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Current Opinion in Immunology

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https://www.readbyqxmd.com/read/28088708/germinal-centers-programmed-for-affinity-maturation-and-antibody-diversification
#1
REVIEW
Oliver Bannard, Jason G Cyster
The seminal discovery by Eisen that antibodies undergo improvements in antigen-binding affinity over the course of an immune response led to a long running search for the underlying mechanism. Germinal centers in lymphoid organs are now recognized to be critically involved in this phenomenon, known as antibody affinity maturation. As well as improving in affinity for specific epitopes, some antibody responses maintain or even increase their breadth of antigen-recognition over time. This has led to another intense line of research aimed at understanding how broadly neutralizing anti-pathogen responses are generated...
January 12, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28088707/dna-sensing-and-immune-responses-in-cancer-therapy
#2
REVIEW
Jian Qiao, Haidong Tang, Yang-Xin Fu
The identification of critical DNA sensors and their pathways has led to revealing the central role of DNA sensing in immune system. It has been initially demonstrated that DNA sensing and immune responses have high impacts on the development and prevention of infection and inflammatory. In addition to toll-like receptor pathways, there is now also emerging evidence that cytosolic enzyme cyclic GMP-AMP synthase (cGAS) is essential for the recognition of not only pathogen-derived DNA but also tumor DNA for innate sensing...
January 12, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28088061/galectins-emerging-regulatory-checkpoints-linking-tumor-immunity-and-angiogenesis
#3
REVIEW
Santiago P Méndez-Huergo, Ada G Blidner, Gabriel A Rabinovich
Immune checkpoints, a plethora of inhibitory pathways aimed at maintaining immune cell homeostasis, may be co-opted by cancer cells to evade immune destruction. Therapies targeting immune checkpoints have reached a momentum yielding significant clinical benefits in patients with various malignancies by unleashing anti-tumor immunity. Galectins, a family of glycan-binding proteins, have emerged as novel regulatory checkpoints that promote immune evasive programs by inducing T-cell exhaustion, limiting T-cell survival, favoring expansion of regulatory T cells, de-activating natural killer cells and polarizing myeloid cells toward an immunosuppressive phenotype...
January 11, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/27984782/nk-cells-in-host-responses-to-viral-infections
#4
REVIEW
Viola C Lam, Lewis L Lanier
Natural killer (NK) cells are cytotoxic innate lymphocytes that play an important role in viral clearance. NK cell responses to viral infections were originally believed to be non-specific and lacked immune memory recall responses. It is now appreciated that NK cell responses to viral infections can be specific and in some cases memory recall responses are established. Increasing evidence also illuminates the complexity of NK cell interactions with both innate and adaptive immune cells. Here, we summarize the evidence for NK cell-specific memory responses to viral infections and the intricate reciprocal interactions between NK cells and other immune cells that dictate their activation and effector functions...
December 13, 2016: Current Opinion in Immunology
https://www.readbyqxmd.com/read/27951434/neutrophil-migration-in-inflammation-intercellular-signal-relay-and-crosstalk
#5
REVIEW
Sioh-Yang Tan, Wolfgang Weninger
Neutrophils are innate effector cells armed with a potent machinery to combat damage and infection within tissues. Their ability to rapidly respond to danger signals and mobilise is crucial to their role. After extravasation, neutrophil populations often exhibit swarming behaviour. Swarming occurs in distinct phases and is coordinated via inter-neutrophil signal relay in the form of small molecule mediators. Neutrophils also engage in multi-dimensional crosstalk with tissue-resident cells and incoming leukocytes in the inflammatory milieu...
December 9, 2016: Current Opinion in Immunology
https://www.readbyqxmd.com/read/27940327/peptide-vaccines-in-cancer-old-concept-revisited
#6
REVIEW
Takumi Kumai, Hiroya Kobayashi, Yasuaki Harabuchi, Esteban Celis
Synthetic peptide vaccines aim to elicit and expand tumor-specific T cells capable of controlling or eradicating the tumor. Despite the high expectations based on preclinical studies, the results of clinical trials using peptide vaccines have been disappointing. Thus, many researchers in the field have considered peptide vaccines as outdated and no longer viable for cancer therapy. However, recent progress in understanding the critical roles of immune adjuvants, modes of vaccine administration and T cell dynamics has lead to a rebirth of this approach and reconsidering the use of peptide vaccines for treating malignant disorders...
December 8, 2016: Current Opinion in Immunology
https://www.readbyqxmd.com/read/27907816/nucleic-acid-sensing-tlrs-trafficking-and-regulation
#7
REVIEW
Olivia Majer, Bo Liu, Gregory M Barton
Toll-like receptors (TLRs) play an important role in innate immune responses against pathogenic microorganisms or tissue damage. Nucleic acid (NA)-sensing TLRs localize in intracellular vesicular compartments and recognize foreign-derived and host-derived nucleic acid ligands. Inappropriate activation of NA-sensing TLRs can cause pathogenic inflammation and autoimmunity. Multiple regulatory mechanisms exist to limit recognition of self-NAs. This review summarizes recent progress that has been made in understanding how NA-sensing TLRs are regulated via trafficking, proteolytic cleavage, as well as ligand processing and recognition...
November 28, 2016: Current Opinion in Immunology
https://www.readbyqxmd.com/read/27855321/plasmacytoid-dendritic-cells-in-autoimmunity
#8
REVIEW
Santosh K Panda, Roland Kolbeck, Miguel A Sanjuan
Plasmacytoid dendritic cells (pDC) is a unique cell population that produces large amounts of type I interferon upon recognition of nucleic acids placing them at the crossroad of both innate and adaptive immunity. Their ability to produce interferon makes them central to anti-viral responses. They are also responsive to circulating autoantibodies bound to nuclear antigens and in that scenario the release of interferons initiate self-directed immune responses. There are now a growing number of autoimmune disorders where unabated activation of pDC is suspected to be pathogenic...
November 14, 2016: Current Opinion in Immunology
https://www.readbyqxmd.com/read/27842238/alternative-inflammasome-activation-enables-il-1%C3%AE-release-from-living-cells
#9
REVIEW
Moritz M Gaidt, Veit Hornung
Classical modes of NLRP3 activation entail a priming step that enables its activation (signal 1) and a potassium efflux-dependent activation signal (signal 2) that triggers pyroptosome formation and pyroptosis, a lytic cell death necessary for IL-1β release. Opposing to that, human monocytes engage an alternative NLRP3 inflammasome pathway in response to LPS that proceeds in the absence of signal 2 activation and enables IL-1β secretion without pyroptosis. This specifically relies on Caspase-8 to propagate signaling to NLRP3, leading to inflammasome activation in absence of pyroptosome formation...
November 11, 2016: Current Opinion in Immunology
https://www.readbyqxmd.com/read/27842237/early-innate-immune-responses-to-bacterial-lps
#10
REVIEW
Charles V Rosadini, Jonathan C Kagan
A mammalian receptor for bacterial lipopolysaccharide (LPS), Toll-like receptor 4 (TLR4), plays a beneficial role in controlling bacterial infections, but is also a main driver of aberrant inflammation in lethal sepsis. As a result, investigation of TLR4 signaling has been a major area of research. Despite this focus, our understanding of the mechanisms that regulate TLR4 activities remains primitive. Nowhere is our knowledge of TLR4 biology more lacking than at the receptor-proximal level, where many factors act in concert to regulate LPS signaling...
November 11, 2016: Current Opinion in Immunology
https://www.readbyqxmd.com/read/27839940/editorial-overview-autoimmunity
#11
EDITORIAL
Kathryn Haskins, Jane Hoyt Buckner
No abstract text is available yet for this article.
November 10, 2016: Current Opinion in Immunology
https://www.readbyqxmd.com/read/27835762/il-15-signaling-in-nk-cell-cancer-immunotherapy
#12
REVIEW
Jai Rautela, Nicholas D Huntington
While cancer has been traditionally treated by chemotherapy, radiation, targeted therapies and surgery, a fifth pillar of cancer treatment, immunotherapy, has emerged over the past 10 years and revolutionized our war on cancer. The benchmark for drugs in this category has been set by the development of CD8 T cell checkpoint (CTLA-4 and PD-1/PD-L1) inhibitors. These therapies effectively expand and reactivate the pool of tumor-specific T cells leading to objective response rates of up to 50% in patients with certain cancers...
November 8, 2016: Current Opinion in Immunology
https://www.readbyqxmd.com/read/27821272/targeting-cytokine-signaling-in-autoimmunity-back-to-the-future-and-beyond
#13
REVIEW
Kiyoshi Hirahara, Daniella Schwartz, Massimo Gadina, Yuka Kanno, John J O'Shea
Cytokines represent structurally diverse soluble factors with critical roles in normal immune function and the pathogenesis of autoimmunity. The emergence of many successful biological therapies targeting cytokines and cytokine receptors exemplifies the importance of cytokines in driving human autoimmune disease; unsurprisingly, there is no paucity of reviews on this subject. Nonetheless, many patients with autoimmune disease do not respond to biologicals, and cure remains an unmet goal. Thus, targeting the intracellular pathways employed by cytokines provides new therapeutic opportunities...
December 2016: Current Opinion in Immunology
https://www.readbyqxmd.com/read/27744240/t-cell-exhaustion-and-immune-mediated-disease-the-potential-for-therapeutic-exhaustion
#14
REVIEW
Eoin F McKinney, Kenneth Gc Smith
T cell exhaustion represents a continuous spectrum of cellular dysfunction induced during chronic viral infection, facilitating viral persistence and associating with poor clinical outcome. Modulation of T cell exhaustion can restore function in exhausted CD8 T cells, promoting viral clearance. Exhaustion has also been implicated as playing an important role in anti-tumour responses, whereby exhausted tumour-infiltrating lymphocytes fail to control tumour progression. More recently exhaustion has been linked to long-term clinical outcome in multiple autoimmune diseases but, in contrast to cancer or infection, it is associated with a favourable clinical outcome characterised by fewer relapses...
December 2016: Current Opinion in Immunology
https://www.readbyqxmd.com/read/27718448/endoplasmic-reticulum-stress-in-beta-cells-and-autoimmune-diabetes
#15
REVIEW
Amy L Clark, Fumihiko Urano
Type 1 diabetes results from the autoimmune destruction of pancreatic β cells, leading to insulin deficiency and hyperglycemia. Although multiple attempts have been made to slow the autoimmune process using immunosuppressive or immunomodulatory agents, there are still no effective treatments that can delay or reverse the progression of type 1 diabetes in humans. Recent studies support endoplasmic reticulum (ER) as a novel target for preventing the initiation of the autoimmune reaction, propagation of inflammation, and β cell death in type 1 diabetes...
December 2016: Current Opinion in Immunology
https://www.readbyqxmd.com/read/27718447/targeting-b-cells-in-treatment-of-autoimmunity
#16
REVIEW
S Elizabeth Franks, Andrew Getahun, P Mark Hogarth, John C Cambier
B cells have emerged as effective targets for therapeutic intervention in autoimmunities in which the ultimate effectors are antibodies, as well as those in which T cells are primary drivers of inflammation. Proof of this principle has come primarily from studies of the efficacy of Rituximab, an anti-CD20 mAb that depletes B cells, in various autoimmune settings. These successes have inspired efforts to develop more effective anti-CD20s tailored for specific needs, as well as biologicals and small molecules that suppress B cell function without the risks inherent in B cell depletion...
December 2016: Current Opinion in Immunology
https://www.readbyqxmd.com/read/27710840/macrophages-and-dendritic-cells-in-islets-of-langerhans-in-diabetic-autoimmunity-a-lesson-on-cell-interactions-in-a-mini-organ
#17
REVIEW
Javier A Carrero, Stephen T Ferris, Emil R Unanue
Islets of Langerhans of all species harbor a small number of resident macrophages. These macrophages are found since birth, do not exchange with blood monocytes, and are maintained by a low level of replication. Under steady state conditions, the islet macrophages are in an activated state. Islet macrophages have an important homeostatic role in islet physiology. At the start of the autoimmune process in the NOD mouse, a small number of CD103+ dendritic cells (DC) are found at about the same time that CD4+ T cells also appear in islets...
December 2016: Current Opinion in Immunology
https://www.readbyqxmd.com/read/27710839/environmental-control-of-autoimmune-inflammation-in-the-central-nervous-system
#18
REVIEW
Veit Rothhammer, Francisco J Quintana
Multiple sclerosis (MS) is a chronic autoimmune inflammatory demyelinating disorder of the central nervous system (CNS), which causes severe disability and requires extensive medical attention and treatment. While the infiltration of pathogenic immune cells into the CNS leads to the formation of inflammatory lesions in its initial relapsing-remitting stage, late stages of MS are characterized by progressive neuronal loss and demyelination even without continued interaction with the peripheral immune compartment...
December 2016: Current Opinion in Immunology
https://www.readbyqxmd.com/read/27636649/t-cells-in-systemic-lupus-erythematosus
#19
REVIEW
Abel Suárez-Fueyo, Sean J Bradley, George C Tsokos
Systemic Lupus Erythematosus is an autoimmune disorder caused by a complex combination of genetic, epigenetic and environmental factors. Different polymorphisms and epigenetic modifications lead to altered gene expression and function of several molecules which lead to abnormal T cell responses. Metabolic and functional alterations result in peripheral tolerance failures and biased differentiation of T cells into pro-inflammatory and B cell-helper phenotypes as well as the accumulation of disease-promoting memory T cells...
December 2016: Current Opinion in Immunology
https://www.readbyqxmd.com/read/27588918/t-follicular-helper-cells-in-human-autoimmunity
#20
REVIEW
Hideki Ueno
Studies with mouse models have established the pathogenic roles of T follicular helper (Tfh) cells in antibody-mediated autoimmune diseases. In contrast, evidence in human autoimmune pathogenesis has been lacking for years. Recent progress in understanding on the biology of human Tfh cells and on the approaches assessing their response has enabled gaining insights into the alterations of Tfh response and the underlying mechanisms. For example, increase of circulating Tfh (cTfh) cells expressing PD-1 and/or ICOS and alterations in the composition of cTfh subsets have emerged as a common feature in a broad range of autoimmune diseases...
December 2016: Current Opinion in Immunology
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