 Your new post is loading...
Your new post is loading...
|
Scooped by
Gilbert C FAURE
November 19, 2017 6:48 AM
|
In order to be capable of engaging the key elements of adaptive immunity (specificity, memory, diversity, self/nonself discrimination), antigens have to be processed and presented to immune cells. Antigen presentation is mediated by MHC class I molecules, and the class II molecules found on the surface of antigen-presenting cells (APCs) and certain other cells.
|
|
Scooped by
Gilbert C FAURE
November 19, 2017 6:46 AM
|
J Immunol. 2017 Nov 17. pii: ji1700841. doi: 10.4049/jimmunol.1700841. [Epub ahead of print]
|
|
Scooped by
Gilbert C FAURE
November 18, 2017 3:50 AM
|
|
|
Scooped by
Gilbert C FAURE
November 17, 2017 3:51 AM
|
|
|
Scooped by
Gilbert C FAURE
November 15, 2017 2:22 PM
|
|
Suggested by
Société Francaise d'Immunologie
November 14, 2017 1:44 PM
|
bioRxiv - the preprint server for biology, operated by Cold Spring Harbor Laboratory, a research and educational institution
|
|
Scooped by
Gilbert C FAURE
November 14, 2017 1:32 PM
|
Researchers at the Max Planck Institute, Goethe University and Martin Luther University are deciphering the structure of the MHC-I peptide-loading complex.
|
|
Suggested by
Société Francaise d'Immunologie
November 13, 2017 11:34 AM
|
Neuropilins (NRPs) are non-tyrosine kinase cell surface glycoproteins expressed in all vertebrates and widely conserved across species. The two isoforms, NRP1 and NRP2 mainly act as co-receptors for class III Semaphorins and for members of the Vascular Endothelial Growth Factor (VEGF) family of molecules and are widely known for their role in a wide array of physiological processes like cardiovascular, neuronal development and patterning, angiogenesis, lymphangiogenesis as well as various clinical disorders. Intriguingly, additional roles for NRPs occur with myeloid and lymphoid cells, in normal physiological as well as different pathological conditions, including cancer, immunological disorders, and bone diseases. However, little is known concerning the molecular pathways that govern these functions. Additionally, NRP1 expression has been characterized in different immune cellular phenotypes including macrophages, dendritic cells (DCs), and T cell subsets, especially regulatory T cell (Treg) populations. In contrast, the functions of NRP2 in immune cells is less well known. In this Review, we briefly summarize the genomic organization, structure, and binding partners of the NRPs, and extensively discuss the recent advances in their role and function in different immune cell subsets and their clinical implications.
|
|
Scooped by
Gilbert C FAURE
November 13, 2017 3:10 AM
|
Type 2 diabetes mellitus (DM) is associated with the down modulation of Th1, Th2 and Th17 responses in latent Mycobacterium tuberculosis infection but the role of prediabetes (PDM) in this setting is not well understood. To examine the role of CD4+ and CD8+ T cell cytokines in latent tuberculosis (LTB) with coincident PDM, we studied the baseline, mycobacterial, control antigen and mitogen–stimulated T cell cytokine responses in LTB individuals with (LTB-PDM; n = 20) or without (LTB-NDM; n = 20) concomitant prediabetes. LTB-PDM is characterized by diminished frequencies of mono–and dual–functional CD4+ Th1 and Th17 cells and mono-functional Th2 cells at baseline and/or following mycobacterial—antigen stimulation in comparison to LTB-NDM. LTB-PDM is also characterized by diminished frequencies of mono–functional CD8+ Tc1, Tc2 and Tc17 cells at baseline and/or following mycobacterial–antigen stimulation in comparison to LTB-NDM. LTB-PDM is therefore characterized by diminished frequencies of antigen–specific Th1/Tc1 and Th17/Tc17 cells, indicating that PDM is associated with alterations of the immune response in latent TB associated with compromised CD4+ and CD8+ T cell function.
|
|
Suggested by
Société Francaise d'Immunologie
November 9, 2017 2:08 AM
|
The large majority of classified primary immune deficiency (PID) diseases present
in childhood. Yet, most patients with PID are adults, with a large proportion experiencing
onset of symptoms beyond their childhood years. Most of these are diagnosed predominantly
with antibody defects, but cellular and other disorders are increasingly being identified
in older patients as well. Moreover, advances in clinical immunology are allowing
pediatric patients, even those with severe disease, to reach adulthood.
|
|
Scooped by
Gilbert C FAURE
November 7, 2017 11:41 AM
|
As cardiac cells begin to die by the masses after a heart attack, the immune system kicks into action as if there were a pathogen invading the body. In a n
|
|
Scooped by
Gilbert C FAURE
November 6, 2017 1:15 PM
|
bioRxiv - the preprint server for biology, operated by Cold Spring Harbor Laboratory, a research and educational institution
|
|
Suggested by
Société Francaise d'Immunologie
November 5, 2017 2:29 PM
|
|
|
|
Scooped by
Gilbert C FAURE
November 19, 2017 6:47 AM
|
Methods for the targeted disruption of protein function have revolutionized science
and greatly expedited the systematic characterization of genes. Two main approaches
are currently used to disrupt protein function: DNA knockout and RNA interference,
which act at the genome and mRNA level, respectively. A method that directly alters
endogenous protein levels is currently not available. Here, we present Trim-Away,
a technique to degrade endogenous proteins acutely in mammalian cells without prior
modification of the genome or mRNA.
|
|
Scooped by
Gilbert C FAURE
November 19, 2017 6:40 AM
|
|
|
Scooped by
Gilbert C FAURE
November 17, 2017 5:13 AM
|
|
|
Scooped by
Gilbert C FAURE
November 16, 2017 2:44 PM
|
The T cell receptor (TCR) repertoire can provide a personalised biomarker for infectious and non-infectious diseases. We describe a protocol for amplifying, sequencing and analysing TCRs which is robust, sensitive and versatile. The key experimental step is ligation of a single stranded oligonucleotide to the 3’ end of the TCR cDNA. This allows amplification of all possible rearrangements using a single set of primers per locus. It also introduces a unique molecular identifier to label each starting cDNA molecule. This molecular identifier is used to correct for sequence errors and for effects of differential PCR amplification efficiency, thus producing more accurate measures of the true TCR frequency within the sample. This integrated experimental and computational pipeline is applied to the analysis of human memory and naive subpopulations, and results in consistent measures of diversity and inequality. After error correction, the distribution of TCR sequence abundance in all subpopulations followed a power law over a wide range of values. The power law exponent differed between naïve and memory populations, but was consistent between individuals. The integrated experimental and analysis pipeline we describe is appropriate to studies of T cell responses in a broad range of physiological and pathological contexts.
|
|
Suggested by
Société Francaise d'Immunologie
November 14, 2017 1:44 PM
|
Wild animals’ immune responses contribute to their evolutionary fitness. These responses are moulded by selection to be appropriate to the actual antigenic environment in which the animals live, but without imposing an excessive energetic demand which compromises other component of fitness. But, exactly what these responses are, and how they compare with those of laboratory animals, has been little studied. Here we review the very small number of published studies of immune responses of wild rodents, finding general agreement that their humoral (antibody) responses are highly elevated when compared with those of laboratory animals, and that wild rodents’ cellular immune system reveals extensive antigenic exposure. In contrast, proliferative and cytokine responses of ex vivo stimulated immune cells of wild rodents are typically depressed compared with those of laboratory animals. Collectively, these responses are appropriate to wild animals’ lives, because the elevated responses reflect the cumulative exposure to infection, while the depressed proliferative and cytokine responses are indicative of effective immune homeostasis that minimises immunopathology. A more comprehensive understanding of the immune ecology of wild animals requires (i) understanding the antigenic load to which wild animals are exposed, and identification of any key antigens that mould the immune repertoire, (ii) identifying immunoregulatory processes of wild animals and the events that induce them, and (iii) understanding the actual resource state of wild animals, and the immunological consequences that flow from this. Together, by extending studies of wild rodents, particularly addressing these questions (while drawing on our immunological understanding of laboratory animals), we will be better able to understand how rodents’ immune responses contribute to their fitness in the wild.
|
|
Scooped by
Gilbert C FAURE
November 14, 2017 1:43 PM
|
During αβT cell development, the thymus medulla represents an essential microenvironment for T cell tolerance. This functional specialization is attributed to its typical organized topology consisting of a branching structure that contains medullary thymic epithelial cell (mTEC) networks to support negative selection and Foxp3+ T-regulatory cell (T-reg) development. Here, by performing TEC-specific deletion of the thymus medulla regulator lymphotoxin β receptor (LTβR), we show that thymic tolerance mechanisms operate independently of LTβR-mediated mTEC development and organization. Consistent with this, mTECs continue to express Fezf2 and Aire, regulators of intrathymic self-antigens, and support T-reg development despite loss of LTβR-mediated medulla organogenesis. Moreover, we demonstrate that LTβR controls thymic tolerance by regulating the frequency and makeup of intrathymic dendritic cells (DCs) required for effective thymocyte negative selection. In all, our study demonstrates that thymus medulla specialization for thymic tolerance segregates from medulla organogenesis and instead involves LTβR-mediated regulation of the thymic DC pool.
|
|
Scooped by
Gilbert C FAURE
November 14, 2017 1:01 PM
|
bioRxiv - the preprint server for biology, operated by Cold Spring Harbor Laboratory, a research and educational institution
|
Suggested by
LIGHTING
November 13, 2017 11:32 AM
|
Natural Killer (NK) cells, lymphocytes of the innate immune system with strong cytotoxic activity, play a major role in the immune response against tumours.
|
|
Scooped by
Gilbert C FAURE
November 9, 2017 3:16 AM
|
IUIS - International Union of Immunological Societies
|
|
Scooped by
Gilbert C FAURE
November 9, 2017 1:48 AM
|
Pancreatic ductal adenocarcinoma is a lethal cancer with fewer than 7% of patients surviving past 5 years. T-cell immunity has been linked to the exceptional outcome of the few long-term survivors1,2, yet the relevant antigens remain unknown. Here we use genetic, immunohistochemical and transcriptional immunoprofiling, computational biophysics, and functional assays to identify T-cell antigens in long-term survivors of pancreatic cancer. Using whole-exome sequencing and in silico neoantigen prediction, we found that tumours with both the highest neoantigen number and the most abundant CD8+ T-cell infiltrates, but neither alone, stratified patients with the longest survival. Investigating the specific neoantigen qualities promoting T-cell activation in long-term survivors, we discovered that these individuals were enriched in neoantigen qualities defined by a fitness model, and neoantigens in the tumour antigen MUC16 (also known as CA125). A neoantigen quality fitness model conferring greater immunogenicity to neoantigens with differential presentation and homology to infectious disease-derived peptides identified long-term survivors in two independent datasets, whereas a neoantigen quantity model ascribing greater immunogenicity to increasing neoantigen number alone did not. We detected intratumoural and lasting circulating T-cell reactivity to both high-quality and MUC16 neoantigens in long-term survivors of pancreatic cancer, including clones with specificity to both high-quality neoantigens and predicted cross-reactive microbial epitopes, consistent with neoantigen molecular mimicry. Notably, we observed selective loss of high-quality and MUC16 neoantigenic clones on metastatic progression, suggesting neoantigen immunoediting. Our results identify neoantigens with unique qualities as T-cell targets in pancreatic ductal adenocarcinoma. More broadly, we identify neoantigen quality as a biomarker for immunogenic tumours that may guide the application of immunotherapies.
|
|
Scooped by
Gilbert C FAURE
November 7, 2017 11:40 AM
|
TLR8 is the major endosomal sensor of degraded RNA in human monocytes and macrophages. It has been implicated in the sensing of viruses and more recently also bacteria. We previously identified a TLR8-IRF5 signaling pathway which mediates IFNβ and IL-12 induction by S. aureus, and which is antagonized by TLR2. The relative importance of TLR8 for the sensing of various bacterial species is however still unclear. We here compared the role of TLR8 and IRF5 for the sensing of Group B Streptococcus (GBS), S. aureus, and E. coli in human primary monocytes and monocyte derived macrophages (MDM). GBS induced stronger IFNβ and TNF production as well as IRF5 nuclear translocation compared to S. aureus grown to the stationary phase, while S. aureus in exponential growth appeared similarly potent to GBS. Cytokine induction in primary human monocytes by GBS was not dependent on hemolysins, and induction of IFNβ and IL12 as well as IRF5 activation were reduced with TLR2 ligand co-stimulation. Heat inactivation of GBS reduced IRF5 and NF-kB translocation, while only the viable E. coli activated IRF5. The attenuated stimulation correlated with loss of bacterial RNA integrity. The E. coli-induced IRF5 translocation was not inhibited by TLR2 co-stimulation, suggesting that IRF5 was activated via a TLR8-independent mechanism. Gene silencing of MDM by RNAi revealed that GBS-induced IFNβ, IL-12p35, and TNF production was dependent on TLR8 and IRF5. In contrast, cytokine induction by E. coli was TLR8 independent, but still partly dependent on IRF5. We conclude that TLR8-IRF5 signaling is more important for the sensing of GBS than for stationary grown S. aureus in human primary monocytes and MDM, likely due to reduced resistance of GBS to phagosomal degradation and to a lower production of TLR2 activating lipoproteins. TLR8 does not sense viable E. coli, while IRF5 still contributes to E. coli-induced cytokine production, possibly via a cytosolic nucleic acid sensing mechanism.
|
|
Scooped by
Gilbert C FAURE
November 6, 2017 1:13 PM
|
|
Scoop.it!
