Parasite proteins called PfEMP1 that are inserted on the surface of infected erythrocytes, play a key role in the severe pathology associated with infection by the Plasmodium falciparum malaria parasite.
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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The SLAMF Family (SLAMF) of cell surface glycoproteins is comprised of nine glycoproteins and whilst SLAMF1, 3, 5, 6, 7, 8, 9 are self-ligand receptors, SLAMF2 and SLAMF4 interact with each other.
Gilbert C FAURE's insight:
Collectively, these receptors modulate a wide range of functions, such as myeloid cell and lymphocyte development, and T and B cell responses to microbes and parasites. In addition, several SLAMF receptors serve as microbial sensors, which either positively or negatively modulate the function of macrophages, dendritic cells, neutrophils, and NK cells in response to microbial challenges. The SLAMF receptor–microbe interactions contribute both to intracellular microbicidal activity as well as to migration of phagocytes to the site of inflammation. In this review, we describe the current knowledge on how the SLAMF receptors and their specific adapters SLAM-associated protein and EAT-2 regulate innate and adaptive immune responses to microbes. 
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Cellular immunity against viral infection and tumour cells depends on antigen presentation by major histocompatibility complex class I (MHC I) molecules.
Gilbert C FAURE's insight:
Cellular immunity against viral infection and tumour cells depends on antigen presentation by major histocompatibility complex class I (MHC I) molecules. Intracellular antigenic peptides are transported into the endoplasmic reticulum by the transporter associated with antigen processing (TAP) and then loaded onto the nascent MHC I molecules, which are exported to the cell surface and present peptides to the immune system1. Cytotoxic T lymphocytes recognize non-self peptides and program the infected or malignant cells for apoptosis. Defects in TAP account for immunodeficiency and tumour development. To escape immune surveillance, some viruses have evolved strategies either to downregulate TAP expression or directly inhibit TAP activity. So far, neither the architecture of TAP nor the mechanism of viral inhibition has been elucidated at the structural level. Here we describe the cryo-electron microscopy structure of human TAP in complex with its inhibitor ICP47, a small protein produced by the herpes simplex virus I. Here we show that the 12 transmembrane helices and 2 cytosolic nucleotide-binding domains of the transporter adopt an inward-facing conformation with the two nucleotide-binding domains separated. The viral inhibitor ICP47 forms a long helical hairpin, which plugs the translocation pathway of TAP from the cytoplasmic side. Association of ICP47 precludes substrate binding and prevents nucleotide-binding domain closure necessary for ATP hydrolysis. This work illustrates a striking example of immune evasion by persistent viruses. By blocking viral antigens from entering the endoplasmic reticulum, herpes simplex virus is hidden from cytotoxic T lymphocytes, which may contribute to establishing a lifelong infection in the host.
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Serum anti-glycan antibodies play important roles in many immune processes and are of particular interest as biomarkers for many diseases.
Gilbert C FAURE's insight:
In this study we evaluated the effects of age, race, gender, and blood type on anti-glycan antibody profiles in the serum of 135 healthy subjects. As expected, IgG and IgM antibody signals to blood group antigens correlated strongly with blood type. Interestingly, antibodies to other non-ABH glycans, such as the alpha-Gal antigen, also correlated with blood type. A statistically significant decline in IgM signals with age was observed for many antibody subpopulations, but not for IgG. Moreover, statistically significant correlations between race and IgG levels to certain LacNAc-containing glycans were observed. The results have important implications for designing studies and interpreting results in the area of biomarker discovery and for the development of vaccines.
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The term “common variable immunodeficiency” (CVID) was coined in 1971 by a World Health Organization committee to...
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International Congress of Immunology 2016, 21-26 August, Melbourne, Australia
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a few days left to submit abstracts
Abstract Submission Closes: 25 January 2016
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Trypanosoma cruzi is the etiologic agent of Chagas disease, a neglected tropical disease that affects millions of people mainly in Latin America. To establish a life-long infection, T.
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Phosphatidylinositol 4,5-biphosphate (PIP2) is critical for T lymphocyte activation serving as a substrate for the generation of second messengers and the remodeling of actin cytoskeleton necessary for the clustering of lipid rafts, TCR, and...
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Editorial: Innate Immune Cell Determinants of T Cell Immunity: From Basic Mechanisms to Clinical Implications
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The Human Protein Kinases Protein Kinases are key regulators of cell function that constitute one of the largest and most functionally diverse gene families. By adding phosphate groups to substrate proteins, they direct the activity, localization and overall function of many proteins, and serve to orchestrate the activity of almost all cellular processes. Kinases are particularly prominent in signal transduction and co-ordination of complex functions such as the cell cycle. The diversity of essential functions mediated by kinases is shown by the conservation of some 50 distinct kinase families between yeast, invertebrate and mammalian kinomes. Of the 518 human protein kinases, 478 belong to a single superfamily whose catalytic domains are related in sequence. These can be clustered into groups, families and sub-families, of increasing sequence similarity and biochemical function. The kinase dendrograms (above) show the sequence similarity between these catalytic domains: the distance along the branches between two kinases is proportional to the divergence between their sequences. Seven major groups are labeled and colored distinctly. For instance, the tyrosine kinases form a distinct group, whose members phosphorylate proteins on tyrosine residues, whereas enzymes in all other groups phosphorylate primarily serine and threonine residues. The relationships shown on the tree can in some instances be used to predict protein substrates and biological function for many of the over 100 uncharacterized kinases presented here. A further 40 ‘atypical’ kinases have no sequence similarity to typical kinases, but are known or predicted to have enzymatic activity, and some are predicted to have a similar structural fold to typical kinases. - See more at: http://www.cellsignal.com/common/content/content.jsp?id=kinases#sthash.43sJsvKk.dpuf Via Krishan Maggon
Gilbert C FAURE's insight:
dendrogram Thanks cellsignal.com
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Tetraspanin-enriched microdomains (TEMs) are specialized membrane platforms driven by protein-protein interactions that integrate membrane receptors and adhesion molecules.
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Felix Heymann& Frank TackeNature Reviews Gastroenterology & Hepatology (2016) doi:10.1038/nrgastro.2015.200Published online 13 January 2016
Gilbert C FAURE's insight:
The liver is a central immunological organ with a high exposure to circulating antigens and endotoxins from the gut microbiota, particularly enriched for innate immune cells (macrophages, innate lymphoid cells, mucosal-associated invariant T (MAIT) cells). In homeostasis, many mechanisms ensure suppression of immune responses, resulting in tolerance....
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To the amazement of researchers in immunology and genetics, a previously unsuspected mechanism is activated in the presence of pathogens after only a few hours. "In the hours following an attack by bacteria, we observed the ...
Gilbert C FAURE's insight:
"We were surprised that the bacterial infection caused thousands of changes in DNA methylation, while this epigenetic imprint was thought to be stable and non-reactive to environmental perturbations," he added. To reach this conclusion, the researcher and his team inoculated a live strain of Mycobacterium tuberculosis (the pathogen that causes tuberculosis in humans) to dendritic cells, which make up the innate immune system "In addition to observing thousands of DNA methylation changes very quickly after infection, there was a significant loss of methylation, which was strongly linked to the activation of neighbouring genes," said the principal investigator of the study. Another surprising fact was that the reaction took place in the dendritic cells, whereas the latter did not multiply. "Normally demethylation occurs during cell division. The rapid triggering of this epigenetic change in cells that did not divide surprised us," said Alain Pacis, a doctoral student and first author of the study. "We must further explore the mechanism that makes this process possible."
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Keystone Symposia, a non-profit organization dedicated to connecting the scientific community for the benefit of the world community
Gilbert C FAURE's insight:
Meeting Summary Persistent infections are a major source of morbidity and mortality around the world. However, it is increasingly clear that the bacterial microbiome, the virome and the mycobiome can have beneficial roles for the host. Chronic infections with pathogens represent a failure of sterilizing immunity, but the mechanisms responsible for persistence and the balance between host health and disease resulting from infection are not completely understood. Recent discoveries reveal that multiple components of both the infecting organism and the host response to infection determine infection outcome, illustrating that a range of disciplines must be brought together to understand the fundamental mechanisms of chronic infection. This meeting is designed to bring together diverse communities of researchers at the cutting edge of their fields to understand whether and how to manipulate persistent infections to prevent disease and enhance health.
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Interested in #immunology & #dataviz? Check out @ImmuneSpace to explore & analyze human #immuneprofiling data: https://t.co/4OGjWfcng2
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Both dengue NS1 antigen and serum interleukin (IL)-10 levels have been shown to associate with severe clinical disease in acute dengue infection, and IL-10 has also been shown to suppress dengue-specific T cell responses.
Gilbert C FAURE's insight:
Summary
Both dengue NS1 antigen and serum interleukin (IL)-10 levels have been shown to associate with severe clinical disease in acute dengue infection, and IL-10 has also been shown to suppress dengue-specific T cell responses. Therefore, we proceeded to investigate the mechanisms by which dengue NS1 contributes to disease pathogenesis and if it is associated with altered IL-10 production. Serum IL-10 and dengue NS1 antigen levels were assessed serially in 36 adult Sri Lankan individuals with acute dengue infection. We found that the serum IL-10 levels correlated positively with dengue NS1 antigen levels (Spearman's r = 0·47, P < 0·0001), and NS1 also correlated with annexin V expression by T cells in acute dengue (Spearman's r = 0·63, P = 0·001). However, NS1 levels did not associate with the functionality of T cell responses or with expression of co-stimulatory molecules. Therefore, we further assessed the effect of dengue NS1 on monocytes and T cells by co-culturing primary monocytes and peripheral blood mononuclear cells (PBMC), with varying concentrations of NS1 for up to 96 h. Monocytes co-cultured with NS1 produced high levels of IL-10, with the highest levels seen at 24 h, and then declined gradually. Therefore, our data show that dengue NS1 appears to contribute to pathogenesis of dengue infection by inducing IL-10 production by monocytes.
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"It’s hard to recall a revolution that has swept biology more swiftly than CRISPR." https://t.co/bjzIYtcQZB https://t.co/YjQnA1YRIE...
Gilbert C FAURE's insight:
OPEN and history
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TRAVEL AWARDS IUIS/AAI
Gilbert C FAURE's insight:
This year the schedule is as follows: the Long Beach Convention Center, Long Beach, California).
AAI will provide registration and housing (for up to 7 nights) for
To apply for these travel awards, please send your curriculum
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Today the Federation of American Societies for Experimental Biology (FASEB) issued<em> <a href="/Portals/2/PDFs/opa/2016/FASEB_Enhancing Research Reproducibility.pdf">Enhancing Research Reproducibility</a></em>, a...
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Gilbert C FAURE's insight:
en avril 2016
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Early life differentiation and regulatory function of human T cells is confined to particular anatomical sites.
Gilbert C FAURE's insight:
It is unclear how the immune response in early life becomes appropriately stimulated to provide protection while also avoiding excessive activation as a result of diverse new antigens. T cells are integral to adaptive immunity; mouse studies indicate that tissue localization of T cell subsets is important for both protective immunity1, 2, 3, 4 and immunoregulation5, 6. In humans, however, the early development and function of T cells in tissues remain unexplored. We present here an analysis of lymphoid and mucosal tissue T cells derived from pediatric organ donors in the first two years of life, as compared to adult organ donors, revealing early compartmentalization of T cell differentiation and regulation. Whereas adult tissues contain a predominance of memory T cells7, 8, in pediatric blood and tissues the main subset consists of naive recent thymic emigrants, with effector memory T cells (TEM) found only in the lungs and small intestine. Additionally, regulatory T (Treg) cells comprise a high proportion (30–40%) of CD4+ T cells in pediatric tissues but are present at much lower frequencies (1–10%) in adult tissues. Pediatric tissue Treg cells suppress endogenous T cell activation, and early T cell functionality is confined to the mucosal sites that have the lowest Treg:TEMcell ratios, which suggests control in situ of immune responses in early life.
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OIST researchers reconstruct the 3-D structure of a malaria protein in combination with human antibodies.
Gilbert C FAURE's insight:
One strategy used by the pathogen to amplify its spreading probability is the formation of rosette-shaped clusters of uninfected erythrocytes surrounding a malaria-infected red blood cell. Since the parasite in the central cell of the rosette can easily infect the surrounding cells, the rosette enhances the infection. Moreover, rosetting is associated with severe malaria and high fever. In small blood vessels big rosettes bind to the walls of the capillaries, obstructing the normal blood flow, causing the body to react with high fever. Since children and elderly people have thinner capillaries, they are at higher risk of severe malaria. One of the key players in the formation of the rosette is the protein PfEMP1, Plasmodium falciparum erythrocyte membrane protein-1. PfEMP1 sticks out of the infected red blood cell and deceives one of the first defenses against malaria called the IgM antibodies. IgMs bind to the pathogen or pathogen-infected cells and call other immune molecules, like the complement system, for backup. OIST researchers have shown that the IgM bind one or two PfEMP1 proteins, forming a bouquet type shape on the surface of the infected cells. The malaria parasite exploits these IgM to its own advantage, because the bouquet attracts more red blood cells facilitating the formation of rosettes. Moreover, the IgMs in the bouquet are not able to bind the complement system and to destroy the infected cell. "The bond between PfEMP1s and IgMs is like the perfect velcro: not too loose, not too strong. It is devilish engineered to fool our immune system," comments Prof. Skoglund.
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Editorial: Epigenetics of B Cells and Antibody Responses
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Gilbert C FAURE's insight:
Immunity. 2015 Mar 17;42(3):419-30. doi: 10.1016/j.immuni.2015.02.005. Network integration of parallel metabolic and transcriptional data reveals metabolic modules that regulate macrophage polarization. Jha AK1, Huang SC2, Sergushichev A3, Lampropoulou V2, Ivanova Y2, Loginicheva E2, Chmielewski K1, Stewart KM1, Ashall J2, Everts B2, Pearce EJ2,Driggers EM4, Artyomov MN5. Author information Abstract
Macrophage polarization involves a coordinated metabolic and transcriptional rewiring that is only partially understood. By using an integrated high-throughput transcriptional-metabolic profiling and analysis pipeline, we characterized systemic changes during murine macrophage M1 and M2 polarization. M2 polarization was found to activate glutamine catabolism and UDP-GlcNAc-associated modules. Correspondingly, glutamine deprivation or inhibition of N-glycosylation decreased M2 polarization and production of chemokine CCL22. In M1 macrophages, we identified a metabolic break at Idh, the enzyme that converts isocitrate to alpha-ketoglutarate, providing mechanistic explanation for TCA cycle fragmentation. (13)C-tracer studies suggested the presence of an active variant of the aspartate-arginosuccinate shunt that compensated for this break. Consistently, inhibition of aspartate-aminotransferase, a key enzyme of the shunt, inhibited nitric oxide and interleukin-6 production in M1 macrophages, while promoting mitochondrial respiration. This systems approach provides a highly integrated picture of the physiological modules supporting macrophage polarization, identifying potential pharmacologic control points for both macrophage phenotypes.
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Recent advances in genome analysis have provided important insights into the genetic architecture of infectious and inflammatory diseases.
Gilbert C FAURE's insight:
Trends
Alterations in numbers and activity of immune cells and associated responses result in infectious and inflammatory diseases, which are two of the most common disease areas in humans. Complex genomic data sets involving hundreds of genes are emerging from genome-wide association studies of susceptibility to common inflammatory diseases, and from whole-exome sequencing of patients suffering from primary immunodeficiencies. Combined analysis of risk loci for 22 common human inflammatory diseases, and of all primary immunodeficiencies with a known genetic lesion identifies a highly significant genetic overlap between the two groups of diseases. The cellular and molecular pathways anchored around these genes are therefore required for protection against infections, but their persistent or dysregulated engagement for pathological inflammation in humans.
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