Testing the 'toxin hypothesis of allergy': mast cells, IgE, and innate and acquired immune responses to venoms.
Abstract Work in mice indicates that innate functions of mast cells, particularly degradation of venom toxins by mast cell-derived proteases, can enhance resistance to certain arthropod or reptile venoms. Recent reports indicate that acquired Th2 immune responses associated with the production of IgE antibodies, induced by Russell's viper venom or honeybee venom, or by a component of honeybee venom, bee venom phospholipase 2 (bvPLA2), can increase the resistance of mice to challenge with potentially lethal doses of either of the venoms or bvPLA2. These findings support the conclusion that, in contrast to the detri...
Source: Current Opinion in Immunology - July 23, 2015 Category: Allergy & Immunology Authors: Tsai M, Starkl P, Marichal T, Galli SJ Tags: Curr Opin Immunol Source Type: research

Environmental protection from allergic diseases: From humans to mice and back.
Abstract Allergic diseases have a strong environmental component, illustrated by the rapid rise of their prevalence in the Western world. Environmental exposures have been consistently shown to either promote or protect against allergic disease. Here we focus on protective exposures and the pathways they regulate. Traditional farming, natural environments with high biodiversity, and pets in the home (particularly dogs) have the most potent and consistent allergy-protective effects and are actively investigated to identify the environmental and host-based factors that confer allergy protection. Recent work emphasiz...
Source: Current Opinion in Immunology - July 23, 2015 Category: Allergy & Immunology Authors: Schaub B, Vercelli D Tags: Curr Opin Immunol Source Type: research

Host-pathogen interactions in malaria: cross-kingdom signaling and mitochondrial regulation.
Abstract Malaria parasite-host interactions are complex and have confounded available drugs and the development of vaccines. Further, we now appreciate that interventions for malaria elimination and eradication must include therapeutics with intrinsic transmission blocking activity to treat the patient and prevent disease spread. Studies over the past 15 years have revealed significant conservation in the response to infection in mosquito and human hosts. More recently, we have recognized that conserved cell signaling cascades in mosquitoes and humans dictate infection outcome through the regulation of mitochondri...
Source: Current Opinion in Immunology - July 22, 2015 Category: Allergy & Immunology Authors: Luckhart S, Pakpour N, Giulivi C Tags: Curr Opin Immunol Source Type: research

Type 2 responses at the interface between immunity and fat metabolism.
Abstract Adipose tissue resident leukocytes are often cast solely as the effectors of obesity and its attendant pathologies; however, recent observations have demonstrated that these cells support and effect 'healthy' physiologic function as well as pathologic dysfunction. Importantly, these two disparate outcomes are underpinned by similarly disparate immune programs; type 2 responses instruct and promote metabolic normalcy, while type 1 responses drive tissue dysfunction. In this Review, we summarize the literature regarding type 2 immunity's role in adipose tissue physiology and allude to its potential therapeu...
Source: Current Opinion in Immunology - July 20, 2015 Category: Allergy & Immunology Authors: Odegaard JI, Chawla A Tags: Curr Opin Immunol Source Type: research

Engineering humoral immunity as prophylaxis or therapy.
Abstract PURPOSE OF THE REVIEW: In this review, we will discuss the field of engineered humoral immunity with an emphasis on recent work using viral vectors to produce antibodies in vivo. As an alternative to passive transfer of monoclonal antibody protein, a transgene encoding an antibody is delivered to cells via vector transduction, resulting in expression and secretion by the host cell. This review will summarize the evidence in support of this strategy as an alternative to traditional vaccines against infection and as novel therapeutics for a variety of diseases. RECENT FINDINGS: Historically, humoral im...
Source: Current Opinion in Immunology - July 14, 2015 Category: Allergy & Immunology Authors: Deal CE, Balazs AB Tags: Curr Opin Immunol Source Type: research

Host-virus interactions in hepatitis B virus infection.
Abstract Hepatitis B virus (HBV) is a noncytopathic, hepatotropic, double-stranded DNA virus that causes acute and chronic hepatitis. Although HBV does not induce a measurable innate immune response in the infected liver, the outcome of infection is determined by the kinetics, breadth, vigor, trafficking, and effector functions of HBV-specific adaptive T cell responses, and the development of neutralizing antibodies. Dysregulation of one or more of these events leads to persistent HBV infection and a variably severe chronic necroinflammatory liver disease that fosters the development of hepatocellular carcinoma. D...
Source: Current Opinion in Immunology - July 14, 2015 Category: Allergy & Immunology Authors: Guidotti LG, Isogawa M, Chisari FV Tags: Curr Opin Immunol Source Type: research

Early innate responses to pathogens: pattern recognition by unconventional human T-cells.
Abstract Although typically viewed as a feature of innate immune responses, microbial pattern recognition is increasingly acknowledged as a function of particular cells nominally categorized within the adaptive immune system. Groundbreaking research over the past three years has shown how unconventional human T-cells carrying invariant or semi-invariant TCRs that are not restricted by classical MHC molecules sense microbial compounds via entirely novel antigen presenting pathways. This review will focus on the innate-like recognition of non-self metabolites by Vγ9/Vδ2 T-cells, mucosal-associated invari...
Source: Current Opinion in Immunology - July 13, 2015 Category: Allergy & Immunology Authors: Liuzzi AR, McLaren JE, Price DA, Eberl M Tags: Curr Opin Immunol Source Type: research

Malaria vaccine clinical trials: what's on the horizon.
Abstract Significant progress toward a malaria vaccine, specifically for Plasmodium falciparum, has been made in the past few years with the completion of numerous clinical trials. Each trial has utilized a unique combination of antigens, delivery platforms, and adjuvants, which has provided the research community with a wealth of critical information to apply towards the development of next generation malaria vaccines. Despite the progress toward a P. falciparum vaccine, P. vivax vaccine research requires more momentum and additional investigations to identify novel vaccine candidates. In this review, recently co...
Source: Current Opinion in Immunology - July 11, 2015 Category: Allergy & Immunology Authors: Moreno A, Joyner C Tags: Curr Opin Immunol Source Type: research

Macrophage engulfment of a cell or nanoparticle is regulated by unavoidable opsonization, a species-specific 'Marker of Self' CD47, and target physical properties.
Abstract Professional phagocytes of the mononuclear phagocyte system (MPS), especially ubiquitous macrophages, are commonly thought to engulf or not a target based strictly on 'eat me' molecules such as Antibodies. The target might be a viable 'self' cell or a drug-delivering nanoparticle, or it might be a cancer cell or a microbe. 'Marker of Self' CD47 signals into a macrophage to inhibit the acto-myosin cytoskeleton that makes engulfment efficient. In adhesion of any cell, the same machinery is generally activated by rigidity of target surfaces, and recent results confirm phagocytosis is likewise driven by the r...
Source: Current Opinion in Immunology - July 11, 2015 Category: Allergy & Immunology Authors: Sosale NG, Spinler KR, Alvey C, Discher DE Tags: Curr Opin Immunol Source Type: research

Serology in the 21st century: the molecular-level analysis of the serum antibody repertoire.
Abstract The ensemble of antibodies found in serum and secretions represents the key adaptive component of B-cell mediated humoral immunity. The antibody repertoire is shaped by the historical record of exposure to exogenous factors such as pathogens and vaccines, as well as by endogenous host-intrinsic factors such as genetics, self-antigens, and age. Thanks to very recent technology advancements it is now becoming possible to identify and quantify the individual antibodies comprising the serological repertoire. In parallel, the advent of high throughput methods for antigen and immunosignature discovery opens up ...
Source: Current Opinion in Immunology - July 9, 2015 Category: Allergy & Immunology Authors: Wine Y, Horton AP, Ippolito GC, Georgiou G Tags: Curr Opin Immunol Source Type: research

Innate immune interactions within the central nervous system modulate pathogenesis of viral infections.
Abstract The innate immune system mediates protection against neurotropic viruses that replicate in the central nervous system (CNS). Virus infection within specific cells of the CNS triggers activation of several families of pattern recognition receptors including Toll-like receptors, retinoic acid-inducible gene I like receptors, nucleotide-binding oligomerization domain-like receptors, and cytosolic DNA sensors. In this review, we highlight recent advances in our understanding of how cell-intrinsic host defenses within the CNS modulate infection of different DNA and RNA viruses. PMID: 26163762 [PubMed - as...
Source: Current Opinion in Immunology - July 8, 2015 Category: Allergy & Immunology Authors: Nair S, Diamond MS Tags: Curr Opin Immunol Source Type: research

Immunological features underlying viral hemorrhagic fevers.
Abstract Several enveloped RNA viruses of the arenavirus, bunyavirus, filovirus and flavivirus families are associated with a syndrome known as viral hemorrhagic fever (VHF). VHF is characterized by fever, vascular leakage, coagulation defects and multi organ system failure. VHF is currently viewed as a disease precipitated by viral suppression of innate immunity, which promotes systemic virus replication and excessive proinflammatory cytokine responses that trigger the manifestations of severe disease. However, the mechanisms by which immune dysregulation contributes to disease remain poorly understood. Infection...
Source: Current Opinion in Immunology - July 7, 2015 Category: Allergy & Immunology Authors: Messaoudi I, Basler CF Tags: Curr Opin Immunol Source Type: research

Supramolecular peptide vaccines: tuning adaptive immunity.
Abstract Successful immunotherapies must be designed to elicit targeted immune responses having a specifiable phenotype across many dimensions, including the phenotypes of T cells, B cells, antigen-presenting cells, and others. For synthetic or subunit vaccines, stimulation of strong enough immune responses usually requires adjuvants, which can cause local inflammation and complicate the targeting of such phenotypes. Supramolecular materials provide routes for reducing or eliminating supplemental adjuvants. Owing to their compositional controllability, supramolecular assemblies show promise for fine-tuning immune ...
Source: Current Opinion in Immunology - July 7, 2015 Category: Allergy & Immunology Authors: Wen Y, Collier JH Tags: Curr Opin Immunol Source Type: research

Engineering antigen-specific immunological tolerance.
We present here recent developments in approaches, based on engineered peptides, proteins and biomaterials, that harness mechanisms of peripheral tolerance both prophylactically and therapeutically to induce antigen-specific immunological tolerance. These mechanisms are based on responses of B and T lymphocytes to other cells in their immune environment that result in cellular deletion or ignorance to particular antigens, or in development of active immune regulatory responses. Several of these approaches are moving toward clinical development, and some are already in early stages of clinical testing. PMID: 26163377 [...
Source: Current Opinion in Immunology - July 7, 2015 Category: Allergy & Immunology Authors: Kontos S, Grimm AJ, Hubbell JA Tags: Curr Opin Immunol Source Type: research

HIV and mucosal barrier interactions: consequences for transmission and pathogenesis.
Abstract The mucosal barrier plays an integral function in human health as it is the primary defense against pathogens, and provides a critical transition between the external environment and the human internal body. In the context of HIV infection, the most relevant mucosal surfaces include those of the gastrointestinal (GI) and genital tract compartments. Several components help maintain the effectiveness of this mucosal surface, including the physical anatomy of the barrier, cellular immunity, soluble factors, and interactions between the epithelial barrier and the local microenvironment, including mucus and ho...
Source: Current Opinion in Immunology - July 4, 2015 Category: Allergy & Immunology Authors: Burgener A, McGowan I, Klatt NR Tags: Curr Opin Immunol Source Type: research

Manipulating the in vivo immune response by targeted gene knockdown.
Abstract Aptamers, nucleic acids selected for high affinity binding to proteins, can be used to activate or antagonize immune mediators or receptors in a location and cell-type specific manner and to enhance antigen presentation. They can also be linked to other molecules (other aptamers, siRNAs or miRNAs, proteins, toxins) to produce multifunctional compounds for targeted immune modulation in vivo. Aptamer-siRNA chimeras (AsiCs) that induce efficient cell-specific knockdown in immune cells in vitro and in vivo can be used as an immunological research tool or potentially as an immunomodulating therapeutic. PM...
Source: Current Opinion in Immunology - July 3, 2015 Category: Allergy & Immunology Authors: Lieberman J Tags: Curr Opin Immunol Source Type: research

TB vaccines; promoting rapid and durable protection in the lung.
Abstract TB vaccine discovery has focused on IFN-γ both for the selection of antigens and vaccine delivery strategies. Recent breakthroughs in our understanding of the requirements for immunological memory and the expression of immunity to TB in the lung now provide a framework for reconsidering that strategy. We will discuss the status of the TB vaccine field, recent insights into the role of central memory cells and the potential of tissue-resident memory cells in vaccine promoted protection against TB. PMID: 26113434 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - June 22, 2015 Category: Allergy & Immunology Authors: Andersen P, Urdahl KB Tags: Curr Opin Immunol Source Type: research

Pertussis vaccines and the challenge of inducing durable immunity.
Abstract Pertussis has re-emerged as an important public health concern. In the 1990s whole-cell pertussis vaccines were replaced with less reactogenic acellular vaccines consisting of purified pertussis components. However, recent data show that protection from acellular pertussis vaccines is not long-lasting. Antibody levels wane rapidly following vaccination, likely a result of the inability of acellular pertussis antigens to stimulate long-lasting B cell memory. In addition, T cell responses to acellular pertussis vaccines are mixed Th2/Th1, while whole-cell pertussis vaccination and infection stimulate Th17 r...
Source: Current Opinion in Immunology - June 16, 2015 Category: Allergy & Immunology Authors: Warfel JM, Edwards KM Tags: Curr Opin Immunol Source Type: research

Novel antigens for RSV vaccines.
Abstract Respiratory syncytial virus (RSV) remains a leading global cause of infant mortality and adult morbidity. Infection, which recurs throughout life, elicits only short-lived immunity. The development of a safe and efficacious vaccine has, thus far, been elusive. Recent technological advances, however, have yielded promising RSV vaccine candidates that are based on solving atomic-level structures of surface glycoproteins interacting with neutralizing antibodies. The class I fusion glycoprotein, F, serves as the primary antigenic component of most vaccines, and is the target of the only licensed monoclonal an...
Source: Current Opinion in Immunology - June 9, 2015 Category: Allergy & Immunology Authors: Graham BS, Modjarrad K, McLellan JS Tags: Curr Opin Immunol Source Type: research

New approaches to HIV vaccine development.
Abstract Development of a safe and effective vaccine for HIV is a major global priority. However, to date, efforts to design an HIV vaccine with methods used for development of other successful viral vaccines have not succeeded due to HIV diversity, HIV integration into the host genome, and ability of HIV to consistently evade anti-viral immune responses. Recent success in isolation of potent broadly neutralizing antibodies (bnAbs), in discovery of mechanisms of bnAb induction, and in discovery of atypical mechanisms of CD8T cell killing of HIV-infected cells, have opened new avenues for strategies for HIV vaccine...
Source: Current Opinion in Immunology - June 4, 2015 Category: Allergy & Immunology Authors: Haynes BF Tags: Curr Opin Immunol Source Type: research

The role of active vaccination in cancer immunotherapy: lessons from clinical trials.
Abstract In the past few years, a number of different immunotherapeutic strategies have shown impressive results in cancer patients. These successful approaches include blockade of immunosuppressive molecules like PD-1 and CTLA-4, adoptive transfer of patient derived and genetically modified T-cells, and vaccines that stimulate tumor antigen specific T-cells. However, several large vaccine trials recently failed to reach designated primary endpoints. In light of the success of other immunotherapeutic approaches, these negative results raise the questions of why vaccines have not generated a better response, and wh...
Source: Current Opinion in Immunology - June 3, 2015 Category: Allergy & Immunology Authors: Kissick HT, Sanda MG Tags: Curr Opin Immunol Source Type: research

Spatially and temporally controlled immune cell interactions using microscale tools.
Abstract Many critical immunological responses are mediated by cell-cell interactions. Despite their capabilities, traditional techniques that rely on snapshot analysis or ensemble measurements can only provide a fragmentary picture of the complexity of these interactions. Emerging classes of new and versatile microscale tools hold great potential for enabling detailed investigation of these interactions with precise control in space and time, multiplexed measurement capability and high-throughput single-cell analysis. These features allow new ways of examining immune cell interactions that are not possible with t...
Source: Current Opinion in Immunology - June 3, 2015 Category: Allergy & Immunology Authors: Dura B, Voldman J Tags: Curr Opin Immunol Source Type: research

Inflammatory damage on respiratory and nervous systems due to hRSV infection.
Abstract The exacerbated inflammatory response elicited by human Respiratory Syncytial Virus (hRSV) in the lungs of infected patients causes a major health burden in the pediatric and elderly population. Since the discovery of hRSV, the exacerbated host immune-inflammatory response triggered by this virus has been extensively studied. In this article, we review the effects on the airways caused by immune cells and cytokines/chemokines secreted during hRSV infection. While molecules such as interferons contribute at controlling viral infection, IL-17 and others produce damage to the hRSV-infected lung. In addition ...
Source: Current Opinion in Immunology - May 27, 2015 Category: Allergy & Immunology Authors: Bohmwald K, Espinoza JA, Becerra D, Rivera K, Lay MK, Bueno SM, Riedel CA, Kalergis AM Tags: Curr Opin Immunol Source Type: research

New approaches in vaccine-based immunotherapy for human papillomavirus-induced cancer.
Abstract The identification of human papillomavirus as the etiological factor for cervical cancer provides an opportunity to treat these malignancies by vaccination. Although therapeutic vaccination against viral oncogenes regularly induces a specific T cell response, clinical effectivity remains low. Three factors are particularly important for clinical outcome: the balance between cytotoxic T cells and regulatory immune subsets, the balance between cytotoxic T cells and tumor cells and finally the killing efficiency of cytotoxic T cells within the tumor. To improve these three factors, therapeutic vaccination is...
Source: Current Opinion in Immunology - May 19, 2015 Category: Allergy & Immunology Authors: van der Sluis TC, van der Burg SH, Arens R, Melief CJ Tags: Curr Opin Immunol Source Type: research

HIV therapeutic vaccines: moving towards a functional cure.
Abstract Anti-viral T-cell and B-cell responses play a crucial role in suppressing HIV and SIV replication during chronic infection. However, these infections are rarely controlled by the host immune response, and most infected individuals need lifelong antiretroviral therapy (ART). Recent advances in our understanding of how anti-HIV immune responses are elicited and regulated prompted a surge of interest in harnessing these responses to reduce the HIV 'residual disease' that is present in ART-treated HIV-infected individuals. Novel approaches that are currently explored include both conventional therapeutic vacc...
Source: Current Opinion in Immunology - May 18, 2015 Category: Allergy & Immunology Authors: Mylvaganam GH, Silvestri G, Amara RR Tags: Curr Opin Immunol Source Type: research

Understanding the host-pathogen interaction saves lives: lessons from vaccines and vaccinations.
Abstract Vaccines are one of the most successful and cost-effective public health tools employed to date, yet these benefits are only realized when the life-saving intervention reaches each and every targeted individual. Vaccine development is prioritized based on a number of factors such as health burden, feasibility, and determination of potential target populations. But only through an arduous process of pre-clinical development and progressive clinical trials does a vaccine become licensed and recommended for use. Once used in a wider and more diverse population safety issues, long-term impact and other uninte...
Source: Current Opinion in Immunology - May 11, 2015 Category: Allergy & Immunology Authors: Garon JR, Orenstein WA Tags: Curr Opin Immunol Source Type: research

Editorial overview: Antigen processing and presentation: Where cellular immunity begins.
PMID: 25964203 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - May 8, 2015 Category: Allergy & Immunology Authors: Shastri N, Yewdell JW Tags: Curr Opin Immunol Source Type: research

Host-pathogen interaction during bacterial vaccination.
Abstract Vaccines have been developed and deployed against several important bacterial pathogens of humans, including Neisseria meningitidis, Bordetella pertussis, Streptococcus pneumoniae and Mycobacterium tuberculosis. These vaccines are generally considered a successful public health measure and are effective at controlling disease symptoms and/or burden. However, a troubling consequence of recent vaccination programs has been the selection of vaccine escape mutants, whereby the pathogen displays a different repertoire of immune targets than those represented in the vaccine formulation. To address these issues ...
Source: Current Opinion in Immunology - May 7, 2015 Category: Allergy & Immunology Authors: Barnett TC, Lim JY, Soderholm AT, Rivera-Hernandez T, West NP, Walker MJ Tags: Curr Opin Immunol Source Type: research

Editorial overview: Cytokines: New roles for old friends!
PMID: 25944778 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - May 2, 2015 Category: Allergy & Immunology Authors: Hunter CA, Ziegler SF Tags: Curr Opin Immunol Source Type: research

Regulation of human helper T cell subset differentiation by cytokines.
Abstract Since the discovery of Th1 and Th2 cells in the late 1980s, the family of effector CD4(+) helper T (Th) cell subsets has expanded. The differentiation of naïve CD4(+) T cells is largely determined when they interact with dendritic cells (DCs) in lymphoid organs, and cytokines play a major role in the regulation of Th differentiation in the early stages. Recent studies show that the developmental mechanism of certain Th subsets is not fully shared between mice and humans. Here we will review recent discoveries on the roles of cytokines in the regulation of Th differentiation in humans, and discuss the...
Source: Current Opinion in Immunology - April 10, 2015 Category: Allergy & Immunology Authors: Schmitt N, Ueno H Tags: Curr Opin Immunol Source Type: research

Editorial overview: Tumour immunology.
PMID: 25823946 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - March 27, 2015 Category: Allergy & Immunology Authors: Schreiber H, Greenberg P Tags: Curr Opin Immunol Source Type: research

CD1d-dependent endogenous and exogenous lipid antigen presentation.
Abstract Invariant natural killer T (iNKT) cells recognize endogenous and exogenous lipids in the context of CD1d molecules, and through the activation and maturation of dendritic cells and B cells, can significantly enhance priming of antigen-specific T and B cell responses. Recent findings have provided important insights into the recognition of several novel endogenous lipids by iNKT cells, and into the mechanisms controlling their generation and loading onto CD1d molecules. In this review we discuss these latest findings and describe the role of autophagy in iNKT cell development and activation. PMID: 258...
Source: Current Opinion in Immunology - March 21, 2015 Category: Allergy & Immunology Authors: McEwen-Smith RM, Salio M, Cerundolo V Tags: Curr Opin Immunol Source Type: research

Advances in IL-21 biology-enhancing our understanding of human disease.
Abstract Cytokines play critical roles in regulating the development and function of immune cells. Cytokines function by binding specific multimeric receptor complexes and activating intracellular signaling pathways that often involve JAKs and STATs. In addition to contributing to immunity, when production of cytokines is perturbed, they can contribute to disease. IL-21 is a pleiotropic cytokine produced predominantly by CD4(+) T cells and NKT cells. Gene-targeting studies in mice and in vitro analyses of human and murine lymphocytes have revealed central roles of IL-21 in regulating effector functions of T cells,...
Source: Current Opinion in Immunology - March 19, 2015 Category: Allergy & Immunology Authors: Tangye SG Tags: Curr Opin Immunol Source Type: research

Primary immunoglobulin repertoire development: time and space matter.
Abstract The primary immunoglobulin repertoire develops via opposing forces of expanding diversification balanced by contracting selection mechanisms. The resulting shape is essential for host health and immune fitness. While the molecular mechanisms of Ig diversification have largely been defined, selection forces shaping emerging Ig repertoires are poorly understood. During lifetime, human and mouse early B cell development occurs at distinct locations-beginning in fetal liver before transferring to bone marrow and spleen by the end of gestation. During an early life window of time, the murine gut lamina propria...
Source: Current Opinion in Immunology - March 19, 2015 Category: Allergy & Immunology Authors: Granato A, Chen Y, Wesemann DR Tags: Curr Opin Immunol Source Type: research

IL-17 and neutrophils: unexpected players in the type 2 immune response.
l D Abstract The study of immunity to helminth infection has been central to understanding the function of type 2 cytokines and their targets. Although type 2 cytokines are considered anti-inflammatory and promote tissue repair, they also contribute to allergy and fibrosis. Here, we utilise data from helminth infection models, to illustrate that IL-17 and neutrophils, typically associated with pro-inflammatory responses, are intimately linked with type 2 immunity. Neutrophils work with IL-4Rα-activated macrophages to control incoming larvae but this comes at a cost of enhanced tissue damage. Chitinase like p...
Source: Current Opinion in Immunology - March 17, 2015 Category: Allergy & Immunology Authors: Allen JE, Sutherland TE, Rückerl D Tags: Curr Opin Immunol Source Type: research

Editorial overview: Lymphocyte development and activation: Lymphocytes, integrators of information.
PMID: 25776004 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - March 13, 2015 Category: Allergy & Immunology Authors: Roose J, Fagarasan S Tags: Curr Opin Immunol Source Type: research

New insights into type I interferon and the immunopathogenesis of persistent viral infections.
Abstract Most viruses generate potent T cell responses that rapidly control infection. However, certain viruses can subvert the immune response to establish persistent infections. The inability to clear virus induces an immunosuppressive program leading to the sustained expression of many immunoregulatory molecules that down-regulate T cell responses. Further, viral persistence is associated with multiple immune dysfunctions including lymphoid disorganization, defective antigen presentation, aberrant B cell responses and hypergammaglobulinemia. Although best known for its antiviral activity, recent data has highli...
Source: Current Opinion in Immunology - March 12, 2015 Category: Allergy & Immunology Authors: Snell LM, Brooks DG Tags: Curr Opin Immunol Source Type: research

Transport and quality control of MHC class I molecules in the early secretory pathway.
Abstract Folding and peptide binding of major histocompatibility complex (MHC) class I molecules have been thoroughly researched, but the mechanistic connection between these biochemical events and the progress of class I through the early secretory pathway is much less well understood. This review focuses on the question how the partially assembled forms of class I (which lack high-affinity peptide and/or the light chain beta-2 microglobulin) are retained inside the cell. Such investigations offer researchers exciting chances to understand the connections between class I structure, conformational dynamics, peptid...
Source: Current Opinion in Immunology - March 10, 2015 Category: Allergy & Immunology Authors: Springer S Tags: Curr Opin Immunol Source Type: research

The IL-6/gp130/STAT3 signaling axis: recent advances towards specific inhibition.
Abstract Interleukin-6 has long been recognized as a prototypic pro-inflammatory cytokine that is involved in the pathogenesis of all inflammatory diseases. Activation of the gp130 homodimer by IL-6 leads to the initiation of Jak/STAT signaling, a pathway that is often constitutively switched on in inflammatory malignancies. However, a plethora of studies in the last decade has convincingly shown that only signaling via the soluble IL-6R (trans-signaling) accounts for the deleterious effects of IL-6, whereas classic signaling via the membrane-bound receptor is essential for the regenerative and anti-bacterial effe...
Source: Current Opinion in Immunology - March 4, 2015 Category: Allergy & Immunology Authors: Garbers C, Aparicio-Siegmund S, Rose-John S Tags: Curr Opin Immunol Source Type: research

The regulation of T follicular helper responses during infection.
Abstract Following infection, naïve CD4 T cells can differentiate into various functionally distinct effector and memory subsets, including T follicular helper (TFH) cells that orchestrate germinal center (GC) reactions necessary for high-affinity, pathogen-specific antibody responses. The origins and function of this cell type have been extensively examined in response to subunit immunization with model antigens. More recently, we are beginning to also appreciate the extent to which microbial infections shape the generation, function and maintenance of TFH cells. Here, we review recent advances and highlight...
Source: Current Opinion in Immunology - February 26, 2015 Category: Allergy & Immunology Authors: Butler NS, Kulu DI Tags: Curr Opin Immunol Source Type: research

The interplay of effector and regulatory T cells in cancer.
Abstract Regulatory T (Treg) cells suppress effector T (Teff) cells and prevent immune-mediated rejection of cancer. Much less appreciated are mechanisms by which Teff cells antagonize Treg cells. Herein, we consider how complex reciprocal interactions between Teff and Treg cells shape their population dynamics within tumors. Under states of tolerance, including during tumor escape, suppressed Teff cells support Treg cell populations through antigen-dependent provision of interleukin (IL)-2. During immune activation, Teff cells can lose this supportive capacity and directly antagonize Treg cell populations to neut...
Source: Current Opinion in Immunology - February 26, 2015 Category: Allergy & Immunology Authors: Roychoudhuri R, Eil RL, Restifo NP Tags: Curr Opin Immunol Source Type: research

Targeting cancer-specific mutations by T cell receptor gene therapy.
Abstract The ease of sequencing the cancer genome, identifying all somatic mutations and grafting mutation-specific T cell receptor (TCR) genes into T cells for adoptive transfer allow, for the first time, a truly tumor-specific and effective therapy. Mutation-specific TCR gene therapy might achieve optimal efficacy with least possible toxicity. Recent clinical data confirm the long-standing evidence from experimental cancer models that antigens encoded by the tumor-specific somatic mutations are potentially the best targets for adoptive T cell therapy. Open questions are, how many somatic mutations create suitabl...
Source: Current Opinion in Immunology - February 26, 2015 Category: Allergy & Immunology Authors: Blankenstein T, Leisegang M, Uckert W, Schreiber H Tags: Curr Opin Immunol Source Type: research

Myeloid-derived suppressor cell impact on endogenous and adoptively transferred T cells.
Abstract Novel models of autochthonous tumorigenesis and adoptive T cell therapy (ATT) are providing new clues regarding the pro-tumorigenic and immunosuppressive effects of myeloid-derived suppressor cells (MDSC), and their interaction with T cells. New findings are shifting the perception of the main level at which MDSC act, from direct cell-to-cell suppression to others, such as limiting T cell infiltration. Adoptively transferred, high-avidity T cells recognizing peptides with high-affinity for MHC-I eliminated large tumors. However, low-avidity T cells or low-affinity peptides resulted in failure to eradicate...
Source: Current Opinion in Immunology - February 26, 2015 Category: Allergy & Immunology Authors: Arina A, Bronte V Tags: Curr Opin Immunol Source Type: research

The immunology of influenza virus-associated bacterial pneumonia.
Abstract Infection with influenza virus has been a significant cause of morbidity and mortality for more than a hundred years. Severe disease and increased mortality often results from bacterial super-infection of patients with influenza virus infection. Preceding influenza infection alters the host's innate and adaptive immune responses, allowing increased susceptibility to secondary bacterial pneumonia. Recent advances in the field have helped to define how influenza alters the immune response to bacteria through the dysregulation of phagocytes, antimicrobial peptides, and lymphocytes. Viral-induced interferons ...
Source: Current Opinion in Immunology - February 24, 2015 Category: Allergy & Immunology Authors: Robinson KM, Kolls JK, Alcorn JF Tags: Curr Opin Immunol Source Type: research

New insights into tumor immunity revealed by the unique genetic and genomic aspects of ovarian cancer.
Abstract Ovarian cancer is a challenging disease that nonetheless provokes brisk, prognostically favorable immune responses in many patients. The biology of ovarian cancer offers unique insights into the factors that engender protective tumor immunity. Tumor-infiltrating lymphocyte (TIL) patterns range from CD8+ TIL alone to complex aggregates that additionally include CD4+ and CD20+ TIL. Patient survival rates increase in step with TIL complexity, suggesting cooperative interactions between these lymphocyte subsets. TIL are associated with high-grade serous histology and BRCA1 disruption; the latter may promote i...
Source: Current Opinion in Immunology - February 21, 2015 Category: Allergy & Immunology Authors: Nelson BH Tags: Curr Opin Immunol Source Type: research

Epithelial cytokines and pulmonary allergic inflammation.
This article focuses on evidence for the role of IL-25, IL-33 and TSLP in human allergic disease and discusses their potential as therapeutic targets for severe asthma. PMID: 25705788 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - February 20, 2015 Category: Allergy & Immunology Authors: Lloyd CM, Saglani S Tags: Curr Opin Immunol Source Type: research

THEMIS: a critical TCR signal regulator for ligand discrimination.
Abstract Genetic approaches identified THEMIS as a critical element driving positive selection of CD4(+)CD8(+) thymocytes towards maturation. THEMIS is expressed only in the T-cell lineage, and is recruited to the proximity of signaling T-cell antigen receptors (TCR) by association with the membrane scaffold LAT. However, its molecular role remained an enigma until recently. Conventionally positively-selected T-cells are lacking in THEMIS-deficient mice, leading to the initial hypothesis that THEMIS positively regulates TCR signaling. Recent data show that THEMIS deficiency increases rather than decreases TCR sign...
Source: Current Opinion in Immunology - February 17, 2015 Category: Allergy & Immunology Authors: Gascoigne NR, Acuto O Tags: Curr Opin Immunol Source Type: research

Protein networks and activation of lymphocytes.
Abstract The signal transduction pathways initiated by lymphocyte activation play a critical role in regulating host immunity. High-resolution mass spectrometry has accelerated the investigation of these complex and dynamic pathways by enabling the qualitative and quantitative investigation of thousands of proteins and phosphoproteins simultaneously. In addition, the unbiased and wide-scale identification of protein-protein interaction networks and protein kinase substrates in lymphocyte signaling pathways can be achieved by mass spectrometry-based approaches. Critically, the integration of these discovery-driven ...
Source: Current Opinion in Immunology - February 13, 2015 Category: Allergy & Immunology Authors: Helou YA, Salomon AR Tags: Curr Opin Immunol Source Type: research

B cells take the front seat: dysregulated B cell signals orchestrate loss of tolerance and autoantibody production.
Abstract A significant proportion of autoimmune-associated genetic variants are expressed in B cells, suggesting that B cells may play multiple roles in autoimmune pathogenesis. In this review, we highlight recent studies demonstrating that even modest alterations in B cell signaling are sufficient to promote autoimmunity. First, we describe several examples of genetic variations promoting B cell-intrinsic initiation of autoimmune germinal centers and autoantibody production. We highlight how dual antigen receptor/toll-like receptor signals greatly facilitate this process and how activated, self-reactive B cells m...
Source: Current Opinion in Immunology - February 10, 2015 Category: Allergy & Immunology Authors: Jackson SW, Kolhatkar NS, Rawlings DJ Tags: Curr Opin Immunol Source Type: research

Differentiation and maintenance of long-lived plasma cells.
Abstract Long-lived plasma cells, which mostly reside in the bone marrow have been shown to be vital for protection from recurrent infections. Recent gene-targeting and cell-ablation experiments have solidified the concept that their survival depends on both cell-intrinsic programs and extrinsic factors. The BTB transcription factor ZBTB20, which is expressed at high levels in long-lived plasma cells, is critical for their survival. On the other hand, eosinophils, megakaryocytes and monocytes function to establish a niche for long-lived plasma cells by secreting cytokines and growth factors such as APRIL and IL6. ...
Source: Current Opinion in Immunology - February 9, 2015 Category: Allergy & Immunology Authors: Kometani K, Kurosaki T Tags: Curr Opin Immunol Source Type: research