Role of germinal centers for the induction of broadly-reactive memory B cells.
Abstract Virus-specific memory B cells (Bmem) play a crucial role in protecting against variant viruses. The ability to recognize these variant viruses, defined as antibody breadth, is achieved in Bmem populations by two very different pathways, germline-encoded cross-reactivity and affinity-driven, somatic evolution in germinal centers (GCs) for conserved viral epitopes. The latter class of broadly-reactive Bmem cells are not cross-reactive per se, but bind epitopes crucial for viral fitness. Although these conserved epitopes are often weakly immunogenic, the GC reaction is surprisingly permissive for the continu...
Source: Current Opinion in Immunology - March 26, 2017 Category: Allergy & Immunology Authors: Takahashi Y, Kelsoe G Tags: Curr Opin Immunol Source Type: research

Stromal networking: cellular connections in the germinal centre.
Abstract Secondary lymphoid organs are organized into distinct zones, governed by different types of mesenchymal stromal cells. These stromal cell subsets are critical for the generation of protective humoral immunity because they direct the migration of, and interaction between, multiple immune cell types to form the germinal centre. The germinal centre response generates long-lived antibody-secreting plasma cells and memory B cells which can provide long-term protection against re-infection. Stromal cell subsets mediate this response through control of immune cell trafficking, activation, localization and antige...
Source: Current Opinion in Immunology - March 17, 2017 Category: Allergy & Immunology Authors: Denton AE, Linterman MA Tags: Curr Opin Immunol Source Type: research

Deconstructing the germinal center, one cell at a time.
Abstract Successful vaccination relies on driving the immune response towards high specificity, affinity and longevity. Germinal centers facilitate the evolution of antigen-specific B cells by iterative rounds of diversification, selection, and differentiation to memory and plasma cells. Experimental evidence points to B cell receptor affinity and amount of antigen presented to follicular helper T cells as main drivers of clonal evolution. Concurrent studies suggest that modifiers of cognate contact, temporal mechanisms, and stochastic factors can also shape diversity and influence differentiation to memory and pl...
Source: Current Opinion in Immunology - March 17, 2017 Category: Allergy & Immunology Authors: Dufaud CR, McHeyzer-Williams LJ, McHeyzer-Williams MG Tags: Curr Opin Immunol Source Type: research

Stimulating CD27 to quantitatively and qualitatively shape adaptive immunity to cancer.
Abstract The capacity of the immune system to recognize and respond to tumors has been appreciated for over 100 years. However, clinical success has largely depended on the elucidation of the positive and negative regulators of effector cells after their activation via the antigen cell receptor. On the one hand, effector cells upregulate checkpoint molecules that are thought to play a role in limiting immunopathology. On the other, second and third waves of costimulation are often required to promote the expansion, survival and differentiation of effector cells. While it is clear that the immune system can be unle...
Source: Current Opinion in Immunology - March 16, 2017 Category: Allergy & Immunology Authors: Bullock TN Tags: Curr Opin Immunol Source Type: research

An antigen to remember: regulation of B cell memory in health and disease.
Abstract Vaccine success relies on the formation of immunity. Humoral immunity is critical and is mediated by long-lived antibody-secreting cells and memory B cells (MBCs). Chronic infectious diseases cause a significant global burden of disease; pathogens that evade the immune system can cause phenotypical and functional changes to immune memory populations. Thus, recent studies have focused on MBC subset function. IgM(+) MBCs have emerged as important early responders in malaria. Atypical MBCs have functional qualities associated with exhaustion in chronic infectious diseases, but the requirements for their form...
Source: Current Opinion in Immunology - March 16, 2017 Category: Allergy & Immunology Authors: Pupovac A, Good-Jacobson KL Tags: Curr Opin Immunol Source Type: research

Plasma cell and memory B cell differentiation from the germinal center.
Abstract Germinal centers (GCs) form in secondary lymphoid tissues in response to antigenic challenge and are the site of somatic hypermutation, generating GC B cells with increasing affinity for the inciting agent that are positively selected over time. However, it is not until GC B cells differentiate into memory B cells and plasma cells and egress from the GC back into the circulation that effective long-lived humoral immunity is conferred upon the host. Here we review what is known about the signals that initiate the transition from a GC B cell into the memory B cell and plasma cell compartments and the downst...
Source: Current Opinion in Immunology - March 16, 2017 Category: Allergy & Immunology Authors: Suan D, Sundling C, Brink R Tags: Curr Opin Immunol Source Type: research

Targeting NK-cell checkpoints for cancer immunotherapy.
Botet M, Melero I Abstract Natural Killer (NK) cells are cytotoxic lymphocytes specialized in early defense against virus-infected and transformed cells. NK-cell function is regulated by activating and inhibitory surface receptors recognizing their ligands on transformed cells. Modulation of NK numbers and/or function by a variety of agents such as cytokines and monoclonal antibodies may result in enhanced anti-tumor activity. Recombinant cytokines (i.e., IL-15 and IL-2), antibodies blocking inhibitory receptors (i.e., KIR, NKG2A and TIGIT) and agonists delivering signals via CD137, NKG2D and CD16 stand out as the...
Source: Current Opinion in Immunology - February 22, 2017 Category: Allergy & Immunology Authors: Muntasell A, Ochoa MC, Cordeiro L, Berraondo P, López-Díaz de Cerio A, Cabo M, López-Botet M, Melero I Tags: Curr Opin Immunol Source Type: research

Immunoprofiling as a predictor of patient's response to cancer therapy-promises and challenges.
Abstract Immune cell infiltration is common to many tumors and has been recognized by pathologists for more than 100 years. The application of digital imaging and objective assessment software allowed a concise determination of the type and quantity of immune cells and their location relative to the tumor and, in the case of colon cancer, characterized overall survival better than AJCC TNM staging. Subsequently, expression of PD-L1, by 50% or more tumor cells, identified NSCLC patients with double the response rate to anti-PD-1. Soon, automated staining methods will improve reproducibility of multiplex staining an...
Source: Current Opinion in Immunology - February 18, 2017 Category: Allergy & Immunology Authors: Bethmann D, Feng Z, Fox BA Tags: Curr Opin Immunol Source Type: research

Oncogenic growth factor signaling mediating tumor escape from cellular immunity.
Abstract Unrestrained growth factor signals can promote carcinogenesis, as well as other hallmarks of cancer such as immune evasion. Our understanding of the function and complex regulation of HER family of receptors has led to the development of targeted therapeutic agents that suppress tumor growth. However, these receptors also mediate escape from recognition by the host immune system. We discuss how HER family of oncogenic receptors downregulate tumor antigen presentation and upregulate suppressive membrane-bound or soluble secreted inhibitory molecules that ultimately lead to impaired cellular immunity mediat...
Source: Current Opinion in Immunology - February 13, 2017 Category: Allergy & Immunology Authors: Concha-Benavente F, Ferris RL Tags: Curr Opin Immunol Source Type: research

Dendritic cells in cancer: the role revisited.
Abstract Dendritic cells (DCs) with their potent antigen presenting ability are long considered as critical factor in antitumor immunity. Despite high potential in promoting antitumor responses, tumor-associated DCs are largely defective in their functional activity and can contribute to immune suppression in cancer. In recent years existence of immune suppressive regulatory DCs in tumor microenvironment was described. Monocytic myeloid derived suppressor cells (M-MDSCs) can contribute to the pool of tumor associated DCs by differentiating to inflammatory DCs (inf-DCs), which appear to have specific phenotype and ...
Source: Current Opinion in Immunology - February 10, 2017 Category: Allergy & Immunology Authors: Veglia F, Gabrilovich DI Tags: Curr Opin Immunol Source Type: research

Immune checkpoint receptors in cancer: redundant by design?
Abstract Co-inhibitory receptors expressed on activated immune cells function to regulate T cell tolerance to self-antigens, also serving by tumor cells to escape from eradication by the host immune system. Therefore, blockade of immune checkpoint receptors (ICR) has become a promising immunotherapeutic strategy for treatment of a wide variety of cancers. However, blockade of one of the immune checkpoint receptors alone is often not sufficiently effective; co-blockade shows synergic effects in reversing immunosuppression. In this article, we summarize the expression patterns, mechanisms of action of different ICRs...
Source: Current Opinion in Immunology - February 9, 2017 Category: Allergy & Immunology Authors: Li J, Ni L, Dong C Tags: Curr Opin Immunol Source Type: research

Murine models of germinal center derived-lymphomas.
Abstract The germinal center (GC) reaction is an adaptive immune response to select B cells bearing high-affinity B cell receptors (BCRs) to undergo further differentiation into antibody-producing cells or memory B cells. To drive affinity maturation, (GC) B cells undergo rounds of hypermutation and rapid proliferation, which can enhance susceptibility to malignant transformation. Lymphomas frequently originate from GC B cells, but the etiology for most lymphoma subtypes is unknown. Work in the past decade has more fully documented the mutational landscape in lymphomas, but the impact of these genomic lesions is o...
Source: Current Opinion in Immunology - February 1, 2017 Category: Allergy & Immunology Authors: Ramezani-Rad P, Rickert RC Tags: Curr Opin Immunol Source Type: research

Host-microbiota interactions: epigenomic regulation.
Abstract The coevolution of mammalian hosts and their commensal microbiota has led to the development of complex symbiotic relationships between resident microbes and mammalian cells. Epigenomic modifications enable host cells to alter gene expression without modifying the genetic code, and therefore represent potent mechanisms by which mammalian cells can transcriptionally respond, transiently or stably, to environmental cues. Advances in genome-wide approaches are accelerating our appreciation of microbial influences on host physiology, and increasing evidence highlights that epigenomics represent a level of reg...
Source: Current Opinion in Immunology - January 16, 2017 Category: Allergy & Immunology Authors: Woo V, Alenghat T Tags: Curr Opin Immunol Source Type: research

DNA sensing and immune responses in cancer therapy.
Abstract 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. The strategies through activating DNA sensing pathways toward enhancing antitumor imm...
Source: Current Opinion in Immunology - January 12, 2017 Category: Allergy & Immunology Authors: Qiao J, Tang H, Fu YX Tags: Curr Opin Immunol Source Type: research

Germinal centers: programmed for affinity maturation and antibody diversification.
Abstract 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 ...
Source: Current Opinion in Immunology - January 12, 2017 Category: Allergy & Immunology Authors: Bannard O, Cyster JG Tags: Curr Opin Immunol Source Type: research

Galectins: emerging regulatory checkpoints linking tumor immunity and angiogenesis.
ch GA Abstract 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 po...
Source: Current Opinion in Immunology - January 11, 2017 Category: Allergy & Immunology Authors: Méndez-Huergo SP, Blidner AG, Rabinovich GA Tags: Curr Opin Immunol Source Type: research

NK cells in host responses to viral infections.
Abstract 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 i...
Source: Current Opinion in Immunology - December 13, 2016 Category: Allergy & Immunology Authors: Lam VC, Lanier LL Tags: Curr Opin Immunol Source Type: research

Neutrophil migration in inflammation: intercellular signal relay and crosstalk.
Abstract 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. The complexity of neutrophil crosstalk with other innate immune ce...
Source: Current Opinion in Immunology - December 9, 2016 Category: Allergy & Immunology Authors: Tan SY, Weninger W Tags: Curr Opin Immunol Source Type: research

Peptide vaccines in cancer-old concept revisited.
Abstract 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 trea...
Source: Current Opinion in Immunology - December 8, 2016 Category: Allergy & Immunology Authors: Kumai T, Kobayashi H, Harabuchi Y, Celis E Tags: Curr Opin Immunol Source Type: research

Nucleic acid-sensing TLRs: trafficking and regulation.
Abstract 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 p...
Source: Current Opinion in Immunology - November 28, 2016 Category: Allergy & Immunology Authors: Majer O, Liu B, Barton GM Tags: Curr Opin Immunol Source Type: research

Plasmacytoid dendritic cells in autoimmunity.
Abstract 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. Here, we discuss the differen...
Source: Current Opinion in Immunology - November 14, 2016 Category: Allergy & Immunology Authors: Panda SK, Kolbeck R, Sanjuan MA Tags: Curr Opin Immunol Source Type: research

Early innate immune responses to bacterial LPS.
Abstract 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. Several recent studies have begun filling these gaps in...
Source: Current Opinion in Immunology - November 11, 2016 Category: Allergy & Immunology Authors: Rosadini CV, Kagan JC Tags: Curr Opin Immunol Source Type: research

Alternative inflammasome activation enables IL-1 β release from living cells.
Alternative inflammasome activation enables IL-1β release from living cells. Curr Opin Immunol. 2016 Nov 11;44:7-13 Authors: Gaidt MM, Hornung V Abstract 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 secretio...
Source: Current Opinion in Immunology - November 11, 2016 Category: Allergy & Immunology Authors: Gaidt MM, Hornung V Tags: Curr Opin Immunol Source Type: research

Editorial overview: Autoimmunity.
PMID: 27839940 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - November 10, 2016 Category: Allergy & Immunology Authors: Haskins K, Buckner JH Tags: Curr Opin Immunol Source Type: research

IL-15 signaling in NK cell cancer immunotherapy.
Abstract 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. However, the significant number of patients and cancer types that altogether fail ...
Source: Current Opinion in Immunology - November 8, 2016 Category: Allergy & Immunology Authors: Rautela J, Huntington ND Tags: Curr Opin Immunol Source Type: research

Targeting cytokine signaling in autoimmunity: back to the future and beyond.
Abstract 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. A subset of cy...
Source: Current Opinion in Immunology - November 4, 2016 Category: Allergy & Immunology Authors: Hirahara K, Schwartz D, Gadina M, Kanno Y, O'Shea JJ Tags: Curr Opin Immunol Source Type: research

Understanding mechanisms of autoimmunity through translational research in vitiligo.
Abstract Vitiligo is an autoimmune disease of the skin that leads to life-altering depigmentation and remains difficult to treat. However, clinical observations and translational studies over 30-40 years have led to the development of an insightful working model of disease pathogenesis: Genetic risk spanning both immune and melanocyte functions is pushed over a threshold by known and suspected environmental factors to initiate autoimmune T cell-mediated killing of melanocytes. While under cellular stress, melanocytes appear to signal innate immunity to activate T cells. Once the autoimmune T cell response is estab...
Source: Current Opinion in Immunology - October 17, 2016 Category: Allergy & Immunology Authors: Strassner JP, Harris JE Tags: Curr Opin Immunol Source Type: research

T cell exhaustion and immune-mediated disease-the potential for therapeutic exhaustion.
Abstract 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 infect...
Source: Current Opinion in Immunology - October 13, 2016 Category: Allergy & Immunology Authors: McKinney EF, Smith KG Tags: Curr Opin Immunol Source Type: research

Advances in food allergy oral immunotherapy: toward tolerance.
Abstract The incidence of food allergy, a disease characterized by adverse immune responses that can render common foods life-threatening, is rising. Yet our current standard of care is simply avoidance of allergenic foods and administration of emergency medications upon accidental exposure. Significant advances have been made in food allergy oral immunotherapy, which is emerging as a potential preventive and curative treatment for this disease. The fundamental strategy of oral immunotherapy is to mitigate adverse immune responses to allergenic food proteins through repeated exposure; reduced reactivity to food al...
Source: Current Opinion in Immunology - October 13, 2016 Category: Allergy & Immunology Authors: Hussey Freeland DM, Fan-Minogue H, Spergel JM, Chatila TA, Nadeau KC Tags: Curr Opin Immunol Source Type: research

A roadmap of the generation of neoantigens as targets of the immune system in type 1 diabetes.
Abstract Type 1 diabetes (T1D) is an autoimmune disease characterized by the selective destruction of the insulin-producing beta cells. Beta cell dysfunction caused by an inflammatory microenvironment is believed to trigger the peripheral activation of CD4 and CD8 autoreactive T cells. This review will compile post-transcriptional and post-translational modifications (PTM) involved in the generation of beta cell neoantigens and proposes a reconstruction of the sequence of events connecting environmental changes and autoimmunity. PMID: 27723537 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - October 7, 2016 Category: Allergy & Immunology Authors: Roep BO, Kracht MJ, van Lummel M, Zaldumbide A Tags: Curr Opin Immunol Source Type: research

Targeting B cells in treatment of autoimmunity.
Abstract 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. Here we review the cu...
Source: Current Opinion in Immunology - October 5, 2016 Category: Allergy & Immunology Authors: Franks SE, Getahun A, Hogarth PM, Cambier JC Tags: Curr Opin Immunol Source Type: research

Endoplasmic reticulum stress in beta cells and autoimmune diabetes.
Abstract 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. This review highlights recent findings on ER ...
Source: Current Opinion in Immunology - October 5, 2016 Category: Allergy & Immunology Authors: Clark AL, Urano F Tags: Curr Opin Immunol Source Type: research

Environmental control of autoimmune inflammation in the central nervous system.
This article reviews mechanisms of disease pathogenesis in MS and their modulation by environmental factors such as geographical localization, the gut microbiome and the diet. PMID: 27710839 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - October 3, 2016 Category: Allergy & Immunology Authors: Rothhammer V, Quintana FJ Tags: Curr Opin Immunol Source Type: research

Macrophages and dendritic cells in islets of Langerhans in diabetic autoimmunity: a lesson on cell interactions in a mini-organ.
Abstract 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. In the absence of the CD103+ DC in the Batf3 deficient mice, autoimmu...
Source: Current Opinion in Immunology - October 3, 2016 Category: Allergy & Immunology Authors: Carrero JA, Ferris ST, Unanue ER Tags: Curr Opin Immunol Source Type: research

T cells in Systemic Lupus Erythematosus.
os GC Abstract 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. Understanding these T cell alterations and their origins is necessary to devel...
Source: Current Opinion in Immunology - September 13, 2016 Category: Allergy & Immunology Authors: Suárez-Fueyo A, Bradley SJ, Tsokos GC Tags: Curr Opin Immunol Source Type: research

The concept of allergen-associated molecular patterns (AAMP).
m E Abstract For proteins to become allergenic, they need to acquire features enabling them to induce B cell activation and isotype switch to IgE production. Crosslinking of the B-cell receptor (BCR) is the most efficient way to productively activate B-cells. The IgE-crosslinking capability of allergens is equally crucial in the effector phase of immediate type allergy. Antigens, which acquire enhanced crosslinking capacity by oligomerization, aggregation, or the expression of repetitive epitopes may therefore gain allergenic potency. The accumulated evidence for repetitive epitope display by allergens suggests th...
Source: Current Opinion in Immunology - September 9, 2016 Category: Allergy & Immunology Authors: Pali-Schöll I, Jensen-Jarolim E Tags: Curr Opin Immunol Source Type: research

Editorial overview: Allergy and hypersensitivity.
PMID: 27623177 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - September 9, 2016 Category: Allergy & Immunology Authors: McCluskey J, O'Hehir RE Tags: Curr Opin Immunol Source Type: research

T follicular helper cells in human autoimmunity.
Abstract 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 ...
Source: Current Opinion in Immunology - August 30, 2016 Category: Allergy & Immunology Authors: Ueno H Tags: Curr Opin Immunol Source Type: research

Editorial overview: Host pathogens: the interplay between host innate and adaptive immune systems and pathogens.
PMID: 27553507 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - August 20, 2016 Category: Allergy & Immunology Authors: Zhou P, Chen ZW Tags: Curr Opin Immunol Source Type: research

The role of FOXP3 in autoimmunity.
Abstract FOXP3 controls the development and function of T regulatory cells (Tregs). Autoimmunity is linked to changes in FOXP3 activity that can occur at multiple levels and lead to Treg dysfunction. For example, changes in IL-2 signaling, FOXP3 transcription and/or post-translational modifications can all contribute to loss of self-tolerance. As additional pathways of FOXP3 regulation are elucidated, new therapeutic approaches to increase Treg activity either by cell therapy or pharmacological intervention are being tested. Early success from pioneering studies of Treg-based therapy in transplantation has promote...
Source: Current Opinion in Immunology - August 18, 2016 Category: Allergy & Immunology Authors: Pesenacker AM, Cook L, Levings MK Tags: Curr Opin Immunol Source Type: research

Neoantigens encoded in the cancer genome.
Abstract Somatic mutations in the genome represent one of the major drivers of malignancy. However, non-synonymous mutations are also a source of mutated peptides that are presented by HLA molecules to induce protective CD4 and CD8 T cell responses. Consistent with this notion, the mutation burden of a tumor is correlated with local immunity as well as outcome of therapy and patient survival. Furthermore, neoantigen-specific T cells appear sufficient to control tumors prophylactically and therapeutically. While the role of neoantigens as a determinant of the foreignness of human cancers is now well established, ma...
Source: Current Opinion in Immunology - August 9, 2016 Category: Allergy & Immunology Authors: Schumacher TN, Hacohen N Tags: Curr Opin Immunol Source Type: research

Editorial overview: Cancer immunology: genomics & biomarkers: Cancer immunity through the prism of genomics and proteomics.
Editorial overview: Cancer immunology: genomics & biomarkers: Cancer immunity through the prism of genomics and proteomics. Curr Opin Immunol. 2016 Aug 6; Authors: Schumacher TN, Hacohen N PMID: 27506117 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - August 6, 2016 Category: Allergy & Immunology Authors: Schumacher TN, Hacohen N Tags: Curr Opin Immunol Source Type: research

DNA-reactive B cells in lupus.
Abstract IgG anti-DNA antibodies are both diagnostic and pathogenic for systemic lupus erythematosus (SLE). They contribute to tissue inflammation through direct tissue binding and to systemic inflammation through activation of Toll-like receptors by nucleic acid-containing immune complexes. IgG DNA-reactive antibodies originate when B cell tolerance mechanisms are impaired. The heterogeneous immune perturbations in SLE lead to the survival and activation of DNA-reactive B cells in various B cell subsets at distinct stages of B cell maturation and differentiation. We propose that the spectrum of B cell alterations...
Source: Current Opinion in Immunology - August 6, 2016 Category: Allergy & Immunology Authors: Suurmond J, Calise J, Malkiel S, Diamond B Tags: Curr Opin Immunol Source Type: research

AIRE-mutations and autoimmune disease.
ye ES Abstract The gene causing the severe organ-specific autoimmune disease autoimmune polyendocrine syndrome type-1 (APS-1) was identified in 1997 and named autoimmune regulator (AIRE). AIRE plays a key role in shaping central immunological tolerance by facilitating negative selection of T cells in the thymus, building the thymic microarchitecture, and inducing a specific subset of regulatory T cells. So far, about 100 mutations have been identified. Recent advances suggest that certain mutations located in the SAND and PHD1 domains exert a dominant negative effect on wild type AIRE resulting in milder seemingly...
Source: Current Opinion in Immunology - August 6, 2016 Category: Allergy & Immunology Authors: Bruserud Ø, Oftedal BE, Wolff AB, Husebye ES Tags: Curr Opin Immunol Source Type: research

Editorial overview: Vaccines: novel technologies for vaccine development.
PMID: 27499109 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - August 4, 2016 Category: Allergy & Immunology Authors: Rappuoli R, De Gregorio E Tags: Curr Opin Immunol Source Type: research

Protective immune responses of major V γ2Vδ2 T-cell subset in M. tuberculosis infection.
Protective immune responses of major Vγ2Vδ2 T-cell subset in M. tuberculosis infection. Curr Opin Immunol. 2016 Aug 1;42:105-112 Authors: Chen ZW Abstract Recent observation that prenyl pyrophosphates bind the Ig superfamily protein butyrophilin 3A1 (BTN3A1) suggests that modifying BTN3A1 activates major γδ T-cell subset, Vγ2Vδ2 T cells. Studies also show that microbial phosphoantigen HMBPP is required for expansion, pulmonary response, effector functions and memory polarization of Vγ2Vδ2 T cells during infections. Broad repertoires of cytokines involve ...
Source: Current Opinion in Immunology - August 1, 2016 Category: Allergy & Immunology Authors: Chen ZW Tags: Curr Opin Immunol Source Type: research

The science of vaccine adjuvants: advances in TLR4 ligand adjuvants.
Abstract TLR ligands are used in modern vaccine adjuvants, TLR4 ligand-based adjuvants are the most advanced in commercial vaccines. Increased understanding of TLR4 receptor-ligand interactions enables chemical synthesis and modification of new leads and our understanding of the biological/immunological mechanisms of combination adjuvants enables formulation of potent and safe vaccine compositions. Characterization of non-glycolipid TLR4 ligands provided new mechanistic information that could lead to new formulations. This review discusses advances in TLR4 agonist design-both glycolipid and non-glycolipid based TL...
Source: Current Opinion in Immunology - July 5, 2016 Category: Allergy & Immunology Authors: Reed SG, Hsu FC, Carter D, Orr MT Tags: Curr Opin Immunol Source Type: research

Systems biology and the quest for correlates of protection to guide the development of an HIV vaccine.
Abstract Over the last three decades, a myriad of data has been generated regarding HIV/SIV evolution, immune evasion, immune response, and pathogenesis. Much of this data can be integrated and potentially used to generate a successful vaccine. Although individual approaches have begun to shed light on mechanisms involved in vaccine-conferred protection from infection, true correlates of protection have not yet been identified. The systems biology approach helps unify datasets generated using different techniques and broaden our understanding of HIV immunopathogenesis. Moreover, systems biology is a tool that can ...
Source: Current Opinion in Immunology - July 5, 2016 Category: Allergy & Immunology Authors: Kuri-Cervantes L, Fourati S, Canderan G, Sekaly RP Tags: Curr Opin Immunol Source Type: research

Chimeric antigen receptors: driving immunology towards synthetic biology.
Abstract The advent of second generation chimeric antigen receptors and the CD19 paradigm have ushered a new therapeutic modality in oncology. In contrast to earlier forms of adoptive cell therapy, which were based on the isolation and expansion of naturally occurring T cells, CAR therapy is based on the design and manufacture of engineered T cells with optimized properties. A new armamentarium, comprising not only CARs but also chimeric costimulatory receptors, chimeric cytokine receptors, inhibitory receptors and synthetic Notch receptors, expressed in naïve, central memory or stem cell-like memory T cells,...
Source: Current Opinion in Immunology - June 30, 2016 Category: Allergy & Immunology Authors: Sadelain M Tags: Curr Opin Immunol Source Type: research

High-throughput genomic profiling of tumor-infiltrating leukocytes.
Abstract Tumors are complex ecosystems comprised of diverse cell types including malignant cells, mesenchymal cells, and tumor-infiltrating leukocytes (TILs). While TILs are well known to play important roles in many aspects of cancer biology, recent developments in immuno-oncology have spurred considerable interest in TILs, particularly in relation to their optimal engagement by emerging immunotherapies. Traditionally, the enumeration of TIL phenotypic diversity and composition in solid tumors has relied on resolving single cells by flow cytometry and immunohistochemical methods. However, advances in genome-wide ...
Source: Current Opinion in Immunology - June 30, 2016 Category: Allergy & Immunology Authors: Newman AM, Alizadeh AA Tags: Curr Opin Immunol Source Type: research