Immunology
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Accumulating evidence suggests that T cells and autoantibodies reactive with myelin oligodendrocyte glycoprotein (MOG) play a critical role in the pathogenesis of multiple sclerosis (MS). In the present study, we have tried to elucidate the pathomechanisms of development and progression of the disease by analysing T cells and autoantibodies in MOG-induced rat experimental autoimmune encephalomyelitis (EAE), which exhibits various clinical subtypes mimicking MS. Analysis using overlapping peptides revealed that encephalitogenic epitopes resided in peptide 7 (P7, residue 91-108) and P8 (residue 103-125) of MOG. ⋯ Analysis of antibodies against conformational epitope (cme) suggests that anti-MOG(cme) may play a role in the pathogenicity of anti-MOG antibodies. Collectively, these findings demonstrated that relapse of a certain type of MOG-induced EAE occurs without autoantibodies but that autoantibodies may play a role in disease progression. Relapses and the progression of MS-mimicking EAE are differently immunoregulated so immunotherapy should be designed appropriately on the basis of precise information.
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The endogenous cannabinoid system plays an important role in regulating the immune system. Modulation of endogenous cannabinoids represents an attractive alternative for the treatment of inflammatory disorders. This study investigated the effects of URB597, a selective inhibitor of fatty acid amide hydrolase (FAAH), the enzyme catalysing degradation of the endogenous cannabinoid anandamide, and AM404, an inhibitor of anandamide transport, on lipopolysaccharide (LPS)-induced increases in plasma cytokine levels in rats. ⋯ In conclusion, inhibition of endocannabinoid degradation or transport in vivo potentiates LPS-induced increases in circulating TNF-alpha levels, an effect which may be mediated by PPARgamma and is also reduced by pharmacological blockade of CB1, CB2 and TRPV1. The immunosuppressive effect of AM404 on IL-1beta levels is mediated by the cannabinoid CB1 receptor. Improved understanding of endocannabinoid-mediated regulation of immune function has fundamental physiological and potential therapeutic significance.
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We investigated whether a vaccine derived from an apathogenic reassortant type A H5N1 influenza strain could induce immune responses in vivo that mediated protection from highly pathogenic avian influenza virus infection in mice. After two subcutaneous immunizations with formalin-inactivated H5N1 whole virus particles (whole particle vaccine), significant killing specific for cells presenting a nucleoprotein peptide from the vaccine strain of the virus was observed. ⋯ Finally, whole particle vaccines of H5N1 protected mice against infection by an H5N1 highly pathogenic avian influenza virus more effectively than did ether-split vaccines. These results suggest that formalin-inactivated virus particles of apathogenic strains are effective for induction of both cytotoxic T-lymphocyte and antibody responses against highly pathogenic avian influenza viruses in vivo, resulting in protection from infection by a highly pathogenic H5N1 virus.
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Nasal carriage of Staphylococcus aureus is an important source of nosocomial infection and community-acquired methicillin-resistant S. aureus (MRSA). Previous studies by our laboratory revealed that nasal carriage of S. aureus is accompanied by subclinical inflammation, which is insufficient to prevent colonization, and that carriage might also be a result of adaptation and selection of certain S. aureus strains to the host's nasal environment. In the present study we observed that a carrier strain of S. aureus preferentially colonizes and attaches to nasal epithelial cells (NEC) compared to a non-carrier S. aureus strain. ⋯ While both strains up-regulated the expression of the pattern recognition receptor, Toll-like receptor 2 (TLR2), NEC exposed to the nasal carrier strain had a 4-hr delay in TLR2 expression compared with NEC exposed to non-carrier S. aureus. Moreover, even after 20 hr of colonization the expression of two principal epithelial antimicrobial peptides, human beta-defensin-2 and human beta-defensin-3, was negligibly induced in NEC exposed to the nasal carrier strain of S. aureus in comparison to the non-carrier strain. These results suggest that carrier strains of S. aureus retain a competitive advantage over non-carrier strains by delaying the host's innate response to epithelial colonization and infection.
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The results of various animal model studies of tuberculosis (TB) suggest that culture filtrate proteins (CFPs), which are antigens secreted by Mycobacterium tuberculosis, are largely responsible for improvements in TB vaccines. The great obstacle to developing protein subunit vaccines is that adjuvants are required in order to stimulate relevant protective immune responses. Acting as immune adjuvants, CpG-oligodeoxynucleotides (CpG-ODNs) promote the activation of Th1 cells and of pro-inflammatory cytokines. ⋯ Despite the stronger Th1 response seen in both groups, believed to be necessary for protection against TB, only mice immunized with CFP/IFA were protected after M. tuberculosis infection. Lung histology revealed that lung parenchyma were better preserved in CFP/IFA-immunized mice, which also presented intense lymphocyte recruitment to the lesion, whereas CFP/CpG-immunized mice presented severe pulmonary injury accompanied by necrosis. Based on the data presented, we discuss the widely accepted paradigm that high levels of IFN-gamma are directly correlated with protection against experimental TB.