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Taking immune cells for a test drive | Broad Institute of MIT and Harvard

Taking immune cells for a test drive | Broad Institute of MIT and Harvard | immunology | Scoop.it

Via Krishan Maggon
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This work is the first installment from the ImmVar group, explained Christophe Benoist. This analysis was coordinated with parallel studies within the ImmVar project on regulatory genetics in resting blood cells, and in activated T lymphocytes, such that the innate and adaptive arms of the immune system are represented. “It’s been a fun program for all the collaborators,” said Benoist, Broad associate member, professor at HMS, and leader of the ImmVar consortium. “The team has done a fantastic job in putting together this beautiful paper, but stay tuned for other important stories to come.”

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Teaching and Learning Immunology. Information you never would have searched for!
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This topic is focusing mainly on fundamental systemic immunology.

 

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History of Immunology

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Innate lymphoid cell function in the context of adaptive immunity. - PubMed - NCBI

Innate lymphoid cell function in the context of adaptive immunity. - PubMed - NCBI | immunology | Scoop.it
Nat Immunol. 2016 Jun 21;17(7):783-789. doi: 10.1038/ni.3484.
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Development of innate lymphoid cells. - PubMed - NCBI

Development of innate lymphoid cells. - PubMed - NCBI | immunology | Scoop.it
Nat Immunol. 2016 Jun 21;17(7):775-782. doi: 10.4038/ni.3481. REVIEW
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SnapShot: Interactions between B Cells and T Cells: Cell

SnapShot: Interactions between B Cells and T Cells: Cell | immunology | Scoop.it
Abstract Dynamic interactions between B and T cells underpin the development of adaptive humoral immune responses to infections and vaccines. Recent advances in the molecular and spatiotemporal control of these interactions during primary responses have contributed greatly to elucidating the molecular pathogenesis of numerous immunodeficiency and autoimmune diseases. The next challenge is to determine how and where memory B and T cells interact during secondary responses to facilitate the rapid and robust response that characterizes anamnestic immunity. 

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Homeobox NKX2-3 promotes marginal-zone lymphomagenesis by activating B-cell receptor signalling and shaping lymphocyte dynamics

Homeobox NKX2-3 promotes marginal-zone lymphomagenesis by activating B-cell receptor signalling and shaping lymphocyte dynamics | immunology | Scoop.it
The homeobox NKX2 family of transcriptional factors has been shown to regulate fundamental developmental processes.
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Controversial role of mast cells in skin cancers

Controversial role of mast cells in skin cancers | immunology | Scoop.it
Cancer development is a multi-step process characterized by genetic and epigenetic alterations during tumor initiation and progression. The stromal microenvironment can promote tumor development.
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...  Mast cells, widely distributed throughout all tissues, are a stromal component of many solid and hematologic tumors. Mast cells can be found in human and mouse models of skin cancers such as melanoma, basal and squamous cell carcinomas, primary cutaneous lymphomas, hemangiomas and Merkel cell carcinoma. However, human and animal studies addressing potential functions of mast cells and their mediators in skin cancers have provided conflicting results. In several studies mast cells play a pro-tumorigenic role, whereas in others they play an anti-tumorigenic role. Other studies have failed to demonstrate a clear role for tumor-associated mast cells. Many unanswered questions need to be addressed before we understand whether tumor-associated mast cells are adversaries, allies or simply innocent bystanders in different types and subtypes of skin cancers.
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T helper 1 immunity requires complement-driven NLRP3 inflammasome activity in CD4+ T cells

T helper 1 immunity requires complement-driven NLRP3 inflammasome activity in CD4+ T cells | immunology | Scoop.it
The classical view of immune activation is that innate immune cells, such as macrophages and dendritic cells, recognize invading microbes and then alert adaptive immune cells, such as T cells, to respond. Arbore et al. now show that innate and adaptive immunity converge in human and mouse T cells. Activated T cells express components of the complement cascade, which in turn leads to the assembly of NLRP3 inflammasomes—both critical components of innate immunity that help hosts detect and eliminate microbes. In T cells, complement and inflammasomes work together to push T cells to differentiate into a specialized subset of T cells important for eliminating intracellular bacteria.

Science , this issue p. [10.1126/science.aad1210][1]

[1]: /lookup/doi/10.1126/science.aad1210
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Estimating Time of Infection Using Prior Serological and Individual Information Can Greatly Improve Incidence Estimation of Human and Wildlife Infections

Author Summary Human and wildlife diseases can be tracked by looking at incidence, which is the number of new infections per time unit (typically day, week or month).
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Clonal redemption of autoantibodies by somatic hypermutation away from self-reactivity during human immunization

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Clonal anergy is an enigmatic self-tolerance mechanism because no apparent purpose is served by retaining functionally silenced B cells bearing autoantibodies. Human autoantibodies with IGHV4-34*01 heavy chains bind to poly-N-acetyllactosamine carbohydrates (I/i antigen) on erythrocytes and B lymphocytes, cause cold agglutinin disease, and are carried by 5% of naive B cells that are anergic. We analyzed the specificity of three IGHV4-34*01 IgG antibodies isolated from healthy donors immunized against foreign rhesus D alloantigen or vaccinia virus. Each IgG was expressed and analyzed either in a hypermutated immune state or after reverting each antibody to its unmutated preimmune ancestor. In each case, the preimmune ancestor IgG bound intensely to normal human B cells bearing I/i antigen. Self-reactivity was removed by a single somatic mutation that paradoxically decreased binding to the foreign immunogen, whereas other mutations conferred increased foreign binding. These data demonstrate the existence of a mechanism for mutation away from self-reactivity in humans. Because 2.5% of switched memory B cells use IGHV4-34*01 and >43% of these have mutations that remove I/i binding, clonal redemption of anergic cells appears efficient during physiological human antibody responses.
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Inflammasomes: mechanism of assembly, regulation and signalling : Nature Reviews Immunology : Nature Publishing Group

Inflammasomes: mechanism of assembly, regulation and signalling : Nature Reviews Immunology : Nature Publishing Group | immunology | Scoop.it
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Rescooped by Gilbert C FAURE from Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights
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Epicutaneous immunotherapy induces gastrointestinal LAP+ Tregs and prevents food-induced anaphylaxis - Journal of Allergy and Clinical Immunology

Epicutaneous immunotherapy induces gastrointestinal LAP+ Tregs and prevents food-induced anaphylaxis - Journal of Allergy and Clinical Immunology | immunology | Scoop.it
Epicutaneous #immunotherapy induces gastrointestinal LAP+ Tregs and prevents food-induced #anaphylaxis https://t.co/4noEzH4vFQ

Conclusions Our data highlights the immune communication between skin and gastrointestinal tract, and identifies novel mechanisms by which epicutaneous tolerance can suppress food-induced anaphylaxis. 

 Key words: Epicutaneous immunotherapy, oral immunotherapy, food allergy, regulatory T cells, mast cells

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Leticia Tordesillas, PhD, Lucie Mondoulet, PhD, Ana Belen Blazquez, PhD, Pierre-Henri Benhamou, PhD, Hugh A. Sampson, MD, M. Cecilia Berin, PhD
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Acute serum amyloid A is an endogenous TLR2 ligand that mediates inflammatory and angiogenic mechanisms

Introduction
Acute-phase serum amyloid A (A-SAA) has cytokine-like properties and is expressed at sites of inflammation.
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Privileged Antigen Presentation in Splenic B Cell Follicles Maximizes T Cell Responses in Prime-Boost Vaccination

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Transcriptional regulation of lymphocytes by PLZF [Immunology and Inflammation]

The transcription factor PLZF [promyelocytic leukemia zinc finger, encoded by zinc finger BTB domain containing 16 (Zbtb16)] is induced during the development of innate and innate-like lymphocytes to direct their acquisition of a T-helper effector...
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NK cells and type 1 innate lymphoid cells: partners in host defense. - PubMed - NCBI

NK cells and type 1 innate lymphoid cells: partners in host defense. - PubMed - NCBI | immunology | Scoop.it
Nat Immunol. 2016 Jun 21;17(7):758-764. doi: 10.1038/ni.3482. REVIEW
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BSI June 2016

Scientific knowledge, like air, water or even disease, does not respect borders drawn on a map. Science is inherently an international endeavour, and this is particularly true for immunology. Researchers have always discovered more working together than in isolation, and have worked hard to build a strong, global scienti c community. That the UK is a world-leader, ranking rst amongst the G7 countries for the quality of our research in infection and immunology,1 is a cause of celebration. The strength of our immunological science is an asset we are able to project to attract the best and the brightest minds from around the world – minds that contribute to the success of our institutions and, ultimately, to the innovations and knowledge that keep the UK at the forefront of immunological science.
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Sex Differences in Immune Response | The Scientist Magazine®

Sex Differences in Immune Response | The Scientist Magazine® | immunology | Scoop.it
Female mice lacking an immune receptor are better than males at fighting certain viral infections.
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Clinical Immunology Highlighted article 

Clinical Immunology Highlighted article  | immunology | Scoop.it

Siglec-1-positive plasmacytoid dendritic cells (pDCs) in human peripheral blood: A semi-mature and myeloid-like subset imbalance
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Siglec-1-positive plasmacytoid dendritic cells (pDCs) in human peripheral blood: A semi-mature and myeloid-like subset imbalanced during protective and autoimmune responses Theresa R. Wilhelm, Adriano Taddeo, Oliver Winter, Axel Ronald Schulz, Julia-Nora Mälzer, Cristina Domingo, Robert Biesen, Tobias Alexander, Andreas Thiel, Andreas Radbruch, Falk Hiepe, Velia Gerl Clinical Immunology, Volume 163, February 2016, Pages 42–51 Full article on Science Direct - free access until 18 August 2016
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mTORC2 in Thymic Epithelial Cells Controls Thymopoiesis and T Cell Development

Articles from the current issue of @J_Immunol #STEM #Immunology mTORC2 in Thymic Epithelial Cells Controls Thym... https://t.co/D8io3hDzAM
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Super-resolution microscopy reveals unprecedented detail of immune cells' surface

Super-resolution microscopy reveals unprecedented detail of immune cells' surface | immunology | Scoop.it
When the body is fighting an invading pathogen, white blood cells--including T cells--must respond. Now, Salk Institute researchers have imaged how vital receptors on the surface of T cells bundle together when activated.
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Specialized proteasome subunits have an essential role in the thymic selection of CD8+ T

Specialized proteasome subunits have an essential role in the thymic selection of CD8+ T cells Eleanor Z Kincaid, Shigeo Murata, Keiji Tanaka & Kenneth L Rock AffiliationsContributionsCorresponding author Nature Immunology (2016) doi:10.1038/ni.3480 Received 05 March 2015 Accepted 02 May 2016 Published online 13 June 2016
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The cells that stimulate positive selection express specialized proteasome β-subunits different from those expressed by all other cells, including those involved in negative selection. Mice that lack all four specialized proteasome β-subunits, and therefore express only constitutive proteasomes in all cells, had a profound defect in the generation of CD8+ T cells. While a defect in positive selection would reflect an inability to generate the appropriate positively selecting peptides, a block at negative selection would point to the potential need to switch peptides between positive selection and negative selection to avoid the two processes' often cancelling each other out. We found that the block in T cell development occurred around the checkpoints of positive selection and, unexpectedly, negative selection as well.
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Do innate NK cells truly show memory-like response to antigens? Monobenzone [hapten] study | NIHilist's Immunology

Do innate NK cells truly show memory-like response to antigens? Monobenzone [hapten] study | NIHilist's Immunology | immunology | Scoop.it
Do NK cells truly show memory-like response to antigen? Monobenzone [hapten] study
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Frontiers | Combined Expression of IFN-γ, IL-17, and IL-4 mRNA by Recall PBMCs Moderately Discriminates Active Tuberculosis from Latent Mycobacterium tuberculosis Infection in Patients with Miscell...

Frontiers | Combined Expression of IFN-γ, IL-17, and IL-4 mRNA by Recall PBMCs Moderately Discriminates Active Tuberculosis from Latent Mycobacterium tuberculosis Infection in Patients with Miscell... | immunology | Scoop.it
New biomarkers are needed for discriminating active tuberculosis (TB) from latent TB infection (LTBI) especially in vulnerable groups representing the major diagnostic challenge. This pilot study was carried out to explore the diagnostic potential of selected genes, IFN-γ, IL-17, IL-4, and FoxP3, associated with TB immunity and immunopathology. IFN-γ, IL-17, IL-4, and FoxP3 mRNA expression levels were measured by quantitative reverse transcription PCR (RT-qPCR) from antigen-stimulated PBMCs of patients with active TB (n = 25); patients with miscellaneous inflammatory disorders and concomitant LTBI (n = 20), rheumatoid arthritis (RA) being the most predominant in the group (n = 11); and in healthy Bacillus Calmette-Guérin BCG vaccinees (n = 8). While the levels of FoxP3 mRNA did not differ between the tested groups, the cumulative expression levels of PPD-stimulated IFN-γ, IL-17, and IL-4 mRNAs were found to distinguish active TB from the whole group of LTBI with 48% sensitivity and 85% specificity. When restricting the LTBI group to RA cases only, the sensitivity was 56% and specificity 100%. When interpreting the result as positive in at least one of mRNAs IFN-γ, IL-17 or IL-4, sensitivity of 64% and specificities of 75% (heterogeneous group of LTBI) or 100% (LTBI with RA) were achieved. Poor discrimination of active TB from LTBI with miscellaneous inflammatory underlying conditions by using combined quantitative expression of IFN-γ, IL-17 and IL-4 mRNA seems not to be of high diagnostic potential.
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The Monospecificity of Novel Anti-HLA-E Monoclonal Antibodies Enables Reliable Immunodiagnosis, Immunomodulation of HLA-E, and Upregulation of CD8+ T Lymphocytes

The Monospecificity of Novel Anti-HLA-E Monoclonal Antibodies Enables Reliable Immunodiagnosis, Immunomodulation of HLA-E, and Upregulation of CD8+ T Lymphocytes | immunology | Scoop.it
Abstract In human cancers, over-expression of HLA-E is marked by gene expression. However, immunolocalization of HLA-E on tumor cells is impeded by the HLA-Ia reactivity of commercial anti-HLA-E monoclonal antibodies (MAbs). So there was a clear need to develop monospecific anti-HLA-E MAbs for reliable immunodiagnosis of HLA-E, particularly considering the prognostic relevance of HLA-E in human cancer. HLA-E overexpression is correlated with disease progression and poor survival of patients, both of which are attributed to the suppression of anti-tumor activity of cytotoxic T cells mediated by HLA-E. The suppression mechanism involves the binding of HLA-E-specific amino acids located on the α1 and α2 helices of HLA-E to the inhibitory receptors (CD94/NKG2a) on CD8+ T lymphocytes. An anti-HLA-E MAb that recognizes these HLA-E-specific sequences can not only be a monospecific MAb with potential for specific immunolocalization of HLA-E but can also block the sequences from interacting with the CD94/NKG2a receptors. We therefore developed several clones that secrete such HLA-E-specific MAbs; then we assessed the ability of the MAbs to bind to the amino acid sequences interacting with the CD94/NKG2a receptors by inhibiting them from binding to HLA-E with peptides that inhibit receptor binding. Elucidation of the immunomodulatory capabilities of these monospecific MAbs showed that they can induce proliferation of CD8+ T cells with or without co-stimulation. These novel MAbs can serve a dual role in combating cancer by blocking interaction of HLA-E with CD94/NKG2a and by promoting proliferation of both non-activated and activated CD8+ cytotoxic αβ T cells.

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Monoclon Antib Immunodiagn Immunother. 2015 Jun;34(3):135-53. doi: 10.1089/mab.2014.0096. 
The Monospecificity of Novel Anti-HLA-E Monoclonal Antibodies Enables Reliable Immunodiagnosis, Immunomodulation of HLA-E, and Upregulation of CD8+ T Lymphocytes. 
Ravindranath MH1, Terasaki PI1, Pham T1, Jucaud V1.
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Antigen Recognition: Michael Dustin

Dustin introduces the immunological synapse, the molecular interaction by which T cells and antigen presenting cells communicate.
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