Diversification of the antibody repertoire is essential for the normal operation of the vertebrate adaptive immune system.
Immunology
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Teaching and Learning Immunology. Information you never would have searched for!
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Gilbert C FAURE
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Eosinophils perform numerous tasks. They are involved in inflammatory reactions associated with innate immune defence against parasitic infections and are also involved in pathological processes in response to allergens. 
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Epigenetic modifications, such as histone post-translational modifications, DNA methylation, and alteration of gene expression by non-coding RNAs, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), are heritable changes that are independent from the genomic DNA sequence. These regulate gene activities and, therefore, cellular functions. Epigenetic modifications act in concert with transcription factors and play critical roles in B cell development and differentiation, thereby modulating antibody responses to foreign- and self-antigens. Upon antigen encounter by mature B cells in the periphery, alterations of these lymphocytes epigenetic landscape are induced by the same stimuli that drive the antibody response. Such alterations instruct B cells to undergo immunoglobulin (Ig) class switch DNA recombination (CSR) and somatic hypermutation (SHM), as well as differentiation to memory B cells or long-lived plasma cells for the immune memory. Inducible histone modifications, together with DNA methylation and miRNAs modulate the transcriptome, particularly the expression of activation-induced cytidine deaminase, which is essential for CSR and SHM, and factors central to plasma cell differentiation, such as B lymphocyte-induced maturation protein-1. These inducible B cell-intrinsic epigenetic marks guide the maturation of antibody responses. Combinatorial histone modifications also function as histone codes to target CSR and, possibly, SHM machinery to the Ig loci by recruiting specific adaptors that can stabilize CSR/SHM factors. In addition, lncRNAs, such as recently reported lncRNA-CSR and an lncRNA generated through transcription of the S region that form G-quadruplex structures, are also important for CSR targeting. Epigenetic dysregulation in B cells, including the aberrant expression of non-coding RNAs and alterations of histone modifications and DNA methylation, can result in aberrant antibody responses to foreign antigens, such as those on microbial pathogens, and generation of pathogenic autoantibodies, IgE in allergic reactions, as well as B cell neoplasia. Epigenetic marks would be attractive targets for new therapeutics for autoimmune and allergic diseases, and B cell malignancies. Via Krishan Maggon
Krishan Maggon 's curator insight,
December 17, 2015 4:53 AM
REVIEW ARTICLE Front. Immunol., 14 December 2015 | http://dx.doi.org/10.3389/fimmu.2015.00631 Epigenetics of Peripheral B-Cell Differentiation and the Antibody Response
Hong Zan* and Paolo Casali* Department of Microbiology and Immunology, University of Texas School of Medicine, UT Health Science Center, San Antonio, TX, USA
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Neutrophils prepare niche in the lung for breast cancer cell colonization
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Primary immunodeficiencies (PID) are congenital disorders of immune competence, which are mainly characterized by a pathological susceptibility to infection.
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From
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Ludwig Maximilian University researchers have elucidated how a cellular sensor that triggers the innate immune system distinguishes viral from cellular nucleic acids – and why it must expend energy to do so.
Gilbert C FAURE's insight:
innate immune recognition The breakthrough came with the recent discovery of a mutation in RIG-I, which deprives the protein of its ability to hydrolyze bound ATP. This mutation turns out to be the underlying cause of Singleton-Merten Syndrome, a rare form of autoimmune disease characterized by tooth loss, bone demineralization and calcification of the vasculature. Hopfner's team has now shown that the mutant form of RIG-I is also unable to tell the difference between friend and foe, such that the RIG-I-dependent signal relay is activated by cellular, as well as viral, RNA molecules.
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The function of group 3 innate lymphoid cells (ILC3 cells) is still being determined.
Gilbert C FAURE's insight:
Intestinal T cells and group 3 innate lymphoid cells (ILC3 cells) control the composition of the microbiota and gut immune responses. Within the gut, ILC3 subsets coexist that either express or lack the natural cytoxicity receptor (NCR) NKp46. We identified here the transcriptional signature associated with the transcription factor T-bet–dependent differentiation of NCR− ILC3 cells into NCR+ ILC3 cells. Contrary to the prevailing view, we found by conditional deletion of the key ILC3 genes Stat3, Il22, Tbx21 and Mcl1 that NCR+ ILC3 cells were redundant for the control of mouse colonic infection with Citrobacter rodentium in the presence of T cells. However, NCR+ ILC3 cells were essential for cecal homeostasis. Our data show that interplay between intestinal ILC3 cells and adaptive lymphocytes results in robust complementary failsafe mechanisms that ensure gut homeostasis.
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Just 2.4% of citations from an immunology journal present disagreements with previous work.
Gilbert C FAURE's insight:
Oettl’s team checked through more than 760,000 citations (referring to around 150,000 papers) from nearly 16,000 articles in the Journal of Immunology. They asked a team of immunologists to help them by manually classifying 'negative' citations from their context in around 15,000 examples. Wording along the lines of “The data therefore contrast with reports that …” or “This conclusion appeared inconsistent with …” was regarded as negative, for instance. Then, the researchers used automated text analysis, based on an algorithm trained with the manually-classified dataset, to analyse the rest. They found that 2.4% of the citations were “negative”, and that some 7.1% of the more than 150,000 papers cited received at least one negative citation.
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Eur J Immunol. 2015 Dec 2. doi: 10.1002/eji.201545839. [Epub ahead of print]
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Data from: Annotation of pseudogenic gene segments by massively parallel sequencing of rearranged lymphocyte r... https://t.co/Ik6Gf25n4Z
Gilbert C FAURE's insight:
data available online... the future
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New Spotlight @TrendsBiochem : Rosetta Stone of NLR Innate Immunity https://t.co/HObIrHa6vS
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Editorial: CD1- and MR1-Restricted T Cells in Antimicrobial Immunity
Gilbert C FAURE's insight:
CD1, iNKT, MAIT...
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The Danish medicinal industry comments on UCPH's new MSc in Immunology and Inflammation.
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B cells undergo a number of different developmental stages, from initial formation of their B cell receptor (BCR) genes to differentiation into antibody-secreting plasma cells.
Gilbert C FAURE's insight:
Because the BCR is vital in these differentiation steps, autoreactive and exogenous antigen binding to the BCR exert critical selection pressures to shape the B cell repertoire. Older people are more prone to infectious disease, less able to respond well to vaccination and more likely to have autoreactive antibodies. Here we review evidence of changes in B cell repertoires in older people, which may be a reflection of age-related changes in B cell selection processes.
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An overview of primary immunodeficiency disease symptoms, diagnosis, treatment and management written and reviewed by leading experts in allergy, asthma and immunology.
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Pathogenic bacteria are detected by pattern-recognition receptors (PRRs) expressed on innate immune cells, which activate intracellular signal transduction pathways to elicit an immune response.
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New Immunity paper on antigen processing by dendritic cells with contributions from our lab https://t.co/E1T93sATno #proteomics #vib #ugent
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NATURE REVIEWS IMMUNOLOGY | REVIEW
Gilbert C FAURE's insight:
Inflammatory and apoptotic caspases are central players in inflammation and apoptosis, respectively. However, recent studies have revealed that these caspases have functions beyond their established roles. In addition to mediating cleavage of the inflammasome-associated cytokines interleukin-1β (IL-1β) and IL-18, inflammatory caspases modulate distinct forms of programmed cell death and coordinate cell-autonomous immunity and other fundamental cellular processes. Certain apoptotic caspases assemble structurally diverse and dynamic complexes that direct inflammasome and interferon responses to fine-tune inflammation. In this Review, we discuss the expanding and interconnected roles of caspases that highlight new aspects of this family of cysteine proteases in innate immunity.
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Author Summary Infants born to dengue immune mothers acquire maternal dengue antibodies.
Gilbert C FAURE's insight:
Author Summary
Infants born to dengue immune mothers acquire maternal dengue antibodies. These antibodies, though initially protective, decline during the first year of life to levels thought to be disease enhancing, before reaching undetectable levels. We show that in this population, DENV-2 and DENV-4 almost exclusively cause disease in the presence of dengue antibody, despite infections occurring in others. We also observe serotype-specificity in the mean age of infant cases, consistent with differential waning of antibody to each serotype. These results highlight serotype-specificity in the way the immune response interacts with infection to cause disease. In addition, we show that the mean age of infant cases over time is informative about transmission in the whole population. Therefore, ongoing surveillance for dengue in infants could provide useful insights into dengue epidemiology, particularly after the introduction of a dengue vaccine targeting adults and older children.
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Two types of memory T cells can preserve immunological memories for more than a decade, a study shows.
Gilbert C FAURE's insight:
Scanning electron microscope image of a human lymphocyteWIKIMEDIA, NCI Following genetically marked donor memory T cells infused into hematopoietic stem cell transplantation patients, a team led by researchers at the University Vita-Salute San Raffaele in Milan, Italy, found that two types of less-differentiated memory T cells can persist for up to 14 years. The team’s results, published today (December 9) in Science Translational Medicine, demonstrate that the survival of these immune cells depends on the type of memory T cells initially introduced into patients, and whether these cells continue to encounter antigens over time.
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A webinar on the intricacies of the porcine CD4+ T cell immune response. The focus of the presentation will be on discoveries made on the characterization and ...
Gilbert C FAURE's insight:
human like pigs have TH17 cells...
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Trends Biochem Sci. 2015 Nov 26. pii: S0968-0004(15)00233-9. doi: 10.1016/j.tibs.2015.11.008. [Epub ahead of print]
Gilbert C FAURE's insight:
inflammasome ...
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The online version of Human Immunology at ScienceDirect.com, the world's leading platform for high quality peer-reviewed full-text journals.
Gilbert C FAURE's insight:
HLA typing... NGS
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RT @celltherapynews: Humanized Mouse Models for Transplant Immunology @UofT https://t.co/RGNFecy4QB
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Mast cell proteases are thought to be involved with tumor progression and neo-vascularization. However, their exact role is still unclear.
Gilbert C FAURE's insight:
. The present study was undertaken to further elucidate the function of specific subtypes of recombinant mouse mast cell proteases (rmMCP-6 and 7) in neo-vascularization. SVEC4-10 cells were cultured on Geltrex® with either rmMCP-6 or 7 and tube formation was analyzed by fluorescence microscopy and scanning electron microscopy.
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