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The role of endogenous natural IgM in promoting the adaptive Ab response was investigated in newly constructed mutant mice in which B cells do not secrete IgM but still express surface IgM and IgD and undergo class switching to ex...
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The role of endogenous natural IgM in promoting the adaptive Ab response was investigated in newly constructed mutant mice in which B cells do not secrete IgM but still express surface IgM and IgD and undergo class switching to express other Ig isotypes. While the mutant mice had relatively normal numbers of conventional B (B-2) cells in all tissues examined, unexpectedly, B-1 cells in the peritoneum and spleen were approximately threefold more abundant. The elevated levels of B-1 cells were already detectable at 4 wk of age and were stably maintained throughout life. The levels of serum IgG2a, IgG3, and IgA were also elevated in the mutant mice at an early age. IgG2a response to a T cell-independent Ag was augmented, whereas IgG Ab responses to suboptimal doses of a T cell-dependent Ag were impaired. The latter defect was associated with fewer splenic germinal centers, impaired Ab affinity maturation, and less Ag trapping on follicular dendritic cells. Together, these findings demonstrate a physiologic role of natural IgM in the feedback regulation of B-1 cell development, the regulation of IgG2a production, and the promotion of efficient B-2 cell Ab responses.
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P>According to the hygiene hypothesis, the increased incidence of allergic and autoimmune diseases in developed countries is mainly explained by the decreased contact between the human population and certain environmental agents a...
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P>According to the hygiene hypothesis, the increased incidence of allergic and autoimmune diseases in developed countries is mainly explained by the decreased contact between the human population and certain environmental agents as lactobacillus, mycobacteria and helminths. In this study, we evaluated the effect of multiple infections with Strongyloides venezuelensis on the development of experimental autoimmune encephalomyelitis (EAE) in Lewis rats. Multiple infections before EAE induction were not able to change the evolution of the disease. No alterations were observed in weight loss, clinical score and inflammation intensity at the central nervous system. The presence of significant levels of parasite-specific IgG1 but not IgG2b suggested a Th2 polarization. However, the percentage and absolute number of CD4+CD25+Foxp3+ T cells were not changed, being their levels in the spleen and lymph nodes of infected rats comparable to the ones found in normal animals. These results suggest that a Th2-polarized response without concomitant expansion of Foxp3+ regulatory T cells was not able to modify EAE progression. Even though these results do not threaten the hygiene hypothesis, they suggest that this paradigm might be an oversimplification. They also emphasize the need of a study to compare the immunoregulatory ability associated with different helminth spp.
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Aim: Parvovirus B19 (B19V) infection is mainly manifested as erythema infectiosum in children. Primary B19V infection during pregnancy is accompanied by a 30% risk of fetal infection, especially in epidemic conditions. Given the i...
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Aim: Parvovirus B19 (B19V) infection is mainly manifested as erythema infectiosum in children. Primary B19V infection during pregnancy is accompanied by a 30% risk of fetal infection, especially in epidemic conditions. Given the important impact of parvovirus B19 infection on maternal and neonate health, this study assessed parvovirus B19 susceptibility among women of childbearing age in Mashhad, northeast Iran. Materials & Methods: Serum samples were collected from 185 women aged 20-35 years living in Mashhad. Cluster sampling was performed in different health centers located in the city to cover the main city area. A commercial ELISA kit was used to measure IgG antibodies against B19V. This study was performed in accordance with the ethical standards mentioned in the declaration of Helsinki. Informed consent was taken from all participants. A questionnaire was filled by each participant. SPSS software Version 11.5 was used for statistical analyses. Findings: Anti-B19 IgG was observed in about 31% of women. Seroprevalence of anti- B19 antibodies among different age groups (with 5-year intervals) was not significantly different ( p =.839). Also, there was no significant difference among different city areas of Mashhad in terms of anti-B19 IgG seropositivity (p>.05). Conclusion: The prevalence of parvovirus B19 infection varies in different parts of the world. Comparing to other reports, the present study results revealed a rather low immunity against parvovirus B19 among women in Mashhad. These findings highlight the potential risk of B19 infection in non-immune/susceptible mothers, which may lead to sever outcomes, especially during epidemics.
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Abstract IgG4-related disease (IgG4-RD), which usually occurs in middle-aged and elderly men, is a newly recognized fibroinflammatory condition characterized by swelling and sclerosis of involved organs, increased IgG4-positive pl...
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Abstract IgG4-related disease (IgG4-RD), which usually occurs in middle-aged and elderly men, is a newly recognized fibroinflammatory condition characterized by swelling and sclerosis of involved organs, increased IgG4-positive plasma cell infiltration in lesions, and elevated IgG4 concentration in serum. Despite growing interest in the research, the pathophysiological mechanism remains elusive. Most IgG4-RD patients respond well to steroid therapy initially, but recurrent and refractory cases are common, especially in advanced fibrotic stage. Recent studies have documented the heterogeneity of the B cell lineages, which suggests their multiple functions in IgG4-RD beyond IgG4 production, such as cytokine secretion, antigen presentation, autoantibody production, and modulation of T and B cell interactions. Thus, a critical balance exists between pathogenic and regulatory B subsets to prevent immunopathology. A prompt response to B cell depletion therapy reported in recent cases strongly suggests the imbalance within B cell lineages in IgG4-RD. A more precise understanding of the pathogenesis of IgG4-RD will open up new perspectives for therapeutic strategy. With a particular emphasis on the novel B cell-targeted therapeutic strategies, this review highlights the immunologic features of IgG4-RD and the possible roles of B cell lineages in the pathogenesis of IgG4-RD.
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Исследована ферментативная активность препаратов иммуноглобулинов IgG_1, IgG_2 IgG_4, выделенных из сыворотки крови больных острым...
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Исследована ферментативная активность препаратов иммуноглобулинов IgG_1, IgG_2 IgG_4, выделенных из сыворотки крови больных острым вирусным гепатитом В и больных хроническим вирусным гепатитом С с исходом в цирроз. В пробах обнаружена ДНКазная активность, достоверно превышающаятаковую иммуноглобулинов, выделенных из сыворотки крови здоровых доноров, а также пероксидазная, оксидазная и эетеразная активности, уровень которых недостоверно отличается от донорского. Изучено взаимодействие препаратов иммуноглобулинов с катионами различных металлов. Установлено, что при добавлении а пробы раствора CuSO_4 в конечной концентрации 4,7 x 10~6 М во всех 14 пробах имеет место достоверное увеличение активности по сравнению с исходной {в среднем в 7,8±2,97 раза). Наблюдаемая активность частично ингибируется при добавлении р-ра етафилококкового протеина А. Замечено, что высокая ДНКазная и пероксидазная активности IyG чаще наблюдались у больных с циррозом печени. Разница в уровнях активности IgG мзжду больными с циррозом печени и вирусным гепатитом без признаков цирроза недостоверна.
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Recent studies have provided considerable insight into the mechanism of BCR-mediated B-cell activation, but the inhibitory signals transferred by Fc gamma Rs leading to down-regulation of BCR-activated B lymphocytes are not clarif...
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Recent studies have provided considerable insight into the mechanism of BCR-mediated B-cell activation, but the inhibitory signals transferred by Fc gamma Rs leading to down-regulation of BCR-activated B lymphocytes are not clarified yet. In the present paper the authors give an overview on new findings regarding BCR structure and signal transduction mechanisms induced by the B-cell antigen receptor complex and outline, partly based on their own observations, the possible mechanisms resulting in Fc gamma R-mediated inhibition of B cells.
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Females often exhibit superior immune responses compared to males toward vaccines and pathogens such as influenza viruses and SARS-CoV-2. To help explain these differences, we first studied serum immunoglobulin isotype patterns in...
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Females often exhibit superior immune responses compared to males toward vaccines and pathogens such as influenza viruses and SARS-CoV-2. To help explain these differences, we first studied serum immunoglobulin isotype patterns in C57BL/6 male and female mice. We focused on IgG2b, an isotype that lends to virus control and that has been previously shown to be elevated in murine females compared to males. Improvements in IgG2b serum levels, and/or IgG2b ratios with other non-IgM isotypes, were observed when: (i) wildtype (WT) female mice were compared to estrogen receptor knockout mice (IgG2b, IgG2b/IgG3, IgG2b/IgG1, and IgG2b/IgA were all higher in WT mice), (ii) unmanipulated female mice were compared to ovariectomized mice (IgG2b/IgA was higher in unmanipulated animals), (iii) female mice were supplemented with estrogen in the context of an inflammatory insult (IgG2b and IgG2b/IgG3 were improved by estrogen supplementation), and (iv) male mice were supplemented with testosterone, a hormone that can convert to estrogen in vivo (IgG2b, IgG2b/IgG3, IgG2b/IgG1, and IgG2b/IgA were all improved by supplementation). We next examined data from three sets of previously described male and female human blood samples. In each case, there were higher IgG2 levels, and/or ratios of IgG2 with non-IgM isotypes, in human females compared to males. The effects of sex and sex hormones in the mouse and human studies were subtle, but frequent, suggesting that sex hormones represent only a fraction of the factors that influence isotype patterns. Examination of the gene loci suggested that upregulation of murine IgG2b or human IgG2 could be mediated by estrogen receptor binding to estrogen response elements and cytosine-adenine (CA) repeats upstream of respective Cγ genes. Given that murine IgG2b and human IgG2 lend to virus control, the isotype biases in females may be sufficient to improve outcomes following vaccination or infection. Future attention to sex hormone levels, and consequent immunoglobulin isotype patterns, in clinical trials are encouraged to support the optimization of vaccine and drug products for male and female hosts.
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Due to their specificity to B. pertussis antigens, immunoglobulin G (IgG) antibodies should be measured primarily for diagnosing pertussis. We compared the diagnostic performance of commercially available enzyme-linked immunosorbe...
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Due to their specificity to B. pertussis antigens, immunoglobulin G (IgG) antibodies should be measured primarily for diagnosing pertussis. We compared the diagnostic performance of commercially available enzyme-linked immunosorbent assays (ELISAs) and chemiluminescent immunoassays (CLIAs) measuring IgG to B. pertussis antigens. An in-house ELISA with purified pertussis toxin (PT) was used as reference system. Commercial assays using PT only as coating antigen showed better performance as compared to those using a mixture of different antigens. The best diagnostic performances were achieved by CLIAs. Results were analyzed using a dual cutoff of either >= 125 IU/mL anti-PT IgG or >= 62 IU/mL anti-PT IgG for the in-house ELISA and accordingly to package inserts for commercial assays. Using the in-house ELISA at a 62 IU/mL cutoff, as the gold standard for interpretation of results from the commercial kits, resulted in lower sensitivity and higher specificity as compared to 125 IU/mL, thus, it may be especially useful in outbreak situations when high specificity is required. (C) 2017 Elsevier Inc. All rights reserved.
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Nascent C3b can form ester bonds with various target molecules on the cell surface and in the fluid phase. Previously, we showed that C3b(2)--IgG complexes represent the major covalent product of C3 activation in serum [Lutz, Stam...
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Nascent C3b can form ester bonds with various target molecules on the cell surface and in the fluid phase. Previously, we showed that C3b(2)--IgG complexes represent the major covalent product of C3 activation in serum [Lutz, Stammler, Jelezarova, Nater and Spath (1996) Blood 88, 184--193]. In the present report, binding of alternative pathway proteins to purified C3b(2)--IgG complexes was studied in the fluid phase by using biotinylated IgG for C3b(2)--IgG generation and avidin-coated plates to capture complexes. Up to seven moles of properdin 'monomer' bound per mole of C3b(2)--IgG at physiological conditions in the absence of any other complement protein. At low properdin/C3b(2)--IgG ratios bivalent binding was preferred. Neither factor H nor factor B affected properdin binding. On the other hand, properdin strongly stimulated factor B binding. Interactions of all three proteins with C3b(2)--IgG exhibited pH optima. An ionic strength optimum was most pronounced for properdin, while factor B binding was largely independent of the salt concentration. C3b(2)--IgG complexes were powerful precursors of the alternative pathway C3 convertase. In the presence of properdin, C3 convertase generated from C3b(2)--IgG cleaved about sevenfold more C3 than the enzyme generated on C3b. C3b(2)--IgG complexes could therefore maintain the amplification loop of complement longer than free C3b.
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The occurrence of abnormally low serum immunoglobulin (Ig) levels is well-known in B chronic lymphocytic leukemia (CLL), but published data on IgG subclass levels are virtually absent. We measured serum IgG subclass levels in 52 B...
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The occurrence of abnormally low serum immunoglobulin (Ig) levels is well-known in B chronic lymphocytic leukemia (CLL), but published data on IgG subclass levels are virtually absent. We measured serum IgG subclass levels in 52 B CLL outpatients, most in stage A and untreated, using an indirect immunoenzymatic assay with monoclonal antibodies. Mean levels of all Ig isotypes were lower than in normal controls in the whole group of patients, except for IgG2 in those studied at diagnosis. Levels of IgG1, IgG2, IgA, and IgM were lower in patients with a long disease duration than in those studied earlier. IgG subclass deficiencies occurred in 54% of cases and the most frequently affected isotype was IgG1. Every possible combination of IgG subclass and Ig class deficiencies from the selective deficiency of a single subclass to a combined deficiency of all isotypes was observed. This marked heterogeneity argues against the occurrence of isolated defects of one of the cytokines involved in Ig switching as a cause of hypoimmunoglobulinemia in CLL. Copyright 1999 Academic Press.
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