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Immune Protection (immune + protection)
Selected AbstractsTumour cell,dendritic cell fusion for cancer immunotherapy: comparison of therapeutic efficiency of polyethylen-glycol versus electro-fusion protocolsEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 3 2002M. Lindner Abstract Background ,Fusion of tumour cells with dendritic cells (DC) is a powerful new technology to increase tumour vaccine immunogenicity. The aim of this study was to compare fusion protocols with syngenic DCs with respect to the efficiency of polyethylen-glycol-(PEG) and electric pulse-mediated fusions for induction of protective anti-tumour immune responses. As a model we chose a low immunogenic and metastatic murine mammary carcinoma cell line, which mimics clinically relevant tumour features. Methods FACS-staining, chromium release assay, therapeutic immunization, adoptive transfer. Results ,We show that the parental line with low cell surface expression of MHC molecules as well as a lacZ transfectant becomes highly immunogenic upon fusion with DCs. This was true for PEG- as well as for electro-fused cells. Immunization with products of DCs and tumour cells cocultivated for 16 h without the fusing agent PEG also caused induction of profound anti-tumour immunity, while this was not the case when using parental tumour cells or their lacZ transfectants as vaccines. Immune protection against the parental tumour cells after vaccination with fused cells was long-lasting and could be transferred via immune spleen cells into immuno-incompetent nude (nu/nu) mice. Conclusion ,Fusion products of DA3hi mammary carcinoma cells and DCs produced by an electric pulse were similar to those produced by PEG fusion with regard to vaccine potency in prophylactic antitumour immunization assays in vivo. Therefore, both techniques seem to be promising for clinical application. [source] The antimicrobial activity of CCL28 is dependent on C-terminal positively-charged amino acidsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 1 2010Bin Liu Abstract Several chemokines have been shown to act as antimicrobial proteins, suggesting a direct contribution to innate immune protection. Based on the study of defensins and other antimicrobial peptides, it has been proposed that cationic amino acids in these proteins play a key role in their antimicrobial activity. The primary structure requirements necessary for the antimicrobial activity of chemokines, however, have not yet been elucidated. Using mouse CCL28, we have identified a C-terminal region of highly-charged amino acids (RKDRK) that is essential to the antimicrobial activity of the murine chemokine. Additionally, other positively-charged amino acids in the C-terminus of the protein contribute to the observed antimicrobial effect. Charge reversal and deletion mutations support our hypothesis that C-terminal positively-charged amino acids are essential for the antimicrobial activity of CCL28. Results also demonstrate that although the C-terminal region of the chemokine is essential, it is not sufficient for full antimicrobial activity of CCL28. [source] CD8+ T-cell responses to Theileria parva are preferentially directed to a single dominant antigen: Implications for parasite strain-specific immunityEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 9 2009Niall D. MacHugh Abstract Although immunodominance of CD8+ T-cell responses is a well-recognised feature of viral infections, its role in responses to more antigenically complex pathogens is less clear. In previous studies we have observed that CD8+ T-cell responses to Theileria parva exhibit different patterns of parasite strain specificity in cattle of different MHC genotypes. In the current study, we demonstrated that animals homozygous for the A10 and A18 MHC haplotypes have detectable responses to only one of 5 T. parva antigens. Over 60% of the responding T cells from the A18+ and A10+ animals recognised defined epitopes in the Tp1 and Tp2 antigens, respectively. Comparison of T-cell receptor , chain expression profiles of CD8+ T-cell lines and CD8+ T cells harvested ex vivo confirmed that the composition of the T-cell lines was representative of the in vivo memory CD8+ T-cell populations. Analysis of the Tp1 and Tp2 antigens revealed sequence polymorphism, which was reflected by differential recognition by T-cell lines. In conclusion, we have demonstrated a profound immunodominance in the CD8+ T-cell response to T. parva, which we propose is a major determinant of the parasite strain specificity of the response and hence immune protection. [source] Decreased specific CD8+ T,cell cross-reactivity of antigen recognition following vaccination with Melan-A peptideEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2006Victor Appay Abstract The aim of T,cell vaccines is the expansion of antigen-specific T,cells able to confer immune protection against pathogens or tumors. Although increase in absolute cell numbers, effector functions and TCR repertoire of vaccine-induced T,cells are often evaluated, their reactivity for the cognate antigen versus their cross-reactive potential is rarely considered. In fact, little information is available regarding the influence of vaccines on T,cell fine specificity of antigen recognition despite the impact that this feature may have in protective immunity. To shed light on the cross-reactive potential of vaccine-induced cells, we analyzed the reactivity of CD8+ T,cells following vaccination of HLA-A2+ melanoma patients with Melan-A peptide, incomplete Freund's adjuvant and CpG-oligodeoxynucleotide adjuvant, which was shown to induce strong expansion of Melan-A-reactive CD8+ T,cells in vivo. A collection of predicted Melan-A cross-reactive peptides, identified from a combinatorial peptide library, was used to probe functional antigen recognition of PBMC ex vivo and Melan-A-reactive CD8+ T,cell clones. While Melan-A-reactive CD8+ T,cells prior to vaccination are usually constituted of widely cross-reactive naive cells, we show that peptide vaccination resulted in expansion of memory T,cells displaying a reactivity predominantly restricted to the antigen of interest. Importantly, these cells are tumor-reactive. [source] Immune-related mechanisms participating in resistance and susceptibility to glutamate toxicityEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2002Hadas Schori Abstract Glutamate is an essential neurotransmitter in the CNS. However, at abnormally high concentrations it becomes cytotoxic. Recent studies in our laboratory showed that glutamate evokes T cell-mediated protective mechanisms. The aim of the present study was to examine the nature of the glutamate receptors and signalling pathways that participate in immune protection against glutamate toxicity. We show, using the mouse visual system, that glutamate-induced toxicity is strain dependent, not only with respect to the amount of neuronal loss it causes, but also in the pathways it activates. In strains that are genetically endowed with the ability to manifest a T cell-dependent neuroprotective response to glutamate insult, neuronal losses due to glutamate toxicity were relatively small, and treatment with NMDA-receptor antagonist worsened the outcome of exposure to glutamate. In contrast, in mice devoid of T cell-dependent endogenous protection, NMDA receptor antagonist reduced the glutamate-induced neuronal loss. In all strains, blockage of the AMPA/KA receptor was beneficial. Pharmacological (with ,2 -adrenoceptor agonist) or molecular intervention (using either mice overexpressing Bcl-2, or DAP-kinase knockout mice) protected retinal ganglion cells from glutamate toxicity but not from the toxicity of NMDA. The results suggest that glutamate-induced neuronal toxicity involves multiple glutamate receptors, the types and relative contributions of which, vary among strains. We suggest that a multifactorial protection, based on an immune mechanism independent of the specific pathway through which glutamate exerts its toxicity, is likely to be a safer, more comprehensive, and hence more effective strategy for neuroprotection. It might suggest that, because of individual differences, the pharmacological use of NMDA-antagonist for neuroprotective purposes might have an adverse effect, even if the affinity is low. [source] Microbes versus microbes: immune signals generated by probiotic lactobacilli and their role in protection against microbial pathogensFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 4 2002Martin L Cross Abstract Probiotic lactic acid bacteria can signal the immune system through innate cell surface pattern recognition receptors or via direct lymphoid cell activation. In some cases, this action has been shown to be sufficient to modulate local- and systemic-level in vivo immune responses. Practical applications of probiotics include their use in anti-tumour and anti-allergy immunotherapy, but there is also increasing evidence that some probiotics can stimulate a protective immune response sufficiently to enhance resistance to microbial pathogens. This review outlines the experimental and clinical evidence for enhanced anti-microbial immune protection by probiotic lactic acid bacteria, focussing on those studies where a correlative or suggestive link has been shown between immune modulation and enhanced protection. [source] Interleukin-13 in the skin and interferon-, in the liver are key players in immune protection in human schistosomiasisIMMUNOLOGICAL REVIEWS, Issue 1 2004Alain Dessein Summary:, Immunity against schistosomes includes anti-infection immunity, which is mainly active against invading larvae in the skin, and anti-disease immunity, which controls abnormal fibrosis in tissues invaded by schistosome eggs. Anti-infection immunity is T-helper 2 (Th2) cell-dependent and is controlled by a major genetic locus that is located near the Th2 cytokine locus on chromosome 5q31-q33. Mutations in the gene encoding interleukin (IL)-13 that decrease or increase IL-13 production account, at least in part, for that genetic control. In contrast, protection against hepatic fibrosis is dependent on interferon (IFN)-, and is controlled by a major genetic locus that is located on 6q23, near the gene encoding the IFN-, receptor , chain. Mutations that modulate IFN-, gene transcription are associated with different susceptibility to disease. These data indicate that IL-13 in the skin and IFN-, in the liver are key players in protective immunity against schistosomes. These roles relate to the high anti-fibrogenic activities of IFN-, and to the unique ability of IL-13 in Th2 priming in the skin and in the mobilization of eosinophils in tissues. The coexistence of strong IFN-, and IL-13-mediated immune responses in the same subject may involve the compartmentalization of the anti-schistosome immune response between the skin and the liver. [source] Innate immune responses induced by CpG oligodeoxyribonucleotide stimulation of ovine blood mononuclear cellsIMMUNOLOGY, Issue 2 2003Angelo Mena Summary Examples exist in the literature that demonstrate that treatment with immunostimulatory cytosine,phosphate,guanosine (CpG)-DNA can protect mice against infection by intracellular pathogens. There are, however, few studies reporting that CpG-DNA offers similar disease protection in other species. In this study, we assessed the potential of a class A and class B CpG oligodeoxynucleotide (ODN) to induce innate immune responses in sheep, an outbred species. Using peripheral blood mononuclear cells, we have for the first time demonstrated CpG-ODN-induced innate immune responses, including natural-killer-like activity [non-major histocompatibility complex (MHC)-restricted cytotoxicity], interferon-, secretion and 2,-5,A oligoadenylate synthetase activity, that could contribute to immune protection in sheep. The type and magnitude of these responses were dependent on ODN class and non-MHC-restricted killing was not associated with interferon-, production. The latter observation is in contrast with observations reported for mice and humans. These observations support the conclusion that differences in CpG-ODN-induced responses exist among species and that specific ODN sequences can significantly influence innate immune responses. [source] MF59® -adjuvanted vaccines for seasonal and pandemic influenza prophylaxisINFLUENZA AND OTHER RESPIRATORY VIRUSES, Issue 6 2008Angelika Banzhoff Abstract, Influenza is a major cause of worldwide morbidity and mortality through frequent seasonal epidemics and infrequent pandemics. Morbidity and mortality rates from seasonal influenza are highest in the most frail, such as the elderly, those with underlying chronic conditions and very young children. Antigenic mismatch between strains recommended for vaccine formulation and circulating viruses can further reduce vaccine efficacy in these populations. Seasonal influenza vaccines with enhanced, cross-reactive immunogenicity are needed to address these problems and can confer a better immune protection, particularly in seasons were antigenic mismatch occurs. A related issue for vaccine development is the growing threat of pandemic influenza caused by H5N1 avian strains. Vaccines against strains with pandemic potential offer the best approach for reducing the potential impact of a pandemic. However, current non-adjuvanted pre-pandemic vaccines offer suboptimal immunogenicity against H5N1. For both seasonal and pre-pandemic vaccines, the addition of adjuvants may be the best approach for providing enhanced cross-reactive immunogenicity. MF59®, the first oil-in-water emulsion licensed as an adjuvant for human use, can enhance vaccine immune responses through multiple mechanisms. A trivalent MF59-adjuvanted seasonal influenza vaccine (Fluad®) has shown to induce significantly higher immune responses to influenza vaccination in the elderly, compared with non-adjuvanted vaccines, and to provide cross-reactive immunity against divergent influenza strains. Similar results have been generated with a MF59-adjuvanted H5N1 pre-pandemic vaccine, which showed higher and broader immunogenicity compared with non-adjuvanted pre-pandemic vaccines. [source] Upregulation of genes orchestrating keratinocyte differentiation, including the novel marker gene ID2, by contact sensitizers in human bulge-derived keratinocytesJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 1 2010Yoshie Yoshikawa Abstract In the epidermis, keratinocytes are involved in physical and first-line immune protection of the host. In this study, we analyzed the molecular responses to certain contact sensitizers (2,4-dinitrochlorobenzene and NiSO4) and irritants (sodium dodecyl sulfate and benzalkonium chloride) in cultured human keratinocytes from the bulge region of a plucked hair follicle (bulge-derived keratinocytes [BDKs]) and compared these molecular responses to those with the human monocytic leukemia cell line, THP-1. The BDKs, individually established without invasive biopsies, showed high reactivity to these stimulants. As a primary response to the contact sensitizers, the NRF2-mediated signaling pathway was upregulated in BDKs and THP-1. The expression of IL1B and IL8 genes was not induced by the irritants but by the sensitizers in THP-1. However, the expression of the IL1B and IL8 genes was induced at higher levels by the irritants in BDKs than by the sensitizers. Many genes orchestrating keratinocyte differentiation, including ID2, were significantly upregulated in response to the sensitizers in BDKs but not those in THP-1. The use of the ID2 gene to discriminate between sensitizers and irritants might be effective as a novel marker for application during in vitro sensitization with BDKs. © 2010 Wiley Periodicals, Inc. J Biochem Mol Toxicol 24:10,20, 2010; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20307 [source] Protection against atypical furunculosis in Atlantic halibut, Hippoglossus hippoglossus (L.); comparison of a commercial furunculosis vaccine and an autogenous vaccineJOURNAL OF FISH DISEASES, Issue 6 2003S Gudmundsdóttir Abstract Atlantic halibut, Hippoglossus hippoglossus (L.), was shown to be sensitive to infection by three different isolates of Aeromonas salmonicida ssp. achromogenes in pre-challenge tests using intraperitoneal (i.p.) and intramuscular (i.m.) injections as well as bath challenges. A commercial furunculosis vaccine, Alphaject 1200, and an autogenous vaccine, AAS, based on the challenge strain, induced immune protection as shown in challenge tests 8 weeks post-immunization. The survival rate of vaccinated fish after i.p. challenge was 100%, whereas mortality of control fish was 61%. Employing i.m. challenge, relative percentage survival induced by the furunculosis vaccine and the AAS vaccine was 47 and 44, respectively. Mortality of i.m. injected controls was 68%. Vaccinated fish behaved normally following vaccination but the weight gain was significantly reduced in vaccinated fish 8 weeks post-vaccination compared with control fish receiving phosphate-buffered saline. At the same time, intra-abdominal adhesions were observed in fish injected with either of the two vaccines or adjuvant alone. Antibody response against A. salmonicida ssp. achromogenes was detected in sera from fish receiving either vaccine. [source] UV-induced immune suppression and sunscreenPHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE, Issue 3 2000E. M. Gil Sun protection factor (SPF) that measures sunscreen protection against erythema and edema may not be enough to measure a sunscreen's activity against many other biologic reactions induced by ultraviolet radiation (UV). It may be better to evaluate sunscreen efficacy using various tools including immune protection factor (IPF), mutation protection factor (MPF) and protection against photocarcinogenesis. In terms of immune protection, sunscreens protected against UV-induced immune suppression significantly. But protection in some cases was partial and often the IPF of sunscreens were less than the SPF. IPF may differ with various immunological endpoints, and it may be better to use a couple of different assays to measure sunscreen protection more objectively. Sunscreen use protects against most UV-induced non-melanoma skin cancers and actinic keratoses but its activity against melanoma is not clear. More studies with broad-spectrum stable sunscreens and better models for the investigation of malignant melanoma are required. [source] ORIGINAL ARTICLE: Estradiol Limits Viral Replication Following Intravaginal Immunization Leading to Diminished Mucosal IgG Response and Non-sterile Protection Against Genital Herpes ChallengeAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 4 2010Amy Gillgrass Citation Gillgrass A, Chege D, Bhavanam S, Kaushic C. Estradiol limits viral replication following intravaginal immunization leading to diminished mucosal IgG response and non-sterile protection against genital herpes challenge. Am J Reprod Immunol 2010; 63: 299,309 Problem, Previously we reported that ovariectomized (OVX) mice receiving estradiol (E) prior to immunization with an attenuated strain of HSV-2 (TK-HSV-2) were not protected. Lack of protection in the E group was because of the inability of TK-HSV-2 to penetrate the thick keratinized epithelium. In this study, we determined the outcome of immunization after the thickening of vaginal epithelium following E-treatment waned. OVX, C57BL/6 mice were given Progesterone (P), E or saline (S) for 3 days and immunized with IVAG TK-HSV-2. Method of study, To determine the time point at which E-treated mice could be successfully immunized, the mice were inoculated with TK-HSV-2 between days 1 and 7 (ED1,ED7) post-E-treatment and challenged with IVAG HSV-2 three weeks later. Results, The level of infection post-immunization correlated with HSV-2-specific IgG antibody level, which correlated with sterile protection. No viral infection was observed in ED1,ED3 groups and no specific antibodies were detected, resulting in no protection. Moderate infection was seen in ED5 group, resulting in low antibody production and non-sterile protection in 87.5% of mice. High antibody titers and sterile protection were observed in all groups that experienced robust infection post-immunization. Conclusion, The results show that estradiol leads to limited viral replication and diminished mucosal IgG response, resulting in non-sterile immune protection against genital herpes infection. [source] Antigen Presentation by Human Uterine Epithelial Cells to Autologous T CellsAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2006John V. Fahey Problem, Epithelial cells, as sentinels of immune protection in the endometrium, use innate immune mechanisms to protect against infection from pathogenic microbes. Our goal in this study was to assess the ability of human uterine epithelial cells to present antigen to cells of the adaptive immune system. Method of study, Highly purified preparations of uterine epithelial cells from 11 patients were assessed for their ability to present tetanus toxoid (TT) to autologous T cells. Leukocyte contamination in the epithelial cell preparations was numerically and functionally determined. Using confocal microscopy, epithelial cells were tested for the expression of CD40 and CD1d. Results, Purified preparations of endometrial epithelial cells isolated from every patient presented TT recall antigen to autologous T cells. Leukocyte contamination of epithelial cell preparations was insignificant. Uterine epithelial cells express CD40 and CD1d. Conclusion, Antigen presentation is an additional aspect of uterine epithelial cell function in maintaining women's health. [source] BK Viral Loads and Immune Monitoring in Renal Transplant RecipientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2007S. F. Lacey BK virus-specific T-cell responses in recipients of kidney transplantation are important for control of viral load and protection against polyomavirus-associated nephropathy, but the specific correlates of immune protection are still unclear. See also article by Binggeli et al in this issue on page 1131. [source] Evolutionary origin of Venturia canescens virus-like particles ,ARCHIVES OF INSECT BIOCHEMISTRY AND PHYSIOLOGY (ELECTRONIC), Issue 3 2006Annette Reineke Abstract Insect host-parasitoid interactions provide fascinating examples of evolutionary adaptations in which the parasitoid employs a variety of measures and countermeasures to overcome the immune responses of its host. Maternal factors introduced by the female wasps during egg deposition play an important role in interfering with cellular and humoral components of the host's immune defence. Some of these components actively suppress host immune components and some are believed to confer protection for the developing endoparasitoid by rather passive means. The Venturia canescens/Ephestia kuehniella parasitoid-host system is unique among other systems in that the cellular defence capacity of the host remains virtually intact after parasitization. This system raises some important questions that are discussed in this mini-review: If immune protection of the egg and the emerging larva is achieved by surface properties comprising glycoproteins and virus-like particles (VLPs) produced by the female wasp, why is the prophenoloxidase activating cascade blocked in parasitized caterpillars? Another question is the evolutionary origin of these particles, given that the functional role and structural features of V. canescens VLP proteins are more related to cellular proteins than to viruses. Arch. Insect Biochem. Physiol. 61:123,133, 2006. © 2006 Wiley-Liss, Inc. [source] | |||||||||||||