virus strains in controls, and only against A/H3N2 in HIV-1-infected children. The comparison of post-vaccination HI titers between HIV-1+ patients and HIV-1 negative controls showed significantly higher HI titers against the three strains in controls. In addition, post vaccination protective HI titers (defined as equal to or higher than 1:40 against the strains A/H3N2 and B were observed in a lower proportion of HIV-1+ children than in controls, while a similar proportion of individuals from each group achieved protective HI titers against the A/H1N1 strain. The CD4+ T cell count, CD4/CD8 T cells ratio, and serum viral load were not affected by influenza virus vaccination when pre- vs post-vaccination values were compared. These findings suggest that despite the fact that HAART is efficient in controlling HIV-1 replication and in increasing CD4+ T cell count in HIV-1-infected children, restoration of immune competence and response to cognate antigens remain incomplete, indicating that additional therapeutic strategies are required to achieve a full reconstitution of immune functions.

  20. IRON AND HUMORAL IMMUNE RESPONSE IN PIGS FED PHYTASE-ADDED RATIONS WITH LOWER PHOSPHORUS LEVELS FERRO E IMUNIDADE HUMORAL EM SUÍNOS ALIMENTADOS COM FITASE E NÍVEIS REDUZIDOS DE FÓSFORO

    Directory of Open Access Journals (Sweden)

    Luiz Augusto Batista Brito

    2007-12-01

    Full Text Available

    Endogenous enzymes such as phytase have been widely used in swine production to increase phosphorus, amino acid and energy availability from feeds. This study aimed to evaluate the immune system through quantification of blood components associated to iron metabolism and determine humoral immune response elements in pigs fed phytase-added diets without micro minerals and vitamins and partial or total deletion of inorganic phosphorus. Forty-eight crossbred females with initial weight of 60 kg were randomly sorted into six groups of eight animals each, as follows: G1 -standard (complete ration (control group; G2 - standard ration except that micromineral and vitamin supplement was deleted; G3 - group 2 ration with phytase, G4 - group 2 ration less 1/3 of inorganic P with phytase, G5 -  group 2 ration less 2/3 of inorganic P with phytase and G6 - group 2 ration without inorganic P with phytase. Statistical difference (p>0,05 was not recorded neither in white cells and platelet counts nor hemoglobin, serum iron levels, considering all the animals in all treatments. Nevertheless, pigs up to 100 kg that consumed diet without micro minerals and vitamins, total deletion of inorganic P and phytase addition presented increased ferritin levels (p>0,05 when compared to animals fed similar diet with inorganic phosphorus and phytase. The enzyme guaranteed maintenance of iron stocks even in the absence of supplementation. Such difference was not recorded with 120-kg animals fed similar rations. Average total protein, IgG and IgM levels were not influenced by phytase, mineral and vitamin supplementation or inorganic phosphorus levels. The results demonstrate that decrease of inorganic phos-phorus, withdrawal of vitamin and mineral supplements and phytase addition in diets of finishing pigs do not lead to significant changes in hematological, biochemical and humoral immune response parameters.

  1. The Humoral Immune Response of Elks (Cervus elaphus nelsoni) and Mice to Vaccination with Brucella abortus Strain RB51

    OpenAIRE

    Colby, Lesley A.

    1997-01-01

    Vaccine Brucella abortus strain RB51, unlike the wild strain 2308 and another vaccine strain (strain 19) does not induce anti-O-chain antibodies. An efficacious vaccine strain that fails to produce an O-chain and thus a lack of an anti-O-chain humoral response greatly simplifies identification of vaccinated versus field strain infected animals. The three primary objectives of this research were the following: 1) to develop a serological assay to detect anti-RB51 antibodies in vaccinated elk (...

  2. Immunomodulatory effect of shikonin derivatives isolated from Lithospermum canescens on cellular and humoral immunity in Balb/c mice.

    Science.gov (United States)

    Pietrosiuk, A; Skopińska-Rózewska, E; Furmanowa, M; Wiedenfeld, H; Sommer, E; Sokolnicka, I; Rogala, E; Radomska-Leśniewska, D; Bany, J; Malinowski, M

    2004-08-01

    The immunomodulatory activity of acetylshikonin (ACS) and isobutyrylshikonin (IBS) was studied in female and male inbred Balb/c mice, and in F1 hybrids (Balb/c x C3H). ACS and IBS were isolated from Lithospermum canescens Lehm. (Boraginaceae) roots. Splenocytes from mice fed 40 microg of ACS had higher proliferative potential in cultures with PHA than corresponding controls and also higher migratory in vitro activity than splenocytes obtained from control animals. ACS at a 40 microg daily dose stimulated G-v-H reaction but inhibited it at a 200 microg dose. IBS at a 40 microg dose significantly increased humoral response.

  3. Potential Suppressive Effects of Two C60 Fullerene Derivatives on Acquired Immunity.

    Science.gov (United States)

    Hirai, Toshiro; Yoshioka, Yasuo; Udaka, Asako; Uemura, Eiichiro; Ohe, Tomoyuki; Aoshima, Hisae; Gao, Jian-Qing; Kokubo, Ken; Oshima, Takumi; Nagano, Kazuya; Higashisaka, Kazuma; Mashino, Tadahiko; Tsutsumi, Yasuo

    2016-12-01

    The therapeutic effects of fullerene derivatives on many models of inflammatory disease have been demonstrated. The anti-inflammatory mechanisms of these nanoparticles remain to be elucidated, though their beneficial roles in allergy and autoimmune diseases suggest their suppressive potential in acquired immunity. Here, we evaluated the effects of C60 pyrrolidine tris-acid (C60-P) and polyhydroxylated fullerene (C60(OH)36) on the acquired immune response in vitro and in vivo. In vitro, both C60 derivatives had dose-dependent suppressive effects on T cell receptor-mediated activation of T cells and antibody production by B cells under anti-CD40/IL-4 stimulation, similar to the actions of the antioxidant N-acetylcysteine. In addition, C60-P suppressed ovalbumin-specific antibody production and ovalbumin-specific T cell responses in vivo, although T cell-independent antibodies responses were not affected by C60-P. Together, our data suggest that fullerene derivatives can suppress acquired immune responses that require T cells.

  4. Plum pox virus capsid protein suppresses plant pathogen-associated molecular pattern (PAMP)-triggered immunity.

    Science.gov (United States)

    Nicaise, Valerie; Candresse, Thierry

    2017-08-01

    The perception of pathogen-associated molecular patterns (PAMPs) by immune receptors launches defence mechanisms referred to as PAMP-triggered immunity (PTI). Successful pathogens must suppress PTI pathways via the action of effectors to efficiently colonize their hosts. So far, plant PTI has been reported to be active against most classes of pathogens, except viruses, although this defence layer has been hypothesized recently as an active part of antiviral immunity which needs to be suppressed by viruses for infection success. Here, we report that Arabidopsis PTI genes are regulated upon infection by viruses and contribute to plant resistance to Plum pox virus (PPV). Our experiments further show that PPV suppresses two early PTI responses, the oxidative burst and marker gene expression, during Arabidopsis infection. In planta expression of PPV capsid protein (CP) was found to strongly impair these responses in Nicotiana benthamiana and Arabidopsis, revealing its PTI suppressor activity. In summary, we provide the first clear evidence that plant viruses acquired the ability to suppress PTI mechanisms via the action of effectors, highlighting a novel strategy employed by viruses to escape plant defences. © 2016 BSPP AND JOHN WILEY & SONS LTD.

  5. Visceral schistosomiasis of domestic animals in India: humoral immune status of infected cattle, sheep and goats against major polypeptide antigens of Schistosoma indicum and S. spindale.

    Science.gov (United States)

    Singh, A; Singh, A; Chaudhri, S S

    2004-04-01

    Polypeptide profiles of Schistosoma indicum and S. spindale adult worm homogenates were obtained by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. Humoral immune status of infected cattle, sheep and goats against Schistosoma indicum and S. spindale Ags was determined by immunoblot analysis and by indirect ELISA using four major polypeptides of approximate molecular masses 45 kDa, 40 kDa, 28 kDa and 15 kDa electro-eluted from the gel slices. Cattle sera samples had higher levels of antibodies against Si/s40 and Si/s28 than against Si/s45 antigen. Reasons have been discussed for the absence of detectable levels of anti-Si/s28, -Si/s45 and -Si/s40 antibodies in a significant number of sera samples from S. indicum egg-positive sheep.

  6. Infection with the Lyme disease pathogen suppresses innate immunity in mice with diet-induced obesity.

    Science.gov (United States)

    Zlotnikov, Nataliya; Javid, Ashkan; Ahmed, Mijhgan; Eshghi, Azad; Tang, Tian Tian; Arya, Anoop; Bansal, Anil; Matar, Fatima; Parikh, Maitry; Ebady, Rhodaba; Koh, Adeline; Gupta, Nupur; Song, Peng; Zhang, Yang; Newbigging, Susan; Wormser, Gary P; Schwartz, Ira; Inman, Robert; Glogauer, Michael; Moriarty, Tara J

    2017-05-01

    Obesity is a major global public health concern. Immune responses implicated in obesity also control certain infections. We investigated the effects of high-fat diet-induced obesity (DIO) on infection with the Lyme disease bacterium Borrelia burgdorferi in mice. DIO was associated with systemic suppression of neutrophil- and macrophage-based innate immune responses. These included bacterial uptake and cytokine production, and systemic, progressive impairment of bacterial clearance, and increased carditis severity. B. burgdorferi-infected mice fed normal diet also gained weight at the same rate as uninfected mice fed high-fat diet, toll-like receptor 4 deficiency rescued bacterial clearance defects, which greater in female than male mice, and killing of an unrelated bacterium (Escherichia coli) by bone marrow-derived macrophages from obese, B. burgdorferi-infected mice was also affected. Importantly, innate immune suppression increased with infection duration and depended on cooperative and synergistic interactions between DIO and B. burgdorferi infection. Thus, obesity and B. burgdorferi infection cooperatively and progressively suppressed innate immunity in mice. © 2016 The Authors Cellular Microbiology Published by John Wiley & Sons Ltd.

  7. NLRP3 signaling drives macrophage-induced adaptive immune suppression in pancreatic carcinoma

    Science.gov (United States)

    Daley, Donnele; Mani, Vishnu R.; Mohan, Navyatha; Akkad, Neha; Savadkar, Shivraj; Lee, Ki Buom; Torres-Hernandez, Alejandro; Aykut, Berk; Diskin, Brian; Wang, Wei; Farooq, Mohammad S.; Mahmud, Arif I.; Werba, Gregor; Morales, Eduardo J.; Lall, Sarah; Rubin, Amanda G.; Berman, Matthew E.; Hundeyin, Mautin

    2017-01-01

    The tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDA) is characterized by immune tolerance, which enables disease to progress unabated by adaptive immunity. However, the drivers of this tolerogenic program are incompletely defined. In this study, we found that NLRP3 promotes expansion of immune-suppressive macrophages in PDA. NLRP3 signaling in macrophages drives the differentiation of CD4+ T cells into tumor-promoting T helper type 2 cell (Th2 cell), Th17 cell, and regulatory T cell populations while suppressing Th1 cell polarization and cytotoxic CD8+ T cell activation. The suppressive effects of NLRP3 signaling were IL-10 dependent. Pharmacological inhibition or deletion of NLRP3, ASC (apoptosis-associated speck-like protein containing a CARD complex), or caspase-1 protected against PDA and was associated with immunogenic reprogramming of innate and adaptive immunity within the TME. Similarly, transfer of PDA-entrained macrophages or T cells from NLRP3−/− hosts was protective. These data suggest that targeting NLRP3 holds the promise for the immunotherapy of PDA. PMID:28442553

  8. Suppression of intestinal immunity through silencing of TCTP by RNAi in transgenic silkworm, Bombyx mori.

    Science.gov (United States)

    Hu, Cuimei; Wang, Fei; Ma, Sanyuan; Li, Xianyang; Song, Liang; Hua, Xiaoting; Xia, Qingyou

    2015-12-10

    Intestinal immune response is a front line of host defense. The host factors that participate in intestinal immunity response remain largely unknown. We recently reported that Translationally Controlled Tumor Protein (BmTCTP) was obtained by constructing a phage display cDNA library of the silkworm midgut and carrying out high throughput screening of pathogen binding molecules. To further address the function of BmTCTP in silkworm intestinal immunity, transgenic RNAi silkworms were constructed by microinjection piggBac plasmid to Dazao embryos. The antimicrobial capacity of transgenic silkworm decreased since the expression of gut antimicrobial peptide from transgenic silkworm was not sufficiently induced during oral microbial challenge. Moreover, dynamic ERK phosphorylation from transgenic silkworm midgut was disrupted. Taken together, the innate immunity of intestinal was suppressed through disruption of dynamic ERK phosphorylation after oral microbial infection as a result of RNAi-mediated knockdown of midgut TCTP in transgenic silkworm. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Mycotoxin Patulin Suppresses Innate Immune Responses by Mitochondrial Dysfunction and p62/Sequestosome-1-dependent Mitophagy.

    Science.gov (United States)

    Tsai, Wan-Ting; Lo, Yin-Chiu; Wu, Ming-Sian; Li, Chia-Yang; Kuo, Yi-Ping; Lai, Yi-Hui; Tsai, Yu; Chen, Kai-Chieh; Chuang, Tsung-Hsien; Yao, Chun-Hsu; Lee, Jinq-Chyi; Hsu, Li-Chung; Hsu, John T-A; Yu, Guann-Yi

    2016-09-09

    Innate immune responses are important for pathogen elimination and adaptive immune response activation. However, excess inflammation may contribute to immunopathology and disease progression (e.g. inflammation-associated hepatocellular carcinoma). Immune modulation resulting from pattern recognition receptor-induced responses is a potential strategy for controlling immunopathology and related diseases. This study demonstrates that the mycotoxin patulin suppresses Toll-like receptor- and RIG-I/MAVS-dependent cytokine production through GSH depletion, mitochondrial dysfunction, the activation of p62-associated mitophagy, and p62-TRAF6 interaction. Blockade of autophagy restored the immunosuppressive activity of patulin, and pharmacological activation of p62-dependent mitophagy directly reduced RIG-I-like receptor-dependent inflammatory cytokine production. These results demonstrated that p62-dependent mitophagy has an immunosuppressive role to innate immune response and might serve as a potential immunomodulatory target for inflammation-associated diseases. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Mycotoxin Patulin Suppresses Innate Immune Responses by Mitochondrial Dysfunction and p62/Sequestosome-1-dependent Mitophagy *

    Science.gov (United States)

    Tsai, Wan-Ting; Lo, Yin-Chiu; Wu, Ming-Sian; Li, Chia-Yang; Kuo, Yi-Ping; Lai, Yi-Hui; Tsai, Yu; Chen, Kai-Chieh; Chuang, Tsung-Hsien; Yao, Chun-Hsu; Lee, Jinq-Chyi; Hsu, Li-Chung; Hsu, John T.-A.; Yu, Guann-Yi

    2016-01-01

    Innate immune responses are important for pathogen elimination and adaptive immune response activation. However, excess inflammation may contribute to immunopathology and disease progression (e.g. inflammation-associated hepatocellular carcinoma). Immune modulation resulting from pattern recognition receptor-induced responses is a potential strategy for controlling immunopathology and related diseases. This study demonstrates that the mycotoxin patulin suppresses Toll-like receptor- and RIG-I/MAVS-dependent cytokine production through GSH depletion, mitochondrial dysfunction, the activation of p62-associated mitophagy, and p62-TRAF6 interaction. Blockade of autophagy restored the immunosuppressive activity of patulin, and pharmacological activation of p62-dependent mitophagy directly reduced RIG-I-like receptor-dependent inflammatory cytokine production. These results demonstrated that p62-dependent mitophagy has an immunosuppressive role to innate immune response and might serve as a potential immunomodulatory target for inflammation-associated diseases. PMID:27458013

  11. Assessment of yeast cell wall as replacements for antibiotic growth promoters in broiler diets: effects on performance, intestinal histo-morphology and humoral immune responses.

    Science.gov (United States)

    Ghosh, T K; Haldar, S; Bedford, M R; Muthusami, N; Samanta, I

    2012-04-01

    The study compared the effects of an antibiotic growth promoter (AGP), yeast (Saccharomyces cerevisiae) and yeast cell wall (YCW) on performance, microbiology and histo-morphology of the small intestine and humoral immune responses in Ross 308 broilers. The treatments (eight replicates/treatment, n = 12/replicate) were negative control (NC, without AGP), positive control (PC, supplemented with bacitracin methylene disalicylate, 400 mg/kg), Y and YCW (supplemented with yeast and YCW, respectively, 1000 mg/kg). Live weight at 42 days improved (p = 0.086) in the PC, Y and YCW groups. Feed conversion ratio was better (p = 0.039) in the YCW group compared with the other groups. Antibiotic growth promoter in the PC group shortened the villi in duodenum (p = 0.044). Mucosal Escherichia coli number was higher in the PC group (p < 0.001), whereas in the digesta E. coli number was lower (p = 0.001) in the PC, Y and YCW groups in relation to the NC. Mucosal Salmonella populations increased (p = 0.0001) in the PC group, whereas in the digesta, all treatments reduced the Salmonella (p = 0.0001). Following oral challenge with Salmonella pullorum, YCW increased E. coli numbers on the mucosa (p < 0.001) whereas in the digesta the Y group had lower (p < 0.0001) number of E. coli. In the digesta, Salmonella count was lower in the YCW group compared with the other treatments (p < 0.01). Yeast cell wall -treated birds exhibited better (p < 0.05) humoral immune response against Newcastle disease which was far more persistent over time than in any other treatments. It was concluded that the yeast and the yeast cell wall may have effects identical to BMD on performance of broilers and thus may constitute an effective replacement strategy in the dietary regimens for broiler chickens. © 2011 Blackwell Verlag GmbH.

  12. Suppression of the cutaneous immune response following topical application of the prostaglandin PGE2

    Energy Technology Data Exchange (ETDEWEB)

    Rheins, L.A.; Barnes, L.; Amornsiripanitch, S.; Collins, C.E.; Nordlund, J.J.

    1987-04-15

    UVB irradiation (290-320 nm) and topical applications of arachidonic acid (AA) in mice decrease the number of identifiable Langerhans cells and alter the cutaneous immune response. Application of contact allergens such as dinitrofluorobenzene (DNFB) to irradiated or AA-treated skin induces antigen-specific tolerance. Indomethacin (IM), a cyclooxygenase inhibitor, administered orally to mice prior to UVB irradiation or prior to the topical application of arachidonic acid, abrogates suppression of contact hypersensitivity (CHS) to DNFB. This suggests a byproduct of arachidonic acid generated through the cyclooxygenase pathway may be involved in the immune suppression. Topical application of various prostaglandins (PGE2, PGD2, PGF2 alpha, and CTXA2) did not cause alterations in the population density of the identifiable Ia+ dendritic Langerhans cells. PGE2, but no other tested agent, produced a suppression of the CHS response to DNFB. These observations suggests that of the various prostaglandins, PGE2 might be one of several biochemical signals which mediate the suppression of contact hypersensitivity reactions following ultraviolet radiation exposure. However, the mechanisms by which PGE2 produces its suppressive effects have not been identified.

  13. DNA vaccination of neonate piglets in the face of maternal immunity induces humoral memory and protection against a virulent pseudorabies virus challenge.

    Science.gov (United States)

    Fischer, Laurent; Barzu, Simona; Andreoni, Christine; Buisson, Nathalie; Brun, André; Audonnet, Jean Christophe

    2003-04-02

    DNA vaccination represents a unique opportunity to overcome the limitations of conventional vaccine strategy in early life in the face of maternal-derived immunity. We used the model of pseudorabies virus (PRV) infection in pigs to further explore the potential of DNA vaccination in piglets born to sows repeatedly vaccinated with a PRV inactivated vaccine. A single immunisation of 8-week-old piglets with a DNA vaccine expressing secreted forms of PRV gB, gC, and gD, triggered an active serological response, confirming that DNA vaccination can over-ride significant residual maternal-derived immunity. A clear anamnestic response was evidenced when a secondary DNA vaccination was performed at 11 weeks of age, suggesting that DNA vaccination, performed in the face of passive immunity, elicited a strong humoral memory. We subsequently explored the potential of DNA vaccination in neonate piglets (5-6 days of age) in the face of very high titres of maternal antibodies and demonstrated that very high titres of passive antibodies selectively inhibited serological responses but not the establishment of potent memory responses. Finally, we demonstrated that DNA vaccination provided protection against an infectious PRV challenge at the end of the fattening period (i.e. at approximately 5 months of age). Collectively, our results pave the way for a new flexible vaccination program, which could ensure uninterrupted protection of fattening pigs over their entire economical life under field conditions.

  14. Evaluation of Humoral Immune Response against Somatic and Excretory-Secretory Antigens of Dicrocoelium Dendriticum in Infected Sheep by Western Blot

    Directory of Open Access Journals (Sweden)

    Mohammad Hosein Razi Jalali

    2013-12-01

    Full Text Available Introduction and objective: Dicrocoelium dendriticum is a worldwide spread parasite of liver, bile ducts and gallbladder of especially ruminants and humans as well. Identification of specific antigens is useful for early diagnosis of the infection. The goal of this study was the isolation and identification of excretory-secretory and somatic antigens from D. dendriticum by sodium dodecyl sulphate (SDS-PAGE and evaluation of humoral immune response against these antigens.   Methods: The parasites were collected and washed by phosphate buffered saline (PBS and supplemented by antibiotic for several times. For preparing somatic antigens, parasites were sonicated and centrifuged prior to collect supernatant. For preparing excretory-secretory antigens the viable parasites were transferred to the sterile medium. The samples were centrifuged and supernatants were collected. The sera of infected sheep with different infection degrees were collected too. Somatic and excretory-secretory proteins were isolated with SDS PAGE and stained with coomassie blue. Immunogenicity properties of the resulting proteins were determined using western blot analysis.   Results: The total extract of somatic antigens analyzed by SDS-PAGE revealed 21 proteins. In mild infection, bands of 130 KDa were immune dominant. In moderate infections 48, 80 and 130 KDa and in heavy infections 48, 60, 80, 130 KDa were detected as immune dominant bands. In excretory- secretory antigens seven bands of protein were detected. In mild infection 130 KDa, in moderate infection 100, 120 and 130 KDa and in heavy infection 45, 80, 85, 100, 120 and 130 KDa were immune dominant bands.   Conclusion: Probably the most immunogenic protein band during different degrees of infection was 130KDa that can be used for vaccination and inducing immunity.

  15. Low molecular weight Cooperia oncophora antigens: characterization and humoral immune responses in calves mono-infected with 100,000 infective larvae.

    Science.gov (United States)

    Parmentier, H K; Ploeger, H W; Nieuwland, M G; Souren, P J; Van Pinxteren, L A; Rietveld, F W; De Vries Reilingh, G; Kloosterman, A

    1995-10-01

    Characteristics of the humoral immune response of Cooperia oncophora-infected calves to low molecular weight antigens of C. oncophora were studied. Immunoblotting with sera obtained from calves 6 weeks after a single oral infection with 100,000 third-stage (L3) C. oncophora larvae revealed several corresponding antigenic fragments between adult worms and the fourth-stage (L4) larvae. No reactivity in the immune sera was found against the L3 stage. A previously defined complex of low molecular weight proteins (12-15 kDa) was found on both L4 and adult Cooperia stages, but not on the L3 stage. C. oncophora adults differed from the L4 larvae at the 31/32 and 37 kDa level. Several adult and L4 proteins were bound by biotinylated Concanavalin A, as was also true for L3 proteins. A 31/32 kDa glycoprotein of adult worms was recognised by a monoclonal antibody with specificity for phosphorylcholine. Using monoclonal antibodies in ELISA and Western blotting, the serum antibody response of C. oncophora-infected calves to adult worm antigen was almost entirely IgG1. Binding of the IgG1 antibodies was restricted to a complex of reduced 12-15 kDa protein(s) and a 27 kDa fragment of adult worms. The data suggest that the systemic humoral immune response of calves during a primary infection with C. oncophora consists mainly of an IgG1 response, and is directed to a non-glycosylated Cooperia protein (molecular weight estimated at 12-15 kDa under reducing conditions and 18 kDa under nonreducing conditions). This protein is probably present in both L4 larvae and adults. Since it was not bound by immune sera from calves mono-infected with several other nematodes, the 12-15 kDa protein complex may represent a Cooperia-specific component that can be used for serodiagnosis.

  16. Humoral Immune Reconstitution Kinetics after Allogeneic Hematopoietic Stem Cell Transplantation in Children: A Maturation Block of IgM Memory B Cells May Lead to Impaired Antibody Immune Reconstitution.

    Science.gov (United States)

    Abdel-Azim, Hisham; Elshoury, Amro; Mahadeo, Kris M; Parkman, Robertson; Kapoor, Neena

    2017-09-01

    Although T cell immune reconstitution after allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been well studied, long-term B cell immune reconstitution remains less characterized. We evaluated humoral immune reconstitution among 71 pediatric allo-HSCT recipients. Although tetanus toxoid antibody levels were normal at 1 year after allo-HSCT, antipolysaccharide carbohydrate antibodies remained persistently low for up to 5 years. While naive B cell counts normalized by 6 months, IgM memory B cell deficiency persisted for up to 2 years (P = .01); switched memory B cell deficiency normalized by 1 year after allo-HSCT. CD4(+) T cell immune reconstitution correlated with that of switched memory B cells as early as 6 months after allo-HSCT (r = .55, P = .002) but did not correlate with IgM memory B cells at any time point after allo-HSCT. Taken together, this suggests that allo-HSCT recipients have impaired antibody immune reconstitution, mainly due to IgM memory B cell maturation block, compared with more prompt T cell-dependent switched memory cell immune reconstitution. We further explored other factors that might affect humoral immune reconstitution. The use of total body irradiation was associated with lower naive B cells counts at 6 months after HSCT (P = .04) and lower IgM (P = .008) and switched (P = .003) memory B cells up to 2 years. Allo-HSCT recipients with extensive chronic graft-versus-host disease had lower IgM memory B cell counts (P = .03) up to 2 years after allo-HSCT. The use of cord blood was associated with better naive (P = .01), IgM (P = .0005), and switched memory (P = .006) B cells immune reconstitution. These findings may inform future prophylaxis and treatment strategies regarding risk of overwhelming infection, graft-versus-host disease, and post-allogeneic HSCT revaccination. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights

  17. Synthetic double-stranded RNAs are adjuvants for the induction of T helper 1 and humoral immune responses to human papillomavirus in rhesus macaques.

    Directory of Open Access Journals (Sweden)

    Christiane Stahl-Hennig

    2009-04-01

    for virus-specific Th1 and humoral immune responses in nonhuman primates.

  18. The paradox of chronic neuroinflammation, systemic immune suppression and autoimmunity after traumatic chronic spinal cord injury

    Science.gov (United States)

    Kopp, Marcel A.; Brommer, Benedikt; Popovich, Phillip G.

    2014-01-01

    During the transition from acute to chronic stages of recovery after spinal cord injury (SCI), there is an evolving state of immunologic dysfunction that exacerbates the problems associated with the more clinically obvious neurologic deficits. Since injury directly affects cells embedded within the “immune privileged/specialized” milieu of the spinal cord, maladaptive or inefficient responses are likely to occur. Collectively, these responses qualify as part of the continuum of “SCI disease” and are important therapeutic targets to improve neural repair and neurological outcome. Generic immune suppressive therapies have been largely unsuccessful, mostly because nflammation and immunity exert both beneficial (plasticity enhancing) and detrimental (e.g. glia- and neurodegenerative; secondary damage) effects and these functions change over time. Moreover, “compartmentalized” investigations, limited to only intraspinal inflammation and associated cellular or molecular changes in the spinal cord, neglect the reality that the structure and function of the CNS is influenced by systemic immune challenges and that the immune system is hardwired into the nervous system. Here, we consider this interplay during the progression from acute to chronic SCI. Specifically, we survey impaired/non-resolving intraspinal inflammation and the paradox of systemic inflammatory responses in the face of ongoing chronic immune suppression and autoimmunity. The concepts of systemic inflammatory response syndrome (SIRS), compensatory anti-inflammatory response syndrome (CARS) and ‘neurogenic’ spinal cord injury-induced immune depression syndrome (SCI-IDS) are discussed as determinants of impaired ‘host-defense’ and trauma-induced autoimmunity. PMID:25017893

  19. Probiotic Cheese Attenuates Exercise-induced Immune Suppression In Wistar Rats

    OpenAIRE

    Lollo P.C.B.; Cruz A.G.; Morato P.N.; Moura C.S.; Carvalho-Silva L.B.; Oliveira C.A.F.; Faria J.A.F.; Amaya-Farfan J.

    2012-01-01

    Intense physical activity results in a substantial volume of stress and hence a significant probability of immunosuppression in athletes, with milk proteins being, perhaps, the most recommended protein supplements. Consumption of a probiotic cheese can attenuate immune suppression induced by exhausting exercise in rats. A popular Brazilian fresh cheese (Minas Frescal cheese) containing Lactobacillus acidophilus LA14 and Bifidobacterium longum BL05 was fed for 2 wk to adult Wistar rats, which ...

  20. IMMUNE SUPPRESSION OF CHALLENGED VACCINATES AS A RIGOROUS ASSESSMENT OF STERILE PROTECTION BY LENTIVIRAL VACCINES

    OpenAIRE

    Craigo, Jodi K.; Durkin, Shannon; Sturgeon, Timothy J.; Tagmyer, Tara; Cook, Sheila J.; Issel, Charles J.; Montelaro, Ronald C.

    2006-01-01

    We previously reported that an experimental live-attenuated equine infectious anemia virus (EIAV) vaccine, containing a mutated S2 accessory gene, provided protection from disease and detectable infection after virulent virus (EIAVPV) challenge [1,2]. To determine if attenuated EIAV vaccines actually prevent persistent infection by challenge virus, we employed a 14-day dexamethasone treatment of vaccinated horses post-challenge to suppress host immunity and amplify replication levels of any i...

  1. Systemic immune suppression in glioblastoma: the interplay between CD14+HLA-DRlo/neg monocytes, tumor factors, and dexamethasone

    OpenAIRE

    Gustafson, Michael P.; Lin, Yi; New, Kent C.; Bulur, Peggy A.; O'Neill, Brian Patrick; Gastineau, Dennis A.; Dietz, Allan B.

    2010-01-01

    Patients with glioblastoma (GBM) exhibit profound systemic immune defects that affect the success of conventional and immune-based treatments. A better understanding of the contribution of the tumor and/or therapy on systemic immune suppression is necessary for improved therapies, to monitor negative effects of novel treatments, to improve patient outcomes, and to increase understanding of this complex system. To characterize the immune profile of GBM patients, we phenotyped peripheral blood ...

  2. Human papillomavirus (HPV upregulates the cellular deubiquitinase UCHL1 to suppress the keratinocyte's innate immune response.

    Directory of Open Access Journals (Sweden)

    Rezaul Karim

    Full Text Available Persistent infection of basal keratinocytes with high-risk human papillomavirus (hrHPV may cause cancer. Keratinocytes are equipped with different pattern recognition receptors (PRRs but hrHPV has developed ways to dampen their signals resulting in minimal inflammation and evasion of host immunity for sustained periods of time. To understand the mechanisms underlying hrHPV's capacity to evade immunity, we studied PRR signaling in non, newly, and persistently hrHPV-infected keratinocytes. We found that active infection with hrHPV hampered the relay of signals downstream of the PRRs to the nucleus, thereby affecting the production of type-I interferon and pro-inflammatory cytokines and chemokines. This suppression was shown to depend on hrHPV-induced expression of the cellular protein ubiquitin carboxyl-terminal hydrolase L1 (UCHL1 in keratinocytes. UCHL1 accomplished this by inhibiting tumor necrosis factor receptor-associated factor 3 (TRAF3 K63 poly-ubiquitination which lead to lower levels of TRAF3 bound to TANK-binding kinase 1 and a reduced phosphorylation of interferon regulatory factor 3. Furthermore, UCHL1 mediated the degradation of the NF-kappa-B essential modulator with as result the suppression of p65 phosphorylation and canonical NF-κB signaling. We conclude that hrHPV exploits the cellular protein UCHL1 to evade host innate immunity by suppressing PRR-induced keratinocyte-mediated production of interferons, cytokines and chemokines, which normally results in the attraction and activation of an adaptive immune response. This identifies UCHL1 as a negative regulator of PRR-induced immune responses and consequently its virus-increased expression as a strategy for hrHPV to persist.

  3. A novel hydrophobized polysaccharide/oncoprotein complex vaccine induces in vitro and in vivo cellular and humoral immune responses against HER2-expressing murine sarcomas.

    Science.gov (United States)

    Gu, X G; Schmitt, M; Hiasa, A; Nagata, Y; Ikeda, H; Sasaki, Y; Akiyoshi, K; Sunamoto, J; Nakamura, H; Kuribayashi, K; Shiku, H

    1998-08-01

    To elicit specific cellular immune responses against cancer, the development of efficient devices to deliver tumor antigen peptides to the MHC class I pathway constitutes a central issue. We report here a novel formula of hydrophobized polysaccharide nanoparticles, which can deliver a HER2 oncoprotein containing an epitope peptide to the MHC class I pathway. A protein consisting of the 147 amino-terminal amino acids of oncogene erbB-2/neu/HER2 (HER2) was complexed with two kinds of hydrophobized polysaccharides, cholesteryl group-bearing mannan (CHM) and cholesteryl group-bearing pullulan (CHP), to form nanoparticles (CHM-HER2 and CHP-HER2). CHM-HER2 and CHP-HER2 were able to induce CD3+/CD8+ CTLs against HER2-transfected syngeneic fibrosarcoma cell lines. In contrast, the oncoprotein alone failed to do so. These CTLs were Kd-restricted and specifically recognized a peptide (position 63-71) that was a part of a truncated HER2 protein used as an immunogen. In addition, vaccination by CHM-HER2 complexes led to a strongly enhanced production of IgG antibodies against HER2, whereas vaccination with HER2 proteins alone resulted in a production of antibodies at a marginal level. Mice immunized with CHM-HER2 or CHP-HER2 before tumor challenge successfully rejected HER2-transfected tumors. The complete rejection of tumors also occurred when CHM-HER2 was applied not later than 3 days after tumor implantation. In the effector phase of in vivo tumor rejection, CD8+ T cells played a major role. The results suggest that a sort of hydrophobized polysaccharide may help soluble proteins to induce cellular immunity as well enhance humoral immunity; hence, such a novel vaccine may be of potential benefit to cancer prevention and cancer therapy.

  4. Humoral immune responses to VP4 and its cleavage products VP5* and VP8* in infants vaccinated with rhesus rotavirus.

    Science.gov (United States)

    Padilla-Noriega, L; Fiore, L; Rennels, M B; Losonsky, G A; Mackow, E R; Greenberg, H B

    1992-06-01

    The humoral immune response to rhesus rotavirus (RRV) VP4 and its cleavage products VP5* and VP8* was determined in paired serum samples from 44 infants vaccinated with RRV or human rotavirus-RRV reassortants and 5 placebo recipients. Our aim was to try to measure the response to those regions of VP4 most closely related to protection. An enzyme-linked immunosorbent assay (ELISA) was used to measure the immunoglobulin G immune response to baculovirus-expressed full-length RRV VP4, full-length VP8*, and the amino-terminal polypeptide of VP5* called VP5*(1) (amino acids 248 to 474). The two antigenic regions of VP4 selected for study, VP5*(1) and VP8*, have previously been shown to contain most of the cross-reactive and strain-specific neutralization epitopes, respectively, while the remaining carboxy-terminal half of VP5* (amino acids 475 to 776) has not been clearly associated with neutralization. All three recombinant proteins were antigenically conserved, since they reacted with a library of neutralizing monoclonal antibodies directed at VP4. There was a high percentage of seroresponders to VP4 (61%) or to VP8* (52%), but fewer infants seroresponded to VP5*(1) (11%). In addition, infants responding to VP5*(1) had considerably lower titers than to VP4 or VP8*. Immune response to VP4 correlated strongly with the responses detected by the plaque reduction neutralization assay but did not correlate with the responses detected by the ELISA to whole RRV. These data imply that the VP5*(1) region is less immunogenic than the VP8* region of VP4 in infants immunized with RRV or RRV reassortants. The low immunogenicity of VP5* might adversely affect the efficacy of RRV vaccine candidates.

  5. Immune Suppression during Oncolytic Virotherapy for High-Grade Glioma; Yes or No?

    Science.gov (United States)

    Koks, Carolien A E; De Vleeschouwer, Steven; Graf, Norbert; Van Gool, Stefaan W

    2015-01-01

    Oncolytic viruses have been seriously considered for glioma therapy over the last 20 years. The oncolytic activity of several oncolytic strains has been demonstrated against human glioma cell lines and in in vivo xenotransplant models. So far, four of these stains have additionally completed the first phase I/II trials in relapsed glioma patients. Though safety and feasibility have been demonstrated, therapeutic efficacy in these initial trials, when described, was only minor. The role of the immune system in oncolytic virotherapy for glioma remained much less studied until recent years. When investigated, the immune system, adept at controlling viral infections, is often hypothesized to be a strong hurdle to successful oncolytic virotherapy. Several preclinical studies have therefore aimed to improve oncolytic virotherapy efficacy by combining it with immune suppression or evasion strategies. More recently however, a new paradigm has developed in the oncolytic virotherapy field stating that oncolytic virus-mediated tumor cell death can be accompanied by elicitation of potent activation of innate and adaptive anti-tumor immunity that greatly improves the efficacy of certain oncolytic strains. Therefore, it seems the three-way interaction between oncolytic virus, tumor and immune system is critical to the outcome of antitumor therapy. In this review we discuss the studies which have investigated how the immune system and oncolytic viruses interact in models of glioma. The novel insights generated here hold important implications for future research and should be incorporated into the design of novel clinical trials.

  6. A novel nematode effector suppresses plant immunity by activating host reactive oxygen species-scavenging system.

    Science.gov (United States)

    Lin, Borong; Zhuo, Kan; Chen, Shiyan; Hu, Lili; Sun, Longhua; Wang, Xiaohong; Zhang, Lian-Hui; Liao, Jinling

    2016-02-01

    Evidence is emerging that plant-parasitic nematodes can secrete effectors to interfere with the host immune response, but it remains unknown how these effectors can conquer host immune responses. Here, we depict a novel effector, MjTTL5, that could suppress plant immune response. Immunolocalization and transcriptional analyses showed that MjTTL5 is expressed specifically within the subventral gland of Meloidogyne javanica and up-regulated in the early parasitic stage of the nematode. Transgenic Arabidopsis lines expressing MjTTL5 were significantly more susceptible to M. javanica infection than wild-type plants, and vice versa, in planta silencing of MjTTL5 substantially increased plant resistance to M. javanica. Yeast two-hybrid, coimmunoprecipitation and bimolecular fluorescent complementation assays showed that MjTTL5 interacts specifically with Arabidopsis ferredoxin : thioredoxin reductase catalytic subunit (AtFTRc), a key component of host antioxidant system. The expression of AtFTRc is induced by the infection of M. javanica. Interaction between AtFTRc and MjTTL could drastically increase host reactive oxygen species-scavenging activity, and result in suppression of plant basal defenses and attenuation of host resistance to the nematode infection. Our results demonstrate that the host ferredoxin : thioredoxin system can be exploited cunningly by M. javanica, revealing a novel mechanism utilized by plant-parasitic nematodes to subjugate plant innate immunity and thereby promoting parasitism. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

  7. The complementary roles of cellular and humoral immunity in resistance to re-infection with LCM virus

    DEFF Research Database (Denmark)

    Thomsen, Allan Randrup; Marker, O

    1988-01-01

    markedly reduced both virus take and the LCMV-specific immune response. In contrast, transfer of primed cells did not have an immediate effect on virus titres in naive recipients; instead an enhanced immune response was detected and accelerated virus clearance was the result. Based on these observations we......The mechanisms underlying resistance to re-infection with lymphocytic choriomeningitis virus (LCMV) were investigated. Rechallenge with moderate doses of virus (10(3) LD50) did not lead to detectable re-infection nor to re-induction of virus-specific cytotoxicity. When higher doses of virus were...... used for rechallenge (10(6) - 10(8) LD50), significant re-infection as well as reactivation of cytotoxicity were observed. Both resistance and memory expression were controlled by an antigen-specific, radio-resistant factor in the immune mouse. Transfusion of serum from immune mice to naive recipients...

  8. Cellular and humoral immunity after infection with B. pertussis : the role of age, antigen and vaccination history

    NARCIS (Netherlands)

    van Twillert, I

    2017-01-01

    Pertussis (whooping cough), is a bacterial disease of the respiratory tract, caused by the human pathogen Bordetella pertussis. Vaccination against pertussis has dramatically lowered pertussis incidence and mortality rates; however pertussis still occurs. The duration of immunity to B. pertussis

  9. Comparison of Single and Blend Acidifiers as Alternative to Antibiotics on Growth Performance, Fecal Microflora, and Humoral Immunity in Weaned Piglets

    Directory of Open Access Journals (Sweden)

    S. T. Ahmed

    2014-01-01

    Full Text Available The banning of the use of antibiotics as feed additive has accelerated investigations of alternative feed additives in animal production. This experiment investigated the effect of pure citric acid or acidifier blend supplementation as substitute for antibiotic growth promoters on growth performance, fecal microbial count, and humoral immunity in weaned piglets challenged with Salmonella enterica serover Typhimurium and Escherichia coli KCTC 2571. A total of 60 newly weaned piglets (crossbred, 28-d-old; average 8 kg initial weight were randomly assigned to four dietary treatments in a completely randomized design. Dietary treatments included NC (negative control; basal diet, PC (positive control; basal diet+0.002% apramycin, T1 (basal diet+0.5% pure citric acid, and T2 (basal diet+0.4% acidifier blend. All piglets were orally challenged with 5 mL of culture fluid containing 2.3×108 cfu/mL of E. coli KCTC 2571 and 5.9×108 cfu/mL of S. typhimurium at the beginning of the experiment. The PC group showed the highest ADG and ADFI, whereas gain:feed was improved in the PC and T1 group (p0.05. From these above results, it can be concluded that, as alternatives to antibiotics dietary acidification with pure citric acid or acidifiers blend did not fully ameliorate the negative effects of microbial challenges in respect of growth performance and microbial environment, however improved immunity suggested further research with different dose levels.

  10. Effect of supplementing gilts' diets with different levels of vitamin E and different fats on the humoral and cellular immunity of gilts and their progeny.

    Science.gov (United States)

    Nemec, M; Butler, G; Hidiroglou, M; Farnworth, E R; Nielsen, K

    1994-03-01

    The effects of supplementing gestation and lactation diets of gilts with different combinations of vitamin E at or above NRC recommended levels (22, 44, or 88 IU/kg during gestation and 55, 110, and 220 IU/kg during lactation) and types of fat (5% added tallow or fish oil or no added fat) on humoral and cellular immunity of gilts and their pigs were evaluated. With only two exceptions, total IgG, IgM, and IgA in colostrum, milk, and plasma of gilts and in plasma of their pigs did not show significant (P > .05) effects, and no interactions between vitamin E and fat supplementation were observed. Cellular immunity was measured as lymphocyte proliferation response to phytohemagglutinin (PHA), concanavalin A (Con A), purified protein derivative of Mycobacterium avium, keyhole limpet hemocyanin, Escherichia coli lipopolysaccharide (LPS), and Salmonella typhimurium LPS. Only the nonspecific mitogens, PHA and Con A, induced proliferation of gilt and pig lymphocytes. Fish oil supplementation in the gilts' diets resulted in lower (P gilts and slower (P gilts. However, the rate of acquisition of PHA response and Con A response in newborn pigs was greater (P < .05) for groups supplemented with 110 and 220 IU/kg of vitamin E than for the group supplemented with 55 IU/kg vitamin E.

  11. Mexican Trypanosoma cruzi (TCI Strains with Different Degrees of Virulence Induce Diverse Humoral and Cellular Immune Responses in a Murine Experimental Infection Model

    Directory of Open Access Journals (Sweden)

    B. Espinoza

    2010-01-01

    Full Text Available It is has been shown that the majority of T. cruzi strains isolated from Mexico belong to the T. cruzi I (TCI. The immune response produced in response to Mexican T. cruzi I strains has not been well characterized. In this study, two Mexican T. cruzi I strains were used to infect Balb/c mice. The Queretaro (TBAR/MX/0000/Queretaro(Qro strain resulted in 100% mortality. In contrast, no mortality was observed in mice infected with the Ninoa (MHOM/MX/1994/Ninoa strain. Both strains produced extended lymphocyte infiltrates in cardiac tissue. Ninoa infection induced a diverse humoral response with a higher variety of immunoglobulin isotypes than were found in Qro-infected mice. Also, a stronger inflammatory TH1 response, represented by IL-12p40, IFNγ, RANTES, MIG, MIP-1β, and MCP-1 production was observed in Qro-infected mice when compared with Ninoa-infected mice. We propose that an exacerbated TH1 immune response is a likely cause of pathological damage observed in cardiac tissue and the primary cause of death in Qro-infected mice.

  12. Immunoblot detection of class-specific humoral immune response to outer membrane proteins isolated from Salmonella typhi in humans with typhoid fever.

    Science.gov (United States)

    Ortiz, V; Isibasi, A; García-Ortigoza, E; Kumate, J

    1989-07-01

    The studies reported here were undertaken to assess the ability of the outer membrane proteins (OMPs) of Salmonella typhi to induce a humoral immune response in humans with typhoid fever. OMPs were isolated with the nonionic detergent Triton X-100 and were found to be contaminated with approximately 4% lipopolysaccharide. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis patterns showed protein bands with molecular size ranges from 17 to 70 kilodaltons; the major groups of proteins were those that correspond to the porins and OmpA of gram-negative bacteria. Rabbit antiserum to OMPs or to S. typhi recognized OMPs after absorption with lipopolysaccharide. Sera from patients with typhoid fever contained immunoglobulin M antibodies which reacted with a protein of 28 kilodaltons and immunoglobulin G antibodies which reacted mainly with the porins, as determined by immunoblotting. These results indicate that the porins are the major immunogenic OMPs from S. typhi and that the immune response induced in the infection could be related to the protective status.

  13. Human cytomegalovirus-induced NKG2C(hi) CD57(hi) natural killer cells are effectors dependent on humoral antiviral immunity.

    Science.gov (United States)

    Wu, Zeguang; Sinzger, Christian; Frascaroli, Giada; Reichel, Johanna; Bayer, Carina; Wang, Li; Schirmbeck, Reinhold; Mertens, Thomas

    2013-07-01

    Recent studies indicate that expansion of NKG2C-positive natural killer (NK) cells is associated with human cytomegalovirus (HCMV); however, their activity in response to HCMV-infected cells remains unclear. We show that NKG2C(hi) CD57(hi) NK cells gated on CD3(neg) CD56(dim) cells can be phenotypically identified as HCMV-induced NK cells that can be activated by HCMV-infected cells. Using HCMV-infected autologous macrophages as targets, we were able to show that these NKG2C(hi) CD57(hi) NK cells are highly responsive to HCMV-infected macrophages only in the presence of HCMV-specific antibodies, whereas they are functionally poor effectors of natural cytotoxicity. We further demonstrate that NKG2C(hi) CD57(hi) NK cells are intrinsically responsive to signaling through CD16 cross-linking. Our findings show that the activity of pathogen-induced innate immune cells can be enhanced by adaptive humoral immunity. Understanding the activity of NKG2C(hi) CD57(hi) NK cells against HCMV-infected cells will be of relevance for the further development of adoptive immunotherapy.

  14. Structure-based stabilization of HIV-1 gp120 enhances humoral immune responses to the induced co-receptor binding site.

    Directory of Open Access Journals (Sweden)

    Barna Dey

    2009-05-01

    Full Text Available The human immunodeficiency virus type 1 (HIV-1 exterior envelope glycoprotein, gp120, possesses conserved binding sites for interaction with the primary virus receptor, CD4, and also for the co-receptor, generally CCR5. Although gp120 is a major target for virus-specific neutralizing antibodies, the gp120 variable elements and its malleable nature contribute to evasion of effective host-neutralizing antibodies. To understand the conformational character and immunogenicity of the gp120 receptor binding sites as potential vaccine targets, we introduced structure-based modifications to stabilize gp120 core proteins (deleted of the gp120 major variable regions into the conformation recognized by both receptors. Thermodynamic analysis of the re-engineered core with selected ligands revealed significant stabilization of the receptor-binding regions. Stabilization of the co-receptor-binding region was associated with a marked increase in on-rate of ligand binding to this site as determined by surface plasmon resonance. Rabbit immunization studies showed that the conformational stabilization of core proteins, along with increased ligand affinity, was associated with strikingly enhanced humoral immune responses against the co-receptor-binding site. These results demonstrate that structure-based approaches can be exploited to stabilize a conformational site in a large functional protein to enhance immunogenic responses specific for that region.

  15. Flow of Aqueous Humor

    Science.gov (United States)

    ... National Glaucoma Research Home Flow of Aqueous Humor Flow of Aqueous Humor Most, but not all, forms ... aqueous humor) produced by the eye's ciliary body flows out freely (follow blue arrow). Aqueous humor flows ...

  16. Monocytic suppressor cells derived from human peripheral blood suppress xenogenic immune reactions.

    Science.gov (United States)

    Maeda, Akira; Kawamura, Takuji; Ueno, Takehisa; Usui, Noriaki; Miyagawa, Shuji

    2014-01-01

    Myeloid-derived suppressor cells (MDSC) were initially found to contribute to the immunosuppression in tumor patients and have recently been recognized as a subset of innate immune cells that are capable of regulating adaptive immunity. A variety of innate immune stimuli such as Lipopolysaccharide (LPS), which act as a double-edged sword, induce both the maturation of dendritic cells (DC) and the expansion of MDSCs. In this study, we isolated MDSCs from peripheral blood mononuclear cells and examined the suppressive effect of MDSCs against cytotoxic T lymphocyte (CTL)-mediated xenocytotoxicity. Peripheral blood monocytes cultured in the presence of GM-CSF and IL-4 were stimulated with polyiosinic-polycytidylic acid [poly (I:C)] or LPS. Flow cytometric analyses revealed that LPS and poly I:C stimulation allows the CD33(+) CD14(+) HLA-DR(-) subset to be significantly increased. To assess the suppressive capacity of MDSCs in xenotoxicity, CTL assay was performed. Poly (I:C)-activated MDSCs dramatically suppressed the CTL xenocytotoxicity. Phagocytosis assays revealed that activated MDSCs aggressively phagocytose the xenogenic CTLs. Characterization of MDSCs by real-time PCR revealed that poly (I:C) and LPS-stimulated MDSCs expressed significant amounts of mRNA for indolamine 2,3-dioxygenase (IDO) compared to untreated MDSCs. Furthermore, when MDSCs were incubated with the IDO inhibitor, the MDSC-induced suppression of xenocytotoxicity was abolished. Taken together, the possibility that activated MDSCs could induce apoptosis in xenogenic CTLs via an IDO-dependent manner and aggressively phagocytose apoptotic CTLs cannot be excluded. These findings indicate that MDSCs have a great deal of potential as a therapeutic strategy for dealing with xenograft rejection. Further investigations of the underlying mechanisms will facilitate the development of this therapeutic strategy. © 2013 John Wiley & Sons A/S.

  17. Phytoconstituents of Jatropha curcas L. leaves and their immunomodulatory activity on humoral and cell-mediated immune response in chicks.

    Science.gov (United States)

    Abd-Alla, Howaida I; Moharram, Fatma A; Gaara, Ahmed H; El-Safty, Mounir M

    2009-01-01

    A novel biflavone di-C-glucoside, 6,6"-di-C-beta-D-glucopyranoside-methylene-(8,8")-biapigenin (1), was isolated from the leaves of Jatropha curcas L. (Euphorbiaceae), together with six known compounds; apigenin 7-O-beta-D-neohesperidoside (2), apigenin 7-O-beta-D-galactoside (3), orientin (4), vitexin (5), vicenin II (6), and apigenin (7). Their structures were determined on the basis of extensive chemical and spectroscopic analyses (UV, NMR and HRESI-MS). The immunomodulatory effect of an 80% aqueous methanol extract (AME) and compounds 1-5 (0.25 mg/kg body wt) to one-day-old specific pathogen-free (SPF) chicks was determined. Stimulation of both humoral and cell-mediated seroresponse was observed, especially those of AME and compound 1. Remarkable effective increases of the antibody titers, lymphocyte and macrophage cells, in blood were recorded. SPF chicks treated with the tested samples exhibited protection against Newcastle disease challenge virus after being vaccinated.

  18. Cellular and humoral immunity, mood and exam stress: the influences of self-hypnosis and personality predictors.

    Science.gov (United States)

    Gruzelier, J; Smith, F; Nagy, A; Henderson, D

    2001-08-01

    The effects of self-hypnosis training on immune function and mood were examined in medical students at exam time. Hypnosis involved relaxation and imagery directed at improved immune function and increased energy, alertness and concentration. Hypotheses were made about activated and withdrawn personality differences. Eight high and eight low hypnotically susceptible participants were given 10 sessions of hypnosis, one live and nine tape-recorded, and were compared with control subjects (N=12). CD3, CD4, CD8, CD19 and CD56 NK cells and blood cortisol were assayed. Life-style, activated vs. withdrawn temperament, arousal and anxiety questionnaires were administered. Self-hypnosis buffered the decline found in controls in NK (Pexam levels of T and B lymphocytes (P&z.Lt;0.08-Pstress in young, healthy adults have implications for illness prevention and for patients with compromised immunity.

  19. Detection of Pneumocystis in the nasal swabs of immune-suppressed rats by use of PCR and microscopy

    OpenAIRE

    Can, H?seyin; Caner, Ay?e; D??kaya, Mert; De?irmenci, Aysu; Kara?al?, Sabire; Polat, Ceylan; G?r?z, Y?ksel; ?ner, Ahmet

    2013-01-01

    Background Detection of Pneumocystis jiroveci colonization in lungs or oral samples due to high sensitivity of PCR methods results in undue treatment of patients without any symptoms of Pneumocystis pneumonia. The aim of the present study is to demonstrate Pneumocystis carinii in rats, immune suppressed by oral and subcutaneous administration of dexamethasone. Material/Methods Blood, oral, nasal and eye swabs were collected prior to immune suppression and 2, 6, 12 weeks after administration o...

  20. Sympathetic‐mediated activation versus suppression of the immune system: consequences for hypertension

    Science.gov (United States)

    Case, Adam J.

    2016-01-01

    Abstract It is generally well‐accepted that the immune system is a significant contributor in the pathogenesis of hypertension. Specifically, activated and pro‐inflammatory T‐lymphocytes located primarily in the vasculature and kidneys appear to have a causal role in exacerbating elevated blood pressure. It has been proposed that increased sympathetic nerve activity and noradrenaline outflow associated with hypertension may be primary contributors to the initial activation of the immune system early in the disease progression. However, it has been repeatedly demonstrated in many different human and experimental diseases that sympathoexcitation is immunosuppressive in nature. Moreover, human hypertensive patients have demonstrated increased susceptibility to secondary immune insults like infections. Thus, it is plausible, and perhaps even likely, that in diseases like hypertension, specific immune cells are activated by increased noradrenaline, while others are in fact suppressed. We propose a model in which this differential regulation is based upon activation status of the immune cell as well as the resident organ. With this, the concept of global immunosuppression is obfuscated as a viable target for hypertension treatment, and we put forth the concept of focused organ‐specific immunotherapy as an alternative option. PMID:26830047

  1. Sympathetic-mediated activation versus suppression of the immune system: consequences for hypertension.

    Science.gov (United States)

    Case, Adam J; Zimmerman, Matthew C

    2016-02-01

    It is generally well-accepted that the immune system is a significant contributor in the pathogenesis of hypertension. Specifically, activated and pro-inflammatory T-lymphocytes located primarily in the vasculature and kidneys appear to have a causal role in exacerbating elevated blood pressure. It has been proposed that increased sympathetic nerve activity and noradrenaline outflow associated with hypertension may be primary contributors to the initial activation of the immune system early in the disease progression. However, it has been repeatedly demonstrated in many different human and experimental diseases that sympathoexcitation is immunosuppressive in nature. Moreover, human hypertensive patients have demonstrated increased susceptibility to secondary immune insults like infections. Thus, it is plausible, and perhaps even likely, that in diseases like hypertension, specific immune cells are activated by increased noradrenaline, while others are in fact suppressed. We propose a model in which this differential regulation is based upon activation status of the immune cell as well as the resident organ. With this, the concept of global immunosuppression is obfuscated as a viable target for hypertension treatment, and we put forth the concept of focused organ-specific immunotherapy as an alternative option. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

  2. Endoplasmic Reticulum Stress Caused by Lipoprotein Accumulation Suppresses Immunity against Bacterial Pathogens and Contributes to Immunosenescence

    Directory of Open Access Journals (Sweden)

    Jogender Singh

    2017-05-01

    Full Text Available The unfolded protein response (UPR is a stress response pathway that is activated upon increased unfolded and/or misfolded proteins in the endoplasmic reticulum (ER, and enhanced ER stress response prolongs life span and improves immunity. However, the mechanism by which ER stress affects immunity remains poorly understood. Using the nematode Caenorhabditis elegans, we show that mutations in the lipoproteins vitellogenins, which are homologs of human apolipoprotein B-100, resulted in upregulation of the UPR. Lipoprotein accumulation in the intestine adversely affects the immune response and the life span of the organism, suggesting that it could be a contributing factor to immunosenescence. We show that lipoprotein accumulation inhibited the expression of several immune genes encoding proteins secreted by the intestinal cells in an IRE-1-independent manner. Our studies provide a mechanistic explanation for adverse effects caused by protein aggregation and ER stress on immunity and highlight the role of an IRE-1-independent pathway in the suppression of the expression of genes encoding secreted proteins.

  3. Suppression of plant resistance gene-based immunity by a fungal effector.

    Directory of Open Access Journals (Sweden)

    Petra M Houterman

    2008-05-01

    Full Text Available The innate immune system of plants consists of two layers. The first layer, called basal resistance, governs recognition of conserved microbial molecules and fends off most attempted invasions. The second layer is based on Resistance (R genes that mediate recognition of effectors, proteins secreted by pathogens to suppress or evade basal resistance. Here, we show that a plant-pathogenic fungus secretes an effector that can both trigger and suppress R gene-based immunity. This effector, Avr1, is secreted by the xylem-invading fungus Fusarium oxysporum f.sp. lycopersici (Fol and triggers disease resistance when the host plant, tomato, carries a matching R gene (I or I-1. At the same time, Avr1 suppresses the protective effect of two other R genes, I-2 and I-3. Based on these observations, we tentatively reconstruct the evolutionary arms race that has taken place between tomato R genes and effectors of Fol. This molecular analysis has revealed a hitherto unpredicted strategy for durable disease control based on resistance gene combinations.

  4. Orally administered marine (1-3)-Beta-D-glucan Phycarine stimulates both humoral and cellular immunity

    Czech Academy of Sciences Publication Activity Database

    Větvička, V.; Dvořák, B.; Větvičková, J.; Richter, Jan; Křižan, Jiří; Šíma, Petr; Yvin, J.; C.

    2007-01-01

    Roč. 40, - (2007), s. 291-298 ISSN 0141-8130 R&D Projects: GA ČR GA301/05/0078 Institutional research plan: CEZ:AV0Z50200510 Keywords : phagocytosis * immunity * cancer Subject RIV: EE - Microbiology, Virology Impact factor: 1.578, year: 2007

  5. Sensitivity of humoral immune parameters of poultry to minor macro- and micronutrient differences in two nutritionally complete layer feeds

    NARCIS (Netherlands)

    Adriaansen-Tennekes, R.; Vries Reilingh, de G.; Nieuwland, M.G.B.; Pieters, R.H.H.; Loveren, van H.; Huber, M.; Hoogenboom, R.; Parmentier, H.K.; Savelkoul, H.F.J.

    2011-01-01

    The effect of differences in the composition of nutrients of two nutritionally complete layer diets on parameters from innate and adaptive immunity of chickens were examined. The diets were based on ingredients grown either organically or conventionally. As individual differences in nutrient

  6. Effect of 3 months vitamin E supplementation on indices of the cellular and humoral immune response in elderly subjects

    NARCIS (Netherlands)

    Waart, de F.; Portengen, L.; Doekes, G.; Verwaal, C.J.; Kok, F.J.

    1997-01-01

    It has been suggested that decreased immune responsiveness in the elderly may be counteracted by the antioxidant vitamin E. In a 3-month double-blind placebo-controlled intervention trial among elderly subjects aged 65 years and over we studied the effects of a daily dose of 100 mg

  7. Proteomic Identification of saeRS-Dependent Targets Critical for Protective Humoral Immunity against Staphylococcus aureus Skin Infection.

    Science.gov (United States)

    Zhao, Fan; Cheng, Brian L; Boyle-Vavra, Susan; Alegre, Maria-Luisa; Daum, Robert S; Chong, Anita S; Montgomery, Christopher P

    2015-09-01

    Recurrent Staphylococcus aureus skin and soft tissue infections (SSTIs) are common despite detectable antibody responses, leading to the belief that the immune response elicited by these infections is not protective. We recently reported that S. aureus USA300 SSTI elicits antibodies that protect against recurrent SSTI in BALB/c but not C57BL/6 mice, and in this study, we aimed to uncover the specificity of the protective antibodies. Using a proteomic approach, we found that S. aureus SSTI elicited broad polyclonal antibody responses in both BALB/c and C57BL/6 mice and identified 10 S. aureus antigens against which antibody levels were significantly higher in immune BALB/c serum. Four of the 10 antigens identified are regulated by the saeRS operon, suggesting a dominant role for saeRS in protection. Indeed, infection with USA300Δsae failed to protect against secondary SSTI with USA300, despite eliciting a strong polyclonal antibody response against antigens whose expression is not regulated by saeRS. Moreover, the antibody repertoire after infection with USA300Δsae lacked antibodies specific for 10 saeRS-regulated antigens, suggesting that all or a subset of these antigens are necessary to elicit protective immunity. Infection with USA300Δhla elicited modest protection against secondary SSTI, and complementation of USA300Δsae with hla restored protection but incompletely. Together, these findings support a role for both Hla and other saeRS-regulated antigens in eliciting protection and suggest that host differences in immune responses to saeRS-regulated antigens may determine whether S. aureus infection elicits protective or nonprotective immunity against recurrent infection. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  8. Humoral immune response of C57Bl/6j and BALB/c mice immunized with irradiated tachyzoites of Toxoplasma gondii RH strain and oral challenge with ME-49 strain

    Energy Technology Data Exchange (ETDEWEB)

    Jimenez Galisteo Junior, Andres [Instituto de Pesquisas Energeticas e Nucleares IPEN/CNEN-SP, Sao Paulo, SP (Brazil). Centro de Biotecnologia; Instituto de Medicina Tropical de Sao Paulo, Sao Paulo, SP (Brazil). Lab. de Protozoologia; E-mail: galisteo@usp.br; Zorgi, Nahiara Esteves; Andrade Junior, Heitor Franco de [Instituto de Medicina Tropical de Sao Paulo, Sao Paulo, SP (Brazil). Lab. de Protozoologia; Alves, Janaina Baptista; Nascimento, Nanci do [Instituto de Pesquisas Energeticas e Nucleares IPEN/CNEN-SP, Sao Paulo, SP (Brazil). Centro de Biotecnologia; Hiramoto, Roberto Mitsuyoshi [instituto Adolfo Lutz, Sao Paulo, SP (Brazil)

    2007-07-01

    Toxoplasmosis, a prevalent widespread infection in man and animals, is mainly transmitted by oral route, through ingestion of oocysts from water and food contaminated with cat feces or infected animal tissue cysts in undercooked meat. Vaccine development implies in effective intestinal immunity, the first site of parasite entry. Radiation (255 Gy/{sup 60}Co) sterilized T. gondii RH strain tachyzoites (RST) induced significant protection when parentally administered, similar to chronically infected and acute disease protected animal. We study the humoral immune response in C57Bl/6j and BALB/c mice immunized with 10{sup 7} RST, by oral (with aluminium hydroxide 3%) or parenteral 3 biweekly administrations. T. gondii antigens specific ELISA for IgG, IgA, IgG1, IgG2a and IgG2b detection was performed in weekly blood samples during immunization. Also we evaluate of the intestinal epithelial of immunized mice the integrity of the radiated parasites by electronic microscopy. After 2 weeks, immunized and control animals were challenged with 10 cysts of ME-49 strain p.o. Protection was determined at the 30th day by brain cyst counting. As it was possible to observe in the intestinal mucosal, the aluminium hydroxide seems to maintain unchanged the parasite morphology and its mechanisms of invasion, probably due to keeping it safe from extreme pH condition of stomach. All immunized groups presented significant protection when challenged with ME-49; however, BALB/c mice showed better protection levels, with only one positive animal on brain microscopic analysis. IgG production in the serum of the animals was higher in groups immunized by i.p route, however, IgA and IgG1 levels were higher in BALB/c mice immunized by oral route. This higher protection found in BALB/c group could probably also be related to the Th2 response, demonstrated by higher IgG1 levels. All these data provide insights in oral immunization schedules for toxoplasmosis prevention, suggesting that oral

  9. Subcutaneous Immunization with Fusion Protein DnaJ-ΔA146Ply without Additional Adjuvants Induces both Humoral and Cellular Immunity against Pneumococcal Infection Partially Depending on TLR4

    Directory of Open Access Journals (Sweden)

    Yufeng Su

    2017-06-01

    Full Text Available Subunit vaccines that are poorly immunogenic are often combined with adjuvants for immunization. Our previous research identified a pneumolysin variant (ΔA146Ply, a Toll-like receptor 4 agonist, that was an effective adjuvant in the protection of fusion protein DnaJ-ΔA146Ply against mucosal Streptococcus pneumoniae infections. For pneumococcal vaccines, World Health Organization recommend injection as a regular vaccination approach. Subcutaneous immunization is a common and effective method of injection, so we explored the immunity mechanism of subcutaneous immunization with DnaJ-ΔA146Ply. We found that mice immunized subcutaneously with fusion proteins ΔA146Ply-DnaJ and DnaJ-ΔA146Ply produced a higher anti-DnaJ IgG titer than when DnaJ alone was administered. DnaJ-ΔA146Ply induced both B-cell and T-cell-dependent protection against both colonization and lethal pneumococcal infections. Levels of IFN-γ, IL-4, and IL-17A were also elevated in DnaJ-ΔA146Ply immunized mice. However, all these effects were negated in TLR4−/− mice compared to WT mice immunized with DnaJ-ΔA146Ply. B-cell-deficient μMT mice, nude mice, IFN-γ−/−, and IL-4−/− mice immunized with DnaJ-ΔA146Ply could not resist infection with pneumococci. IL-17A−/− and TLR4−/− mice did not benefit from DnaJ-ΔPly immunization in colonization experiments although their survival was not impaired compared with WT mice. Collectively, our data indicated that ΔA146Ply can be a potential subcutaneous adjuvant, and the DnaJ-ΔA146Ply fusion protein induces both humoral and cellular immune response to resist S. pneumoniae infection. The protective effect of colonization also depends on TLR4.

  10. A Novel Rabies Vaccine Expressing CXCL13 Enhances Humoral Immunity by Recruiting both T Follicular Helper and Germinal Center B Cells.

    Science.gov (United States)

    Wang, Zhao; Li, Mingming; Zhou, Ming; Zhang, Yajing; Yang, Jie; Cao, Yandi; Wang, Kunlun; Cui, Min; Chen, Huanchun; Fu, Zhen F; Zhao, Ling

    2017-02-01

    Rabies remains a public health threat in most parts of the world, and approximately 99% of the cases are transmitted by dogs. There is an urgent need to develop an efficacious and affordable vaccine to control canine-transmitted rabies in developing countries. Our previous studies demonstrate that overexpression of chemokines/cytokines such as CCL-3 (MIP-1α) and granulocyte-macrophage colony-stimulating factor (GM-CSF) can enhance the immunogenicity of rabies vaccines. In the present study, the chemokine CXCL13 was inserted into the genome of the recombinant rabies virus (rRABV) strain LBNSE, and the effect of the chemokine CXCL13 on the immunogenicity of RABV was investigated. It was found that LBNSE-CXCL13 recruited follicular helper T (Tfh) and germinal center (GC) B cells, promoted the formation of GCs, and increased the population of plasma cells in immunized mice. Further studies showed that mice immunized with LBNSE-CXCL13 produced more rabies virus-neutralizing antibodies (VNAs) and developed better protection than those immunized with the parent virus LBNSE or the GM-CSF-expressing RABV (LBNSE-GM-CSF). Collectively, these findings provide a better understanding of the role of CXCL13 expression in the immunogenicity of the RABV, which may help in designing more-efficacious rabies vaccines. Rabies is endemic in most parts of the world, and more effort is needed to develop affordable and effective vaccines to control or eliminate this disease. The chemokine CXCL13 recruits both Tfh and B cells, which is essential for the homing of Tfh cells and the development of B cell follicles. In this study, the effect of the overexpression of CXCL13 on the immunogenicity of the RABV was evaluated in a mouse model. We found that CXCL13 expression promoted humoral immunity by recruiting Tfh and GC B cells, facilitating the formation of GCs, and increasing the number of plasma cells. As expected, the overexpression of CXCL13 resulted in enhanced virus-neutralizing antibody

  11. Homologous RXLR effectors from Hyaloperonospora arabidopsidis and Phytophthora sojae suppress immunity in distantly related plants.

    Science.gov (United States)

    Anderson, Ryan G; Casady, Megan S; Fee, Rachel A; Vaughan, Martha M; Deb, Devdutta; Fedkenheuer, Kevin; Huffaker, Alisa; Schmelz, Eric A; Tyler, Brett M; McDowell, John M

    2012-12-01

    Diverse pathogens secrete effector proteins into plant cells to manipulate host cellular processes. Oomycete pathogens contain large complements of predicted effector genes defined by an RXLR host cell entry motif. The genome of Hyaloperonospora arabidopsidis (Hpa, downy mildew of Arabidopsis) contains at least 134 candidate RXLR effector genes. Only a small subset of these genes is conserved in related oomycetes from the Phytophthora genus. Here, we describe a comparative functional characterization of the Hpa RXLR effector gene HaRxL96 and a homologous gene, PsAvh163, from the Glycine max (soybean) pathogen Phytophthora sojae. HaRxL96 and PsAvh163 are induced during the early stages of infection and carry a functional RXLR motif that is sufficient for protein uptake into plant cells. Both effectors can suppress immune responses in soybean. HaRxL96 suppresses immunity in Nicotiana benthamiana, whereas PsAvh163 induces an HR-like cell death response in Nicotiana that is dependent on RAR1 and Hsp90.1. Transgenic Arabidopsis plants expressing HaRxL96 or PsAvh163 exhibit elevated susceptibility to virulent and avirulent Hpa, as well as decreased callose deposition in response to non-pathogenic Pseudomonas syringae. Both effectors interfere with defense marker gene induction, but do not affect salicylic acid biosynthesis. Together, these experiments demonstrate that evolutionarily conserved effectors from different oomycete species can suppress immunity in plant species that are divergent from the source pathogen's host. © 2012 The Authors. The Plant Journal © 2012 Blackwell Publishing Ltd.

  12. Cationic micelle based vaccine induced potent humoral immune response through enhancing antigen uptake and formation of germinal center.

    Science.gov (United States)

    Luo, Zichao; Shi, Shuai; Jin, Ling; Xu, Lu; Yu, Jing; Chen, Hao; Li, Xingyi

    2015-11-01

    Nanoparticles have been proven to be an effective vaccine delivery system that can boost immune responses to subunit vaccines. Herein, we developed and characterized a cationic polymeric polyethylene glycol2000-poly ϵ-caprolactone2000-polyethylenimine2000 (mPEG2000-PCL2000-g-PEI2000) micelle as a potent vaccine delivery system to boost the immune response in vivo. The micelles that we developed exhibited great antigen-loading capability and minimal cytotoxicity in vitro. Meanwhile, micelles facilitated OVA antigen uptake by dendritic cells both in vitro and in vivo. More importantly, a micelle-formulated OVA vaccine could significantly promote anti-OVA antibody production by 190-fold and potently enhance T cell proliferation and the secretion of IL-5 and IFN-γ. We attributed these effects to its ability to promote antigen uptake, antigen deposition, and germinal center formation. In conclusion, the mPEG2000-PCL2000-PEI2000 micelle that we developed has potential as potent vaccine delivery system to induce Th2 immune response. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Food preservatives sodium benzoate and propionic acid and colorant curcumin suppress Th1-type immune response in vitro.

    Science.gov (United States)

    Maier, Elisabeth; Kurz, Katharina; Jenny, Marcel; Schennach, Harald; Ueberall, Florian; Fuchs, Dietmar

    2010-07-01

    Food preservatives sodium benzoate and propionic acid and colorant curcumin are demonstrated to suppress in a dose-dependent manner Th1-type immune response in human peripheral blood mononuclear cells (PBMC) in vitro. Results show an anti-inflammatory property of compounds which however could shift the Th1-Th2-type immune balance towards Th2-type immunity. 2010 Elsevier Ltd. All rights reserved.

  14. Isoflavones, Genistein and Daidzein, Regulate Mucosal Immune Response by Suppressing Dendritic Cell Function

    Science.gov (United States)

    Wei, John; Bhatt, Shiven; Chang, Lisa M.; Sampson, Hugh A.; Masilamani, Madhan

    2012-01-01

    Lipopolysaccharide (LPS), a component of gram-negative bacterial cell walls, has been shown to have a strong adjuvant effect towards inhaled antigens contributing to airway inflammation. Isoflavones are anti-inflammatory molecules present in abundant quantities in soybeans. We investigated the effect of isoflavones on human dendritic cell (DC) activation via LPS stimulation and subsequent DC-mediated effector cell function both in vitro and in a mouse model of upper airway inflammation. Human monocyte-derived DCs (MDDC) were matured with LPS (or TNF-α) +/− isoflavones (genistein or daidzein). The surface expression levels of DC activation markers were analyzed by flow cytometry. Mature DCs +/− isoflavones were washed and cultured with freshly-isolated allogenic naïve CD4+ T cells for 5 days or with autologous natural killer (NK) cells for 2 hours. The percentages of proliferating IFN-γ+ CD4+ T cells and cytokine levels in culture supernatants were assessed. NK cell degranulation and DC cytotoxicity were measured by flow cytometry. Isoflavones significantly suppressed the activation-induced expression of DC maturation markers (CD83, CD80, CD86) and MHC class I but not MHC class II molecules in vitro. Isoflavone treatment inhibited the ability of LPS-DCs to induce IFN-γ in CD4+ T cells. NK cell degranulation and the percentage of dead DCs were significantly increased in isoflavone-treated DC-NK co-culture experiments. Dietary isoflavones suppressed the mucosal immune response to intra-nasal sensitization of mice to ovalbumin. Similar results were obtained when isoflavones were co-administered during sensitization. These results demonstrate that soybean isoflavones suppress immune sensitization by suppressing DC-maturation and its subsequent DC-mediated effector cell functions. PMID:23110148

  15. Isoflavones, genistein and daidzein, regulate mucosal immune response by suppressing dendritic cell function.

    Directory of Open Access Journals (Sweden)

    John Wei

    Full Text Available Lipopolysaccharide (LPS, a component of gram-negative bacterial cell walls, has been shown to have a strong adjuvant effect towards inhaled antigens contributing to airway inflammation. Isoflavones are anti-inflammatory molecules present in abundant quantities in soybeans. We investigated the effect of isoflavones on human dendritic cell (DC activation via LPS stimulation and subsequent DC-mediated effector cell function both in vitro and in a mouse model of upper airway inflammation. Human monocyte-derived DCs (MDDC were matured with LPS (or TNF-α +/- isoflavones (genistein or daidzein. The surface expression levels of DC activation markers were analyzed by flow cytometry. Mature DCs +/- isoflavones were washed and cultured with freshly-isolated allogenic naïve CD4⁺ T cells for 5 days or with autologous natural killer (NK cells for 2 hours. The percentages of proliferating IFN-γ⁺ CD4⁺ T cells and cytokine levels in culture supernatants were assessed. NK cell degranulation and DC cytotoxicity were measured by flow cytometry. Isoflavones significantly suppressed the activation-induced expression of DC maturation markers (CD83, CD80, CD86 and MHC class I but not MHC class II molecules in vitro. Isoflavone treatment inhibited the ability of LPS-DCs to induce IFN-γ in CD4⁺ T cells. NK cell degranulation and the percentage of dead DCs were significantly increased in isoflavone-treated DC-NK co-culture experiments. Dietary isoflavones suppressed the mucosal immune response to intra-nasal sensitization of mice to ovalbumin. Similar results were obtained when isoflavones were co-administered during sensitization. These results demonstrate that soybean isoflavones suppress immune sensitization by suppressing DC-maturation and its subsequent DC-mediated effector cell functions.

  16. Suppression of immune response to Lol pI by administration of idiotype.

    Science.gov (United States)

    Boutin, Y; Hébert, J

    1995-03-01

    Allergic diseases are characterized by an increased production of specific IgE antibodies. Suppression of IgE antibody production may be accomplished through idiotypic manipulation. Using an animal model, we explored the effects of anti-Lol pI monoclonal antibody administration on the subsequent IgE and IgG antibody response against Lol pI. Mice were treated with an anti-Lol pI monoclonal antibody (290A-167), which resulted in the production of anti-idiotypic antibodies as evidenced by their ability to bind to the Fab fraction of 290A-167 and to inhibit the binding of rabbit polyclonal anti-idiotypic antibodies to 290A-167. The animals were then immunized with Lol pI adsorbed onto alum, and the immune response to the protein was analyzed. Antigen-specific IgG1 and IgE responses were strongly suppressed as determined by immunoassay. Suppression of anti-Lol pI IgE antibodies was confirmed by a reduction of end-point titers measured by passive cutaneous anaphylaxis. The suppression of antigen-specific antibody was accompanied by a reduction of anti-Lol pI antibody-producing spleen cells. These data indicate that pretreatment with 290A-167 can strongly downregulate the IgE response to the main allergen of ryegrass pollen, which is associated with an increase in anti-idiotypic antibodies. This approach could provide rapid, long-term hyposensitization in patients with grass pollen allergy.

  17. Oral candidiasis in children with immune suppression: clinical appearance and therapeutic considerations.

    Science.gov (United States)

    Flaitz, C M; Hicks, M J

    1999-01-01

    Children and adolescents with immune compromise and suppression are particularly susceptible to the development of oral candidiasis. In fact, oral candidiasis is the most common oral manifestation in HIV-infected children. Oral candidiasis has been linked to a depressed immune system, more rapid progression to AIDS, more advanced stage of disease in AIDS, and decreased survival. Several different forms of candidiasis may be recognized clinically. These forms are 1) pseudomembraneous candidiasis; 2) erythematous (atrophic) candidiasis; 3) papillary hyperplasia; 4) chronic hyperplastic candidiasis; 5) angular cheilitis; and 6) median rhomboid glossitis. Diagnosis of candidiasis is primarily based upon clinical appearance; in some cases, however, exfoliative cytology and/or biopsy of the lesion may be necessary. It is also possible to culture the lesion to determine the specific subtype of candidia and to evaluate the susceptibility of the fungus to specific antifungal agents. Both topical and systemic treatment by antifungal medications are readily available.

  18. The new normal: immuno-modulatory agents against sepsis immune suppression

    Science.gov (United States)

    Hutchins, Noelle A.; Unsinger, Jacqueline; Hotchkiss, Richard S.; Ayala, Alfred

    2014-01-01

    Sepsis is the leading cause of death amongst critically ill patients in intensive care units, and treatment options are limited. Therapies developed against the pro-inflammatory stage have failed clinically; therefore new approaches that target the host immune response in sepsis are necessary. Increasing evidence suggests that a major pathophysiological event in sepsis is immune suppression, often resulting in secondary fungal, bacterial, or viral infections. Recent studies from animal sepsis models and patient samples suggest that cytokines such as IL-7, IL-15, GM-CSF as well as co-inhibitory molecule blockade, such as anti-PD-1 and anti-BTLA, may have utility in alleviating the clinical morbidity associated with sustained sepsis. This review discusses some of these novel immunomodulatory agents and evaluates their potential use as therapeutics. PMID:24485901

  19. Toxicant-disease-environment interactions associated with suppression of immune system, growth, and reproduction. [PCB

    Energy Technology Data Exchange (ETDEWEB)

    Porter, W.P.; Hinsdill, R.; Fairbrother, A.; Olson, L.J.; Jaeger, J.; Yuill, T.; Bisgaard, S.; Hunter, W.G.; Nolan, K.

    1984-06-01

    The effects of marginal malnourishment, infections, and environmental chemicals on growth and reproductive success in Swiss-Webster white mice and wild deer mice were studied with fractional factorial designs. Interaction effects were discovered. For example, malnourished mice were more sensitive to virus exposure and environmental chemicals (a plant growth regulator or polychlorinated biphenyls). Since several commercial plant growth regulators also appear to suppress the immune system, these results cast doubt on the adequacy of current toxicity testing procedures in which factors are studied individually and not in combination.

  20. [Suppression of tumor immunity by electromagnetic fields and glucocorticoids in mice with implanted Ehrlich carcinoma].

    Science.gov (United States)

    Knezević, Dusko

    2005-01-01

    The immune system plays a major role in the origin, growth and evolution of tumors; factors that decrease the immune response in any way can cause higher tumor incidence and its faster or uncontrolled growth and evolution. The research included 18 healthy male Han: NMRI mice, weighing between 25 and 30g, with ten-day-old tumor deposits, divided into three groups consisting of six mice each. The first group was continuously exposed to extremely low frequency electromagnetic fields (intensity 70-320 microT). The second group was treated with high doses of corticosteroids (dexamethasone). The control group was not treated with corticosteroids, nor was exposed to extremely low frequency electromagnetic fields. The exposure period lasted for ten days. The criteria used to evaluate tumor immunity were: histological findings of leukocyte infiltration around the tumor cells and white blood cell count. The control group presented with excellent immune response to tumor cells. Lymphoplasmacytic infiltrates widely surrounded the tumor. Numerous tumor cells showed signs of cell death. The results showed that exposure of animals to high doses of glucocorticoids resulted in extremely decreased leukocyte infiltration in the tumor tissue (single lymphocytes), while exposure to extremely low frequency electromagnetic fields significantly decreased leukocyte infiltration in comparison to the control group. Comparison of white blood cell count in treated groups revealed that the white blood cell count in both treated groups was decreased, compared with the control group. Extremely low frequency electromagnetic fields significantly suppress the immune response to tumor cells. Dexamethasone treatment resulted in almost complete absence of immune response to tumor cells. Electromagnetic fields and dexamethasone both decrease the white blood cell count.

  1. Proteomics-Based Characterization of the Humoral Immune Response in Sporotrichosis: Toward Discovery of Potential Diagnostic and Vaccine Antigens

    Science.gov (United States)

    Rodrigues, Anderson Messias; Fernandes, Geisa Ferreira; Araujo, Leticia Mendes; Della Terra, Paula Portella; dos Santos, Priscila Oliveira; Pereira, Sandro Antonio; Schubach, Tânia Maria Pacheco; Burger, Eva; Lopes-Bezerra, Leila Maria; de Camargo, Zoilo Pires

    2015-01-01

    Background Sporothrix schenckii and associated species are agents of human and animal sporotrichosis that cause large sapronoses and zoonoses worldwide. Epidemiological surveillance has highlighted an overwhelming occurrence of the highly pathogenic fungus Sporothrix brasiliensis during feline outbreaks, leading to massive transmissions to humans. Early diagnosis of feline sporotrichosis by demonstrating the presence of a surrogate marker of infection can have a key role for selecting appropriate disease control measures and minimizing zoonotic transmission to humans. Methodology We explored the presence and diversity of serum antibodies (IgG) specific against Sporothrix antigens in cats with sporotrichosis and evaluated the utility of these antibodies for serodiagnosis. Antigen profiling included protein extracts from the closest known relatives S. brasiliensis and S. schenckii. Enzyme-linked immunosorbent assays and immunoblotting enabled us to characterize the major antigens of feline sporotrichosis from sera from cats with sporotrichosis (n = 49), healthy cats (n = 19), and cats with other diseases (n = 20). Principal Findings Enzyme-linked immunosorbent assay-based quantitation of anti-Sporothrix IgG exhibited high sensitivity and specificity in cats with sporotrichosis (area under the curve, 1.0; 95% confidence interval, 0.94–1; PSporothrix antigens were remarkably cross-reactive, supporting the hypothesis that antigenic epitopes may be conserved among closely related agents. One-dimensional immunoblotting indicated that 3-carboxymuconate cyclase (a 60-kDa protein in S. brasiliensis and a 70-kDa protein in S. schenckii) is the immunodominant antigen in feline sporotrichosis. Two-dimensional immunoblotting revealed six IgG-reactive isoforms of gp60 in the S. brasiliensis proteome, similar to the humoral response found in human sporotrichosis. Conclusions A convergent IgG-response in various hosts (mice, cats, and humans) has important implications for our

  2. A trifunctional dextran-based nanovaccine targets and activates murine dendritic cells, and induces potent cellular and humoral immune responses in vivo.

    Directory of Open Access Journals (Sweden)

    Limei Shen

    Full Text Available Dendritic cells (DCs constitute an attractive target for specific delivery of nanovaccines for immunotherapeutic applications. Here we tested nano-sized dextran (DEX particles to serve as a DC-addressing nanocarrier platform. Non-functionalized DEX particles had no immunomodulatory effect on bone marrow (BM-derived murine DCs in vitro. However, when adsorbed with ovalbumine (OVA, DEX particles were efficiently engulfed by BM-DCs in a mannose receptor-dependent manner. A DEX-based nanovaccine containing OVA and lipopolysaccharide (LPS as a DC stimulus induced strong OVA peptide-specific CD4(+ and CD8(+ T cell proliferation both in vitro and upon systemic application in mice, as well as a robust OVA-specific humoral immune response (IgG1>IgG2a in vivo. Accordingly, this nanovaccine also raised both a more pronounced delayed-type hypersensitivity response and a stronger induction of cytotoxic CD8(+ T cells than obtained upon administration of OVA and LPS in soluble form. Therefore, DEX-based nanoparticles constitute a potent, versatile and easy to prepare nanovaccine platform for immunotherapeutic approaches.

  3. A novel respiratory syncytial virus (RSV F subunit vaccine adjuvanted with GLA-SE elicits robust protective TH1-type humoral and cellular immunity in rodent models.

    Directory of Open Access Journals (Sweden)

    Stacie L Lambert

    Full Text Available Illness associated with Respiratory Syncytial Virus (RSV remains an unmet medical need in both full-term infants and older adults. The fusion glycoprotein (F of RSV, which plays a key role in RSV infection and is a target of neutralizing antibodies, is an attractive vaccine target for inducing RSV-specific immunity.BALB/c mice and cotton rats, two well-characterized rodent models of RSV infection, were used to evaluate the immunogenicity of intramuscularly administered RSV vaccine candidates consisting of purified soluble F (sF protein formulated with TLR4 agonist glucopyranosyl lipid A (GLA, stable emulsion (SE, GLA-SE, or alum adjuvants. Protection from RSV challenge, serum RSV neutralizing responses, and anti-F IgG responses were induced by all of the tested adjuvanted RSV sF vaccine formulations. However, only RSV sF + GLA-SE induced robust F-specific TH1-biased humoral and cellular responses. In mice, these F-specific cellular responses include both CD4 and CD8 T cells, with F-specific polyfunctional CD8 T cells that traffic to the mouse lung following RSV challenge. This RSV sF + GLA-SE vaccine formulation can also induce robust RSV neutralizing titers and prime IFNγ-producing T cell responses in Sprague Dawley rats.These studies indicate that a protein subunit vaccine consisting of RSV sF + GLA-SE can induce robust neutralizing antibody and T cell responses to RSV, enhancing viral clearance via a TH1 immune-mediated mechanism. This vaccine may benefit older populations at risk for RSV disease.

  4. Recombinant human lactoferrin expressed in glycoengineered Pichia pastoris: effect of terminal N-acetylneuraminic acid on in vitro secondary humoral immune response.

    Science.gov (United States)

    Choi, Byung-Kwon; Actor, Jeffrey K; Rios, Sandra; d'Anjou, Marc; Stadheim, Terrance A; Warburton, Shannon; Giaccone, Erin; Cukan, Michael; Li, Huijuan; Kull, Angela; Sharkey, Nathan; Gollnick, Paul; Kocieba, Maja; Artym, Jolanta; Zimecki, Michal; Kruzel, Marian L; Wildt, Stefan

    2008-08-01

    Traditional production of therapeutic glycoproteins relies on mammalian cell culture technology. Glycoproteins produced by mammalian cells invariably display N-glycan heterogeneity resulting in a mixture of glycoforms the composition of which varies from production batch to production batch. However, extent and type of N-glycosylation has a profound impact on the therapeutic properties of many commercially relevant therapeutic proteins making control of N-glycosylation an emerging field of high importance. We have employed a combinatorial library approach to generate glycoengineered Pichia pastoris strains capable of displaying defined human-like N-linked glycans at high uniformity. The availability of these strains allows us to elucidate the relationship between specific N-linked glycans and the function of glycoproteins. The aim of this study was to utilize this novel technology platform and produce two human-like N-linked glycoforms of recombinant human lactoferrin (rhLF), sialylated and non-sialylated, and to evaluate the effects of terminal N-glycan structures on in vitro secondary humoral immune responses. Lactoferrin is considered an important first line defense protein involved in protection against various microbial infections. Here, it is established that glycoengineered P. pastoris strains are bioprocess compatible. Analytical protein and glycan data are presented to demonstrate the capability of glycoengineered P. pastoris to produce fully humanized, active and immunologically compatible rhLF. In addition, the biological activity of the rhLF glycoforms produced was tested in vitro revealing the importance of N-acetylneuraminic (sialic) acid as a terminal sugar in propagation of proper immune responses.

  5. Immunopotentiation of Different Adjuvants on Humoral and Cellular Immune Responses Induced by HA1-2 Subunit Vaccines of H7N9 Influenza in Mice.

    Directory of Open Access Journals (Sweden)

    Li Song

    Full Text Available In spring 2013, human infections with a novel avian influenza A (H7N9 virus were reported in China. The number of cases has increased with over 200 mortalities reported to date. However, there is currently no vaccine available for the H7 subtype of influenza A virus. Virus-specific cellular immune responses play a critical role in virus clearance during influenza infection. In this study, we undertook a side-by-side evaluation of two different adjuvants, Salmonella typhimurium flagellin (fliC and polyethyleneimine (PEI, through intraperitoneal administration to assess their effects on the immunogenicity of the recombinant HA1-2 subunit vaccine of H7N9 influenza. The fusion protein HA1-2-fliC and HA1-2 combined with PEI could induce significantly higher HA1-2-specific IgG and hemagglutination inhibition titers than HA1-2 alone at 12 days post-boost, with superior HA1-2 specific IgG titers in the HA1-2-fliC group compared with the PEI adjuvanted group. The PEI adjuvanted vaccine induced higher IgG1/IgG2a ratio and significantly increased numbers of IFN-γ- and IL-4-producing cells than HA1-2 alone, suggesting a mixed Th1/Th2-type cellular immune response with a Th2 bias. Meanwhile, the HA1-2-fliC induced higher IgG2a and IgG1 levels, which is indicative of a mixed Th1/Th2-type profile. Consistent with this, significant levels, and equal numbers, of IFN-γ- and IL-4-producing cells were detected after HA1-2-fliC vaccination. Moreover, the marked increase in CD69 expression and the proliferative index with the HA1-2-fliC and PEI adjuvanted vaccines indicated that both adjuvanted vaccine candidates effectively induced antigen-specific cellular immune responses. Taken together, our findings indicate that the two adjuvanted vaccine candidates elicit effective and HA1-2-specific humoral and cellular immune responses, offering significant promise for the development of a successful recombinant HA1-2 subunit vaccine for H7N9 influenza.

  6. The Listeria monocytogenes ChiA chitinase enhances virulence through suppression of host innate immunity.

    Science.gov (United States)

    Chaudhuri, Swarnava; Gantner, Benjamin N; Ye, Richard D; Cianciotto, Nicholas P; Freitag, Nancy E

    2013-03-19

    Environmental pathogens survive and replicate within the outside environment while maintaining the capacity to infect mammalian hosts. For some microorganisms, mammalian infection may be a relatively rare event. Understanding how environmental pathogens retain their ability to cause disease may provide insight into environmental reservoirs of disease and emerging infections. Listeria monocytogenes survives as a saprophyte in soil but is capable of causing serious invasive disease in susceptible individuals. The bacterium secretes virulence factors that promote cell invasion, bacterial replication, and cell-to-cell spread. Recently, an L. monocytogenes chitinase (ChiA) was shown to enhance bacterial infection in mice. Given that mammals do not synthesize chitin, the function of ChiA within infected animals was not clear. Here we have demonstrated that ChiA enhances L. monocytogenes survival in vivo through the suppression of host innate immunity. L. monocytogenes ΔchiA mutants were fully capable of establishing bacterial replication within target organs during the first 48 h of infection. By 72 to 96 h postinfection, however, numbers of ΔchiA bacteria diminished, indicative of an effective immune response to contain infection. The ΔchiA-associated virulence defect could be complemented in trans by wild-type L. monocytogenes, suggesting that secreted ChiA altered a target that resulted in a more permissive host environment for bacterial replication. ChiA secretion resulted in a dramatic decrease in inducible nitric oxide synthase (iNOS) expression, and ΔchiA mutant virulence was restored in NOS2(-/-) mice lacking iNOS. This work is the first to demonstrate modulation of a specific host innate immune response by a bacterial chitinase. Bacterial chitinases have traditionally been viewed as enzymes that either hydrolyze chitin as a food source or serve as a defense mechanism against organisms containing structural chitin (such as fungi). Recent evidence indicates

  7. Characterization of rubella-specific humoral immunity following two doses of MMR vaccine using proteome microarray technology

    Science.gov (United States)

    Haralambieva, Iana H.; Gibson, Michael J.; Kennedy, Richard B.; Ovsyannikova, Inna G.; Warner, Nathaniel D.; Grill, Diane E.

    2017-01-01

    Introduction//Background The lack of standardization of the currently used commercial anti-rubella IgG antibody assays leads to frequent misinterpretation of results for samples with low/equivocal antibody concentration. The use of alternative approaches in rubella serology could add new information leading to a fuller understanding of rubella protective immunity and neutralizing antibody response after vaccination. Methods We applied microarray technology to measure antibodies to all rubella virus proteins in 75 high and 75 low rubella virus-specific antibody responders after two MMR vaccine doses. These data were used in multivariate penalized logistic regression modeling of rubella-specific neutralizing antibody response after vaccination. Results We measured antibodies to all rubella virus structural proteins (i.e., the glycoproteins E1 and E2 and the capsid C protein) and to the non-structural protein P150. Antibody levels to each of these proteins were: correlated with the neutralizing antibody titer (prubella virus-specific neutralizing antibody titers (misclassification error = 0.2). Conclusion Our study supports the use of this new technology, as well as the use of antibody profiles/patterns (rather than single antibody measures) as biomarkers of neutralizing antibody response and correlates of protective immunity in rubella virus serology. PMID:29145521

  8. Cell-Mediated and Humoral Immune Responses after Immunization of Calves with a Recombinant Multiantigenic Mycobacterium avium subsp. paratuberculosis Subunit Vaccine at Different Ages

    DEFF Research Database (Denmark)

    Thakur, Aneesh; Aagaard, Claus; Stockmarr, Anders

    2013-01-01

    Neonates and juvenile ruminants are very susceptible to paratuberculosis infection. This is likely due to a high degree of exposure from their dams and an immature immune system. To test the influence of age on vaccine-induced responses, a cocktail of recombinant Mycobacterium avium subsp. paratu...

  9. The Ustilago maydis effector Pep1 suppresses plant immunity by inhibition of host peroxidase activity.

    Directory of Open Access Journals (Sweden)

    Christoph Hemetsberger

    Full Text Available The corn smut Ustilago maydis establishes a biotrophic interaction with its host plant maize. This interaction requires efficient suppression of plant immune responses, which is attributed to secreted effector proteins. Previously we identified Pep1 (Protein essential during penetration-1 as a secreted effector with an essential role for U. maydis virulence. pep1 deletion mutants induce strong defense responses leading to an early block in pathogenic development of the fungus. Using cytological and functional assays we show that Pep1 functions as an inhibitor of plant peroxidases. At sites of Δpep1 mutant penetrations, H₂O₂ strongly accumulated in the cell walls, coinciding with a transcriptional induction of the secreted maize peroxidase POX12. Pep1 protein effectively inhibited the peroxidase driven oxidative burst and thereby suppresses the early immune responses of maize. Moreover, Pep1 directly inhibits peroxidases in vitro in a concentration-dependent manner. Using fluorescence complementation assays, we observed a direct interaction of Pep1 and the maize peroxidase POX12 in vivo. Functional relevance of this interaction was demonstrated by partial complementation of the Δpep1 mutant defect by virus induced gene silencing of maize POX12. We conclude that Pep1 acts as a potent suppressor of early plant defenses by inhibition of peroxidase activity. Thus, it represents a novel strategy for establishing a biotrophic interaction.

  10. The Necrosome Promotes Pancreas Oncogenesis via CXCL1 and Mincle Induced Immune Suppression

    Science.gov (United States)

    Seifert, Lena; Werba, Gregor; Tiwari, Shaun; Giao Ly, Nancy Ngoc; Alothman, Sara; Alqunaibit, Dalia; Avanzi, Antonina; Barilla, Rocky; Daley, Donnele; Greco, Stephanie H.; Torres-Hernandez, Alejandro; Pergamo, Matthew; Ochi, Atsuo; Zambirinis, Constantinos P.; Pansari, Mridul; Rendon, Mauricio; Tippens, Daniel; Hundeyin, Mautin; Mani, Vishnu R.; Hajdu, Cristina; Engle, Dannielle; Miller, George

    2016-01-01

    Neoplastic pancreatic epithelial cells are widely believed to die via Caspase 8-dependant apoptotic cell death and chemotherapy is thought to further promote tumor apoptosis1. Conversely, disruption of apoptosis is a basic modality cancer cells exploit for survival2,3. However, the role of necroptosis, or programmed necrosis, in pancreatic ductal adenocarcinoma (PDA) is uncertain. There are a multitude of potential inducers of necroptosis in PDA including ligation of TNFR1, CD95, TRAIL receptors, Toll-like receptors, ROS, and Chemotherapeutics4,5. Here we report that the principal components of the necrosome, RIP1 and RIP3, are highly expressed in PDA and are further upregulated by chemotherapy. Blockade of the necrosome in vitro promoted cancer cell proliferation and induced an aggressive oncogenic phenotype. By contrast, in vivo RIP3 deletion or RIP1 inhibition was protective against oncogenic progression and was associated with the development of a highly immunogenic myeloid and T cell infiltrate. The immune-suppressive tumor microenvironment (TME) associated with intact RIP1/RIP3 signaling was in-part contingent on necroptosis-induced CXCL1 expression whereas CXCL1 blockade was protective against PDA. Moreover, we found that cytoplasmic SAP130 was expressed in PDA in a RIP1/RIP3-dependent manner, and Mincle – its cognate receptor – was upregulated in tumor-infiltrating myeloid cells. Mincle ligation by SAP130 promoted oncogenesis whereas Mincle deletion was protective and phenocopied the immunogenic reprogramming of the TME characteristic of RIP3 deletion. Cellular depletion experiments suggested that whereas inhibitory macrophages promote tumorigenesis in PDA, they lose their immune-suppressive effects in the context of RIP3 or Mincle deletion. As such, T cells which are dispensable to PDA progression in hosts with intact RIP3 or Mincle signaling become reprogrammed into indispensable mediators of anti-tumor immunity in absence of RIP3 or Mincle. Our work

  11. The necrosome promotes pancreatic oncogenesis via CXCL1 and Mincle-induced immune suppression.

    Science.gov (United States)

    Seifert, Lena; Werba, Gregor; Tiwari, Shaun; Giao Ly, Nancy Ngoc; Alothman, Sara; Alqunaibit, Dalia; Avanzi, Antonina; Barilla, Rocky; Daley, Donnele; Greco, Stephanie H; Torres-Hernandez, Alejandro; Pergamo, Matthew; Ochi, Atsuo; Zambirinis, Constantinos P; Pansari, Mridul; Rendon, Mauricio; Tippens, Daniel; Hundeyin, Mautin; Mani, Vishnu R; Hajdu, Cristina; Engle, Dannielle; Miller, George

    2016-04-14

    Neoplastic pancreatic epithelial cells are believed to die through caspase 8-dependent apoptotic cell death, and chemotherapy is thought to promote tumour apoptosis. Conversely, cancer cells often disrupt apoptosis to survive. Another type of programmed cell death is necroptosis (programmed necrosis), but its role in pancreatic ductal adenocarcinoma (PDA) is unclear. There are many potential inducers of necroptosis in PDA, including ligation of tumour necrosis factor receptor 1 (TNFR1), CD95, TNF-related apoptosis-inducing ligand (TRAIL) receptors, Toll-like receptors, reactive oxygen species, and chemotherapeutic drugs. Here we report that the principal components of the necrosome, receptor-interacting protein (RIP)1 and RIP3, are highly expressed in PDA and are further upregulated by the chemotherapy drug gemcitabine. Blockade of the necrosome in vitro promoted cancer cell proliferation and induced an aggressive oncogenic phenotype. By contrast, in vivo deletion of RIP3 or inhibition of RIP1 protected against oncogenic progression in mice and was associated with the development of a highly immunogenic myeloid and T cell infiltrate. The immune-suppressive tumour microenvironment associated with intact RIP1/RIP3 signalling depended in part on necroptosis-induced expression of the chemokine attractant CXCL1, and CXCL1 blockade protected against PDA. Moreover, cytoplasmic SAP130 (a subunit of the histone deacetylase complex) was expressed in PDA in a RIP1/RIP3-dependent manner, and Mincle--its cognate receptor--was upregulated in tumour-infiltrating myeloid cells. Ligation of Mincle by SAP130 promoted oncogenesis, whereas deletion of Mincle protected against oncogenesis and phenocopied the immunogenic reprogramming of the tumour microenvironment that was induced by RIP3 deletion. Cellular depletion suggested that whereas inhibitory macrophages promote tumorigenesis in PDA, they lose their immune-suppressive effects when RIP3 or Mincle is deleted. Accordingly, T cells

  12. Ascaridia galli infection influences the development of both humoral and cell-mediated immunity after Newcastle Disease vaccination in chickens

    DEFF Research Database (Denmark)

    Pleidrup, Janne; Dalgaard, Tina S.; Norup, Liselotte R.

    2014-01-01

    blood three weeks after the first ND vaccination as compared to non-parasitized chickens. Finally, A. galli significantly increased local mRNA expression of IL-4 and IL-13 and significantly decreased TGF-ß4 expression in the jejunum two weeks after infection with A. galli. At the time of vaccination......Potent vaccine efficiency is crucial for disease control in both human and livestock vaccination programmes. Free range chickens and chickens with access to outdoor areas have a high risk of infection with parasites including Ascaridia galli, a gastrointestinal nematode with a potential influence...... on the immunological response to vaccination against other infectious diseases. The purpose of this study was to investigate whether A. galli infection influences vaccine-induced immunity to Newcastle Disease (ND) in chickens from an MHC-characterized inbred line. Chickens were experimentally infected with A. galli...

  13. Resposta imune-humoral e celular em bovinos da raça Nelore imunizados com extrato de larvas (L2 e L3 de Dermatobia hominis (Linnaeus Jr., 1781 Immune humoral and cellular response of nelore bovines immunized with larvae extract (L2 and L3 of Dermatobia hominis (Linnaeus Jr., 1781

    Directory of Open Access Journals (Sweden)

    Nelson Luis Mello Fernandes

    2007-06-01

    , making it difficult to industrial use. Nowadays, the chemical control is utilized against dermatobiosis, therefore it leads to rising toxic chemicals in the animals and environment. The immunological challenge with D. hominis larval extract may represent an important altervative for this parasitosis control. Humoral and cellular immune responses were tested in bovine using an antigenic extract prepared with D. hominis larvae. Three groups of 10 months old Nelore females were used. The first group (A received immunogenic larval extract of D. hominis with fifteen-days interval between injections; the group (B was the control and has not received any sort of treatment; and the group (C received an ectoparasitecide treatment based on Dichlorvos associated to Cypermetrina. Aditionally, leucogram and levels of IgG against D. hominis by immunoassay technique were evaluated. As for the humoral immunity, animals from group A presented higher IgG production against D. hominis with maximum levels of circulating antibodies at the 45th day after the first injection. These animals also showed higher production of neutrophils, eosinophils and monocytes than those from groups B and C. The number of D. hominis larvae nodules observed in animals from the group C was 148.3% larger than those from group A and B. The evidence concerning both cellular and humoral immune responses as well as the reduction on nodules number are an indication that the immunization against D. hominis was partially protective for the immunized bovines.

  14. Bacterial Nucleotidyl Cyclase Inhibits the Host Innate Immune Response by Suppressing TAK1 Activation.

    Science.gov (United States)

    He, Chenxi; Zhou, Yilong; Liu, Feng; Liu, Haipeng; Tan, Hao; Jin, Shouguang; Wu, Weihui; Ge, Baoxue

    2017-09-01

    Exoenzyme Y (ExoY) is a type III secretion system effector found in 90% of the Pseudomonas aeruginosa isolates. Although it is known that ExoY is a soluble nucleotidyl cyclase that increases the cytoplasmic levels of nucleoside 3',5'-cyclic monophosphates (cNMPs) to mediate endothelial Tau phosphorylation and permeability, its functional role in the innate immune response is still poorly understood. Transforming growth factor β-activated kinase 1 (TAK1) is critical for mediating Toll-like receptor (TLR) signaling and subsequent activation of NF-κB and AP-1, which are transcriptional activators of innate immunity. Here, we report that ExoY inhibits proinflammatory cytokine production through suppressing the activation of TAK1 as well as downstream NF-κB and mitogen-activated protein (MAP) kinases. Mice infected with ExoY-deficient P. aeruginosa had higher levels of tumor necrosis factor (TNF) and interleukin-6 (IL-6), more neutrophil recruitment, and a lower bacterial load in lung tissue than mice infected with wild-type P. aeruginosa Taken together, our findings identify a previously unknown mechanism by which P. aeruginosa ExoY inhibits the host innate immune response. Copyright © 2017 American Society for Microbiology.

  15. GM-CSF: An Immune Modulatory Cytokine that can Suppress Autoimmunity

    Science.gov (United States)

    Bhattacharya, Palash; Thiruppathi, Muthusamy; Elshabrawy, Hatem A.; Alharshawi, Khaled; Kumar, Prabhakaran; Prabhakar, Bellur S.

    2015-01-01

    GM-CSF was originally identified as a colony stimulating factor (CSF) because of its ability to induce granulocyte and macrophage populations from precursor cells. Multiple studies have demonstrated that GM-CSF is also an immune-modulatory cytokine, capable of affecting not only the phenotype of myeloid lineage cells, but also T-cell activation through various myeloid intermediaries. This property has been implicated in the sustenance of several autoimmune diseases like arthritis and multiple sclerosis. In contrast, several studies using animal models have shown that GM-CSF is also capable of suppressing many autoimmune diseases like Crohn's disease, Type-1 diabetes, Myasthenia gravis and experimental autoimmune thyroiditis. Knockout mouse studies have suggested that the role of GM-CSF in maintaining granulocyte and macrophage populations in the physiological steady state is largely redundant. Instead, its immune-modulatory role plays a significant role in the development or resolution of autoimmune diseases. This is mediated either through the differentiation of precursor cells into specialized non-steady state granulocytes, macrophages and dendritic cells, or through the modulation of the phenotype of mature myeloid cells. Thus, outside of myelopoiesis, GM-CSF has a profound role in regulating the immune response and maintaining immunological tolerance. PMID:26113402

  16. Cellular and humoral immune responses to chimeric EGFP-pseudocapsids derived from the mouse polyomavirus after their intranasal administration.

    Science.gov (United States)

    Fric, Jan; Marek, Martin; Hrusková, Veronika; Holán, Vladimír; Forstová, Jitka

    2008-06-19

    Mouse polyomavirus (MPyV) VP1-pseudocapsids carrying enhanced green fluorescent protein (EGFP-VLPs) were used for intranasal immunization of mice. EGFP-VLPs induced strong anti-VP1 but not anti-EGFP antibody production. In vitro restimulation with antigen-pulsed bone marrow-derived dendritic cells (BMDCs) induced remarkable T-cell proliferative response specific for both VP1 and EGFP antigen and IL-2 and IFN-gamma production. Surprisingly, no specific cytotoxic activities against VP1 and EGFP proteins were detected. After intranasal administration of EGFP-VLPs, as well as after polyomavirus infection, a moderate reduction of CD4(+)CD25(+)Foxp3(+) T cells was observed in spleens but not in lymph nodes and peripheral blood, suggesting that both MPyV virions and pseudocapsids are able to induce changes in distribution of regulatory T cells. Treatment of EGFP-VLPs pulsed BMDCs with inhibitors of endosomal acidification proved that presentation of peptides on MHCgp class II is dependent on acidic endosomal environment. Substantial decrease of CD4-specific T-cell proliferation in the presence of proteasome inhibitor suggests that MHCgp class II might load VPL-derived peptides processed by proteasomes. Thus, polyomavirus derived VLPs appear to be promising delivery and adjuvant vehicles for therapeutic proteins.

  17. Vaccination-Related Side Effects, Humoral Immunity, and Adverse Events during the Civilian Smallpox Vaccination Campaign, Arkansas, 2003.

    Science.gov (United States)

    Haselow, Dirk

    2016-01-01

    Smallpox vaccination has been associated with notable side effects and adverse events. This study assessed the frequency of each among public health workers immunized during the 2003 Arkansas civilian smallpox vaccination campaign to allow individuals and policymakers to make informed decisions whether repeat vaccination, as recommended in 10-year intervals, should be considered. This descriptive study summarizes postvaccination surveillance data for all civilians receiving smallpox vaccine (Dryvax) in Arkansas in 2003. Rates of side effects and adverse events were determined. Vaccinia-specific antibody titers among a subset of public health response team members were also assessed. Of the 1,124 vaccine recipients, 87% had a major take response. Substantial symptomatology, a 2% adverse event rate, a 0.5% hospitalization rate, and zero inadvertent transmission following vaccination were observed. Vaccinia-specific antibody titers increased on average 9-fold from 2.21*10(2) to 2.16*10(3) one month after vaccination. We found no association of age, sex, or racial subgroups with adverse events, hospitalizations, a lower take response rate, or lower postvaccination antibody titers. Prominent side effect profiles and adverse events among study participants seem to support individual and institutional reluctance to vaccinate civilians in the absence of smallpox reemergence. © 2015 Wiley Periodicals, Inc.

  18. Immunomodulatory and antioxidant effect of Leptadenia reticulata leaf extract in rodents: possible modulation of cell and humoral immune response.

    Science.gov (United States)

    Pravansha, S; Thippeswamy, B S; Veerapur, V P

    2012-12-01

    Leptadenia reticulata Linn. (Asclpiadaceae) commonly known as "dodi," is an Indian medicinal plant which is known to have ethno-medical uses such as stimulant, tonic, immunostimulant and is one of the ingredient in ayurvedic formulation called as "Chawanprash," which is widely used in India to increase the strength of immune system. The aim of present study is to evaluate immunomodulatory and antioxidant activity of ethanolic extract of L. reticulata L. leaves in rodents. Haemagglutinating antibody (HA) titre, haematological profile (Hb, WBC, RBC), lipid peroxidation (LPO), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), delayed type of hypersensitivity (DTH) response, neutrophil adhesion test and carbon clearance assay were determined by in vivo experiments. The evaluation of immunomodulatory potential of L. reticulata (100, 200 mg/kg, p.o.) evoked a significant dose-dependent increase in antibody titre values; DTH reaction induced by SRBC and potentiated percentage neutrophil adhesion to nylon fibers as well as phagocytosis in carbon clearance assay. Also it caused significant increase in haematological profile, GSH, SOD, CAT activity and significantly decreased LPO levels in cyclophosphamide-induced immunosuppressed rats. The results obtained in this study indicate that L. reticulata possesses potential immunomodulatory and antioxidant activity and can play a major role in reducing the risk to develop immunodeficiency disorders.

  19. Combination of Aβ Suppression and Innate Immune Activation in the Brain Significantly Attenuates Amyloid Plaque Deposition.

    Science.gov (United States)

    Verbeeck, Christophe; Carrano, Anna; Chakrabarty, Paramita; Jankowsky, Joanna L; Das, Pritam

    2017-12-01

    Anti-Aβ clinical trials are currently under way to determine whether preventing amyloid deposition will be beneficial in arresting progression of Alzheimer disease. Both clinical and preclinical studies suggest that antiamyloid strategies are only effective if started at early stages of the disease process in a primary prevention strategy. Because this approach will be difficult to deploy, strategies for secondary prevention aimed at later stages of disease are also needed. In this study, we asked whether combining innate immune activation in the brain with concurrent Aβ suppression could enhance plaque clearance and could improve pathologic outcomes in mice with moderate amyloid pathologic disorder. Starting at 5 months of age, tet-off amyloid precursor protein transgenic mice were treated with doxycycline (dox) to suppress further amyloid precursor protein/Aβ production, and at the same time mice were intracranially injected with adeno-associated virus 1 expressing murine IL-6 (AAV1-mIL-6). Three months later, mice treated with the combination of Aβ suppression and AAV1-mIL-6 showed significantly less plaque pathologic disorder than dox or AAV1-mIL-6 only groups. The combination of AAV1-mIL-6 + dox treatment lowered total plaque burden by >60% versus untreated controls. Treatment with either dox or AAV1-mIL-6 alone was less effective than the combination. Our results suggest a synergistic mechanism by which the up-regulation of mIL-6 was able to improve plaque clearance in the setting of Aβ suppression. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  20. Humor in systemic lupus erythematosus.

    Science.gov (United States)

    Moura, Cristiano S; Li, Rui; Lawrie, Sarah; Bar-Or, Amit; Clarke, Ann E; Da Costa, Deborah; Banerjee, Devi; Bernatsky, Sasha; Lee, Jennifer L; Pineau, Christian A

    2015-03-01

    Humor has neurophysiological effects influencing the release of cortisol, which may have a direct impact on the immune system. Laughter is associated with a decreased production of inflammatory cytokines both in the general population and in rheumatoid arthritis (RA). Our objective was to explore the effects of humor on serum cytokines [particularly interleukin-6 (IL-6)] and cortisol levels in systemic lupus erythematosus (SLE), after a standard intervention (120 min of visual comedy). We enrolled 58 females with SLE from consecutive patients assessed in the Montreal General Hospital lupus clinic. The subjects who consented to participate were randomized in a 1:1 ratio to the intervention (watching 120 min of comedy) or control group (watching a 120 min documentary). Measurements of cytokine and serum cortisol levels as well as 24-h urine cortisol were taken before, during, and after the interventions. We compared serum cytokine levels and serum and 24-h urine cortisol levels in the humor and control groups and performed regression analyses of these outcomes, adjusting for demographics and the current use of prednisone. There were no significant differences between the control and humor groups in demographics or clinical variables. Baseline serum levels of IL-6, IL-10, tumor necrosis factor-alpha, and B-cell activating factor were also similar in both groups. There was no evidence of a humor effect in terms of decreasing cytokine levels, although there was some suggestion of lowered cortisol secretion in the humor group based the 24-h urinary cortisol levels in a subgroup. In contrast to what has been published for RA, we saw no clear effects of humor in altering cytokine levels in SLE, although interesting trends were seen for lower cortisol levels after humor intervention compared with the control group.

  1. Rubella specific cell-mediated and humoral immunity following vaccination in college students with low antibody titers.

    Science.gov (United States)

    Terada, Kihei; Itoh, Yuri; Wakabayashi, Tokio; Teranishi, Hideto; Akaike, Hiroto; Ogita, Satoko; Ouchi, Kazunobu

    2015-11-09

    This study measured cell-mediated immunity (CMI) and antibodies to clarify the basis of rubella reinfection after vaccination. In a pool of 65 college students, 39 who exhibited hemagglutination-inhibition (HI) antibody titers against rubella of ≤ 1:16 were vaccinated with a rubella vaccine. The CMI was assessed with interferon-gamma release assay. There was low correlation (r = 0.24) between the antibody titers and interferon-gamma levels at pre-vaccination status. Preexisting interferon-gamma levels were low in some subjects with low HI antibody titers of 1:8 and 1:16. Fifty-seven percent (4/7) of the subjects who were antibody-negative with past history of rubella vaccination at entry onto the study exhibited CMI. And 57% (4/7) of the subjects remained antibody-negative following a second vaccination, despite exhibiting CMI. HI antibody titers increased significantly after vaccination, whereas post-vaccination interferon-gamma levels did not exhibit significant increases. When subjects were divided (based on their past history of vaccination and antibody values) into natural infection and vaccination groups, HI antibody titers (mean ± SD) increased to 1:2(4.4 ± 1.4) from 1: 2(3.2 ± 0.4) (p = 0.065) in the natural infection group and to 1:2(4.4 ± 1.0) from 1:2(3.0 ± 0.8) (p rubella reinfection can occur in vaccinated seropositive individuals. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Innate immune humoral factors, C1q and factor H, with differential pattern recognition properties, alter macrophage response to carbon nanotubes.

    Science.gov (United States)

    Pondman, Kirsten M; Pednekar, Lina; Paudyal, Basudev; Tsolaki, Anthony G; Kouser, Lubna; Khan, Haseeb A; Shamji, Mohamed H; Ten Haken, Bennie; Stenbeck, Gudrun; Sim, Robert B; Kishore, Uday

    2015-11-01

    Interaction between the complement system and carbon nanotubes (CNTs) can modify their intended biomedical applications. Pristine and derivatised CNTs can activate complement primarily via the classical pathway which enhances uptake of CNTs and suppresses pro-inflammatory response by immune cells. Here, we report that the interaction of C1q, the classical pathway recognition molecule, with CNTs involves charge pattern and classical pathway activation that is partly inhibited by factor H, a complement regulator. C1q and its globular modules, but not factor H, enhanced uptake of CNTs by macrophages and modulated the pro-inflammatory immune response. Thus, soluble complement factors can interact differentially with CNTs and alter the immune response even without complement activation. Coating CNTs with recombinant C1q globular heads offers a novel way of controlling classical pathway activation in nanotherapeutics. Surprisingly, the globular heads also enhance clearance by phagocytes and down-regulate inflammation, suggesting unexpected complexity in receptor interaction. Carbon nanotubes (CNTs) maybe useful in the clinical setting as targeting drug carriers. However, it is also well known that they can interact and activate the complement system, which may have a negative impact on the applicability of CNTs. In this study, the authors functionalized multi-walled CNT (MWNT), and investigated the interaction with the complement pathway. These studies are important so as to gain further understanding of the underlying mechanism in preparation for future use of CNTs in the clinical setting. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Radiation Therapy Induces Macrophages to Suppress Immune Responses Against Pancreatic Tumors in Mice

    Science.gov (United States)

    Seifert, Lena; Werba, Gregor; Tiwari, Shaun; Ly, Nancy Ngoc Giao; Nguy, Susanna; Alothman, Sara; Alqunaibit, Dalia; Avanzi, Antonina; Daley, Donnele; Barilla, Rocky; Tippens, Daniel; Torres-Hernandez, Alejandro; Hundeyin, Mautin; Mani, Vishnu R.; Hajdu, Cristina; Pellicciotta, Ilenia; Oh, Philmo; Du, Kevin; Miller, George

    2016-01-01

    Background & Aims The role of radiation therapy in the treatment of patients with pancreatic ductal adenocarcinoma (PDA) is controversial. Randomized controlled trials investigating the efficacy of radiation therapy in patients with locally advanced unresectable PDA have reported mixed results, with effects ranging from modest benefit to worse outcome, compared with control therapies. We investigated whether radiation causes inflammatory cells to acquire an immune-suppressive phenotype that limits the therapeutic effects of radiation on invasive PDAs and accelerates progression of pre-invasive foci. Methods We investigated the effects of radiation in p48Cre;LSL-KrasG12D (KC) and p48Cre;LSLKrasG12D;LSL-Trp53R172H (KPC) mice, as well as in C57BL/6 mice with orthotopic tumors grown from FC1242 cells derived from KPC mice. Some mice were given neutralizing antibodies against macrophage colony stimulating factor 1 (CSF1 or MCSF) or F4/80. Pancreata were exposed to doses of radiation ranging from 2–12 Gy and analyzed by flow cytometry. Results Pancreata of KC mice exposed to radiation had a higher frequency of advanced pancreatic intraepithelial lesions and more foci of invasive cancer than pancreata of unexposed mice (controls); radiation reduced survival time by more than 6 months. A greater proportion of macrophages from invasive and pre-invasive pancreatic tumors had an immune-suppressive, M2-like phenotype, compared with control mice. Pancreata from mice exposed to radiation had fewer CD8+ T cells than controls and greater numbers of CD4+ T cells of T-helper 2 and T-regulatory cell phenotypes. Adoptive transfer of T cells from irradiated PDA to tumors of control mice accelerated tumor growth. Radiation induced production of MCSF by PDA cells. An antibody against MCSF prevented radiation from altering the phenotype of macrophages in tumors, increasing the anti-tumor T-cell response and slowing tumor growth. Conclusions Radiation exposure causes macrophages in PDAs

  4. Characterization of a single dose methylprednisolone acetate immune suppression model using Cryptosporidium muris and Cryptosporidium parvum.

    Science.gov (United States)

    Miller, Thomas A; Schaefer, Frank W

    2006-10-10

    An immunosuppressive dose of methylprednisolone acetate (MPA) was compared with a non-immunosuppressive dose using Cryptosporidium oocyst production as an indicator of immunosuppression. To be classified as immunosuppressive, the dose had to satisfy five criteria. First, the dose had to abrogate normal immune defenses allowing the propagation of an organism to which the host is normally resistant, i.e. Cryptosporidium parvum in adult mice. Second, the dose had to decrease overall circulating CD4 T-lymphocyte numbers by greater than 80%. Third, the immunosuppressive dose had to prolong the infection beyond the normal infection length, and fourth, increase the severity of an active infection. Lastly, after complete recovery from a C. muris infection, immunosuppression must suppress the naturally acquired post infection immunity and allow reinfection. In mice immunosuppression with 600 mgMPA/kg lasted approximately 14 days and satisfied all five criteria. Fecal oocyst production could be perpetuated by dosing at 10-day intervals. A 200 mgMPA/kg dose transiently lowered CD4 counts by over 80%, but failed to override the naturally acquired post infection immunity or allow infection with C. parvum. The immunosuppressed blood profile consisted of an immediate sharp rise of mature segmented neutrophils combined with a severe decrease in circulating T-lymphocyte numbers. The rise and fall of neutrophils proved to be a good indicator of the severity and duration of immunosuppression. The thymus and spleen likewise contracted and then expanded in accordance with the steroid effect. The metabolism of MPA resulted in the eventual recovery of immune function signified by the cessation of C. parvum oocyst production. The recovery blood profile was associated with circulating CD8 counts near control levels, continuing 80% depression of CD4 counts and a dropping total neutrophil count. This study shows that the 600 mg/kg MPA dose is a good model for immunosuppression, which

  5. Effects of dietary Spirulina platensis on growth performance, humoral and mucosal immune responses and disease resistance in juvenile great sturgeon (Huso huso Linnaeus, 1754).

    Science.gov (United States)

    Adel, Milad; Yeganeh, Sakineh; Dadar, Maryam; Sakai, Masahiro; Dawood, Mahmoud A O

    2016-09-01

    Dietary supplementation of Spirulina platensis at different levels (0% control, 2.5%, 5% and 10%) was evaluated to find out the effects on growth performance, digestive enzyme activities, humoral and skin innate immune responses and disease resistance in the great sturgeon (Huso huso). After 8 weeks of experimental trial, growth parameters, intestinal lactic acid bacteria count, protease and lipase activities were significantly high in 10% S. platensis fed group (P < 0.05). Similarly, in this group, respiratory burst activity of leucocytes and total protein of serum were also significantly high. Furthermore, supplementation of S. platensis at 5 or 10% exhibited higher serum IgM and lysozyme activity than the other experimental groups (P < 0.05). On the contrary, serum triglycerides and number of blood lymphocytes were lower in experimental groups than that of control group. Total proteins, lysozyme, protease and esterase, as well as in vitro bactericidal activity (against Streptococcus iniae, Yersinia ruckeri, Aeromonas hydrophila and Lactococcus garviea) were significantly high in skin mucus from fish fed 5% and 10% S. platensis, while, alkaline phosphatase was significantly high in fish fed 10% S. platensis (P < 0.05). Further, fish infected with Streptococcus iniae bacteria increased mortality, but it was alleviated by a diet supplemented with S. platensis. The present results demonstrate that this dietary supplementation with S. platensis (mainly at 10% level) could be useful for maintaining the overall health status of great sturgeon. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Towards the conservation of endangered avian species: a recombinant West Nile Virus vaccine results in increased humoral and cellular immune responses in Japanese Quail (Coturnix japonica.

    Directory of Open Access Journals (Sweden)

    Jay A Young

    Full Text Available West Nile Virus (WNV arrived in North America in 1999 and is now endemic. Many families of birds, especially corvids, are highly susceptible to WNV and infection often results in fatality. Avian species susceptible to WNV infection also include endangered species, such as the Greater Sage-Grouse (Centrocercus uropbasianuts and the Eastern Loggerhead Shrike (Lanius ludovicianus migrans. The virus has been shown to contribute towards the likelihood of their extinction. Although a clear and present threat, there exists no avian WNV vaccine available to combat this lethal menace. As a first step in establishing an avian model for testing candidate WNV vaccines, avian antibody based reagents were assessed for cross-reactivity with Japanese quail (Coturnix japonica T cell markers CD4 and CD8; the most reactive were found to be the anti-duck CD8 antibody, clone Du-CD8-1, and the anti-chicken/turkey CD4 antibody, clone CT4. These reagents were then used to assess vaccine performance as well as to establish T cell populations in quail, with a novel population of CD4/CD8 double positive T cells being identified in Japanese quail. Concurrently, non-replicating recombinant adenoviruses, expressing either the WNV envelope or NS3 'genes' were constructed and assessed for effectiveness as avian vaccines. Japanese Quail were selected for testing the vaccines, as they provide an avian model that parallels the population diversity of bird species in the wild. Both the level of WNV specific antibodies and the number of T cells in vaccinated birds were increased compared to unvaccinated controls. The results indicate the vaccines to be effective in increasing both humoral and cellular immune responses. These recombinant vaccines therefore may find utility as tools to protect and maintain domestic and wild avian populations. Their implementation may also arrest the progression towards extinction of endangered avian species and reduce the viral reservoir that

  7. DNA-mediated immunization of glycoprotein 350 of Epstein-Barr virus induces the effective humoral and cellular immune responses against the antigen.

    Science.gov (United States)

    Jung, S; Chung, Y K; Chang, S H; Kim, J; Kim, H R; Jang, H S; Lee, J C; Chung, G H; Jang, Y S

    2001-08-31

    Epstein-Barr virus (EBV) is a human pathogen that is involved in numerous diseases and tumors. Since the EBV infection occurs in the early ages of life, and most of the population is subsequently exposed to EBV, the conventional method of vaccination to induce the prophylactic immunity cannot be considered effective in coping with the virus infection. In this study, we tested whether the injection of a plasmid vector that contained the gene for glycoprotein 350 (gp350), which had been identified as a ligand for virus' adsorption and a target for virus neutralizing antibodies, could induce effective immune responses against the antigen. As a result, the injection of the constructed plasmid vector into mice induced the production of gp350-specific antibodies. A major isotype of the gp350-specific antibodies was IgG1. The antibodies efficiently mediated the antibody-dependent cellular cytotoxicity against the cells expressing the gp350 antigen. In addition, the injection of the constructed plasmid vector stimulated the precursor T cell population that was specific to the gp350 antigen. In addition, gp350-specific cytotoxic T lymphocytes were efficiently stimulated by the injection of the constructed plasmid vector. These results suggested that the injection of the plasmid vector, containing the gp350 gene of Epstein-Barr virus, could be one of the most effective ways to induce both prophylactic and therapeutic vaccinations against the virus infection.

  8. Suppression of antigen-specific antibody responses in mice exposed to perfluorooctanoic acid: Role of PPARalpha and T- and B-cell targeting

    Science.gov (United States)

    T-cell-dependent antibody responses (TDAR) are suppressed in female C57BL/6N mice exposed to ≥3.75 mg/kg of perfluorooctanoic acid (PFOA) for 15 days. To determine if suppression of humoral immunity by PFOA is peroxisome proliferator activated receptor alpha (PPARa)-dependent and...

  9. 7Beta-OH-DHEA counteracts dexamethasone induced suppression of primary immune response in murine spleenocytes.

    Science.gov (United States)

    Sterzl, I; Hampl, R; Sterzl, J; Votruba, J; Stárka, L

    1999-12-15

    The effect of dexamethasone and of three potential antiglucocorticoids, namely dehydroepiandrosterone (DHEA) and its 7alpha-and 7beta-hydroxylated metabolites, on primary immune response has been studied by measuring the number of plaque forming cells (NPFC) and their viability in a cell culture of murine spleenocytes. As expected, dexamethasone suppressed considerably the NPFC as well as their viability. Surprisingly, DHEA as well as its 7alpha-hydroxylated metabolite decreased significantly the NPFC, while the effect of 7beta-hydroxy-DHEA was different: at low doses it decreased the NPFC, but this effect was less pronounced at higher concentrations. In addition, 7beta-hydroxy-DHEA was able to counteract the effect of dexamethasone on the NPFC. None of the natural steroids affected the cell viability.

  10. Engagement of the Mannose Receptor by Tumoral Mucins Activates an Immune Suppressive Phenotype in Human Tumor-Associated Macrophages

    Science.gov (United States)

    Allavena, P.; Chieppa, M.; Bianchi, G.; Solinas, G.; Fabbri, M.; Laskarin, G.; Mantovani, A.

    2010-01-01

    Tumor-Associated Macrophages (TAMs) are abundantly present in the stroma of solid tumors and modulate several important biological processes, such as neoangiogenesis, cancer cell proliferation and invasion, and suppression of adaptive immune responses. Myeloid C-type lectin receptors (CLRs) constitute a large family of transmembrane carbohydrate-binding receptors that recognize pathogens as well as endogenous glycoproteins. Several lines of evidence demonstrate that some CLRs can inhibit the immune response. In this study we investigated TAM-associated molecules potentially involved in their immune suppressive activity. We found that TAMs isolated from human ovarian carcinoma samples predominantly express the CLRs Dectin-1, MDL-1, MGL, DCIR, and most abundantly the Mannose Receptor (MR). Components of carcinomatous ascites and purified tumoral mucins (CA125 and TAG-72) bound the MR and induced its internalization. MR engagement by tumoral mucins and by an agonist anti-MR antibody modulated cytokine production by TAM toward an immune-suppressive profile: increase of IL-10, absence of IL-12, and decrease of the Th1-attracting chemokine CCL3. This study highlights that tumoral mucin-mediated ligation of the MR on infiltrating TAM may contribute to their immune suppressive phenotype. PMID:21331365

  11. Sulphonylurea usage in melioidosis is associated with severe disease and suppressed immune response.

    Directory of Open Access Journals (Sweden)

    Xiang Liu

    2014-04-01

    Full Text Available BACKGROUND: Melioidosis is a problem in the developing tropical regions of Southeast Asia and Northern Australia where the the Gram negative saprophytic bacillus Burkholderia pseudomallei is endemic with the risk of fulminant septicaemia. While diabetes mellitus is a well-established risk factor for melioidiosis, little is known if specific hypoglycemic agents may differentially influence the susceptibility and clinical course of infection with B. pseudomallei (Bp. METHODOLOGY/PRINCIPAL FINDINGS: In this cohort study, patients with pre-existing diabetes and melioidosis were retrospectively studied. OUTCOME MEASURES: mortality, length of stay and development of complications (namely hypotension, intubation, renal failure and septicaemia were studied in relation to prior diabetic treatment regimen. Peripheral blood mononuclear cells (PBMC from diabetic patients and healthy PBMC primed with metformin, glyburide and insulin were stimulated with purified Bp antigens in vitro. Immune response and specific immune pathway mediators were studied to relate to the clinical findings mechanistically. Of 74 subjects, 44 (57.9% had sulphonylurea-containing diabetic regimens. Patient receiving sulphonylureas had more severe septic complications (47.7% versus 16.7% p = 0.006, in particular, hypotension requiring intropes (p = 0.005. There was also a trend towards increased mortality in sulphonylurea-users (15.9% versus 3.3% p = 0.08. In-vitro, glyburide suppressed inflammatory cytokine production in a dose-dependent manner. An effect of the drug was the induction of IL-1R-associated kinase-M at the level of mRNA transcription. CONCLUSION/SIGNIFICANCE: Sulphonylurea treatment results in suppression of host inflammatory response and may put patients at higher risk for adverse outcomes in melioidosis.

  12. Sulphonylurea Usage in Melioidosis Is Associated with Severe Disease and Suppressed Immune Response

    Science.gov (United States)

    Liu, Xiang; Foo, Geraldine; Lim, Wan Peng; Ravikumar, Sharada; Sim, Siew Hoon; Win, Mar Soe; Goh, Jessamine Geraldine; Lim, Joan Hui Juan; Ng, Ying Hui; Fisher, Dale; Khoo, Chin Meng

    2014-01-01

    Background Melioidosis is a problem in the developing tropical regions of Southeast Asia and Northern Australia where the the Gram negative saprophytic bacillus Burkholderia pseudomallei is endemic with the risk of fulminant septicaemia. While diabetes mellitus is a well-established risk factor for melioidiosis, little is known if specific hypoglycemic agents may differentially influence the susceptibility and clinical course of infection with B. pseudomallei (Bp). Methodology/Principal Findings In this cohort study, patients with pre-existing diabetes and melioidosis were retrospectively studied. Outcome measures: mortality, length of stay and development of complications (namely hypotension, intubation, renal failure and septicaemia) were studied in relation to prior diabetic treatment regimen. Peripheral blood mononuclear cells (PBMC) from diabetic patients and healthy PBMC primed with metformin, glyburide and insulin were stimulated with purified Bp antigens in vitro. Immune response and specific immune pathway mediators were studied to relate to the clinical findings mechanistically. Of 74 subjects, 44 (57.9%) had sulphonylurea-containing diabetic regimens. Patient receiving sulphonylureas had more severe septic complications (47.7% versus 16.7% p = 0.006), in particular, hypotension requiring intropes (p = 0.005). There was also a trend towards increased mortality in sulphonylurea-users (15.9% versus 3.3% p = 0.08). In-vitro, glyburide suppressed inflammatory cytokine production in a dose-dependent manner. An effect of the drug was the induction of IL-1R-associated kinase-M at the level of mRNA transcription. Conclusion/Significance Sulphonylurea treatment results in suppression of host inflammatory response and may put patients at higher risk for adverse outcomes in melioidosis. PMID:24762472

  13. Gut Microbiota Promotes Obesity-Associated Liver Cancer through PGE2-Mediated Suppression of Antitumor Immunity.

    Science.gov (United States)

    Loo, Tze Mun; Kamachi, Fumitaka; Watanabe, Yoshihiro; Yoshimoto, Shin; Kanda, Hiroaki; Arai, Yuriko; Nakajima-Takagi, Yaeko; Iwama, Atsushi; Koga, Tomoaki; Sugimoto, Yukihiko; Ozawa, Takayuki; Nakamura, Masaru; Kumagai, Miho; Watashi, Koichi; Taketo, Makoto M; Aoki, Tomohiro; Narumiya, Shuh; Oshima, Masanobu; Arita, Makoto; Hara, Eiji; Ohtani, Naoko

    2017-05-01

    Obesity increases the risk of cancers, including hepatocellular carcinomas (HCC). However, the precise molecular mechanisms through which obesity promotes HCC development are still unclear. Recent studies have shown that gut microbiota may influence liver diseases by transferring its metabolites and components. Here, we show that the hepatic translocation of obesity-induced lipoteichoic acid (LTA), a Gram-positive gut microbial component, promotes HCC development by creating a tumor-promoting microenvironment. LTA enhances the senescence-associated secretory phenotype (SASP) of hepatic stellate cells (HSC) collaboratively with an obesity-induced gut microbial metabolite, deoxycholic acid, to upregulate the expression of SASP factors and COX2 through Toll-like receptor 2. Interestingly, COX2-mediated prostaglandin E 2 (PGE 2 ) production suppresses the antitumor immunity through a PTGER4 receptor, thereby contributing to HCC progression. Moreover, COX2 overexpression and excess PGE 2 production were detected in HSCs in human HCCs with noncirrhotic, nonalcoholic steatohepatitis (NASH), indicating that a similar mechanism could function in humans. Significance: We showed the importance of the gut-liver axis in obesity-associated HCC. The gut microbiota-driven COX2 pathway produced the lipid mediator PGE 2 in senescent HSCs in the tumor microenvironment, which plays a pivotal role in suppressing antitumor immunity, suggesting that PGE 2 and its receptor may be novel therapeutic targets for noncirrhotic NASH-associated HCC. Cancer Discov; 7(5); 522-38. ©2017 AACR. This article is highlighted in the In This Issue feature, p. 443 . ©2017 American Association for Cancer Research.

  14. Expanded Regulatory T Cells in Chronically Friend Retrovirus-Infected Mice Suppress Immunity to a Murine Cytomegalovirus Superinfection

    OpenAIRE

    Duppach, Janine; Francois, Sandra; Jara J Joedicke; Dittmer, Ulf; Kraft, Anke R. M.

    2014-01-01

    It is still unclear whether expanded and activated regulatory T cells (Tregs) in chronic viral infections can influence primary immune responses against superinfections with unrelated viruses. Expanded Tregs found in the spleens of chronically Friend virus (FV)-infected mice decreased murine cytomegalovirus (mCMV)-specific CD8+ T cell responses during acute mCMV superinfection. This suppression of mCMV-specific T cell immunity was found only in organs with FV-induced Treg expansion. Surprisin...

  15. Immune suppression of IgG response against dairy proteins in major depression.

    Science.gov (United States)

    Rudzki, Leszek; Pawlak, Dariusz; Pawlak, Krystyna; Waszkiewicz, Napoleon; Małus, Aleksandra; Konarzewska, Beata; Gałęcka, Mirosława; Bartnicka, Anna; Ostrowska, Lucyna; Szulc, Agata

    2017-07-24

    Interactions between the digestive system, brain functions and immunoglobulin G (IgG) mediated immunity against food antigens became recently a topic of growing interest in psychiatry research. Psychological stress can activate hypothalamic-pituitary-adrenal axis (HPA) with subsequent hypercortisolemia. It can also influence intestinal permeability and dynamics of IgG response. Major depression can by accompanied either by activation of inflammatory response or by immune suppression (e.g. decreased antibody production) where hypercortisolemia is a significant immune modulator. The aim of our study was to assess IgG immune response against 44 food products in depressed patients and controls along with markers of psychological stress, inflammation, psychometric and dietary parameters. Serum IgG concentrations against 44 food antigens, plasma cortisol, TNF-α, IL-6, IL-1b concentrations were measured and psychometric parameters were evaluated using Hamilton Depression Rating (HAM-D 17), Perceived Stress (PSS-10), and Symptom Checklist (SCL-90) scales in 34 depressed patients and 29 controls. Dietary parameters such as frequency of exposure to food antigens, appetite and weight change were assessed. There was a significantly lower IgG concentration against dairy in depressed patients compared to controls (post hoc p IgG concentration against dairy proteins and exposure to dairy between groups (F (2.63) = 3.92, p = 0.025, η(2) = 0.12). There was no significant difference in mean IgG concentration against food antigens between patients and controls. We found increased concentration of cortisol in depressed patients (t (1.61) = 2.37, p = 0.02) compared to controls. Patients with melancholic depression had significantly higher (M rank  = 21.27) concentration of cortisol (U = 41, p = 0.006), when compared with the non-melancholic group of patients (M rank  = 12.16). Cortisol concentration significantly positively correlated with HAM-D 17 (r = 0.442, p

  16. Probiotic cheese attenuates exercise-induced immune suppression in Wistar rats.

    Science.gov (United States)

    Lollo, P C B; Cruz, A G; Morato, P N; Moura, C S; Carvalho-Silva, L B; Oliveira, C A F; Faria, J A F; Amaya-Farfan, J

    2012-07-01

    Intense physical activity results in a substantial volume of stress and hence a significant probability of immunosuppression in athletes, with milk proteins being, perhaps, the most recommended protein supplements. Consumption of a probiotic cheese can attenuate immune suppression induced by exhausting exercise in rats. A popular Brazilian fresh cheese (Minas Frescal cheese) containing Lactobacillus acidophilus LA14 and Bifidobacterium longum BL05 was fed for 2wk to adult Wistar rats, which then were brought to exhaustion on the treadmill. Two hours after exhaustion, the rats were killed and material was collected for the determination of serum uric acid, total and high-density lipoprotein cholesterol fraction, total protein, triacylglycerols, aspartate aminotransferase, alanine aminotransferase, creatine kinase, and blood cell (monocyte, lymphocyte, neutrophil, and leukocyte) counts. Exercise was efficient in reducing lymphocyte counts, irrespective of the type of ingested cheese, but the decrease in the group fed the probiotic cheese was 22% compared with 48% in the animals fed regular cheese. Monocyte counts were unaltered in the rats fed probiotic cheese compared with a significant decrease in the rats fed the regular cheese. Most importantly, ingestion of the probiotic cheese resulted in a >100% increase in serum high-density lipoprotein cholesterol and a 50% decrease in triacylglycerols. We conclude that probiotic Minas Frescal cheese may be a viable alternative to enhance the immune system and could be used to prevent infections, particularly those related to the physical overexertion of athletes. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  17. Making humor together: phenomenology and interracial humor

    Directory of Open Access Journals (Sweden)

    Michael D. Barber

    2016-01-01

    Full Text Available This paper explains humor through phenomenological concepts and methods. The three major theories of humor: Superiority, Relief, and Incongruity depend on the thwarting of intentional expectations. Since one experiences an incongruity between what is intended and what is actually experienced, the incongruity theory affords the best explanation, but intentionality remains fundamental for all theories. Theorists of humor rightly insist that the enjoyment of humorous incongruity completes the definition of humor, but such enjoyment also depends on a special epoché, usually elicited by the cues of an interlocutor who invites the listener to leap together into the humorous finite province of meaning. In this province, actions and statements, hurtful in everyday life, such as a pie thrown at someone who ducks as the pie hits another, produce laughter. This comic epoché resembles the phenomenological epoché in its distancing from everyday life, and, like the phenomenological epoché, it opens everyday experience to reflection. Although one often experiences and enjoys humor alone, humor is thoroughly intersubjective and more frequently occurs when two persons participate in the humorous epoché together. The opportunities for making humor together are enhanced to the extent the partners differ in their expectations and responses to situations. Those differences, including bodily differences, often result from the complex intersubjective networks, including culture. As in the case of a seemingly solitary activity like reflection, which one learns from others and exercises on one’s own autonomously, one internalizes others’ styles of humor and discovers such internalization through reflection on one’s «because motives». On the basis of these features – intentionality, epoché, and intersubjectivity, the paper concludes by briefly examining an example of interracial humor. Despite the racist character of much interracial humor, the example

  18. Immunostimulatory oligodeoxynucleotide from Bifidobacterium longum suppresses Th2 immune responses in a murine model

    Science.gov (United States)

    Takahashi, N; Kitazawa, H; Iwabuchi, N; Xiao, J Z; Miyaji, K; Iwatsuki, K; Saito, T

    2006-01-01

    We have reported previously that novel immunostimulatory sequence (ISS) oligodeoxynucleotide (ODN) BL07S from a probiotic strain of Bifidobacterium longum inhibited immunoglobulin (Ig) E production in vitro. However, whether ISS-ODNs from probiotics regulate T helper type 2 (Th2)-polarized immune reactions in vivo remains unclear. To evaluate the inhibitory effects of ODN BL07S on type I allergic response, BALB/c mice were injected with or without ODN BL07S in the presence of ovalbumin (OVA) on days 0 and 14. Serum Ig levels (IgE, IgG1 and IgG2a) and cytokine levels (interferon (IFN)-γ, interleukin (IL)-12, IL-4, IL-5, IL-10 and IL-13) were investigated in splenocyte cultures from days 14–28. Production of OVA-specific and total IgE were significantly suppressed by administration of ODN BL07S, but not by ODN BL06S, a non-ISS-ODN. Compared to controls, ODN BL07S induced significantly lower levels of Th2 cytokines (IL-4 and IL-5) in splenocyte cultures, and significantly higher levels of serum OVA-specific IgG2a. These effects of ODN BL07S on modulation of Th2 immune response were dose-dependent. The present results demonstrate that ODN BL07S from genomic DNA of B. longum BB536 prevents antigen-induced Th2 immune responses in vivo, suggesting that ISS-ODNs from probiotics might be useful in preventing allergic disease. PMID:16792683

  19. Simulated climate change causes immune suppression and protein damage in the crustacean Nephrops norvegicus.

    Science.gov (United States)

    Hernroth, Bodil; Sköld, Helen Nilsson; Wiklander, Kerstin; Jutfelt, Fredrik; Baden, Susanne

    2012-11-01

    Rising atmospheric carbon dioxide concentration is causing global warming, which affects oceans by elevating water temperature and reducing pH. Crustaceans have been considered tolerant to ocean acidification because of their retained capacity to calcify during subnormal pH. However, we report here that significant immune suppression of the Norway lobster, Nephrops norvegicus, occurs after a 4-month exposure to ocean acidification (OA) at a level predicted for the year 2100 (hypercapnic seawater with a pH lowered by 0.4 units). Experiments carried out at different temperatures (5, 10, 12, 14, 16, and 18°C) demonstrated that the temperature within this range alone did not affect lobster immune responses. In the OA-treatment, hemocyte numbers were reduced by almost 50% and the phagocytic capacity of the remaining hemocytes was inhibited by 60%. The reduction in hemocyte numbers was not due to increased apoptosis in hematopoetic tissue. Cellular responses to stress were investigated through evaluating advanced glycation end products (AGE) and lipid oxidation in lobster hepatopancreata, and OA-treatment was shown to significantly increase AGEs', indicating stress-induced protein alterations. Furthermore, the extracellular pH of lobster hemolymph was reduced by approximately 0.2 units in the OA-treatment group, indicating either limited pH compensation or buffering capacity. The negative effects of OA-treatment on the nephropidae immune response and tissue homeostasis were more pronounced at higher temperatures (12-18°C versus 5°C), which may potentially affect disease severity and spread. Our results signify that ocean acidification may have adverse effects on the physiology of lobsters, which previously had been overlooked in studies of basic parameters such as lobster growth or calcification. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. American Humor. [Course Syllabus].

    Science.gov (United States)

    Sloane, David E. E.

    This syllabus describes a three-credit course entitled "American Humor," offered at the University of New Haven (Connecticut). According to the syllabus, "American Humor" will identify traits of American humor as historical phenomena with relations to national character, business attitudes, regionalism, folk humor, and health;…

  1. NK cells inhibit humoral immunity by reducing the abundance of CD4+ T follicular helper cells during a chronic virus infection.

    Science.gov (United States)

    Cook, Kevin D; Kline, Hannah C; Whitmire, Jason K

    2015-08-01

    There is a need to understand better how to improve B cell responses and immunity to persisting virus infections, which often cause debilitating illness or death. People with chronic virus infection show evidence of improved virus control when there is a strong neutralizing antibody response, and conversely, B cell dysfunction is associated with higher viral loads. We showed previously that NK cells inhibit CD4(+) and CD8(+) T cell responses to disseminating LCMV infection and that depletion of NK cells attenuates chronic infection. Here, we examined the effect of NK cell depletion on B cell responses to LCMV infection in mice. Whereas mice infected acutely generated a peak level of antibody soon after the infection was resolved, mice infected chronically showed a continued increase in antibody levels that exceeded those after acute infection. We found that early NK cell depletion rapidly increased virus-specific antibody levels to chronic infection, and this effect depended on CD4(+) T cells and was associated with elevated numbers of CXCR5(+)CD4(+) TFH cells. However, the NK cell-depleted mice controlled the infection and by 1 mo pi, had lower TFH cell numbers and antibody levels compared with mice with sustained infection. Finally, we show that NK cell depletion improved antiviral CD8(+) T cell responses only when B cells and virus-specific antibody were present. Our data indicate that NK cells diminish immunity to chronic infection, in part, by suppressing TFH cell and antibody responses. © Society for Leukocyte Biology.

  2. Diagnostic value of FDG-PET/(CT) in children with fever of unknown origin and unexplained fever during immune suppression

    NARCIS (Netherlands)

    Blokhuis, Gijsbert J.; Bleeker-Rovers, Chantal P.; Diender, Marije G.; Oyen, Wim J.G.; Draaisma, Jos M. Th.; de Geus-Oei, Lioe-Fee

    2014-01-01

    Purpose Fever of unknown origin (FUO) and unexplained fever during immune suppression in children are challenging medical problems. The aim of this study is to investigate the diagnostic value of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) and FDG-PET combined with computed

  3. Humoral immune response to Plasmodium falciparum vaccine candidate GMZ2 and its components in populations naturally exposed to seasonal malaria in Ethiopia.

    Science.gov (United States)

    Mamo, Hassen; Esen, Meral; Ajua, Anthony; Theisen, Michael; Mordmüller, Benjamin; Petros, Beyene

    2013-02-05

    In Ethiopia, the general population is vulnerable to unpredictable epidemics of Plasmodium falciparum malaria. However, there is little information on the anti-malaria immune profile of the population in the endemic regions of the country. The study was designed to investigate the nature of humoral immune response to malaria in two ethnic groups in two endemic localities: Shewa Robit in north, and Boditi in south Ethiopia which are characterized by varying levels of malaria transmission and altitude. In a cross-sectional study, the study participants were diagnosed for malaria infection microscopically and by the rapid diagnostic test (RDT). Sera were tested by using enzyme-linked immunosorbent assay (ELISA) for total immunoglobulin (Ig) G against P. falciparum blood-stage vaccine candidate GMZ2 and its subunits (Glutamate-rich protein (GLURP-R0), merozoite surface protein 3 (MSP3); as well as IgG subclasses against GLURP-R0 and MSP3. Whereas 23(8.6%) blood smear-positive cases for P. falciparum were detected in Boditi, all Shewa Robit study participants had no detectable P. falciparum infection. In both localities, total IgG prevalence and levels to GMZ2 were significantly higher than the response to the component domains indicating the strong recognition of GMZ2 by antibodies acquired through natural exposure. Total IgG and subclass prevalence and levels were higher in Shewa Robit than Boditi, suggesting difference in the intensity of malaria transmission in the two localities and/or genetic differences between the two populations in their response to the antigens. In both study sites, IgG subclass levels to GLURP-R0 were significantly higher than that to MSP3 for all corresponding subclasses in most individuals, indicating the higher relative antigenicity and probably protective potential of GLURP-R0 compared to MSP3. Against both GLURP-R0 and MSP3, the ratio of cytophilic to noncytophilic antibodies was >1 in the majority of the study participants, in both

  4. Broad-spectrum suppression of innate immunity is required for colonization of Arabidopsis roots by the fungus Piriformospora indica.

    Science.gov (United States)

    Jacobs, Sophie; Zechmann, Bernd; Molitor, Alexandra; Trujillo, Marco; Petutschnig, Elena; Lipka, Volker; Likpa, Volker; Kogel, Karl-Heinz; Schäfer, Patrick

    2011-06-01

    Piriformospora indica is a root-colonizing basidiomycete that confers a wide range of beneficial traits to its host. The fungus shows a biotrophic growth phase in Arabidopsis (Arabidopsis thaliana) roots followed by a cell death-associated colonization phase, a colonization strategy that, to our knowledge, has not yet been reported for this plant. P. indica has evolved an extraordinary capacity for plant root colonization. Its broad host spectrum encompasses gymnosperms and monocotyledonous as well as dicotyledonous angiosperms, which suggests that it has an effective mechanism(s) for bypassing or suppressing host immunity. The results of our work argue that P. indica is confronted with a functional root immune system. Moreover, the fungus does not evade detection but rather suppresses immunity triggered by various microbe-associated molecular patterns. This ability to suppress host immunity is compromised in the jasmonate mutants jasmonate insensitive1-1 and jasmonate resistant1-1. A quintuple-DELLA mutant displaying constitutive gibberellin (GA) responses and the GA biosynthesis mutant ga1-6 (for GA requiring 1) showed higher and lower degrees of colonization, respectively, in the cell death-associated stage, suggesting that P. indica recruits GA signaling to help establish proapoptotic root cell colonization. Our study demonstrates that mutualists, like pathogens, are confronted with an effective innate immune system in roots and that colonization success essentially depends on the evolution of strategies for immunosuppression.

  5. Elicitation and suppression of microbe-associated molecular pattern-triggered immunity in plant-microbe interactions.

    Science.gov (United States)

    He, Ping; Shan, Libo; Sheen, Jen

    2007-06-01

    Recent studies have uncovered fascinating molecular mechanisms underlying plant-microbe interactions that coevolved dynamically. As in animals, the primary plant innate immunity is immediately triggered by the detection of common pathogen- or microbe-associated molecular patterns (PAMPs/MAMPs). Different MAMPs are often perceived by distinct cell-surface pattern-recognition receptors (PRRs) and activate convergent intracellular signalling pathways in plant cells for broad-spectrum immunity. Successful pathogens, however, have evolved multiple virulence factors to suppress MAMP-triggered immunity. Specifically, diverse pathogenic bacteria have employed the type III secretion system to deliver a repertoire of virulence effector proteins to interfere with host immunity and promote pathogenesis. Plants challenged by pathogens have evolved the secondary plant innate immunity. In particular, some plants possess the specific intracellular disease resistance (R) proteins to effectively counteract virulence effectors of pathogens for effector-triggered immunity. This potent but cultivar-specific effector-triggered immunity occurs rapidly with localized programmed cell death/hypersensitive response to limit pathogen proliferation and disease development. Remarkably, bacteria have further acquired virulence effectors to block effector-triggered immunity. This review covers the latest findings in the dynamics of MAMP-triggered immunity and its interception by virulence factors of pathogenic bacteria.

  6. Humoral immune response to AAV

    Directory of Open Access Journals (Sweden)

    Roberto eCalcedo

    2013-10-01

    Full Text Available Adeno-associated virus (AAV is a member of the family parvoviridae that has been widely used as a vector for gene therapy because of its safety profile, its ability to transduce both dividing and non-dividing cells, and its low immunogenicity. AAV has been detected in many different tissues of several animal species but has not been associated with any disease. As a result of natural infections, antibodies to AAV can be found in many animals including humans. It has been shown that pre-existing AAV antibodies can modulate the safety and efficacy of AAV vector-mediated gene therapy by blocking vector transduction or by redirecting distribution of AAV vectors to tissues other than the target organ. This review will summarize antibody responses against natural AAV infections, as well as AAV gene therapy vectors and their impact in the clinical development of AAV vectors for gene therapy. We will also review and discuss the various methods used for AAV antibody detection and strategies to overcome neutralizing antibodies in AAV-mediated gene therapy.

  7. Humoral Immune Response to AAV.

    Science.gov (United States)

    Calcedo, Roberto; Wilson, James M

    2013-10-18

    Adeno-associated virus (AAV) is a member of the family Parvoviridae that has been widely used as a vector for gene therapy because of its safety profile, its ability to transduce both dividing and non-dividing cells, and its low immunogenicity. AAV has been detected in many different tissues of several animal species but has not been associated with any disease. As a result of natural infections, antibodies to AAV can be found in many animals including humans. It has been shown that pre-existing AAV antibodies can modulate the safety and efficacy of AAV vector-mediated gene therapy by blocking vector transduction or by redirecting distribution of AAV vectors to tissues other than the target organ. This review will summarize antibody responses against natural AAV infections, as well as AAV gene therapy vectors and their impact in the clinical development of AAV vectors for gene therapy. We will also review and discuss the various methods used for AAV antibody detection and strategies to overcome neutralizing antibodies in AAV-mediated gene therapy.

  8. Monocyte-lymphocyte cross-communication via soluble CD163 directly links innate immune system activation and adaptive immune system suppression following ischemic stroke.

    Science.gov (United States)

    O'Connell, Grant C; Tennant, Connie S; Lucke-Wold, Noelle; Kabbani, Yasser; Tarabishy, Abdul R; Chantler, Paul D; Barr, Taura L

    2017-10-11

    CD163 is a scavenger receptor expressed on innate immune cell populations which can be shed from the plasma membrane via the metalloprotease ADAM17 to generate a soluble peptide with lympho-inhibitory properties. The purpose of this study was to investigate CD163 as a possible effector of stroke-induced adaptive immune system suppression. Liquid biopsies were collected from ischemic stroke patients (n = 39), neurologically asymptomatic controls (n = 20), and stroke mimics (n = 20) within 24 hours of symptom onset. Peripheral blood ADAM17 activity and soluble CD163 levels were elevated in stroke patients relative to non-stroke control groups, and negatively associated with post-stroke lymphocyte counts. Subsequent in vitro experiments suggested that this stroke-induced elevation in circulating soluble CD163 likely originates from activated monocytic cells, as serum from stroke patients stimulated ADAM17-dependant CD163 shedding from healthy donor-derived monocytes. Additional in vitro experiments demonstrated that stroke-induced elevations in circulating soluble CD163 can elicit direct suppressive effects on the adaptive immune system, as serum from stroke patients inhibited the proliferation of healthy donor-derived lymphocytes, an effect which was attenuated following serum CD163 depletion. Collectively, these observations provide novel evidence that the innate immune system employs protective mechanisms aimed at mitigating the risk of post-stroke autoimmune complications driven by adaptive immune system overactivation, and that CD163 is key mediator of this phenomenon.

  9. The Entomopathogenic Fungi Isaria fumosorosea Plays a Vital Role in Suppressing the Immune System of Plutella xylostella: RNA-Seq and DGE Analysis of Immunity-Related Genes

    Directory of Open Access Journals (Sweden)

    Jin Xu

    2017-07-01

    Full Text Available Most, if not all, entomopathogenic fungi have been used as alternative control agents to decrease the insect resistance and harmful effects of the insecticides on the environment. Among them, Isaria fumosorosea has also shown great potential to control different insect pests. In the present study, we explored the immune response of P. xylostella to the infection of I. fumosorosea at different time points by using RNA-Sequencing and differential gene expression technology at the genomic level. To gain insight into the host-pathogen interaction at the genomic level, five libraries of P. xylostella larvae at 12, 18, 24, and 36 h post-infection and a control were constructed. In total, 161 immunity-related genes were identified and grouped into four categories; immune recognition families, toll and Imd pathway, melanization, and antimicrobial peptides (AMPs. The results of differentially expressed immunity-related genes depicted that 15, 13, 53, and 14 up-regulated and 38, 51, 56, and 49 were down-regulated in P. xylostella at 12, 18, 24, and 36 h post-treatment, respectively. RNA-Seq results of immunity-related genes revealed that the expression of AMPs was reduced after treatment with I. fumosorosea. To validate RNA-Seq results by RT-qPCR, 22 immunity-related genes were randomly selected. In conclusion, our results demonstrate that I. fumosorosea has the potential to suppress the immune response of P. xylostella and can become a potential biopesticide for controlling P. xylostella.

  10. Relationship between Humoral Immune Responses against HPV16, HPV18, HPV31 and HPV45 in 12-15 Year Old Girls Receiving Cervarix® or Gardasil® Vaccine.

    Science.gov (United States)

    Godi, Anna; Bissett, Sara L; Miller, Elizabeth; Beddows, Simon

    2015-01-01

    Human papillomavirus (HPV) vaccines confer protection against the oncogenic genotypes HPV16 and HPV18 through the generation of type-specific neutralizing antibodies raised against virus-like particles (VLP) representing these genotypes. The vaccines also confer a degree of cross-protection against HPV31 and HPV45, which are genetically-related to the vaccine types HPV16 and HPV18, respectively, although the mechanism is less certain. There are a number of humoral immune measures that have been examined in relation to the HPV vaccines, including VLP binding, pseudovirus neutralization and the enumeration of memory B cells. While the specificity of responses generated against the vaccine genotypes are fairly well studied, the relationship between these measures in relation to non-vaccine genotypes is less certain. We carried out a comparative study of these immune measures against vaccine and non-vaccine genotypes using samples collected from 12-15 year old girls following immunization with three doses of either Cervarix® or Gardasil® HPV vaccine. The relationship between neutralizing and binding antibody titers and HPV-specific memory B cell levels for the vaccine genotypes, HPV16 and HPV18, were very good. The proportion of responders approached 100% for both vaccines while the magnitude of these responses induced by Cervarix® were generally higher than those following Gardasil® immunization. A similar pattern was found for the non-vaccine genotype HPV31, albeit at a lower magnitude compared to its genetically-related vaccine genotype, HPV16. However, both the enumeration of memory B cells and VLP binding responses against HPV45 were poorly related to its neutralizing antibody responses. Purified IgG derived from memory B cells demonstrated specificities similar to those found in the serum, including the capacity to neutralize HPV pseudoviruses. These data suggest that pseudovirus neutralization should be used as the preferred humoral immune measure for

  11. Suppressive Effects on the Immune Response and Protective Immunity to a JEV DNA Vaccine by Co-administration of a GM-CSF-Expressing Plasmid in Mice

    Science.gov (United States)

    Chen, Hui; Gao, Na; Fan, Dongying; Wu, Jiangman; Zhu, Junping; Li, Jieqiong; Wang, Juan; Chen, Yanlei; An, Jing

    2012-01-01

    As a potential cytokine adjuvant of DNA vaccines, granulocyte-macrophage colony–stimulating factor (GM-CSF) has received considerable attention due to its essential role in the recruitment of antigen-presenting cells, differentiation and maturation of dendritic cells. However, in our recent study of a Japanese encephalitis virus (JEV) DNA vaccine, co-inoculation of a GM-CSF plasmid dramatically suppressed the specific IgG response and resulted in decreased protection against JEV challenge. It is known that GM-CSF has been used in clinic to treat neutropenia for repopulating myeloid cells, and as an adjuvant in vaccine studies; it has shown various effects on the immune response. Therefore, in this study, we characterized the suppressive effects on the immune response to a JEV DNA vaccine by the co-administration of the GM-CSF-expressing plasmid and clarified the underlying mechanisms of the suppression in mice. Our results demonstrated that co-immunization with GM-CSF caused a substantial dampening of the vaccine-induced antibody responses. The suppressive effect was dose- and timing-dependent and likely related to the immunogenicity of the antigen. The suppression was associated with the induction of immature dendritic cells and the expansion of regulatory T cells but not myeloid-derived suppressor cells. Collectively, our findings not only provide valuable information for the application of GM-CSF in clinic and using as a vaccine adjuvant but also offer further insight into the understanding of the complex roles of GM-CSF. PMID:22493704

  12. RNA viruses can hijack vertebrate microRNAs to suppress innate immunity

    Science.gov (United States)

    Trobaugh, Derek W.; Gardner, Christina L.; Sun, Chengqun; Haddow, Andrew D.; Wang, Eryu; Chapnik, Elik; Mildner, Alexander; Weaver, Scott C.; Ryman, Kate D.; Klimstra, William B.

    2014-02-01

    Currently, there is little evidence for a notable role of the vertebrate microRNA (miRNA) system in the pathogenesis of RNA viruses. This is primarily attributed to the ease with which these viruses mutate to disrupt recognition and growth suppression by host miRNAs. Here we report that the haematopoietic-cell-specific miRNA miR-142-3p potently restricts the replication of the mosquito-borne North American eastern equine encephalitis virus in myeloid-lineage cells by binding to sites in the 3' non-translated region of its RNA genome. However, by limiting myeloid cell tropism and consequent innate immunity induction, this restriction directly promotes neurologic disease manifestations characteristic of eastern equine encephalitis virus infection in humans. Furthermore, the region containing the miR-142-3p binding sites is essential for efficient virus infection of mosquito vectors. We propose that RNA viruses can adapt to use antiviral properties of vertebrate miRNAs to limit replication in particular cell types and that this restriction can lead to exacerbation of disease severity.

  13. BET Bromodomain Inhibition Promotes Anti-tumor Immunity by Suppressing PD-L1 Expression

    Directory of Open Access Journals (Sweden)

    Hengrui Zhu

    2016-09-01

    Full Text Available Restoration of anti-tumor immunity by blocking PD-L1 signaling through the use of antibodies has proven to be beneficial in cancer therapy. Here, we show that BET bromodomain inhibition suppresses PD-L1 expression and limits tumor progression in ovarian cancer. CD274 (encoding PD-L1 is a direct target of BRD4-mediated gene transcription. In mouse models, treatment with the BET inhibitor JQ1 significantly reduced PD-L1 expression on tumor cells and tumor-associated dendritic cells and macrophages, which correlated with an increase in the activity of anti-tumor cytotoxic T cells. The BET inhibitor limited tumor progression in a cytotoxic T-cell-dependent manner. Together, these data demonstrate a small-molecule approach to block PD-L1 signaling. Given the fact that BET inhibitors have been proven to be safe with manageable reversible toxicity in clinical trials, our findings indicate that pharmacological BET inhibitors represent a treatment strategy for targeting PD-L1 expression.

  14. A Murine Model of Persistent Inflammation, Immune Suppression, and Catabolism Syndrome

    Directory of Open Access Journals (Sweden)

    Amanda M. Pugh

    2017-08-01

    Full Text Available Critically ill patients that survive sepsis can develop a Persistent Inflammation, Immunosuppression, and Catabolism Syndrome (PICS, which often leads to extended recovery periods and multiple complications. Here, we utilized a cecal ligation and puncture (CLP method in mice with the goal of creating a model that concurrently displays all the characteristics of PICS. We observed that, after eight days, mice that survive the CLP develop persistent inflammation with significant myelopoiesis in the bone marrow and spleen. These mice also demonstrate ongoing immune suppression, as evidenced by the decreased total and naïve splenic CD4 and CD8 T cells with a concomitant increase in immature myeloid cells. The mice further display significant weight loss and decreased muscle mass, indicating a state of ongoing catabolism. When PICS mice are challenged with intranasal Pseudomonas aeruginosa, mortality is significantly elevated compared to sham mice. This mortality difference is associated with increased bacterial loads in the lung, as well as impaired neutrophil migration and neutrophil dysfunction in the PICS mice. Altogether, we have created a sepsis model that concurrently exhibits PICS characteristics. We postulate that this will help determine the mechanisms underlying PICS and identify potential therapeutic targets to improve outcomes for this patient population.

  15. Growth differentiation factor-15 suppresses maturation and function of dendritic cells and inhibits tumor-specific immune response.

    Directory of Open Access Journals (Sweden)

    Zhizhong Zhou

    Full Text Available Dendritic cells (DCs play a key role in the initiation stage of an antigen-specific immune response. A variety of tumor-derived factors (TDFs can suppress DC maturation and function, resulting in defects in the tumor-specific immune response. To identify unknown TDFs that may suppress DCs maturation and function, we established a high-throughput screening technology based on a human liver tumor T7 phage cDNA library and screened all of the proteins derived from hepatoma cells that potentially interact with immature DCs. Growth/differentiation factor-15 (GDF-15 was detected and chosen for further study. By incubation of DCs cultures with GDF-15, we demonstrate that GDF-15 can inhibit surface protrusion formation during DC maturation; suppress the membrane expression of CD83, CD86 and HLA-DR on DCs; enhance phagocytosis by DCs; reduce IL-12 and elevate TGF-β1 secretion by DCs; inhibit T cell stimulation and cytotoxic T lymphocyte (CTL activation by DCs. By building tumor-bearing mouse models, we demonstrate that GDF-15 can inhibit the ability of DCs to stimulate a tumor-specific immune response in vivo. These results indicate that GDF-15 may be one of the critical molecules that inhibit DC maturation and function and are involved in tumor immune escape. Thus, GDF-15 may be a novel target in tumor immunotherapy.

  16. Antibody-mediated immune suppression is improved when blends of anti-RBC monoclonal antibodies are used in mice.

    Science.gov (United States)

    Bernardo, Lidice; Amash, Alaa; Marjoram, Danielle; Lazarus, Alan H

    2016-08-25

    Although the prevention of hemolytic disease of the fetus and newborn is highly effective using polyclonal anti-D, a recombinant alternative is long overdue. Unfortunately, anti-D monoclonal antibodies have been, at best, disappointing. To determine the primary attribute defining an optimal antibody, we assessed suppression of murine red blood cell (RBC) immunization by single-monoclonal antibodies vs defined blends of subtype-matched antibodies. Allogeneic RBCs expressing the HOD antigen (hen egg lysozyme [HEL]-ovalbumin-human transmembrane Duffy(b)) were transfused into naïve mice alone or together with selected combinations of HEL-specific antibodies, and the resulting suppressive effect was assessed by evaluating the antibody response. Polyclonal HEL antibodies dramatically inhibited the antibody response to the HOD antigen, whereas single-monoclonal HEL antibodies were less effective despite the use of saturating doses. A blend of monoclonal HEL-specific antibodies reactive with different HEL epitopes significantly increased the suppressive effect, whereas a blend of monoclonal antibodies that block each other's binding to the HEL protein did not increase suppression. In conclusion, these data show that polyclonal antibodies are superior to monoclonal antibodies at suppressing the immune response to the HOD cells, a feature that can be completely recapitulated using monoclonal antibodies to different epitopes. © 2016 by The American Society of Hematology.

  17. Venom of parasitoid, Pteromalus puparum, suppresses host, Pieris rapae, immune promotion by decreasing host C-type lectin gene expression.

    Directory of Open Access Journals (Sweden)

    Qi Fang

    Full Text Available Insect hosts have evolved immunity against invasion by parasitoids, and in co-evolutionary response parasitoids have also developed strategies to overcome host immune systems. The mechanisms through which parasitoid venoms disrupt the promotion of host immunity are still unclear. We report here a new mechanism evolved by parasitoid Pteromalus puparum, whose venom inhibited the promotion of immunity in its host Pieris rapae (cabbage white butterfly.A full-length cDNA encoding a C-type lectin (Pr-CTL was isolated from P. rapae. Quantitative PCR and immunoblotting showed that injection of bacterial and inert beads induced expression of Pr-CTL, with peaks of mRNA and Pr-CTL protein levels at 4 and 8 h post beads challenge, respectively. In contrast, parasitoid venom suppressed Pr-CTL expression when co-injected with beads, in a time and dose-dependent manner. Immunolocalization and immunoblotting results showed that Pr-CTL was first detectable in vesicles present in cytoplasm of granulocytes in host hemolymph, and was then secreted from cells into circulatory fluid. Finally, the secreted Pr-CTL bound to cellular membranes of both granulocytes and plasmatocytes. Injection of double-stranded RNA specific for target gene decreased expression of Pr-CTL, and a few other host immune-related genes. Suppression of Pr-CTL expression also down-regulated antimicrobial and phenoloxidase activities, and reducing phagocytotic and encapsulation rates in host. The inhibitory effect of parasitoid venom on host encapsulation is consistent with its effect in suppressing Pr-CTL expression. Binding assay results showed that recombinant Pr-CTL directly attached to the surface of P. puparum egges. We infer that Pr-CTL may serve as an immune signalling co-effector, first binding to parasitoid eggs, regulating expression of a set of immune-related genes and promoting host immunity.P. puparum venom inhibits promotion of host immune responses by silencing expression of host C

  18. Multiple candidate effectors from the oomycete pathogen Hyaloperonospora arabidopsidis suppress host plant immunity.

    Directory of Open Access Journals (Sweden)

    Georgina Fabro

    2011-11-01

    Full Text Available Oomycete pathogens cause diverse plant diseases. To successfully colonize their hosts, they deliver a suite of effector proteins that can attenuate plant defenses. In the oomycete downy mildews, effectors carry a signal peptide and an RxLR motif. Hyaloperonospora arabidopsidis (Hpa causes downy mildew on the model plant Arabidopsis thaliana (Arabidopsis. We investigated if candidate effectors predicted in the genome sequence of Hpa isolate Emoy2 (HaRxLs were able to manipulate host defenses in different Arabidopsis accessions. We developed a rapid and sensitive screening method to test HaRxLs by delivering them via the bacterial type-three secretion system (TTSS of Pseudomonas syringae pv tomato DC3000-LUX (Pst-LUX and assessing changes in Pst-LUX growth in planta on 12 Arabidopsis accessions. The majority (~70% of the 64 candidates tested positively contributed to Pst-LUX growth on more than one accession indicating that Hpa virulence likely involves multiple effectors with weak accession-specific effects. Further screening with a Pst mutant (ΔCEL showed that HaRxLs that allow enhanced Pst-LUX growth usually suppress callose deposition, a hallmark of pathogen-associated molecular pattern (PAMP-triggered immunity (PTI. We found that HaRxLs are rarely strong avirulence determinants. Although some decreased Pst-LUX growth in particular accessions, none activated macroscopic cell death. Fewer HaRxLs conferred enhanced Pst growth on turnip, a non-host for Hpa, while several reduced it, consistent with the idea that turnip's non-host resistance against Hpa could involve a combination of recognized HaRxLs and ineffective HaRxLs. We verified our results by constitutively expressing in Arabidopsis a sub-set of HaRxLs. Several transgenic lines showed increased susceptibility to Hpa and attenuation of Arabidopsis PTI responses, confirming the HaRxLs' role in Hpa virulence. This study shows TTSS screening system provides a useful tool to test whether

  19. Language and Humor.

    Science.gov (United States)

    Richardson, Ian M.

    1989-01-01

    Comparison of advanced and intermediate Saudi Arabian students of English-as-a-Foreign-Language comprehension of humor indicated that both cultural and linguistic awareness were important to understanding humorous materials. (CB)

  20. Serratia marcescens Suppresses Host Cellular Immunity via the Production of an Adhesion-inhibitory Factor against Immunosurveillance Cells*

    Science.gov (United States)

    Ishii, Kenichi; Adachi, Tatsuo; Hamamoto, Hiroshi; Sekimizu, Kazuhisa

    2014-01-01

    Injection of a culture supernatant of Serratia marcescens into the bloodstream of the silkworm Bombyx mori increased the number of freely circulating immunosurveillance cells (hemocytes). Using a bioassay with live silkworms, serralysin metalloprotease was purified from the culture supernatant and identified as the factor responsible for this activity. Serralysin inhibited the in vitro attachment of both silkworm hemocytes and murine peritoneal macrophages. Incubation of silkworm hemocytes or murine macrophages with serralysin resulted in degradation of the cellular immune factor BmSPH-1 or calreticulin, respectively. Furthermore, serralysin suppressed in vitro phagocytosis of bacteria by hemocytes and in vivo bacterial clearance in silkworms. Disruption of the ser gene in S. marcescens attenuated its host killing ability in silkworms and mice. These findings suggest that serralysin metalloprotease secreted by S. marcescens suppresses cellular immunity by decreasing the adhesive properties of immunosurveillance cells, thereby contributing to bacterial pathogenesis. PMID:24398686

  1. Serratia marcescens suppresses host cellular immunity via the production of an adhesion-inhibitory factor against immunosurveillance cells.

    Science.gov (United States)

    Ishii, Kenichi; Adachi, Tatsuo; Hamamoto, Hiroshi; Sekimizu, Kazuhisa

    2014-02-28

    Injection of a culture supernatant of Serratia marcescens into the bloodstream of the silkworm Bombyx mori increased the number of freely circulating immunosurveillance cells (hemocytes). Using a bioassay with live silkworms, serralysin metalloprotease was purified from the culture supernatant and identified as the factor responsible for this activity. Serralysin inhibited the in vitro attachment of both silkworm hemocytes and murine peritoneal macrophages. Incubation of silkworm hemocytes or murine macrophages with serralysin resulted in degradation of the cellular immune factor BmSPH-1 or calreticulin, respectively. Furthermore, serralysin suppressed in vitro phagocytosis of bacteria by hemocytes and in vivo bacterial clearance in silkworms. Disruption of the ser gene in S. marcescens attenuated its host killing ability in silkworms and mice. These findings suggest that serralysin metalloprotease secreted by S. marcescens suppresses cellular immunity by decreasing the adhesive properties of immunosurveillance cells, thereby contributing to bacterial pathogenesis.

  2. Five Xanthomonas type III effectors suppress cell death induced by components of immunity-associated MAP kinase cascades.

    Science.gov (United States)

    Teper, Doron; Sunitha, Sukumaran; Martin, Gregory B; Sessa, Guido

    2015-01-01

    Mitogen-activated protein kinase (MAPK) cascades play a fundamental role in signaling of plant immunity and mediate elicitation of cell death. Xanthomonas spp. manipulate plant signaling by using a type III secretion system to deliver effector proteins into host cells. We examined the ability of 33 Xanthomonas effectors to inhibit cell death induced by overexpression of components of MAPK cascades in Nicotiana benthamiana plants. Five effectors inhibited cell death induced by overexpression of MAPKKKα and MEK2, but not of MAP3Kε. In addition, expression of AvrBs1 in yeast suppressed activation of the high osmolarity glycerol MAPK pathway, suggesting that the target of this effector is conserved in eukaryotic organisms. These results indicate that Xanthomonas employs several type III effectors to suppress immunity-associated cell death mediated by MAPK cascades.

  3. Systemic immune suppression in glioblastoma: the interplay between CD14+HLA-DRlo/neg monocytes, tumor factors, and dexamethasone.

    Science.gov (United States)

    Gustafson, Michael P; Lin, Yi; New, Kent C; Bulur, Peggy A; O'Neill, Brian Patrick; Gastineau, Dennis A; Dietz, Allan B

    2010-07-01

    Patients with glioblastoma (GBM) exhibit profound systemic immune defects that affect the success of conventional and immune-based treatments. A better understanding of the contribution of the tumor and/or therapy on systemic immune suppression is necessary for improved therapies, to monitor negative effects of novel treatments, to improve patient outcomes, and to increase understanding of this complex system. To characterize the immune profile of GBM patients, we phenotyped peripheral blood and compared these to normal donors. In doing so, we identified changes in systemic immunity associated with both the tumor and dexamethasone treated tumor bearing patients. In particular, dexamethasone exacerbated tumor associated lymphopenia primarily in the T cell compartment. We have also identified unique tumor and dexamethasone dependent altered monocyte phenotypes. The major population of altered monocytes (CD14(+)HLA-DR(lo/neg)) had a phenotype distinct from classical myeloid suppressor cells. These cells inhibited T cell proliferation, were unable to fully differentiate into mature dendritic cells, were associated with dexamethasone-mediated changes in CCL2 levels, and could be re-created in vitro using tumor supernatants. We provide evidence that tumors express high levels of CCL2, can contain high numbers of CD14(+) cells, that tumor supernatants can transform CD14(+)HLA-DR(+) cells into CD14(+)HLA-DR(lo/neg) immune suppressors, and that dexamethasone reduces CCL2 in vitro and is correlated with reduction of CCL2 in vivo. Consequently, we have developed a model for tumor mediated systemic immune suppression via recruitment and transformation of CD14(+) cells.

  4. T-cell autophagy deficiency increases mortality and suppresses immune responses after sepsis.

    Directory of Open Access Journals (Sweden)

    Chih-Wen Lin

    Full Text Available Although the role of autophagy in sepsis has been characterized in several organs, its role in the adaptive immune system remains to be ascertained. This study aimed to investigate the role of autophagy in sepsis-induced T cell apoptosis and immunosuppression, using knockout mice with T cell specific deletion of autophagy essential gene Atg7.Sepsis was induced in a cecal ligation and puncture (CLP model, with T-cell-specific Atg7-knockout mice compared to control mice. Autophagic vacuoles examined by electron microscopy were decreased in the spleen after CLP. Autophagy proteins LC3-II and ATG7, and autophagosomes and autolysosomes stained by Cyto-ID Green and acridine orange were decreased in CD4+ and CD8+ splenocytes at 18 h and 24 h after CLP. This decrease in autophagy was associated with increased apoptosis of CD4+ and CD8+ after CLP. Moreover, mice lacking Atg7 in T lymphocytes showed an increase in sepsis-induced mortality, T cell apoptosis and loss of CD4+ and CD8+ T cells, in comparison to control mice. This was accompanied by suppressed cytokine production of Th1/Th2/Th17 by CD4+ T cells, reduced phagocytosis in macrophages and decreased bacterial clearance in the spleen after sepsis.These results indicated that sepsis led to down-regulation of autophagy in T lymphocytes, which may result in enhanced apoptosis induction and decreased survival in sepsis. Autophagy may therefore play a protective role against sepsis-induced T lymphocyte apoptosis and immunosuppression.

  5. The carcinogenic potential of tacrolimus ointment beyond immune suppression: a hypothesis creating case report

    Directory of Open Access Journals (Sweden)

    Vetter Claudia S

    2006-01-01

    Full Text Available Abstract Background Since tacrolimus ointment was approved by the U.S. Food and Drug Administration (FDA as a promising treatment for atopic dermatitis, it has been approved in more than 30 additional countries, including numerous European Union member nations. Moreover, in the current clinical routine the use of this drug is no longer restricted to the approved indication, but has been extended to a wide variety of inflammatory skin diseases including some with the potential of malignant transformation. So far, the side-effects reported from the topical use of tacrolimus have been relatively minor (e.g. burning, pruritus, erythema. Recently, however, the FDA reviewed the safety of topical tacrolimus, which resulted in a warning that the use of calcineurin inhibitors may be associated with an increased risk of cancer. Case presentation Oral lichen planus (OLP was diagnosed in a 56-year-old women in February 1999. After several ineffective local and systemic therapeutic measures an off-label treatment of this recalcitrant condition using Tacrolimus 0.1% ointment was initiated in May 2002. After a few weeks of treatment most of the lesions ameliorated, with the exception of the plaques on the sides of the tongue. Nevertheless, the patient became free of symptoms which, however, reoccurred once tacrolimus was weaned, as a consequence treatment was maintained. In April 2005, the plaques on the left side of the tongue appeared increasingly compact and a biopsy specimen confirmed the suspected diagnosis of an oral squamous cell carcinoma. Conclusion The suspected causal relationship between topical use of tacrolimus and the development of a squamous cell carcinoma prompted us to test the notion that the carcinogenicity of tacrolimus may go beyond mere immune suppression. To this end, tacrolimus has been shown to have an impact on cancer signalling pathways such as the MAPK and the p53 pathway. In the given case, we were able to demonstrate that these

  6. Humor, Abstraction, and Disbelief

    Science.gov (United States)

    Hoicka, Elena; Jutsum, Sarah; Gattis, Merideth

    2008-01-01

    We investigated humor as a context for learning about abstraction and disbelief. More specifically, we investigated how parents support humor understanding during book sharing with their toddlers. In Study 1, a corpus analysis revealed that in books aimed at 1- to 2-year-olds, humor is found more often than other forms of doing the wrong thing…

  7. Building Resilience through Humor.

    Science.gov (United States)

    Berg, Debra Vande; Van Brockern, Steve

    1995-01-01

    Research on resilience suggests that a sense of humor helps to stress-proof children in conflict. Reports on a workshop for educators and youth workers convened to explore ways humor is being used to foster positive development and resilience with troubled youth. Describes applications of humor front-line professionals report as useful in their…

  8. Expression of type I interferon by splenic macrophages suppresses adaptive immunity during sepsis.

    Science.gov (United States)

    Schwandt, Timo; Schumak, Beatrix; Gielen, Gerrit H; Jüngerkes, Frank; Schmidbauer, Patricia; Klocke, Katrin; Staratschek-Jox, Andrea; van Rooijen, Niko; Kraal, Georg; Ludwig-Portugall, Isis; Franken, Lars; Wehner, Sven; Kalff, Jörg C; Weber, Olaf; Kirschning, Carsten; Coch, Christoph; Kalinke, Ulrich; Wenzel, Jörg; Kurts, Christian; Zawatzky, Rainer; Holzmann, Bernhard; Layland, Laura; Schultze, Joachim L; Burgdorf, Sven; den Haan, Joke M M; Knolle, Percy A; Limmer, Andreas

    2012-01-04

    Early during Gram-negative sepsis, excessive release of pro-inflammatory cytokines can cause septic shock that is often followed by a state of immune paralysis characterized by the failure to mount adaptive immunity towards secondary microbial infections. Especially, the early mechanisms responsible for such immune hypo-responsiveness are unclear. Here, we show that TLR4 is the key immune sensing receptor to initiate paralysis of T-cell immunity after bacterial sepsis. Downstream of TLR4, signalling through TRIF but not MyD88 impaired the development of specific T-cell immunity against secondary infections. We identified type I interferon (IFN) released from splenic macrophages as the critical factor causing T-cell immune paralysis. Early during sepsis, type I IFN acted selectively on dendritic cells (DCs) by impairing antigen presentation and secretion of pro-inflammatory cytokines. Our results reveal a novel immune regulatory role for type I IFN in the initiation of septic immune paralysis, which is distinct from its well-known immune stimulatory effects. Moreover, we identify potential molecular targets for therapeutic intervention to overcome impairment of T-cell immunity after sepsis.

  9. Antigen detection in vivo after immunization with different presentation forms of rabies virus antigen, II. Cellular but not humoral systemic immune responses against rabies virus immune stimulating complexes are macrophage dependent

    NARCIS (Netherlands)

    I.J.Th.M. Claassen (Ivo); A.D.M.E. Osterhaus (Albert); M.C.M. Poelen (Martien); N. Rooijen van; H.J.H.M. Claassen (Eric)

    1998-01-01

    textabstractIn this paper we describe the effect of depletion of splenic macrophages on the uptake, and immune response against, different formulations of rabies virus antigen. Splenic macrophages were removed by intravenous injection with clodronate liposomes. beta-propiolacton inactivated rabies

  10. Reduction of porcine circovirus type 2 (PCV2 viremia by a reformulated inactivated chimeric PCV1-2 vaccine-induced humoral and cellular immunity after experimental PCV2 challenge

    Directory of Open Access Journals (Sweden)

    Seo Hwi

    2012-10-01

    Full Text Available Abstract Background The objective of the present study was to elucidate the humoral and cellular immune response mechanisms by which a reformulated inactivated chimeric PCV1-2 vaccine reduces the PCV2 viremia. Forty PCV2 seronegative 3-week-old pigs were randomly divided into the following four groups: vaccinated challenged (T01, vaccinated non-challenged (T02, non-vaccinated challenged (T03, and non-vaccinated non-challenged (T04 animals. The pigs in groups T01 and T02 were immunized with a reformulated inactivated chimeric PCV1-2 vaccine (Fostera™ PCV; Pfizer Animal Health administered as a 2.0 ml dose at 21 days of age. At 35 days of age (0 days post-challenge, the pigs in groups T01 and T03 were inoculated intranasally with 2 ml each of PCV2b. Results A reduction of PCV2 viremia coincided with the appearance of both PCV2-specific neutralizing antibodies (NA and interferon-γ-secreting cells (IFN-γ-SCs in the vaccinated animals. However, the presence of anti-PCV2 IgG antibodies did not correlate with the reduction of PCV2 viremia. Lymphocyte subset analysis indicated that the numbers of CD3+ and CD4+ cells increased in vaccinated animals but the numbers of CD4+ cells decreased transiently in non-vaccinated animals. The observation of a delayed type hypersensitivity response in only the vaccinated animals also supports a CD4+ cell-associated protective cellular immune response induced by the reformulated inactivated chimeric PCV1-2 vaccine. Conclusions The induction of PCV2-specific NA and IFN-γ-SCs, and CD4+ cells by the reformulated inactivated chimeric PCV1-2 vaccine is the important protective immune response leading to reduction of the PCV2 viremia and control of the PCV2 infection. To our knowledge this is the first demonstration of protective humoral and cellular immunity induced by the reformulated inactivated chimeric PCV1-2 vaccine and its effect on reduction of PCV2 viremia by vaccination.

  11. Suppressive effects of a quinoxaline-analogue (Rob 803) on pathogenic immune mechanisms in collagen-induced arthritis.

    Science.gov (United States)

    Westman, E; Thi Ngoc, D D; Klareskog, L; Harris, H Erlandsson

    2008-04-01

    The anti-arthritic effects of the synthetic compound 9-chloro-2,3 dimethyl-6-(N,N-dimetylamino-2-oxoethyl)-6H-indolo[2,3-b] quinoxaline (Rob 803) was evaluated by treating Dark Agouti rats with collagen-induced arthritis using three different protocols. Daily subcutaneous treatment with 40 mg/kg/day of Rob 803 from the day of immunization and 14 days forward suppressed arthritis severity significantly and delayed the onset of clinical arthritis. In contrast, similar treatment initiated when individual rats had developed clinical disease (at a score of 2 points) did not suppress disease. Oral treatment with 35 mg/kg/day of Rob 803 from the day of immunization and 21 days forward resulted in a trend towards disease suppression. In vitro analysis of rats treated subcutaneously with Rob 803 revealed an inhibition of T cell proliferation but no effect on the generation of an anti-CII immunoglobulin G response. Further in vitro analysis demonstrated that Rob 803 also inhibited the generation of nitric oxide in macrophages, although at higher concentrations than needed for inhibitory effects on T cell proliferation. Thus we report that early subcutaneous administration of the synthetic substance Rob 803 has anti-rheumatic effects that are probably mediated by affecting the proliferative capacity of lymph node T cells. Rob 803 should be considered as a new candidate substance for anti-rheumatic treatment.

  12. Natural and Induced Humoral Responses to MUC1

    Energy Technology Data Exchange (ETDEWEB)

    Mensdorff-Pouilly, Silvia von, E-mail: s.vonmensdorff@vumc.nl; Moreno, Maria [Department of Obstetrics and Gynecology, VU University Medical Center, De Boelelaan 1117, Amsterdam 1081 HV (Netherlands); Verheijen, René H. M. [Department of Woman & Baby, Division of Surgical & Oncological Gynaecology, University Medical Center Utrecht, Heidelberglaan 100, Utrecht 3508 GA (Netherlands)

    2011-07-29

    MUC1 is a membrane-tethered mucin expressed on the ductal cell surface of glandular epithelial cells. Loss of polarization, overexpression and aberrant glycosylation of MUC1 in mucosal inflammation and in adenocarcinomas induces humoral immune responses to the mucin. MUC1 IgG responses have been associated with a benefit in survival in patients with breast, lung, pancreatic, ovarian and gastric carcinomas. Antibodies bound to the mucin may curb tumor progression by restoring cell-cell interactions altered by tumor-associated MUC1, thus preventing metastatic dissemination, as well as counteracting the immune suppression exerted by the molecule. Furthermore, anti-MUC1 antibodies are capable of effecting tumor cell killing by antibody-dependent cell-mediated cytotoxicity. Although cytotoxic T cells are indispensable to achieve anti-tumor responses in advanced disease, abs to tumor-associated antigens are ideally suited to address minimal residual disease and may be sufficient to exert adequate immune surveillance in an adjuvant setting, destroying tumor cells as they arise or maintaining occult disease in an equilibrium state. Initial evaluation of MUC1 peptide/glycopeptide mono and polyvalent vaccines has shown them to be immunogenic and safe; anti-tumor responses are scarce. Progress in carbohydrate synthesis has yielded a number of sophisticated substrates that include MUC1 glycopeptide epitopes that are at present in preclinical testing. Adjuvant vaccination with MUC1 glycopeptide polyvalent vaccines that induce strong humoral responses may prevent recurrence of disease in patients with early stage carcinomas. Furthermore, prophylactic immunotherapy targeting MUC1 may be a strategy to strengthen immune surveillance and prevent disease in subjects at hereditary high risk of breast, ovarian and colon cancer.

  13. Expression of immune-response genes in lepidopteran host is suppressed by venom from an endoparasitoid, Pteromalus puparum

    Directory of Open Access Journals (Sweden)

    Fang Qi

    2010-09-01

    Full Text Available Abstract Background The relationships between parasitoids and their insect hosts have attracted attention at two levels. First, the basic biology of host-parasitoid interactions is of fundamental interest. Second, parasitoids are widely used as biological control agents in sustainable agricultural programs. Females of the gregarious endoparasitoid Pteromalus puparum (Hymenoptera: Pteromalidae inject venom along with eggs into their hosts. P. puparum does not inject polydnaviruses during oviposition. For this reason, P. puparum and its pupal host, the small white butterfly Pieris rapae (Lepidoptera: Pieridae, comprise an excellent model system for studying the influence of an endoparasitoid venom on the biology of the pupal host. P. puparum venom suppresses the immunity of its host, although the suppressive mechanisms are not fully understood. In this study, we tested our hypothesis that P. puparum venom influences host gene expression in the two main immunity-conferring tissues, hemocytes and fat body. Results At 1 h post-venom injection, we recorded significant decreases in transcript levels of 217 EST clones (revealing 113 genes identified in silico, including 62 unknown contigs derived from forward subtractive libraries of host hemocytes and in transcript levels of 288 EST clones (221 genes identified in silico, including 123 unknown contigs from libraries of host fat body. These genes are related to insect immune response, cytoskeleton, cell cycle and apoptosis, metabolism, transport, stress response and transcriptional and translational regulation. We verified the reliability of the suppression subtractive hybridization (SSH data with semi-quantitative RT-PCR analysis of a set of randomly selected genes. This analysis showed that most of the selected genes were down-regulated after venom injection. Conclusions Our findings support our hypothesis that P. puparum venom influences gene expression in host hemocytes and fat body. Specifically

  14. Influenza viruses and cross-reactivity in healthy adults: humoral and cellular immunity induced by seasonal 2007/2008 influenza vaccination against vaccine antigens and 2009 A(H1N1) pandemic influenza virus.

    Science.gov (United States)

    Iorio, Anna M; Bistoni, Onelia; Galdiero, Massimiliano; Lepri, Enrica; Camilloni, Barbara; Russano, Anna M; Neri, Mariella; Basileo, Michela; Spinozzi, Fabrizio

    2012-02-21

    We analyzed humoral and cellular immune responses against vaccine antigens and the new A(H1N1) virus in healthy adults before and after immunization with the 2007/2008 commercially available trivalent subunit MF59-adjuvanted influenza vaccine during the Fall 2007, prior to the emergence of the new virus. Antibody titers were significantly boosted only against the three vaccine antigens. Seasonal vaccination boosted pre-existing cellular responses upon stimulation of peripheral blood mononuclear cells not only with the homologous three vaccine antigens, but also with the heterologous new 2009 A(H1N1) and with a highly conserved peptide present in the stalk region of hemagglutinin (HA). These results show that cross-reactive cell responses against the new virus were present before the circulation of the virus and were boosted by seasonal vaccination. The cross-reactivity of cellular responses might, at least in part, explain the low pathogenicity of the new pandemic virus. The finding of cellular immunity, that can be increased by seasonal vaccination, against the conserved HA peptide, underline the potential use, in human vaccines, of conserved peptides of the stalk region of HA characterized by broad immunogenicity in experimental systems. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. MF59- and Al(OH)3-Adjuvanted Staphylococcus aureus (4C-Staph) Vaccines Induce Sustained Protective Humoral and Cellular Immune Responses, with a Critical Role for Effector CD4 T Cells at Low Antibody Titers

    Science.gov (United States)

    Monaci, Elisabetta; Mancini, Francesca; Lofano, Giuseppe; Bacconi, Marta; Tavarini, Simona; Sammicheli, Chiara; Arcidiacono, Letizia; Giraldi, Monica; Galletti, Bruno; Rossi Paccani, Silvia; Torre, Antonina; Fontana, Maria Rita; Grandi, Guido; de Gregorio, Ennio; Bensi, Giuliano; Chiarot, Emiliano; Nuti, Sandra; Bagnoli, Fabio; Soldaini, Elisabetta; Bertholet, Sylvie

    2015-01-01

    Staphylococcus aureus (S. aureus) is an important opportunistic pathogen that may cause invasive life-threatening infections, like sepsis and pneumonia. Due to the increasing antibiotic resistance, the development of an effective vaccine against S. aureus is needed. Although a correlate of protection against staphylococcal diseases is not yet established, several findings suggest that both antibodies and CD4 T cells might contribute to optimal immunity. In this study, we show that adjuvanting a multivalent vaccine (4C-Staph) with MF59, an oil-in-water emulsion licensed in human vaccines, further potentiated antigen-specific IgG titers and CD4 T-cell responses compared to alum and conferred protection in the peritonitis model of S. aureus infection. Moreover, we showed that MF59- and alum-adjuvanted 4C-Staph vaccines induced persistent antigen-specific humoral and T-cell responses, and protected mice from infection up to 4 months after immunization. Furthermore, 4C-Staph formulated with MF59 was used to investigate which immune compartment is involved in vaccine-induced protection. Using CD4 T cell-depleted mice or B cell-deficient mice, we demonstrated that both T and B-cell responses contributed to 4C-Staph vaccine-mediated protective immunity. However, the role of CD4 T cells seemed more evident in the presence of low-antibody responses. This study provides preclinical data further supporting the use of the adjuvanted 4C-Staph vaccines against S. aureus diseases, and provides critical insights on the correlates of protective immunity necessary to combat this pathogen. PMID:26441955

  16. MF59- and Al(OH3-adjuvanted Staphylococcus aureus (4C-Staph vaccines induce sustained protective humoral and cellular immune responses, with a critical role for effector CD4 T cells at low antibody titers.

    Directory of Open Access Journals (Sweden)

    Elisabetta eMonaci

    2015-09-01

    Full Text Available Staphylococcus aureus (S. aureus is an important opportunistic pathogen that may cause invasive life-threatening infections like sepsis and pneumonia. Due to increasing antibiotic-resistance, the development of an effective vaccine against S. aureus is needed. Although a correlate of protection against staphylococcal diseases is not yet established, several findings suggest that both antibodies and CD4 T cells might contribute to optimal immunity. In this study, we show that adjuvanting a multivalent vaccine (4C-Staph with MF59, an oil-in-water emulsion licensed in human vaccines, further potentiated antigen-specific IgG titers and CD4 T cell responses compared to alum and conferred protection in the peritonitis model of S. aureus infection. Moreover, we showed that MF59- and alum-adjuvanted 4C-Staph vaccines induced persistent antigen-specific humoral and T cell responses, and protected mice from infection up to 4 months after immunization. Furthermore, 4C-Staph formulated with MF59 was used to investigate which immune compartment is involved in vaccine-induced protection. Using CD4 T cell-depleted mice or B cell deficient mice, we demonstrated that both T and B cell responses contributed to 4C-Staph vaccine-mediated protective immunity. However, the role of CD4 T cells seemed more evident in the presence of low antibody responses. This study provides preclinical data further supporting the use of the adjuvanted 4C-Staph vaccines against S. aureus diseases, and provides critical insights on the correlates of protective immunity necessary to combat this pathogen.

  17. Increased CD4(+) T cell co-inhibitory immune receptor CEACAM1 in neonatal sepsis and soluble-CEACAM1 in meningococcal sepsis: a role in sepsis-associated immune suppression?

    NARCIS (Netherlands)

    Flier, M. van der; Sharma, D.B.; Estevao, S.; Emonts, M.; Rook, D.; Hazelzet, J.A.; Goudoever, J.B. van; Hartwig, N.G.

    2013-01-01

    The co-inhibitory immune receptor carcinoembryonic antigen-related cell-adhesion molecule 1 (CEACAM1) and its self-ligand CEACAM1 can suppress T cell function. Suppression of T cell function in sepsis is well documented. Late-onset neonatal sepsis in VLBW-infants was associated with an increased

  18. Increased CD4+ T Cell Co-Inhibitory Immune Receptor CEACAM1 in Neonatal Sepsis and Soluble-CEACAM1 in Meningococcal Sepsis: A Role in Sepsis-Associated Immune Suppression?

    NARCIS (Netherlands)

    M. van der Flier (Michiel); D.B. Sharma (Dyana); S. Estevão (Silvia); M. Emonts (Marieke); D. Rook (Denise); J.A. Hazelzet (Jan); J.B. van Goudoever (Hans); N.G. Hartwig (Nico)

    2013-01-01

    textabstractThe co-inhibitory immune receptor carcinoembryonic antigen-related cell-adhesion molecule 1 (CEACAM1) and its self-ligand CEACAM1 can suppress T cell function. Suppression of T cell function in sepsis is well documented. Late-onset neonatal sepsis in VLBW-infants was associated with an

  19. Crimean-Congo Hemorrhagic Fever Virus Suppresses Innate Immune Responses via a Ubiquitin and ISG15 Specific Protease

    Directory of Open Access Journals (Sweden)

    Florine E.M. Scholte

    2017-09-01

    Full Text Available Antiviral responses are regulated by conjugation of ubiquitin (Ub and interferon-stimulated gene 15 (ISG15 to proteins. Certain classes of viruses encode Ub- or ISG15-specific proteases belonging to the ovarian tumor (OTU superfamily. Their activity is thought to suppress cellular immune responses, but studies demonstrating the function of viral OTU proteases during infection are lacking. Crimean-Congo hemorrhagic fever virus (CCHFV, family Nairoviridae is a highly pathogenic human virus that encodes an OTU with both deubiquitinase and deISGylase activity as part of the viral RNA polymerase. We investigated CCHFV OTU function by inactivating protease catalytic activity or by selectively disrupting its deubiquitinase and deISGylase activity using reverse genetics. CCHFV OTU inactivation blocked viral replication independently of its RNA polymerase activity, while deubiquitinase activity proved critical for suppressing the interferon responses. Our findings provide insights into viral OTU functions and support the development of therapeutics and vaccines.

  20. Immune system deregulation in hypertensive patients chronically RAS suppressed developing albuminuria

    OpenAIRE

    Martin-Lorenzo, Marta; Gonzalez-Calero, Laura; Martinez, Paula J.; Baldan-Martin, Montserrat; Lopez, Juan Antonio; Ruiz-Hurtado, Gema; de la Cuesta, Fernando; Segura, Juli?n; Vazquez, Jes?s; Vivanco, Fernando; Barderas, Maria G.; Ruilope, Luis M.; Alvarez-Llamas, Gloria

    2017-01-01

    Albuminuria development in hypertensive patients is an indicator of higher cardiovascular (CV) risk and renal damage. Chronic renin-angiotensin system (RAS) suppression facilitates blood pressure control but it does not prevent from albuminuria development. We pursued the identification of protein indicators in urine behind albuminuria development in hypertensive patients under RAS suppression. Urine was collected from 100 patients classified in three groups according to albuminuria developme...

  1. Healing with humor.

    Science.gov (United States)

    Sherman, K M

    1998-04-01

    A sense of humor can be a positive coping tool in times of stress, illness, and pain. Perioperative nurses are in the unique position to assess the patient's ability to cope and to suggest and model a repertoire of coping strategies that use humor. This article also explores self-care knowledge and ways that nurses can tap into their own resource potential for healing through humor.

  2. Humor and interpersonal attraction.

    Science.gov (United States)

    Murstein, B I; Brust, R G

    1985-12-01

    A humor test composed of cartoons, comic strips, and jokes was administered to 30 college couples (26 single, 4 married) who rated them for humor. Subjects also stated how much they loved and liked their partner, their probability of marrying the partner, and filled out Rubin's Liking and Love Scales. The hypotheses were that similarity of rating of the humorous stimuli would be associated with loving, liking, and predisposition to marry. Hypotheses were confirmed.

  3. Parasites suppress immune-enhancing effect of methionine in nestling great tits.

    Science.gov (United States)

    Wegmann, Michèle; Voegeli, Beatrice; Richner, Heinz

    2015-01-01

    After birth, an organism needs to invest both in somatic growth and in the development of efficient immune functions to counter the effects of pathogens, and hence an investment trade-off is predicted. To explore this trade-off, we simultaneously exposed nestling great tits (Parus major) to a common ectoparasite, while stimulating immune function. Using a 2 × 2 experimental design, we first infested half of the nests with hen fleas (Ceratophyllus gallinae) on day 3 post-hatch and later, on day 9-13 post-hatch, and then supplemented half of the nestlings within each nest with an immuno-enhancing amino acid (methionine). We then assessed the non-specific immune response by measuring both the inflammatory response to a lipopolysaccharide (LPS) and assessing the levels of acute phase proteins (APP). In parasite-infested nestlings, methionine had a negative effect on body mass close to fledging. Methionine had an immune-enhancing effect in the absence of ectoparasites only. The inflammatory response to LPS was significantly lower in nestlings infested with fleas and was also lower in nestlings supplemented with methionine. These patterns of immune responses suggest an immunosuppressive effect of ectoparasites that could neutralise the immune-enhancing effect of methionine. Our study thus suggests that the trade-off between investment in life history traits and immune function is only partly dependent on available resources, but shows that parasites may influence this trade-off in a more complex way, by also inhibiting important physiological functions.

  4. Role of pathogen-derived cell wall carbohydrates and prostaglandin E2 in immune response and suppression of fish immunity by the oomycete Saprolegnia parasitica.

    Science.gov (United States)

    Belmonte, Rodrigo; Wang, Tiehui; Duncan, Gary J; Skaar, Ida; Mélida, Hugo; Bulone, Vincent; van West, Pieter; Secombes, Christopher J

    2014-11-01

    Saprolegnia parasitica is a freshwater oomycete that is capable of infecting several species of fin fish. Saprolegniosis, the disease caused by this microbe, has a substantial impact on Atlantic salmon aquaculture. No sustainable treatment against saprolegniosis is available, and little is known regarding the host response. In this study, we examined the immune response of Atlantic salmon to S. parasitica infection and to its cell wall carbohydrates. Saprolegnia triggers a strong inflammatory response in its host (i.e., induction of interleukin-1β1 [IL-1β1], IL-6, and tumor necrosis factor alpha), while severely suppressing the expression of genes associated with adaptive immunity in fish, through downregulation of T-helper cell cytokines, antigen presentation machinery, and immunoglobulins. Oomycete cell wall carbohydrates were recognized by fish leukocytes, triggering upregulation of genes involved in the inflammatory response, similar to what is observed during infection. Our data suggest that S. parasitica is capable of producing prostaglandin [corrected] E2 (PGE2) in vitro, a metabolite not previously shown to be produced by oomycetes, and two proteins with homology to vertebrate enzymes known to play a role in prostaglandin biosynthesis have been identified in the oomycete genome. Exogenous PGE2 was shown to increase the inflammatory response in fish leukocytes incubated with cell wall carbohydrates while suppressing genes involved in cellular immunity (gamma interferon [IFN-γ] and the IFN-γ-inducible protein [γ-IP]). Inhibition of S. parasitica zoospore germination and mycelial growth by two cyclooxygenase inhibitors (aspirin and indomethacin) also suggests that prostaglandins may be involved in oomycete development. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  5. Very Good Medicine: Indigenous Humor and Laughter

    Science.gov (United States)

    Mala, Cynthia Lindquist

    2016-01-01

    Humor is not only instinctive and a basic human need, but it also is very good medicine. Laughter boosts the immune system, lowers blood pressure, reduces stress hormones, and is linked to healthy functioning organs. [This article was written with Mylo Redwater Smith.

  6. HUMOR: A Crowd-Annotated Spanish Corpus for Humor Analysis

    OpenAIRE

    Castro, Santiago; Cubero, Matías; Garat, Diego; Moncecchi, Guillermo

    2017-01-01

    Computational Humor, as the name implies, studies humor from a computational perspective, and it fosters several tasks, such as humor recognition, humor generation and humor scoring. The area has been little explored, making it attractive to tackle by novel Natural Language Processing and Machine Learning techniques. However, human-curated data is necessary. In this work we present a corpus of almost 40,000 tweets written in Spanish and crowd-annotated by their humor and funniness value with ...

  7. Six Tissue Transcriptomics Reveals Specific Immune Suppression in Spleen by Dietary Polyunsaturated Fatty Acids.

    Directory of Open Access Journals (Sweden)

    Sara L Svahn

    Full Text Available Dietary polyunsaturated fatty acids (PUFA are suggested to modulate immune function, but the effects of dietary fatty acids composition on gene expression patterns in immune organs have not been fully characterized. In the current study we investigated how dietary fatty acids composition affects the total transcriptome profile, and especially, immune related genes in two immune organs, spleen (SPL and bone marrow cells (BMC. Four tissues with metabolic function, skeletal muscle (SKM, white adipose tissue (WAT, brown adipose tissue (BAT, and liver (LIV, were investigated as a comparison. Following 8 weeks on low fat diet (LFD, high fat diet (HFD rich in saturated fatty acids (HFD-S, or HFD rich in PUFA (HFD-P, tissue transcriptomics were analyzed by microarray and metabolic health assessed by fasting blood glucose level, HOMA-IR index, oral glucose tolerance test as well as quantification of crown-like structures in WAT. HFD-P corrected the metabolic phenotype induced by HFD-S. Interestingly, SKM and BMC were relatively inert to the diets, whereas the two adipose tissues (WAT and BAT were mainly affected by HFD per se (both HFD-S and HFD-P. In particular, WAT gene expression was driven closer to that of the immune organs SPL and BMC by HFDs. The LIV exhibited different responses to both of the HFDs. Surprisingly, the spleen showed a major response to HFD-P (82 genes differed from LFD, mostly immune genes, while it was not affected at all by HFD-S (0 genes differed from LFD. In conclusion, the quantity and composition of dietary fatty acids affected the transcriptome in distinct manners in different organs. Remarkably, dietary PUFA, but not saturated fat, prompted a specific regulation of immune related genes in the spleen, opening the possibility that PUFA can regulate immune function by influencing gene expression in this organ.

  8. Humoral immune responses to a recombinant Plasmodium vivax tryptophan-rich antigen among Plasmodium vivax-infected patients and its localization in the parasite.

    Science.gov (United States)

    Siddiqui, Asim A; Khan, Fozia; Sharma, Yagya D

    2015-02-01

    Our recent studies have focused on the identification and characterization of the tryptophan-rich proteins of the Plasmodium vivax parasite where their role in the elicitation of humoral and cellular responses and erythrocyte-binding activity was investigated. Here, we report the humoral responses of a 32.4-kDa P. vivax tryptophan-rich antigen (PvTRAg32.4) among the sera of P. vivax-infected patients. PvTRAg32.4 also contains an unusually high percentage of tryptophan residues (10.7 %) that are positionally conserved with its orthologues in Plasmodium yoelii (PypAg1 and PypAg2) and Plasmodium falciparum (PfTryThrA and PfMATRA). Thirty-four of the 40 (85.0 %) P. vivax isolates showed seropositivity to recombinant PvTRAg32.4 by ELISA. The mean ± SD values of optical density (OD) for P. vivax subjects and naïve individuals were 1.02 ± 0.36 and 0.26 ± 0.11, respectively. In the Western blot analysis, majority of the subjects studied (n = 44) showed reactivity to the recombinant, purified PvTRAg32.4. This antigen does not show binding to the erythrocytes, but the immunofluorescence data reveals that it is expressed in the erythrocytic stages of the parasite. Sequence analysis of the clinical isolates from various parts of the country shows that PvTRAg32.4 is highly conserved. Functional in-depth characterization of more such type of novel proteins in the parasite is warranted for the development of successful malaria intervention methods.

  9. Increase in gut microbiota after immune suppression in baculovirus-infected larvae.

    Science.gov (United States)

    Jakubowska, Agata K; Vogel, Heiko; Herrero, Salvador

    2013-01-01

    Spodoptera exigua microarray was used to determine genes differentially expressed in S. exigua cells challenged with the species-specific baculovirus SeMNPV as well as with a generalist baculovirus, AcMNPV. Microarray results revealed that, in contrast to the host transcriptional shut-off that is expected during baculovirus infection, S. exigua cells showed a balanced number of up- and down-regulated genes during the first 36 hours following the infection. Many immune-related genes, including pattern recognition proteins, genes involved in signalling and immune pathways as well as immune effectors and genes coding for proteins involved in the melanization cascade were found to be down-regulated after baculovirus infection. The down-regulation of immune-related genes was confirmed in the larval gut. The expression of immune-related genes in the gut is known to affect the status of gut microorganisms, many of which are responsible for growth and development functions. We therefore asked whether the down-regulation that occurs after baculovirus infection affects the amount of gut microbiota. An increase in the gut bacterial load was observed and we hypothesize this to be as a consequence of viral infection. Subsequent experiments on virus performance in the presence and absence of gut microbiota revealed that gut bacteria enhanced baculovirus virulence, pathogenicity and dispersion. We discuss the host immune response processes and pathways affected by baculoviruses, as well as the role of gut microbiota in viral infection.

  10. Immunodominant Liver-Specific Expression Suppresses Transgene-Directed Immune Responses in Murine Pompe Disease

    Science.gov (United States)

    Zhang, Ping; Sun, Baodong; Osada, Takuya; Rodriguiz, Ramona; Yang, Xiao Yi; Luo, Xiaoyan; Kemper, Alex R.; Clay, Timothy M.

    2012-01-01

    Abstract Pompe disease can be treated effectively, if immune tolerance to enzyme replacement therapy (ERT) with acid α-glucosidase (GAA) is present. An adeno-associated viral (AAV) vector carrying a liver-specific regulatory cassette to drive GAA expression (AAV-LSPhGAA) established immune tolerance in GAA knockout (KO) mice, whereas ubiquitous expression with AAV-CBhGAA provoked immune responses. Therefore, we investigated the hypothesis that immune tolerance induced by hepatic-restricted expression was dominant. AAV-LSPhGAA and AAV-CBhGAA were administered singly or in combination to groups of adult GAA-KO mice, and AAV-LSPhGAA induced immune tolerance even in combination with AAV-CBhGAA. The dual vector approach to GAA expression improved biochemical correction of GAA deficiency and glycogen accumulations at 18 weeks, and improved motor function testing including wire-hang and grip-strength testing. The greatest efficacy was demonstrated by dual vector administration, when both vectors were pseudotyped as AAV8. T cells from mice injected with AAV-LSPhGAA failed to proliferate at all after an immune challenge with GAA and adjuvant, whereas mock-treated GAA-KO mice mounted vigorous T cell proliferation. Unlike AAV-LSPhGAA, AAV-CBhGAA induced selective cytokine and chemokine expression in liver and spleen after the immune challenge. AAV-CBhGAA transduced dendritic cells and expressed high-level GAA, whereas AAV-LSPhGAA failed to express GAA in dendritic cells. The level of transduction in liver was much higher after dual AAV8 vector administration at 18 weeks, in comparison with either vector alone. Dual vector administration failed to provoke antibody formation in response to GAA expression with AAV-CBhGAA; however, hepatic-restricted expression from dual vector expression did not prevent antibody formation after a strong immune challenge with GAA and adjuvant. The relevance of immune tolerance to gene therapy in Pompe disease indicates that hepatic expression

  11. Aktivitas Ekstrak Daun Kelor terhadap Respons Imun Humoral pada Mencit yang Diinfeksi Salmonella typhi (ACTIVITY OF KELOR LEAF EXTRACT ON HUMORAL IMMUNE RESPONSE IN MICE POST SALMONELLA TYPHI INFECTION

    Directory of Open Access Journals (Sweden)

    Mohammad Hefni

    2013-12-01

    Full Text Available The aim of this research was to analyze the activity of  kelor (Moringa oleifera Lam leaf extract onhumoral immune response in mice infected with Salmonella typhi. Mice were divided into two groups : non-infected and infectedS. typhi groups. Each group was administered orally for 20 days with varied doses ofkelor leaf extract i.e. dose (0 mg/kg BW, dose 1 (14 mg/kg BW, dose 2 (42 mg /kg BW, and dose 3 (84 mg/kg BW.  Then all of the sample in infected groups were injected with 108 cells S. typhi. The humoralimmunity responses were determined by observing the number of lymphoid B cell (B220 and naive Thecell (CD4+CD62L+ by using software BD CellQuest Flowcytometry. The data were analysed using Two-Way ANOVA (P<0.05, with SPSS 16.0 for Windows.  The kelor leaf extract showed imunostimulatoryactivity by significantly improved the number of lymphocyte B cell (B220,  and naive Th Cell (CD4+CD62L+in mice infected with S. typhi.  The lower doses (dose of 14 mg/kg BW, and 42 mg/kg BW of kelor leafextracts was more effective than the highest dose (84 mg/kg BW. On the other  hand, the high dose showedimunosupresor activity on naive Teessor Th Cell.  However, immunosupressor activity on naïve Th cell wasobserved on the mice given the highest dose of extract.

  12. Detection of Pneumocystis in the nasal swabs of immune-suppressed rats by use of PCR and microscopy.

    Science.gov (United States)

    Can, Hüseyin; Caner, Ayşe; Döşkaya, Mert; Değirmenci, Aysu; Karaçalı, Sabire; Polat, Ceylan; Gürüz, Yüksel; Uner, Ahmet

    2013-02-13

    Detection of Pneumocystis jiroveci colonization in lungs or oral samples due to high sensitivity of PCR methods results in undue treatment of patients without any symptoms of Pneumocystis pneumonia. The aim of the present study is to demonstrate Pneumocystis carinii in rats, immune suppressed by oral and subcutaneous administration of dexamethasone. Blood, oral, nasal and eye swabs were collected prior to immune suppression and 2, 6, 12 weeks after administration of dexamethasone. Also, samples were collected from lung, heart, liver, kidney, diaphragm, brain, spleen, tongue, muscle, eye, intestine, and feces. Cysts and trophozoites were investigated in stained slides and MSG gene was detected by PCR. The results showed that weight loss is significantly higher in rats administered oral dexamethasone (Pdexamethasone. PCR was positive in lungs and oral swabs of rats prior to the administration of dexamethasone. After the administration of dexamethasone, the MSG gene was detected in oral swabs, lungs, spleen, kidney and (for the first time) in nasal swabs. PCR was positive in nasal swabs during the second and sixth weeks of oral and subcutaneous administration of dexamethasone, respectively. Presence of P. jiroveci in nasopharyngeal aspirate, oropharyngeal wash, oral swab, induced sputum or BAL, and absence in nasal swab in a patient without symptoms of PCP may support clinician's decision regarding colonization. Overall, detection of P. carinii in nasal swabs of rats by PCR demonstrated that nasal sampling can be used for the diagnosis of Pneumocystis pneumonia.

  13. Multiscale model for the effects of adaptive immunity suppression on the viral therapy of cancer

    Science.gov (United States)

    Paiva, Leticia R.; Silva, Hallan S.; Ferreira, Silvio C.; Martins, Marcelo L.

    2013-04-01

    Oncolytic virotherapy—the use of viruses that specifically kill tumor cells—is an innovative and highly promising route for treating cancer. However, its therapeutic outcomes are mainly impaired by the host immune response to the viral infection. In this paper, we propose a multiscale mathematical model to study how the immune response interferes with the viral oncolytic activity. The model assumes that cytotoxic T cells can induce apoptosis in infected cancer cells and that free viruses can be inactivated by neutralizing antibodies or cleared at a constant rate by the innate immune response. Our simulations suggest that reprogramming the immune microenvironment in tumors could substantially enhance the oncolytic virotherapy in immune-competent hosts. Viable routes to such reprogramming are either in situ virus-mediated impairing of CD8+ T cells motility or blockade of B and T lymphocytes recruitment. Our theoretical results can shed light on the design of viral vectors or new protocols with neat potential impacts on the clinical practice.

  14. Comparative assessment of humoral immune responses of aluminum hydroxide and oil-emulsion adjuvants in Influenza (H9N2) and Newcastle inactive vaccines to chickens.

    Science.gov (United States)

    Jafari, Mahdie; Moghaddam Pour, Masoud; Taghizadeh, Morteza; Masoudi, Shahin; Bayat, Zahra

    2017-02-01

    Context Adjuvants are compounds used in the preparation of inactive vaccines to enhance the immune response. Aluminum hydroxide (alum) is one of the first compounds approved by the Food and Drug Administration, which is used as adjuvants in vaccine products for humans. Montanide ISA 70 is an oil-emulsion adjuvant and is used in poultry inactive vaccines. Objective In this study, the effects of alum adjuvant on the efficiency and induction of immune response in inactive vaccines of Influenza and Newcastle are compared with those of ISA 70. Materials and methods Six groups of 7-d-old specific-pathogen-free chickens were inoculated with 0.3 ml of the prepared vaccines via the subcutaneous route in the neck. Immune response in each group after 7, 14, 21, 31, 41, and 45 d was evaluated using the technique of hemagglutination inhibition. Results The results were compared using SPSS software. Results showed that vaccines containing adjuvant ISA 70 depicted a higher increase in the immune response and adjuvant of 20% alum is similar to adjuvant of ISA 70 in boosting the immune system. There was no statistically significant difference between 10% and 20% alum, but these adjuvants are visibly different from ISA 70. Conclusion In conclusion, alum can be used as an easily accessible, harmless, and effective adjuvant; however, to increase the immune period using the inactive vaccines for poultry, more research would be necessary.

  15. Humoral and In Vivo Cellular Immunity against the Raw Insect-Derived Recombinant Leishmania infantum Antigens KMPII, TRYP, LACK, and papLe22 in Dogs from an Endemic Area

    Science.gov (United States)

    Todolí, Felicitat; Solano-Gallego, Laia; de Juan, Rafael; Morell, Pere; del Carmen Núñez, Maria; Lasa, Rodrigo; Gómez-Sebastián, Silvia; Escribano, José M.; Alberola, Jordi; Rodríguez-Cortés, Alhelí

    2010-01-01

    Leishmania infantum causes visceral leishmaniasis, a severe zoonotic and systemic disease that is fatal if left untreated. Identification of the antigens involved in Leishmania-specific protective immune response is a research priority for the development of effective control measures. For this purpose, we evaluated, in 27 dogs from an enzootic zone, specific humoral and cellular immune response by delayed-type hypersensitivity (DTH) skin test both against total L. infantum antigen and the raw Trichoplusia ni insect-derived kinetoplastid membrane protein-11 (rKMPII), tryparedoxin peroxidase (rTRYP), Leishmania homologue of receptors for activated C kinase (rLACK), and 22-kDa potentially aggravating protein of Leishmania (rpapLe22) antigens from this parasite. rTRYP induced the highest number of positive DTH responses (55% of leishmanin skin test [LST]-positive dogs), showing that TRYP antigen is an important T cell immunogen, and it could be a promising vaccine candidate against this disease. When TRYP-DTH and KMPII-DTH tests were evaluated in parallel, 82% of LST-positive dogs were detected, suggesting that both antigens could be considered as components of a standardized DTH immunodiagnostic tool for dogs. PMID:21118936

  16. Humor, Philosophy and Education

    Science.gov (United States)

    Morreall, John

    2014-01-01

    This article begins by examining the bad reputation humor traditionally had in philosophy and education. Two of the main charges against humor--that it is hostile and irresponsible--are linked to the Superiority Theory. That theory is critiqued and two other theories of laughter are presented--the Relief Theory and the Incongruity Theory. In the…

  17. El humor centenarista

    Directory of Open Access Journals (Sweden)

    Álvaro Sánchez

    1963-01-01

    Full Text Available En el número 7 -volumen IV- de julio de 1961, bajo el título de El Humor Parnasiano, fueron publicados cuatro sonetos humorísticos: dos del Maestro Guillermo Valencia y dos de su discípulo Carlos López Narváez.

  18. Dairy heifers naturally exposed to Fasciola hepatica develop a type-2 immune response and concomitant suppression of leukocyte proliferation.

    Science.gov (United States)

    Graham-Brown, John; Hartley, Catherine; Clough, Helen; Kadioglu, Aras; Baylis, Matthew; Williams, Diana J L

    2017-10-09

    Fasciola hepatica is a parasitic trematode of global importance in livestock. Control strategies reliant on anthelmintics are unsustainable due to the emergence of drug resistance. Vaccines are under development, but efficacy is variable. Evidence from experimental infection suggest vaccine efficacy may be affected by parasite-induced immunomodulation. Little is known about the immune response to F. hepatica following natural exposure. Hence we analysed the immune responses over time in calves naturally exposed to F. hepatica infection.Cohorts of replacement dairy heifer calves (n=42) with no prior exposure to F. hepatica, on three commercial dairy farms, were sampled over the course of a grazing season. Exposure was determined through F. hepatica-specific serum antibody ELISA and fluke egg counts. Concurrent changes in peripheral blood leukocyte sub-populations, lymphocyte proliferation and cytokine responses were measured. Relationships between fluke infection and immune responses were analysed using multivariable linear mixed effect models.All calves from one farm showed evidence of exposure, whilst cohorts from the remaining two farms remained negative over the grazing season. A type-2 immune response was associated with exposure, with increased interleukin (IL)-4 production, IL-5 transcription and eosinophilia. Suppression of parasite-specific PBMC proliferation was evident; while decreased mitogen stimulated IFN-γ production suggested immunomodulation, which was not restricted to parasite-specific responses. Our findings show that the global immune response is modulated towards a non-proliferative type-2 state following natural challenge with F. hepatica This has implications for vaccination programmes in terms of the timing of administration of vaccination programmes, and for host susceptibility to co-infecting pathogens. Copyright © 2017 Graham-Brown et al.

  19. Brugia malayi Microfilariae Induce a Regulatory Monocyte/Macrophage Phenotype That Suppresses Innate and Adaptive Immune Responses

    Science.gov (United States)

    Venugopal, Gopinath; Rao, Gopala B.; Lucius, Richard; Srikantam, Aparna; Hartmann, Susanne

    2014-01-01

    Background Monocytes and macrophages contribute to the dysfunction of immune responses in human filariasis. During patent infection monocytes encounter microfilariae in the blood, an event that occurs in asymptomatically infected filariasis patients that are immunologically hyporeactive. Aim To determine whether blood microfilariae directly act on blood monocytes and in vitro generated macrophages to induce a regulatory phenotype that interferes with innate and adaptive responses. Methodology and principal findings Monocytes and in vitro generated macrophages from filaria non-endemic normal donors were stimulated in vitro with Brugia malayi microfilarial (Mf) lysate. We could show that monocytes stimulated with Mf lysate develop a defined regulatory phenotype, characterised by expression of the immunoregulatory markers IL-10 and PD-L1. Significantly, this regulatory phenotype was recapitulated in monocytes from Wuchereria bancrofti asymptomatically infected patients but not patients with pathology or endemic normals. Monocytes from non-endemic donors stimulated with Mf lysate directly inhibited CD4+ T cell proliferation and cytokine production (IFN-γ, IL-13 and IL-10). IFN-γ responses were restored by neutralising IL-10 or PD-1. Furthermore, macrophages stimulated with Mf lysate expressed high levels of IL-10 and had suppressed phagocytic abilities. Finally Mf lysate applied during the differentiation of macrophages in vitro interfered with macrophage abilities to respond to subsequent LPS stimulation in a selective manner. Conclusions and significance Conclusively, our study demonstrates that Mf lysate stimulation of monocytes from healthy donors in vitro induces a regulatory phenotype, characterized by expression of PD-L1 and IL-10. This phenotype is directly reflected in monocytes from filarial patients with asymptomatic infection but not patients with pathology or endemic normals. We suggest that suppression of T cell functions typically seen in lymphatic

  20. [Effect of bifunctional IL2-GMCSF in promoting dendritic cell activation in vitro in simulated tumor-induced immune suppression].

    Science.gov (United States)

    Wen, Qian; Xiong, Wenjing; Liu, Sudong; Zhou, Chaoying; Ma, Li

    2015-08-01

    To test the effect of bifunctional molecule IL2-GMCSF in promoting the activation of dendritic cells (DCs) cultured in tumor conditioned medium. We prepared a tumor conditioned medium using mouse melanoma cell line B16F10 supplemented with IL2-GMCSF, GM-CSF, IL-2, or the combination of the latter two. After culturing mouse DC cell line DC2.4 in the conditioned medium for 24 h, the DCs were examined for phagocytosis, proliferation, maturation phenotype, cytokine secretion, and signal pathway activation. DC2.4 cells displayed characteristics of immature DCs. After cell culture in the conditioned medium, the cells showed enhanced phagocytosis but significantly suppressed cell proliferation activity. Culture in the conditioned medium also promoted DC cell maturation and secretion of macrophage-derived chemokine (MDC), but inhibited IL-12 secretion. Supplementation of the conditioned medium with IL2-GMCSF promoted phagocytosis, proliferation, maturation, and cytokine (including both IL-12 and MDC) secretion of DC2.4 cells. Compared with GM-CSF, IL2-GMCSF induced a higher level of NF-κB signal pathway activation but suppressed STAT3 activation. Compared with GM-CSF, IL2-GMCSF can better promote DC activation in the context of tumor-induced immune suppression, and thus shows potentials in anti-tumor therapy.

  1. Modulation of Cell-Mediated Immunity to Suppress High Fat Diet-Induced Obesity and Insulin Resistance.

    Science.gov (United States)

    Yan, Linna; Song, Kexiu; Gao, Mingming; Qu, Shen; Liu, Dexi

    2016-02-01

    To assess the effect of immune modulators, cyclosporin A and fingolimod, on high fat diet-induced obesity and insulin resistance. C57BL/6 mice were fed a high fat diet and injected intraperitoneally with cyclosporine A, fingolimod, or vehicle twice weekly for 15 weeks. Body weight and food intake were manually measured every other day. Glucose tolerance test, insulin sensitivity, and body composition were examined and compared between the control and the immune modulator treated animals. Tissue samples were collected at the end of the experiment and examined for serum biochemistry, histology, and mRNA levels of marker genes for inflammation, and glucose and lipid metabolism in white and brown adipose tissues and in the liver. Cyclosporine A and fingolimod suppressed high fat diet-induced weight gain, reduced hepatic fat accumulation, and improved insulin sensitivity. The beneficial effects are associated with altered expression of F4/80, Cd68, Il-6, Tnf-α, and Mcp-1 genes, which are involved in macrophage-related chronic inflammation in adipose and hepatic tissues. Immune modulation represents an important intervention for obesity and obesity-associated insulin resistance.

  2. Extracellular Vesicles from a Helminth Parasite Suppress Macrophage Activation and Constitute an Effective Vaccine for Protective Immunity

    Directory of Open Access Journals (Sweden)

    Gillian Coakley

    2017-05-01

    Full Text Available Recent studies have demonstrated that many parasites release extracellular vesicles (EVs, yet little is known about the specific interactions of EVs with immune cells or their functions during infection. We show that EVs secreted by the gastrointestinal nematode Heligmosomoides polygyrus are internalized by macrophages and modulate their activation. EV internalization causes downregulation of type 1 and type 2 immune-response-associated molecules (IL-6 and TNF, and Ym1 and RELMα and inhibits expression of the IL-33 receptor subunit ST2. Co-incubation with EV antibodies abrogated suppression of alternative activation and was associated with increased co-localization of the EVs with lysosomes. Furthermore, mice vaccinated with EV-alum generated protective immunity against larval challenge, highlighting an important role in vivo. In contrast, ST2-deficient mice are highly susceptible to infection, and they are unable to clear parasites following EV vaccination. Hence, macrophage activation and the IL-33 pathway are targeted by H. polygyrus EVs, while neutralization of EV function facilitates parasite expulsion.

  3. The Role of Non-specific and Specific Immune Systems in Poultry against Newcastle Disease

    Directory of Open Access Journals (Sweden)

    Dyah Ayu Hewajuli

    2015-09-01

    Full Text Available Newcastle disease (ND is caused by avian paramyxovirus-1 which belong to Avulavirus genus and Paramyxoviridae family. The birds have abnormalities in humoral (bursa fabricius and cellular (thymus and spleen lymphoid organs. Lesions decrease the immune system. Immune system consists of non-specific and specific immune systems. The main components of non-specific immunity are physical and chemical barrier (feather and skin or mucosa, phagocytic cells (macrophages and natural