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Soluble Antigens (soluble + antigen)
Selected AbstractsSolutes, but not cells, drain from the brain parenchyma along basement membranes of capillaries and arteries: significance for cerebral amyloid angiopathy and neuroimmunologyNEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 2 2008R. O. Carare Elimination of interstitial fluid and solutes plays a role in homeostasis in the brain, but the pathways are unclear. Previous work suggests that interstitial fluid drains along the walls of arteries. Aims: to define the pathways within the walls of capillaries and arteries for drainage of fluid and solutes out of the brain. Methods: Fluorescent soluble tracers, dextran (3 kDa) and ovalbumin (40 kDa), and particulate fluospheres (0.02 ,m and 1.0 ,m in diameter) were injected into the corpus striatum of mice. Brains were examined from 5 min to 7 days by immunocytochemistry and confocal microscopy. Results: soluble tracers initially spread diffusely through brain parenchyma and then drain out of the brain along basement membranes of capillaries and arteries. Some tracer is taken up by vascular smooth muscle cells and by perivascular macrophages. No perivascular drainage was observed when dextran was injected into mouse brains following cardiac arrest. Fluospheres expand perivascular spaces between vessel walls and surrounding brain, are ingested by perivascular macrophages but do not appear to leave the brain even following an inflammatory challenge with lipopolysaccharide or kainate. Conclusions: capillary and artery basement membranes act as ,lymphatics of the brain' for drainage of fluid and solutes; such drainage appears to require continued cardiac output as it ceases following cardiac arrest. This drainage pathway does not permit migration of cells from brain parenchyma to the periphery. Amyloid-, is deposited in basement membrane drainage pathways in cerebral amyloid angiopathy, and may impede elimination of amyloid-, and interstitial fluid from the brain in Alzheimer's disease. Soluble antigens, but not cells, drain from the brain by perivascular pathways. This atypical pattern of drainage may contribute to partial immune privilege of the brain and play a role in neuroimmunological diseases such as multiple sclerosis. [source] Availability of autoantigenic epitopes controls phenotype, severity, and penetrance in TCR Tg autoimmune gastritisEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 12 2008Ditza Levin Abstract We examined TCR:MHC/peptide interactions and in vivo epitope availability to explore the Th1- or Th2-like phenotype of autoimmune disease in two TCR Tg mouse models of autoimmune gastritis (AIG). The TCR of strains A23 and A51 recognize distinct IAd -restricted peptides from the gastric parietal cell H/K-ATPase. Both peptides form extremely stable MHC/peptide (MHC/p) complexes. All A23 animals develop a Th1-like aggressive, inflammatory AIG early in life, while A51 mice develop indolent Th2-like AIG at 6,8,wk with incomplete penetrance. A51 T cells were more sensitive than A23 to low doses of soluble antigen and to MHC/p complexes. Staining with IAd/peptide tetramers was only detectable on previously activated T cells from A51. Thus, despite inducing a milder AIG, the A51 TCR displays a higher avidity for its cognate IAd/peptide. Nonetheless, in vivo proliferation of adoptively transferred A51 CFSE-labeled T cells in the gastric lymph node was relatively poor compared with A23 T cells. Also, DC from WT gastric lymph node, presenting processed antigen available in vivo, stimulated proliferation of A23 T cells better than A51. Thus, the autoimmune potential of these TCR in their respective Tg lines is strongly influenced by the availability of the peptide epitope, rather than by differential avidity for their respective MHC/p complexes. [source] Intraocular injection of tamoxifen-loaded nanoparticles: a new treatment of experimental autoimmune uveoretinitisEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 12 2004Yvonne de Kozak Abstract In this study, we tested the efficiency of an intravitreal injection of tamoxifen, a non-steroidal estrogen receptor modulator, in retinal soluble antigen (S-Ag)-induced experimental autoimmune uveoretinitis (EAU). To increase the bioavailability of tamoxifen, we incorporated tamoxifen into polyethylene glycol (PEG)-coated nanoparticles (NP-PEG-TAM). The localization of the nanoparticles within the eye was investigated using fluorescent-labeled PEG-coated nanoparticles after injection into the vitreous cavity of rats with EAU. Some nanoparticles were distributed extracellularly throughout the ocular tissues, others were concentrated in resident ocular cells and in infiltrating macrophages. Whereas the injection of free tamoxifen did not alter the course of EAU, injection of NP-PEG-TAM performed 1,2,days before the expected onset of the disease in controls resulted in significant inhibition of EAU. NP-PEG-TAM injection significantly reduced EAU compared to injection of NP-PEG-TAM with 17,-estradiol (E2), suggesting that tamoxifen is acting as a partial antagonist to E2. Diminished infiltration by MHC class,II+ inflammatory cells and low expression of TNF-,, IL-1,, and RANTES mRNA were noted in eyes of NP-PEG-TAM-treated rats. Intravitreal injection of NP-PEG-TAM decreased S-Ag lymphocyte proliferation, IFN-, production by inguinal lymph node cells, and specific delayed-type hypersensitivity indicative of a reduced Th1-type response. It increased the anti-S-Ag IgG1 isotype indicating an antibody class switch to Th2 response. These data suggest that NP-PEG-TAM inhibition of EAU could result from a form of immune deviation. Tamoxifen-loaded nanoparticles may represent a new option for the treatment of experimental uveitis. [source] A potent adjuvant effect of CD40 antibody attached to antigenIMMUNOLOGY, Issue 1 2003Tom A. Barr Summary There is great potential for novel vaccines based on recombinant proteins and synthetic peptides. Unfortunately these antigens often lack the immunogenicity of whole, killed pathogens used in traditional vaccines. Thus there is strong interest in the identification of immunological adjuvants with low reactogenicity, but high potency, to enhance immune responses and realize the potential of these new vaccine strategies. CD40 antibodies have been shown to have adjuvant effects when administered at very high doses. These large doses are impractical and induce a cascade of cytokine release giving rise to septic shock-like symptoms, as well as splenomegaly and polyclonal antibody production. We show here that a very small amount of CD40 antibody can exhibit potent adjuvant effects when attached to soluble antigen. The lack of detectable systemic effects indicates that this method may be a powerful and practical means of enhancing the efficacy of recombinant vaccines. [source] CpG-containing ODN has a limited role in the protection against Toxoplasma gondiiPARASITE IMMUNOLOGY, Issue 2 2004R. Saavedra SUMMARY Bacterial DNA containing immunostimulatory motifs (CpG) induces the development of a TH1 immune response. Since protection against Toxoplasma gondii is correlated with this type of response, the aim of this work was to determine if a synthetic oligodeoxynucleotide (ODN) containing CpG sequences could be useful as adjuvant for the induction of a long-lasting protective immune response against T. gondii. BALB/c mice immunized with a total soluble antigen of T. gondii (TSA2) mixed with ODN-containing CpG sequences developed a typical TH1 response, as determined by antibody isotypes and interferon-, (IFN-,) and interleukin-4 (IL-4) production by spleen cells. However, they did not resist a challenge with the virulent RH strain of the parasite. Absence of protection paralleled with lower levels of IFN-,, when compared with mice vaccinated with the live tachyzoites of the attenuated ts.4 strain of the parasite, which resisted this challenge. Intraperitoneal injection of ODN alone to mice induced a high degree of resistance to a lethal challenge inoculated by the same route. Nevertheless, this nonspecific protection was transient. Thus, the use of ODN containing CpG motifs as adjuvant is of limited value for the induction of a protective immune response against T. gondii. [source] Mycobacterial Hsp65-IgG,expressing tolerogenic B cells confer protection against adjuvant-induced arthritis in Lewis ratsARTHRITIS & RHEUMATISM, Issue 5 2007Shailesh R. Satpute Objective Tolerization of T cells directed against a target autoantigen is a desired goal of experimental approaches for the treatment of autoimmune diseases, and novel and improved methods of tolerance induction are continuously being sought. Because most traditional methods of tolerance induction using soluble antigen are effective in the prevention of autoimmunity but fail to control established disease, this study was carried out to explore an innovative tolerogenic approach for the treatment of ongoing disease, using the rat adjuvant-induced arthritis (AIA) model of human rheumatoid arthritis. Methods Lewis (RT.1l) rats were injected subcutaneously with heat-killed Mycobacterium tuberculosis H37Ra to induce AIA. Before or after AIA induction, Lewis rats were treated intraperitoneally (IP) with tolerogenic B cells expressing a fusion construct of mycobacterial 65-kd heat-shock protein (Hsp65) and IgG heavy-chain. For comparison, control rats were treated IP with ovalbumin (OVA),IgG,expressing B cells or soluble mycobacterial Hsp65, and the effects on AIA were observed. We also tested the immune response to mycobacterial Hsp65 in B cell,tolerized rats. Results Administration of tolerogenic mycobacterial Hsp65,expressing B cells as well as soluble mycobacterial Hsp65, but not OVA-expressing B cells, resulted in a significant decrease in the severity of subsequent AIA. However, in rats with established disease, only the B cell regimen of mycobacterial Hsp65, but not the soluble antigen, suppressed ongoing AIA. Conclusion Mycobacterial Hsp65-IgG,expressing B cells can successfully attenuate the progression of AIA. This study introduces a promising approach for the treatment of arthritis that should be further explored. [source] Mechanism of T cell tolerance induction by murine hepatic Kupffer cells,HEPATOLOGY, Issue 3 2008Qiang You The liver is known to favor the induction of immunological tolerance rather than immunity. Although Kupffer cells (KC) have been indicated to play a role in liver tolerance to allografts and soluble antigens, the mechanisms involved remain unclear. We hypothesized that KCs could promote immune tolerance by acting as incompetent antigen-presenting cells (APC), as well as actively suppressing T cell activation induced by other potent APCs. The expression of antigen presentation-related molecules by KCs was phenotyped by flow cytometry. The abilities of KCs to act as APCs and to suppress T cell activation induced by splenic dendritic cells (DC) were examined by in vitro proliferation assays using CD4+ OVA-TCR (ovalbumin T cell receptor) transgenic T cells. We found that, compared with DCs, KCs expressed significantly lower levels of major histocompatibility complex (MHC) II, B7-1, B7-2, and CD40. This result is consistent with our observation that KCs were not as potent as DCs in eliciting OVA-specific T cell proliferation. However, KCs isolated from polyinosinic:polycytidylic acid,treated mice expressed significantly higher levels of MHC II and costimulatory molecules than did naïve KCs and could stimulate stronger T cell responses. More importantly, we found that KCs could inhibit DC-induced OVA-specific T cell activation. Further investigation of the underlying mechanism revealed that prostaglandins produced by KCs played an important role. The results ruled out the possible involvement of interleukin-10, nitric oxide, 2,3-dioxygenase, and transforming growth factor , in KC-mediated T cell suppression. Conclusion: Our data indicate that KCs are a tolerogenic APC population within the liver. These findings suggest that KCs may play a critical role in regulating immune reactions within the liver and contributing to liver-mediated systemic immune tolerance. (HEPATOLOGY 2008.) [source] The CD8+ dendritic cell subsetIMMUNOLOGICAL REVIEWS, Issue 1 2010Ken Shortman Summary:, Mouse lymphoid tissues contain a subset of dendritic cells (DCs) expressing CD8, together with a pattern of other surface molecules that distinguishes them from other DCs. These molecules include particular Toll-like receptor and C-type lectin pattern recognition receptors. A similar DC subset, although lacking CD8 expression, exists in humans. The mouse CD8+ DCs are non-migrating resident DCs derived from a precursor, distinct from monocytes, that continuously seeds the lymphoid organs from bone marrow. They differ in several key functions from their CD8, DC neighbors. They efficiently cross-present exogenous cell-bound and soluble antigens on major histocompatibility complex class I. On activation, they are major producers of interleukin-12 and stimulate inflammatory responses. In steady state, they have immune regulatory properties and help maintain tolerance to self-tissues. During infection with intracellular pathogens, they become major presenters of pathogen antigens, promoting CD8+ T-cell responses to the invading pathogens. Targeting vaccine antigens to the CD8+ DCs has proved an effective way to induce cytotoxic T lymphocytes and antibody responses. [source] A novel model of sensitization and oral tolerance to peanut proteinIMMUNOLOGY, Issue 3 2004Jessica Strid Summary The prevalence of food allergic diseases is rising and poses an increasing clinical problem. Peanut allergy affects around 1% of the population and is a common food allergy associated with severe clinical manifestations. The exact route of primary sensitization is unknown although the gastrointestinal immune system is likely to play an important role. Exposure of the gastrointestinal tract to soluble antigens normally leads to a state of antigen-specific systemic hyporesponsiveness (oral tolerance). A deviation from this process is thought to be responsible for food-allergic diseases. In this study, we have developed a murine model to investigate immunoregulatory processes after ingestion of peanut protein and compared this to a model of oral tolerance to chicken egg ovalbumin (OVA). We demonstrate that oral tolerance induction is highly dose dependent and differs for the allergenic proteins peanut and OVA. Tolerance to peanut requires a significantly higher oral dose than tolerance to OVA. Low doses of peanut are more likely to induce oral sensitization and increased production of interleukin-4 and specific immunoglobulin E upon challenge. When tolerance is induced both T helper 1 and 2 responses are suppressed. These results show that oral tolerance to peanut can be induced experimentally but that peanut proteins have a potent sensitizing effect. This model can now be used to define regulatory mechanisms following oral exposure to allergenic proteins on local, mucosal and systemic immunity and to investigate the immunomodulating effects of non-oral routes of allergen exposure on the development of allergic sensitization to peanut and other food allergens. [source] Mechanism of antigen presentation after hypertonic loading of soluble antigensIMMUNOLOGY, Issue 4 2002Georg A. Enders Summary Hypertonic loading of proteins into cells has been used to introduce soluble proteins into the major histocompatibility complex class I pathway of antigen presentation followed by cytotoxic T-lymphocyte (CTL) induction. The precise mechanism for this pathway is not completely understood. The antigen is either processed and presented by/on the same cell or by professional antigen-presenting cells (APC) after taking up the antigen from damaged or apoptotic cells. After loading labelled ovalbumin (OVA), it could be co-precipitated with the proteasome complex, supporting the role of this pathway for antigen processing. The processing speed however, appeared to be slow since intact OVA could be detected inside the cells even after 18 hr. This corresponded well with the processing of OVA by isolated proteasomes. On the other hand, enough peptides for recognition of target cells by CTLs were generated in this reaction. One reason for the low level of processing might be that hypertonic loading may damage the cells and inhibit direct processing. In fact, at least 50% of the cells became positive for Annexin V binding after hypertonic loading which indicates severe membrane alterations usually associated with the progress of apoptosis. Annexin V binds to phosphatidylserine residues which also serve as ligand for CD36 expressed on monocytes and some immature dendritic cells. This may direct the phagocytic pathway to hypertonically loaded cells and thus enable professional APCs to present OVA-peptides. Therefore, in addition to the direct processing of OVA, CTLs can be primed by professional APC after uptake of apoptotic, OVA-loaded cells. [source] Intranasal immunization using biphasic lipid vesicles as delivery systems for OmlA bacterial protein antigen and CpG oligonucleotides adjuvant in a mouse modelJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 8 2005V. L. Alcón The nasal mucosa is an important arm of the mucosal system since it is often the first point of contact for inhaled antigens. The ineffectiveness of the simple delivery of soluble antigens to mucosal membranes for immunization has stimulated extensive studies in appropriate delivery systems and adjuvants. We have evaluated biphasic lipid vesicles as a novel intranasal (i.n.) delivery system (designated as vaccine targeting adjuvant, VTA) containing bacterial antigens and CpG oligode-oxynucleotides (ODNs). Results show that administration of antigen and CpG ODNs in biphasic lipid vesicles resulted in greater induction of IgA levels in serum (P<0.05) and mucosal antibody responses such as IgA in nasal secretions and lung (P<0.01) after immunization with a combined subcutaneous (s.c.)/i.n. as compared to s.c./s.c. approach. Based on antibody responses, VTA formulations were found to be suitable as delivery systems for antigens and CpG ODNs by the intranasal route, resulting in a Th2-type of immune response, characterized by IgG1 and IL-4 production at the systemic level. [source] Antemortem diagnosis of canine neural angiostrongylosis using ELISAAUSTRALIAN VETERINARY JOURNAL, Issue 3 2003J LUNN A 5-month-old female Kelpie developed paraparesis, hind limb ataxia and spinal hyperaesthesia 4 days after ovariohysterectomy. Neurological examination demonstrated upper motor neuron signs in the pelvic limbs with lower motor neuron signs in the tail. Cerebrospinal fluid analysis demonstrated an increased protein concentration and marked eosinophilic pleocytosis. The dog was known to have eaten rats, snails and slugs. A tentative diagnosis of neural angiostrongylosis was made and later confirmed using an ELISA based on soluble antigens obtained from larval 4 Angiostrongylus cantonensis. Antibody titres from the patient's serum and CSF were 800 and 6400, respectively. The dog was treated successfully with prednisolone. ELISA testing of serum may provide a non-invasive means for diagnosing neural angiostrongylosis in dogs. [source] | ||||||||||