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Trends in Immunology

Feixiong Cheng, Joseph Loscalzo
Contemporary immunotherapies (e.g., immune checkpoint inhibitors), which enhance the immune response to cancer cells, improve clinical outcomes in several malignancies. A recent study reported the cases of two patients with metastatic melanoma who developed fatal myocarditis during ipilimumab and nivolumab combination immunotherapy; these examples highlight the risk of unbridled activation of the immune system.
December 2, 2016: Trends in Immunology
Lei Xu, Wenshi Wang, Maikel P Peppelenbosch, Qiuwei Pan
No abstract text is available yet for this article.
December 1, 2016: Trends in Immunology
Eri Ishikawa, Daiki Mori, Sho Yamasaki
Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), infects one-third of the world's population and causes 1.5 million deaths each year. The cell envelopes of mycobacteria comprise a wealth of unique glycolipids, including trehalose-6,6'-dimycolate (TDM), lipoarabinomannan (LAM), lipomannan (LM), and phosphatidylinositol (PI) mannosides (PIMs). These lipids are important modulators of the host immune responses during infection and in some cases have been used as adjuvants [e.g., complete Freund's adjuvant (CFA)]...
November 23, 2016: Trends in Immunology
Mark Hermann, Dusan Bogunovic
ISG15 is a type I interferon (IFN)-inducible gene encoding a protein with pleiotropic functions, acting both as a soluble molecule and as a protein modifier. Surprisingly, and despite the antiviral functions of ISG15 described in mice, humans born with inactivating mutations of ISG15 do not present with any overt viral phenotype, but are highly susceptible to environmental mycobacteria and have autoinflammatory disease presentations. In vitro, ISG15 deficiency also leads to persistently high levels of type I IFN-stimulated gene expression and to increased resistance to all viruses tested to date...
November 22, 2016: Trends in Immunology
Cindy Chiang, Michaela U Gack
Mammalian cells recognize virus-derived nucleic acids using a defined set of intracellular sensors including the DNA sensors cyclic GMP-AMP (cGAMP) synthase (cGAS) and interferon gamma (IFNγ)-inducible protein 16 (IFI16) as well as viral RNA receptors of the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) family. Following innate immune recognition, these sensors launch an immune response that is characterized by the transcriptional upregulation of many antiviral molecules, including proinflammatory cytokines, chemokines, and IFN-stimulated genes...
November 15, 2016: Trends in Immunology
Nicolas Vabret, Nina Bhardwaj, Benjamin D Greenbaum
Innate immune cells are endowed with many nucleic acid receptors, but the role of sequence in the detection of foreign organisms remains unclear. Can sequence patterns influence recognition? In addition, how can we infer those patterns from sequence data? Here, we detail recent computational and experimental evidence associated with sequence-specific sensing. We review the mechanisms underlying the detection and discrimination of foreign sequences from self. We also describe quantitative approaches used to infer the stimulatory capacity of a given pathogen nucleic acid species, and the influence of sequence-specific sensing on host-pathogen coevolution, including endogenous sequences of foreign origin...
November 14, 2016: Trends in Immunology
Andreas Krueger, Natalia Ziętara, Marcin Łyszkiewicz
T cells are continually generated in the thymus in a highly dynamic process comprising discrete steps of lineage commitment, T cell receptor (TCR) gene rearrangement, and selection. These steps are linked to distinct rates of proliferation, survival, and cell death, but a quantitative picture of T cell development is only beginning to emerge. Here we summarize recent technical advances, including genetic fate mapping, barcoding, and molecular timers, that have allowed the implementation of computational models to quantify developmental dynamics in the thymus...
November 11, 2016: Trends in Immunology
Jochen Mattner, Stefan Wirtz
The development of immunotherapies represents a major advance towards the effective eradication of malignant tumors. So far, therapeutic approaches have largely focused on T lymphocytes, but the innate arm of the immune system might be similarly important. Innate lymphoid cells (ILCs) are rapidly-responding cells that are functionally analogous to diverse T cell subsets. In recent years these cells have attracted enormous attention owing to their pleiotropic effects in early host defense to infection and organ pathologies...
October 31, 2016: Trends in Immunology
Nicholas A Manieri, Eugene Y Chiang, Jane L Grogan
Immunotherapies that harness the activity of the immune system against tumors are proving to be an effective therapeutic approach in multiple malignancies. Indeed, through accumulation of genetic mutations, many tumors express antigens that can potentially elicit specific tumor immunity. However, tumors can also suppress these responses by activating negative regulatory pathways and checkpoints such as PD-1/PD-L1 and CTLA-4. Blocking these checkpoints on T cells has provided dramatic clinical benefit, but only a subset of patients exhibit clear and durable responses, suggesting that other mechanisms must be limiting the immune response...
October 25, 2016: Trends in Immunology
Felipe A Pinho-Ribeiro, Waldiceu A Verri, Isaac M Chiu
Nociceptor sensory neurons protect organisms from danger by eliciting pain and driving avoidance. Pain also accompanies many types of inflammation and injury. It is increasingly clear that active crosstalk occurs between nociceptor neurons and the immune system to regulate pain, host defense, and inflammatory diseases. Immune cells at peripheral nerve terminals and within the spinal cord release mediators that modulate mechanical and thermal sensitivity. In turn, nociceptor neurons release neuropeptides and neurotransmitters from nerve terminals that regulate vascular, innate, and adaptive immune cell responses...
October 25, 2016: Trends in Immunology
Jacques Deguine
No abstract text is available yet for this article.
October 3, 2016: Trends in Immunology
Rosa Molfetta, Linda Quatrini, Beatrice Zitti, Cristina Capuano, Ricciarda Galandrini, Angela Santoni, Rossella Paolini
NKG2D is an activating receptor that can bind to a large number of stress-induced ligands that are expressed in the context of cancer or viral infection. This receptor is expressed on many cytotoxic lymphocytes, and plays a crucial role in antitumor and antiviral immune responses. However, exposure to NKG2D ligand-expressing target cells promotes receptor endocytosis, ultimately leading to lysosomal receptor degradation and impairment of NKG2D-mediated functions. Interestingly, before being degraded, internalized receptors can signal from the endosomal compartment, leading to the appropriate activation of cellular functional programs...
September 22, 2016: Trends in Immunology
Christian Münz
Autophagy is a group of cellular pathways that deliver cytoplasmic constituents for lysosomal degradation. The peptides generated from these pathways can be presented by MHC II molecules, making autophagy an important source of antigens for CD4(+) T cells. In addition, modules of the molecular machinery of autophagy were found in recent years to also influence extracellular antigen processing for MHC Class I and Class II presentation, as well as regulation of MHC Class I surface expression. These studies paint a more complicated picture of how regulation of individual autophagy proteins influences adaptive immunity...
September 22, 2016: Trends in Immunology
Anthony Bowen, Arturo Casadevall
A generation ago, the immunoglobulin intramolecular signaling, or allosteric, hypothesis was abandoned in favor of the associative hypothesis, which posited that Fc receptor crosslinking produced the increased affinity of antigen-antibody complexes. This essay argues that there is sufficient evidence to resuscitate the allosteric hypothesis, at least for some antibodies.
September 14, 2016: Trends in Immunology
Dragos C Dasoveanu, William D Shipman, Jennifer J Chia, Susan Chyou, Theresa T Lu
During normal and pathologic immune responses, lymph nodes can swell considerably. The lymph node vascular-stromal compartment supports and regulates the developing immune responses and undergoes dynamic expansion and remodeling. Recent studies have shown that dendritic cells (DCs), best known for their antigen presentation roles, can directly regulate the vascular-stromal compartment, pointing to a new perspective on DCs as facilitators of lymphoid tissue function. Here, we review the phases of lymph node vascular-stromal growth and remodeling during immune responses, discuss the roles of DCs, and discuss how this understanding can potentially be used for developing novel therapeutic approaches...
September 13, 2016: Trends in Immunology
Pascale Baden, Michela Deleidi
Mitochondrial antigens can be presented by MHC molecules and initiate adaptive immune responses but the mechanisms of mitochondrial antigen presentation (MitAP) have remained mostly unknown. A recent study proposes a new model whereby MitAP is mediated by a vesicle transport pathway that is suppressed by the Parkinson's disease (PD) associated proteins PTEN-induced putative kinase 1 (PINK1) and Parkin. This discovery brings a new perspective on the link between mitochondrial dysfunction and autoimmunity in PD...
September 13, 2016: Trends in Immunology
Katie Soucy, Rick M Fairhurst, Geoffrey M Lynn, Kevin Fomalont, Thomas A Wynn, Richard M Siegel
Immunology is an increasingly interdisciplinary field. Here we describe a new model for interinstitutional graduate training as partnerships between complementary laboratories. This collaborative model reduces time to graduation without compromising productivity or alumni outcomes. We offer our experience with one such program and thoughts on the ingredients for their success. Despite tremendous recent advances in technology, communications, and the translation of basic scientific discoveries into new diagnostics and therapies for human diseases, graduate training in immunology and other areas of biomedical research in the United States has remained remarkably unchanged since the early 20th century, with coursework and laboratory rotations taking up much of the first 2 years, and a single mentor shepherding the student through a research project over 3 or more subsequent years...
December 2016: Trends in Immunology
Balthasar A Heesters, Cees E van der Poel, Abhishek Das, Michael C Carroll
Unlike T cells that recognize digested peptides, B cells recognize their cognate antigen in its native form. The B cell receptor used in recognition can also be secreted to bind to antigens and initiate multiple effector functions such as phagocytosis, complement activation, or neutralization of receptors. While B cells can interact with soluble antigens, it is now clear that the presentation of membrane-bound antigen plays a crucial role in B cell activation, and in particular during affinity-maturation, the process during which high-affinity B cells are selected...
December 2016: Trends in Immunology
Alycia Gardner, Brian Ruffell
Dendritic cells (DCs) are central regulators of the adaptive immune response, and as such are necessary for T-cell-mediated cancer immunity. In particular, antitumoral responses depend on a specialized subset of conventional DCs that transport tumor antigens to draining lymph nodes and cross-present antigen to activate cytotoxic T lymphocytes. DC maturation is necessary to provide costimulatory signals to T cells, but while DC maturation occurs within tumors, it is often insufficient to induce potent immunity, particularly in light of suppressive mechanisms within tumors...
December 2016: Trends in Immunology
Patrick M Brauer, Jastaranpreet Singh, Sintia Xhiku, Juan Carlos Zúñiga-Pflücker
T cells, as orchestrators of the adaptive immune response, serve important physiological and potentially therapeutic roles, for example in cancer immunotherapy. T cells are readily isolated from patients; however, the yield of antigen-specific T cells is limited, thus making their clinical use challenging. Therefore, the generation of T lymphocytes from hematopoietic stem/progenitor cells (HSPCs) and human pluripotent stem cells (PSCs) in vitro provides an attractive method for the large-scale production and genetic manipulation of T cells...
December 2016: Trends in Immunology
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