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Humoral
Terms modified by Humoral Selected AbstractsHumoral and cardiac effects of TIPS in cirrhotic patients with different "effective" blood volumeHEPATOLOGY, Issue 6 2003Francesco Salerno M.D. The aim of this study was to evaluate the cardiac effects of transjugular intrahepatic portosystemic shunts (TIPS) in cirrhotic patients with different effective blood volume. Two-dimensional echocardiography was performed before and 7 and 28 days after TIPS insertion in 7 cirrhotic patients with PRA <4 ng/mL/h (group A, normal effective blood volume) and 15 with PRA >4 ng/mL/h (group B, reduced effective blood volume). Before TIPS, most cirrhotic patients showed diastolic dysfunction as indicated by reduced early maximal ventricular filling velocity (E)/late filling velocity (A) ratio. Patients of group B differed from patients of group A because of smaller left ventricular volumes and stroke volume, indicating central underfilling. After TIPS insertion, portal decompression was associated with a significant increase of cardiac output (CO) and a decrease of peripheral resistances. The most important changes were recorded in patients of group B, who showed a significant increase of both the end-diastolic left ventricular volumes and the E/A ratio and a significant decrease of PRA. In conclusion, these results show that the hemodynamic effects of TIPS differ according to the pre-TIPS effective blood volume. Furthermore, TIPS improves the diastolic cardiac function of cirrhotic patients with effective hypovolemia. This result is likely due to a TIPS-related improvement of the fullness of central blood volume. [source] Prolonged antigen-exposure with carbohydrate particle based vaccination prevents allergic immune responses in sensitized miceALLERGY, Issue 6 2009S. Thunberg Background:, Defined particles carrying tightly bound allergens at high density have been suggested as alternatives in allergy vaccination. Carbohydrate based particles (CBP), sized 2 ,m, provide a platform for covalent coupling of allergens. Objective:, To investigate the mechanisms of antigen presentation by CBP, as well as cellular and humoral responses after vaccination with the major cat allergen Fel d 1, covalently coupled to CBP. Methods:, Mice (n = 10/group) were subcutaneously vaccinated with CBP-rFel d 1, CBP or phosphate buffer saline (PBS) before sensitization with rFel d 1 and challenged with cat dander extract. Fluorescent and 75Se-radiolabeled tracking of allergens and particles were performed with flow cytometry and whole-body autoradiography. Humoral, cellular and regulatory immune responses were analyzed by ELISA and flow cytometry. Cytokines were measured in bronchoalveolar lavage fluid and splenocyte cultures. Results:, CBP-rFel d 1 prevented induction of airway inflammation and induced allergen-specific T-cell anergy. CBP-rFel d 1 also induced rapid IgM and IgG1-responses compared with soluble rFel d 1. Particles were phagocytosed by antigen-presenting cells and transported to draining lymph nodes and spleen. Moreover, antigen coupled to CBP remained longer at the injection site compared with alum. Conclusions:, Covalent coupling of rFel d 1 to CBP induces rapid antibody production, prevents induction of allergic immune responses and systemic allergen spreading. Thus, CBP comprise several attractive adjuvant features for use in allergy vaccination. Clinical Implications:, Prolonged allergen exposure through covalent coupling to particles suitable for phagocytosis, provides an adjuvant for safer and efficient allergy vaccination. [source] Humoral and Cellular Immune Responses after Influenza Vaccination in Kidney Transplant RecipientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 10 2009S Candon It has been speculated that influenza vaccination of renal allograft recipients could be associated with de novo production and/or increased titers of anti-HLA antibodies (HLA-Ab). To directly address this issue, we recruited 66 stable renal transplant recipients and 19 healthy volunteers during the 2005,2006 vaccination campaign. At day 0 and day 30 following vaccination, HLA-Ab were screened and in parallel influenza-specific antibody and T-cell responses were assessed. Humoral postvaccinal responses to A/H1N1 and A/H3N2 strains, but not B strain, were less frequent in transplanted patients than in control subjects. Significant expansion of influenza-specific IFN-,-producing T cells was observed at similar frequencies in patients and controls. There was no correlation between cellular and humoral postvaccinal responses. No impact of sex, age or immunosuppressive regimen could be evidenced. Vaccination was not associated with any significant change in preexisting or de novo anti-HLA sensitization. No episode of allograft rejection was recorded in any of the patients. Our results suggest that flu vaccination is safe in stable renal transplanted patients. Larger studies are needed for definitive statistical proof of the safety and effectiveness, with regard to the quality of the immune response, of yearly influenza vaccination in immunosuppressed patients. [source] Proinflammatory role of the Th17 cytokine interleukin-22 in collagen-induced arthritis in C57BL/6 miceARTHRITIS & RHEUMATISM, Issue 2 2009Lies Geboes Objective To investigate the role of interleukin-22 (IL-22) in collagen-induced arthritis (CIA), an animal model of rheumatoid arthritis. Methods C57BL/6 mice were immunized with type II collagen (CII) in Freund's incomplete adjuvant with added Mycobacterium tuberculosis, and levels of IL-22 and its specific receptor, IL-22 receptor type I (IL-22RI), were measured in sera and tissue by enzyme-linked immunosorbent assay and real-time quantitative polymerase chain reaction analysis. Clinical and histologic signs of arthritis were recorded and compared with those in C57BL/6 mice deficient in the IL-22 gene (IL-22,/,). Humoral and cellular immune responses against CII were analyzed. In vitro osteoclastogenesis assays were performed on splenocytes. Results Upon immunization with CII in Freund's incomplete adjuvant plus heat-killed Mycobacterium tuberculosis, sera from C57BL/6 mice were found to contain high levels of IL-22, and the specific IL-22RI was expressed in lymphoid tissue, including splenocytes. IL-22,/, mice were less susceptible to CIA than were wild-type mice, as evidenced by their decreased incidence of arthritis and decreased pannus formation. Remarkably, the less severe form of arthritis in IL-22,/, mice was associated with increased production of CII-specific and total IgG antibodies, whereas cellular CII responses were unchanged. In vitro, IL-22 was found to promote osteoclastogenesis, a process that might contribute to its proinflammatory activity in CIA. Conclusion Endogenous IL-22 plays a proinflammatory role in CIA in C57BL/6 mice. Our data also indicate that IL-22 promotes osteoclastogenesis and regulates antibody production. [source] Binding and entry of respiratory syncytial virus into host cells and initiation of the innate immune responseCELLULAR MICROBIOLOGY, Issue 10 2003James Harris Summary Respiratory syncytial virus (RSV) is the most common cause of severe lower respiratory tract infection in infants and the elderly. There is currently no effective antiviral treatment for the infection, but advances in our understanding of RSV uptake, especially the role of surfactant proteins, the attachment protein G and the fusion protein F, as well as the post-binding events, have revealed potential targets for new therapies and vaccine development. RSV infection triggers an intense inflammatory response, mediated initially by the infected airway epithelial cells and antigen-presenting cells. Humoral and cell-mediated immune responses are important in controlling the extent of infection and promoting viral clearance. The initial innate immune response may play a critical role by influencing the subsequent adaptive response generated. This review summarizes our current understanding of RSV binding and uptake in mammalian cells and how these initial interactions influence the subsequent innate immune response generated. [source] Subacute sclerosing panencephalitis: an updateDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 10 2010JOSE GUTIERREZ Subacute sclerosing panencephalitis (SSPE) is a chronic encephalitis occurring after infection with measles virus. The prevalence of the disease varies depending on uptake of measles vaccination, with the virus disproportionally affecting regions with low vaccination rates. The physiopathology of the disease is not fully understood; however, there is evidence that it involves factors that favour humoral over cellular immune response against the virus. As a result, the virus is able to infect the neurons and to survive in a latent form for years. The clinical manifestations occur, on average, 6 years after measles virus infection. The onset of SSPE is insidious, and psychiatric manifestations are prominent. Subsequently, myoclonic seizures usually lead to a final stage of akinetic mutism. The diagnosis is clinical, supported by periodic complexes on electroencephalography, brain imaging suggestive of demyelination, and immunological evidence of measles infection. Management of the disease includes seizure control and avoidance of secondary complications associated with the progressive disability. Trials of treatment with interferon, ribavirin, and isoprinosine using different methodologies have reported beneficial results. However, the disease shows relentless progression; only 5% of individuals with SSPE undergo spontaneous remission, with the remaining 95% dying within 5 years of diagnosis. [source] Circulation in normal and inflamed dental pulpENDODONTIC TOPICS, Issue 1 2007ELLEN BERGGREEN In the pulp, arteries branch into a capillary network before they leave the pulp as venules through the apical foramina. The tissue has low compliance, as it is enclosed in dentin, and has a relatively high blood flow and blood volume. The interstitial fluid pressure (IFP) and colloid osmotic pressure are relatively high whereas the net driving blood pressure is low. The high pulsatile IFP is probably the major force for propelling lymph in the dental pulp. Vasodilation in neighboring tissue as well as arteriovenous (AV) shunts in the pulp itself can contribute to a fall in total and coronal pulpal blood flow, respectively. The pulp blood flow is under nervous, humoral, and local control. Inflammatory vascular responses, vasodilation, and increased vessel permeability induce an increase in IFP that can be followed by a temporarily impaired blood flow response. Lipopolysaccharides (LPS) from bacteria may cause endothelial activation in the pulp, leading to vasoconstriction and reduced vascular perfusion. Lymphatic vessels are identified with specific lymphatic markers in the pulp but so far, little is known about their function. Because of the special circulatory conditions in the pulp, there are several clinical implications that need to be considered in dental treatment. Received 13 February 2009; accepted 28 August 2009. [source] Persistence of vibrios in marine bivalves: the role of interactions with haemolymph componentsENVIRONMENTAL MICROBIOLOGY, Issue 6 2005Carla Pruzzo Summary Marine bivalves are widespread in coastal environments and, due to their filter-feeding habit, they can accumulate large numbers of bacteria thus acting as passive carriers of human pathogens. Bivalves possess both humoral and cellular defence mechanisms that operate in a co-ordinated way to kill and eliminate infecting bacteria. Vibrio species are very abundant in coastal waters and are commonly isolated from edible bivalves tissues where they can persist after depuration processes in controlled waters. Such observations indicate that vibrios are regular components of bivalve microflora and that the molluscs can represent an important ecological niche for these bacteria. Here we tried to summarize data on the interactions between vibrios and bivalve haemolymph; the available evidence supports the hypothesis that persistence of bacteria in bivalve tissues depends, at least in part, on their sensitivity to the bactericidal activity of the haemolymph. Results obtained with an in vitro model of Vibrio cholerae challenged against Mytilus galloprovincialis haemocytes indicate that bacterial surface components, soluble haemolymph factors and the signalling pathways of the haemocyte host are involved in determining the result of vibrio,haemolymph interactions. [source] Immunosuppression in the northern leopard frog (Rana pipiens) induced by pesticide exposureENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 1 2003Mary-Kate Gilbertson Abstract An injection study and a field study were used to investigate the hypothesis that environmental xenobiotics have the potential to alter the immune function of northern leopard frogs (Rana pipiens). Three assays, IgM-specific antibody response to keyhole limpet hemocyanin linked to dinitrophenyl (KLH-DNP), zymozan induced chemiluminescence (CL) of whole blood and the delayed-type hypersensitivity (DTH), were used to assay humoral, innate and cell-mediated immune endpoints. Sublethal doses of DDT (923 ng/g wet wt), malathion (990 ng/g wet wt), and dieldrin (50 ng/g wet wt) were used in the injection study. In all pesticide-injected groups, antibody response was dramatically suppressed, DTH reactions were enhanced, and respiratory burst was lower. When the order of administration of pesticides and antigens was reversed, no differences in immune function between the control and dosed groups were apparent, indicating that frogs exposed to pathogens prior to pesticide exposure can still respond. A field study found significant differences in immune function between frog populations in pesticide-exposed and pesticide-free locations. The antibody response and CL were suppressed and the DTH enhanced in frogs from Essex County (ON, Canada). Overall, the results suggest that exposure to these pesticides can cause both stimulatory and suppressive immune changes in adult frogs and is doing so in wild populations. [source] Immunopathogenesis of cholestatic autoimmune liver diseasesEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 1 2001J. Medina Primary biliary cirrhosis and primary sclerosing cholangitis are well recognized chronic cholestatic liver diseases that are considered to have an autoimmune basis. Recent progress in the study of autoimmune liver diseases has improved the recognition and characterization of these conditions. An important component of this progress has been the identification of liver disease-associated autoantibodies and their respective target antigens, and the development of specific assays for these autoantibodies. In addition, some nonhumoral immunological findings imply an involvement of specific immunopathogenic mechanisms in the development of these conditions. Furthermore, immunogenetic factors associated with increased susceptibility to some of these diseases have been identified. This article reviews the most relevant information relating to the postulated autoimmune pathogenesis of these diseases, with special emphasis on their associated humoral and cellular immunological abnormalities and immunopathogenetic factors. Some of the remaining important unresolved issues relating to the pathogenesis of these diseases, that need to be addressed in further research, are highlighted. [source] ALK-positive anaplastic large-cell lymphoma: strong T and B anti-tumour responses may cause hypocellular aspects of lymph nodes mimicking inflammatory lesionsEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 4 2003B. Borisch Abstract: The anaplastic large cell lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) is a rare type of non-Hodgkin lymphoma which occurs in children mostly. The ALK protein is highly immunogenic and elicits both humoral and cellular immune responses. A 15-yr-old child presented with fever and adenopathy and did not respond to antibiotics. Biopsy of the enlarged lymph node contained almost no lymphoid element except for a few CD8-positive T cells, plasma cells and isolated CD30-positive blasts. The patient's condition improved following lymphadenectomy but relapse occurred 3 months later with multiple nodes, high fever and an abdominal mass. This time an ALK-positive ALCL was diagnosed and the retrospective analysis of the initial biopsy revealed rare, isolated ALK+ cells. Molecular analysis showed T-cell clones and oligoclonal B cells in both biopsies and peripheral blood of the patient. The tumour cells harbour a t(2;5) translocation, revealing a null phenotype by immunohistochemistry and no evidence for T-cell clonality by Southern blotting. The patient's serum contained anti-ALK antibodies. Our findings suggest that the T-cell clones and anti-ALK antibodies in this patient constitute an anti-tumour response that caused the hypocellularity of the initial lymph node. Hypocellular and oedematous lymph nodes occurring in a child with evocative symptoms should be tested for the presence of ALK. [source] The antiapoptotic effects of blood constituents in patients with chronic lymphocytic leukemiaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5 2003Yonit Bomstein Abstract: Objective: Clonal B-lymphocytes of chronic lymphocytic leukemia (B-CLL) are characterized by decreased sensitivity to programmed cell death and, therefore, they accumulate in vivo. However, these malignant cells die rapidly in vitro. In the current study we concentrated on the contribution of autologous serum (AS) and lymphocyte subsets to the survival of the malignant cells in vitro. Methods: Mononuclear cells from the peripheral blood of 26 CLL patients and 24 controls were incubated overnight in the presence or absence of AS and heat-inactivated AS (HI-AS) or fetal calf serum (FCS). Also, isolated B cells were incubated at different concentrations in the presence of AS and/or isolated T cells. The level of apoptosis of CD19+ cells was measured by flow cytometry. Results: Spontaneous apoptosis of unfractionated B-CLL cells incubated with AS, FCS or without serum was significantly lower than the rate of B-cell death in the control group, in similar culture conditions. AS had an antiapoptotic effect on unfractionated B-CLL cells when compared with FCS. The rate of apoptosis of B-CLL cells was directly associated with stage. HI of AS had a variable effect, which was related to the stage of the disease. High concentrations of B cells and the addition of autologous T cells reduced the rate of apoptosis when incubated without serum. The antiapoptotic effect of T cells was most prominent in progressive stages. Conclusions: B-CLL cells exhibit decreased spontaneous apoptosis, which is partially prevented by humoral (AS) and cellular (T cells and B-CLL cells) factors. The equilibrium between apoptotic and antiapoptotic factors changes with disease progression. [source] Targeting of LcrV virulence protein from Yersinia pestis to dendritic cells protects mice against pneumonic plagueEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 10 2010Yoonkyung Do Abstract To help design needed new vaccines for pneumonic plague, we targeted the Yersinia pestis LcrV protein directly to CD8,+ DEC-205+ or CD8,, DCIR2+ DC along with a clinically feasible adjuvant, poly IC. By studying Y. pestis in mice, we could evaluate the capacity of this targeting approach to protect against a human pathogen. The DEC-targeted LcrV induced polarized Th1 immunity, whereas DCIR2-targeted LcrV induced fewer CD4+ T cells secreting IFN-,, but higher IL-4, IL-5, IL-10, and IL-13 production. DCIR-2 targeting elicited higher anti-LcrV Ab titers than DEC targeting, which were comparable to a protein vaccine given in alhydrogel adjuvant, but the latter did not induce detectable T-cell immunity. When DEC- and DCIR2-targeted and F1-V+ alhydrogel-vaccinated mice were challenged 6,wk after vaccination with the virulent CO92 Y. pestis, the protection level and Ab titers induced by DCIR2 targeting were similar to those induced by F1-V protein with alhydrogel vaccination. Therefore, LcrV targeting to DC elicits combined humoral and cellular immunity, and for the first time with this approach, also induces protection in a mouse model for a human pathogen. [source] Mediastinal lymph node CD8,, DC initiate antigen presentation following intranasal coadministration of ,-GalCerEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 8 2007Sung-Youl Ko Abstract Our previous study revealed that ,-galactosylceramide (,-GalCer) is a potent nasal vaccine adjuvant inducing both potent humoral and cellular immune responses and affording complete protection against viral infections and tumors. However, the antigen-presenting cells (APC) that are activated by NKT cells and thereby initiate the immune responses following intranasal coadministration of protein antigen and ,-GalCer are poorly understood. We assessed here where antigen presentation occurs and which APC subset mediates the early stages of immune responses when protein antigen and ,-GalCer are intranasally administered. We show that dendritic cells (DC), but not B cells, initiated the mucosal immune responses at mediastinal lymph nodes. Of the DC subsets, the CD8,,B220,CD11c+ DC subset played the most prominent role in the direct and cross-presentation of protein antigen to naive T cells and in triggering the naive T cells to differentiate into effector T cells. This might be mainly caused by a relatively larger population of CD1dhigh cells of CD8,,B220,CD11c+ DC subset than those of other DC subsets. These results indicate that CD8,,B220,CD11c+ DC is the principal subset becoming immunogenic after interaction with NKT cells and abrogating tolerance to intranasally administered protein antigen when ,-GalCer is coadministered as a nasal vaccine adjuvant. [source] Dissecting cytotoxic T,cell responses towards the NY-ESO-1 protein by peptide/MHC-specific antibody fragmentsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 10 2004Gerhard Held Abstract NY-ESO-1 is a germ cell antigen aberrantly expressed by different tumor types that elicits strong humoral and cellular immune responses, representing one of the most promising candidates for vaccination of cancer patients. A detailed analysis of CD8+ T,cells generated in vaccine trials using NY-ESO-1-derived peptides (157,165 and 157,167) revealed that the dominant immune response was directed against a cryptic epitope (159,167) diverting the immune response from tumor recognition. Only CTL reactivity to the NY-ESO-1157,165 peptide appeared to be capable of lysing NY-ESO-1/HLA-A0201-expressing tumor cells. To study the process of NY-ESO-1 peptide presentation by tumor cells in more detail we generated a high-affinity (KD=60,nM) antibody fragment that specifically recognizes the NY-ESO-1157,165 peptide/HLA-A0201 complex. Peptide variants such as the NY-ESO-1157,167 peptide or the cryptic NY-ESO-1159,167 peptide were not recognized. The antibody fragment blocked in a dose-dependent fashion the recognition of NY-ESO-1/HLA-A2-positive tumor cells by NY-ESO-1157,165 peptide-specific CD8+ T,cells. This antibody fragment is a novel reagent that binds with TCR-like specificity to the NY-ESO-1157,165/HLA-A2 complex thus distinguishing between CTL responses against immunological meaningful or cryptic NY-ESO-1-derived peptides. It may therefore become a useful monitoring tool for the development of NY-ESO-1-based cancer vaccines. [source] Bet,v,1, the major birch pollen allergen, initiates sensitization to Api,g,1, the major allergen in celery: evidence at the T,cell levelEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 12 2003Barbara Bohle Abstract Due to IgE cross-reactivity, birch pollen-allergic individuals frequently develop type,I hypersensitivity reactions to celery tuber. We evaluated the T,cell response to the major allergen in celeriac, Api,g,1, and the cellular cross-reactivity with its homologous major allergen in birch pollen, Bet,v,1. Api,g,1-specific T,cell lines (TCL) and clones (TCC) were established from peripheralblood mononuclear cells of allergic patients. Epitope mapping of Api,g,1 with overlapping Api,g,1-derived peptides revealed one dominant T,cell-activating region, Api,g,1109,126. TCL and TCC generated with Api,g,1 cross-reacted with the birch pollen allergen and, although initially stimulated with the food allergen, cellular responses to Bet,v,1 were stronger than to Api,g,1. Epitopemapping with Bet,v,1-derived peptides revealed that T,cells specific for several distinct epitopes distributed over the complete Bet,v,1 molecule could be activated by Api,g,1. Bet,v,1109,126 was identified as the most important T,cell epitope for cross-reactivity with Api,g,1. This epitope shares 72% amino acid sequence similarity with the major T,cell-activating region of the food allergen, Api,g,1109,126. Our data provide evidence that humoral as well as cellular reactivity to the major celery allergen is predominantly based on cross-reactivity with the major birch pollen allergen. The activation of Bet,v,1-specific Th2 cells by Api,g,1, in particular outside the pollen season, may have consequences for birch pollen-allergic individuals. [source] Efficient mucosal delivery of the HIV-1 Tat protein using the synthetic lipopeptide MALP-2 as adjuvantEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 6 2003Stefan Borsutzky Abstract A major requirement for HIV/AIDS research is the development of a mucosal vaccine that stimulates humoral and cell-mediated immune responses at systemic and mucosal levels, thereby blocking virus replication at the entry port. Thus, a vaccine prototype based on biologically active HIV-1 Tat protein as antigen and the synthetic lipopeptide, macrophage-activating lipopeptide-2 (MALP-2), asa mucosal adjuvant was developed. Intranasal administration to mice stimulated systemic and mucosal anti-Tat antibody responses, and Tat-specific T cell responses, that were more efficient than those observed after i.p. immunization with Tat plus incomplete Freund's adjuvant. Major linear B cell epitopes mapped within aa 1,20 and 46,60, whereas T cell epitopes were identified within aa 36,50 and 56,70. These epitopes have also been described in vaccinated primates and in HIV-1-infected individuals with better prognosis. Analysis of the anti-Tat IgG isotypes in serum, and the cytokine profile of spleen cells indicated that a dominant Th1 helper response was stimulated by Tat plus MALP-2, as opposed to the Th2 response observed with Tat plus incomplete Freund's adjuvant. Tat-specific IFN-,-producing cells were significantly increased only in response to Tat plus MALP-2. These data suggest that Malp-2 may represent an optimal mucosal adjuvant for candidate HIV vaccines based on Tat alone or in combination with other HIV antigens. [source] A review on the interactions between gut microbiota and innate immunity of fishFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 2 2008Geovanny D. Gómez Abstract Although fish immunology has progressed in the last few years, the contribution of the normal endogenous microbiota to the overall health status has been so far underestimated. In this context, the establishment of a normal or protective microbiota constitutes a key component to maintain good health, through competitive exclusion mechanisms, and has implications for the development and maturation of the immune system. The normal microbiota influences the innate immune system, which is of vital importance for the disease resistance of fish and is divided into physical barriers, humoral and cellular components. Innate humoral parameters include antimicrobial peptides, lysozyme, complement components, transferrin, pentraxins, lectins, antiproteases and natural antibodies, whereas nonspecific cytotoxic cells and phagocytes (monocytes/macrophages and neutrophils) constitute innate cellular immune effectors. Cytokines are an integral component of the adaptive and innate immune response, particularly IL-1,, interferon, tumor necrosis factor-,, transforming growth factor-, and several chemokines regulate innate immunity. This review covers the innate immune mechanisms of protection against pathogens, in relation with the installation and composition of the normal endogenous microbiota in fish and its role on health. Knowledge of such interaction may offer novel and useful means designing adequate therapeutic strategies for disease prevention and treatment. [source] Toxicity to Candida albicans mediated by human serum and peripheral blood mononuclear cellsFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 3 2006Joseph M. Bliss Abstract This study evaluates the conditions in which peripheral blood mononuclear cells mediate toxicity to Candida albicans opsonized with heat-inactivated human serum. Serum concentrations as low as 1% resulted in 50% inhibition of C. albicans metabolic activity after incubation with peripheral blood mononuclear cells at an effector to target ratio of 8. Measurable inhibition was also achieved at lower effector to target ratios and lower serum concentrations, and at least a portion of the metabolic inhibition reflected fungal cell death. Depletion of C. albicans -specific antibody decreased the toxic effect while opsonization with purified human IgG restored toxicity, and cell,cell contact between peripheral blood mononuclear cells and fungus was required. Depletion of or enrichment for monocytes from the peripheral blood mononuclear cells preparation diminished the toxic effect and the monocytic cell line, THP-1, was likewise incapable of toxicity. These studies provide evidence that antibody augments antifungal host defense and underscore the complex interrelationship between humoral and cellular immunity in these infections. [source] Testosterone and innate immune function inversely covary in a wild population of breeding Dark-Eyed Juncos (Junco hyemalis)FUNCTIONAL ECOLOGY, Issue 5 2006T. J. GREIVES Summary 1Innate immunity refers to the non-specific components of the primary immune response, which act broadly to destroy pathogens. Effective innate immune responses may save an individual the energetic costs associated with activating subsequent specific immune responses. 2Testosterone can suppress immune function in vitro and in vivo. Most studies examining testosterone's effects on immunity have focused on experimentally elevated testosterone and acquired immune responses (e.g. humoral and cell-mediated responses to foreign antigens). Few studies have investigated the relationship between endogenous levels of testosterone and innate immunity. 3In a wild breeding population of Dark-Eyed Juncos (Junco hyemalis Linnaeus), we asked whether endogenous levels of testosterone measured at several points during the breeding season covaried with two components of innate immunity: total levels of non-specific immunoglobulin-G (IgG), and complement levels. 4Testosterone levels were significantly negatively correlated with both total IgG and complement activity. Both immune measures were also positively correlated with body mass. Taken together with experimental results from the same species, these results suggest that elevated testosterone levels may compromise innate as well as acquired immune function. [source] Tamo selectively modulates nuclear import in DrosophilaGENES TO CELLS, Issue 4 2003Svetlana Minakhina Background: The NF-,B/Rel pathway functions in the establishment of dorsal-ventral polarity and in the innate humoral and cellular immune response in Drosophila. An important aspect of all NF-,B/Rel pathways is the translocation of the Rel proteins from the cytoplasm to the nucleus, where they function as transcription factors. Results: We have identified a new protein, Tamo, which binds to Drosophila Rel protein Dorsal, but not to Dorsal lacking the nuclear localization sequence. Tamo does not bind to the other Drosophila Rel proteins, Dif and Relish. The Tamo-Dorsal complex forms in the cytoplasm and Tamo also interacts with a cytoplasmically orientated nucleoporin. In addition Tamo binds the Ras family small GTPase, Ran. Tamo functions during oogenesis and, based on phenotypic analysis, controls the levels of nuclear Dorsal in early embryos. It further regulates the accumulation of Dorsal in the nucleus after immune challenge. Conclusions:Tamo has an essential function during oogenesis. Tamo interacts with Dorsal and proteins that are part of the nuclear import machinery. We propose that tamo modulates the levels of import of Dorsal and other proteins. [source] Circulating T-Cell Response to Helicobacter pylori Infection in Chronic GastritisHELICOBACTER, Issue 3 2000Zhigang Ren Background.Helicobacter pylori elicits a specific humoral and cellular immune response. There is increasing evidence that the type of T-cell response contributes to clinical outcome in H. pylori infection. Materials and Methods. The host response to H. pylori infection in 34 subjects with chronic gastritis was examined in terms of T-cell proliferation and cytokine production in whole-blood cultures stimulated or unstimulated with H. pylori acid-glycine extract antigens (AGE). Results. The proliferative response in whole-blood cultures was similar for both H. pylori,positive and ,negative subjects stimulated with H. pylori AGE. While an increase in interferon-, (IFN-,) production was observed from both H. pylori,positive and ,negative subjects with gastritis, significantly higher levels of IFN-, were detected in the former when stimulated with H. pylori AGE. In contrast, interleukin 4 (IL-4) was undetectable regardless of antigen stimulation. However, if an in situ IL-4 antibody capture assay was used, antigen-independent production of IL-4 was detected, but there was no difference between H. pylori,positive and ,negative subjects with gastritis. After eradication of H. pylori, antigen-induced production of IL-4 was increased, with no decrease in the levels of secretion of IFN-,. IL-4 production was dependent on CD4+ T cells, as addition of anti-CD4 but not anti-CD8 mouse monoclonal antibody or matched IgG isotype to the whole-blood culture inhibited the production of IL-4. Conclusion. The results suggest that a shift toward a balanced Th1-Th2 response due to an increase in antigen-induced IL-4 production from CD4+ T cells follows eradication. We suggest that the downregulation of mucosal inflammation consequent on reduction in antigen levels or removal of downregulation after eradication of H. pylori contributes to this shift in cytokine balance. [source] Hepatitis B virus precore protein augments genetic immunizations of the truncated hepatitis C virus core in BALB/c mice,HEPATOLOGY, Issue 1 2008Guoyang Liao DNA immunization has been used to induce either humoral or cellular immune responses against many antigens, including hepatitis C virus (HCV). In addition, DNA immunizations can be enhanced or modulated at the nucleotide level. Genetic immunizations were examined in BALB/c mice through the use of plasmids and chimeric DNA constructs encoding HCV core proteins and hepatitis B virus (HBV) precore (preC) regions. Plasmids encoding the truncated HCV core induced potent humoral and cellular responses to HCV; pcDNA3.0A-C154 produced a stronger antibody response than pcDNA3.0A-C191 (P < 0.01) and pcDNA3.0A-C69 (P < 0.05). HBV preC enhanced the humoral and cellular immune responses of BALB/c mice to HCV; however, pcDNA3.0A-C69preC resulted in a weak cytotoxic T lymphocyte (CTL) response. In addition, the humoral and cellular immune responses to HCV of groups immunized with pcDNA3.0A-C154preC and pcDNA3.0A-C191preC plasmids were higher than those of groups immunized with pcDNA3.0A-C154 and pcDNA3.0A-C191. In vivo CTL responses verified that mice immunized with preC core fused DNAs showed significantly high specific lysis compared with mice immunized with HCV cores only (P < 0.01). In our study, pcDNA3.0A-C154preC led to the highest immune response among all DNA constructs. Conclusion: DNA that encodes truncated HCV core proteins may lead to increased immune responses in vivo, and these responses may be enhanced by HBV preC. (HEPATOLOGY 2007.) [source] Modulating tone: the overture of S1P receptor immunotherapeuticsIMMUNOLOGICAL REVIEWS, Issue 1 2008Hugh Rosen Summary: Modulation of complex functions within the immune system has proven to be surprisingly sensitive to alterations in the lysophospholipid sphingosine 1-phosphate (S1P) receptor-ligand rheostat. This has become increasingly evident from both chemical and genetic manipulation of the S1P system, with pharmacological effects upon lymphoid cells, dendritic cell function, as well as vascular interfaces. The integrated immune system, perhaps as a result of its relatively recent evolutionary ontogeny, has selected for a number of critical control points regulated by five distinct high affinity G-protein-coupled receptor subtypes with a shared ligand, with receptors distributed on lymphocytes, dendritic cells, and endothelium. All of these cellular components of the axis are capable of modulating immune responses in vivo, with the impact on the immune response being very different from classical immunosuppressants, by virtue of selective spatial and temporal sparing of humoral and myeloid elements of host defense. Pharmacological subversion of the S1P rheostat is proving to be clinically efficacious in multiple sclerosis, and both the scope and limitations of therapeutic modulation of the S1P axis in immunotherapy are becoming clearer as understanding of the integrated chemical physiology of the S1P system emerges. [source] Understanding the mechanisms and limitations of immune control of HIVIMMUNOLOGICAL REVIEWS, Issue 1 2007Miles P. Davenport Summary:, A large number of experimental studies have been performed over the past decade in an attempt to develop a vaccine for human immunodeficiency virus (HIV). These studies have used a variety of approaches aimed at stimulating both antibody-mediated and cell-mediated immunity. Many of these experiments have been performed in macaque models of HIV. Analysis and modeling of the results of these studies provide the opportunity to investigate the mechanisms and limitations of viral control by humoral and cell-mediated immunity. These studies suggest that CD8+ T cells do ,too little too late' to prevent the establishment of viral infection and latency. By contrast, passively administered antibody acts extremely early to reduce the initial inoculum and slow viral growth. In both cases, reduction in peak viral load appears crucial to the maintenance of CD4+ T cells in acute infection and for effective long-term viral control. The insights gained from studies of simian human immunodeficiency virus infection have important implications for HIV vaccination. However, important questions remain as to whether differences in pathogenesis in HIV will lead to different ,rules of engagement' for immune control of virus. [source] Multiple myeloma biology: lessons from the 5TMM modelsIMMUNOLOGICAL REVIEWS, Issue 1 2003Karin Vanderkerken Summary:, Multiple myeloma (MM) is a B cell neoplasm characterized by the monoclonal proliferation of plasma cells in the bone marrow, the development of osteolytic lesions and the induction of angiogenesis. These different processes require three-dimensional interactions, with both humoral and cellular contacts. The 5TMM models are suitable models to study these interactions. These murine models originate from spontaneously developed myeloma in elderly mice, which are propagated by in vivo transfer of the myeloma cells into young syngeneic mice. In this review we report on studies performed in the 5TMM models with special emphasis on the homing of the myeloma cells, the characterization of the migrating and proliferating clone and the identification of the isotype switch variants. The bone marrow microenvironment was further targeted with osteoprotegerin (OPG) to block the RANK/RANKL/OPG system and with potent bisphosphonates. Both treatments resulted in a significant protection against myeloma-associated bone disease, and they decreased myeloma disease, as evidenced by a lower tumor load and an increased survival of the mice. These different studies demonstrate the strength of these models, not only in unraveling basic biological processes but also in the testing of potentially new therapeutic targets. [source] Effect of mucosal and systemic immunization with virus-like particles of severe acute respiratory syndrome coronavirus in miceIMMUNOLOGY, Issue 2 2010Baojing Lu Summary Nasal administration has emerged as a promising and attractive route for vaccination, especially for the prophylaxis of respiratory diseases. Our previous studies have shown that severe acute respiratory syndrome coronavirus (SARS-CoV) virus-like particles (VLPs) can be assembled using a recombinant baculovirus (rBV) expression system and such VLPs induce specific humoral and cellular immune responses in mice after subcutaneous injection. Here, we investigated mucosal immune responses to SARS-CoV VLPs in a mouse model. Mice were immunized in parallel, intraperitoneally or intranasally, with VLPs alone or with VLPs plus cytosine,phosphate,guanosine (CpG). Immune responses, including the production of SARS-CoV-specific serum immunoglobulin G (IgG) and secretory immunoglobulin A (sIgA), were determined in mucosal secretions and tissues. Both immunizations induced SARS-CoV-specific IgG, although the levels of IgG in groups immunized via the intraperitoneal (i.p.) route were higher. sIgA was detected in saliva in groups immunized intranasally but not in groups immunized intraperitoneally. CpG had an adjuvant effect on IgA production in genital tract washes when administered intranasally but only affected IgA production in faeces samples when administered intraperitoneally. In addition, IgA was also detected in mucosal tissues from the lung and intestine, while CpG induced an increased level of IgA in the intestine. Most importantly, neutralization antibodies were detected in sera after i.p. and intranasal (i.n.) immunizations. Secretions in genital tract washes from the i.n. group also showed neutralization activity. Furthermore, VLPs that were administered intraperitoneally elicited cellular immune responses as demonstrated by enzyme-linked immunospot (ELISPOT) assay analyses. In summary, our study indicates that mucosal immunization with rBV SARS-CoV VLPs represent an effective means for eliciting protective systemic and mucosal immune responses against SARS-CoV, providing important information for vaccine design. [source] Interleukin-21 is a T-helper cytokine that regulates humoral immunity and cell-mediated anti-tumour responsesIMMUNOLOGY, Issue 2 2004Pallavur V. Sivakumar Summary Cytokines and their receptors represent key targets for therapeutic intervention. Ligands are being used to supplement cell numbers that become depleted as a result of disease (organ failure, infection) or subsequent disease treatments (i.e. chemotherapy). Conversely, the inhibition of target cell binding by cytokines is an established strategy for abrogating pathologic cellular activities common to many immunological diseases. Considerable effort in biomedical research is being focused on the cytokine families that play a dominant role in regulating immunity and then prioritizing each member for its therapeutic potential. Currently, the interleukin-2 (IL-2) family of cytokines is widely recognized for its central involvement in controlling lymphocyte function and is the most explored for medical utility. Collectively, these proteins (or their antagonists) are either marketed drugs or have received advanced testing for an impressive array of indications including cancer, infectious disease, transplantation, inflammation and allergic asthma. Here we review the current understanding of IL-21, the most recent member of this cytokine family to be discovered. As will be discussed, IL-21 shares many of the same attributes as its relatives in that it has broad immunoregulatory activity and can modulate both humoral and cell-mediated responses. Its ability to stimulate durable anti-tumour responses in mice defines one therapeutic indication that merits clinical development. [source] The haemopoietic growth factor, Flt3L, alters the immune response induced by transcutaneous immunizationIMMUNOLOGY, Issue 1 2002Maria E. Baca-Estrada Summary Topical application of antigen induces antigen-specific humoral and cellular immune responses. In this study we examined whether expansion of dendritic cells (DC) by Flt3 ligand (Flt3L) treatment influences the induction of immune responses following transcutaneous immunization. Mice were treated intraperitoneally with Flt3L or phosphate-buffered saline (PBS) and immunized transcutaneously with hen egg lysozyme (HEL). Flt3L-treated mice developed lower HEL-specific cellular and humoral immune responses than PBS-treated mice. However, in the presence of cholera toxin (CT), a potent adjuvant for mucosal and transcutaneous immunization, Flt3L-treated mice developed significantly higher cellular and humoral immune responses to HEL when compared to PBS-treated mice. We assessed whether the immunomodulatory effects of CT were a result of activation of epidermal dendritic cells (Langerhans' cells; LC). Our results indicate that within 8,12 hr of topical application of CT, epidermal LC cells lose their dendritic morphology and become rounder in appearance. In addition, we observed enhanced expression of major histocompatibility complex (MHC) class II, and of adhesion molecules CD11c and intracellular adhesion molecule-1 (ICAM-1). Our observations support the concept that the state of activation of DC in the skin is central to the regulation of immune responses. This information is relevant to the design of effective transcutaneous vaccination strategies. [source] Mechanism and therapeutic potential of DNA-based immunization against the envelope proteins of hepatitis B virus in normal and transgenic miceIMMUNOLOGY, Issue 1 2001Yuichiro Oka Summary Two plasmid DNA vectors, pCAGGS(S) encoding the genes of the major envelope protein of hepatitis B virus (HBV), and pCAGGS(S + preS2) encoding the genes of the middle envelope protein were used to study the mechanism and therapeutic potential of DNA-based immunization. Injection of these plasmids into the regenerating bilateral tibialis anterior muscle (TA) of normal C57BL/6 mice induced hepatitis B surface antigen (HBsAg)-specific humoral and cellular immune responses. Seventy-two hours after injection of pCAGGS(S), infiltrating cells including antigen-presenting dendritic cells (DC) were localized around the injection site and HBsAg was expressed by both muscle cells and infiltrating cells. Spleen DC from the mice were exposed to HBsAg for up to 32 weeks after a single injection of pCAGGS(S), because these DC induced the proliferation of HBsAg-specific memory lymphocytes in culture without exogenous HBsAg. A single injection of pCAGGS(S) or pCAGGS(S + preS2) resulted in the clearance of HBsAg in 28 out of 30 HBV-transgenic (Tg) mice. In contrast, more than 7 monthly injections of an HBsAg-based vaccine were required for the clearance of HBsAg in 6 out of 29 HBV-Tg mice. Infiltrating DC at the DNA vaccine injection site may have a role in initiating HBsAg-specific immune response, whereas the persistence of HBsAg exposed spleen DC may contribute to long-lasting immunity. This study also suggested that DNA-based vaccines may be a potent tool for treating chronic HBV carriers. [source] | ||||||||||||||||||||||||||||||||||