Homeostatic inflammation in innate immunity.
Abstract Innate immune sensors respond not only to microbial products but also to endogenous metabolites such as nucleic acids (NAs) and lipids. Toll-like receptors (TLRs) deliver a signal from the plasma membrane and also from endolysosomes, where NAs and lipids are catabolized. Interaction of TLRs with metabolites in endolysosomes leads to homeostatic TLR activation. Dendritic cells expressing NA-sensing TLRs are steadily activated by metabolites derived from the host or commensals and produce type I IFNs, thereby provoking various types of inflammatory conditions. Here, we discuss how homeostatic inflammation i...
Source: Current Opinion in Immunology - September 1, 2014 Category: Allergy & Immunology Authors: Miyake K, Kaisho T Tags: Curr Opin Immunol Source Type: research

Targeting IgE production in mice and humans.
Abstract Immunoglobulin E (IgE) is pathogenic in allergic diseases such as asthma, allergic rhinitis, atopic dermatitis, and food allergy. Recent studies using genetically modified IgE reporter mice indicate that the majority of serum IgE in mice is produced by short-lived IgE plasma cells, with minor contributions from long-lived IgE plasma cells, and implicate IgG1 and IgE memory B cells as potential sources of IgE memory. Clinical studies using antibodies against IL-13 or the IL-4 and IL-13 receptor subunit IL-4Rα, as well as an antibody against the M1 prime domain of human membrane IgE, indicate that, si...
Source: Current Opinion in Immunology - August 22, 2014 Category: Allergy & Immunology Authors: Wu LC, Scheerens H Tags: Curr Opin Immunol Source Type: research

Basophils have emerged as a key player in immunity.
Abstract Basophils had long been neglected in immunological studies, because of their paucity and phenotypic similarity with tissue-resident mast cells. However, recent development of analytical tools has cast new light on this neglected minority, and revealed previously unappreciated roles of basophils, distinct from those of mast cells, in various immune responses. Primary function of basophils appears to be the protection against infections with parasites, including ticks and helminths. This is why basophils are evolutionally conserved well in many animal species, albeit a small number. Nevertheless, basophils ...
Source: Current Opinion in Immunology - July 30, 2014 Category: Allergy & Immunology Authors: Karasuyama H, Yamanishi Y Tags: Curr Opin Immunol Source Type: research

The dissection of complex susceptibility to infectious disease: bacterial, viral and parasitic infections.
r E Abstract Infectious diseases are the result of the exposure of susceptible hosts to pathogenic microbes. Genetic factors are important determinants of host susceptibility and efforts are being made to establish the molecular identity of such genetic susceptibility variants by genome-wide association studies. Results obtained to date partly confirm already known genetic vulnerabilities, but also point to new and unexpected mechanisms of susceptibility that extend from classical innate and acquired immunity to weaknesses in constitutional resistance. These studies also revealed an overlap in genetic control betw...
Source: Current Opinion in Immunology - July 29, 2014 Category: Allergy & Immunology Authors: Abel L, Alcaïs A, Schurr E Tags: Curr Opin Immunol Source Type: research

Genetics of gene expression in immunity to infection.
Abstract Mapping gene expression as a quantitative trait (eQTL mapping) can reveal local and distant associations with functionally important genetic variation informative for disease. Recent studies are reviewed which have demonstrated that this approach is particularly informative when applied to diverse immune cell populations and situations relevant to infection and immunity. Context-specific eQTL have now been characterised following endotoxin activation, induction with interferons, mycobacteria, and influenza, together with genetic determinants of response to vaccination. The application of genetical genomic...
Source: Current Opinion in Immunology - July 28, 2014 Category: Allergy & Immunology Authors: Fairfax BP, Knight JC Tags: Curr Opin Immunol Source Type: research

The cross talk between microbiota and the immune system: metabolites take center stage.
Abstract The human meta-organism consists of more than 90% of microbial cells. The gastrointestinal tract harbors trillions of commensal microorganisms that influence the development and homeostasis of the host. Alterations in composition and function of the microbiota, termed dysbiosis, have been implicated in a multitude of metabolic and inflammatory diseases in humans. Thus, understanding the molecular underpinnings the cross talk between commensal bacteria and their host during homeostasis and dysbiosis may hold the key to understanding many idiopathic diseases. While most attention has focused on the innate r...
Source: Current Opinion in Immunology - July 24, 2014 Category: Allergy & Immunology Authors: Shapiro H, Thaiss CA, Levy M, Elinav E Tags: Curr Opin Immunol Source Type: research

Editorial overview: Host pathogens.
PMID: 25027097 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - July 11, 2014 Category: Allergy & Immunology Authors: Gros P, Belkaid Y Tags: Curr Opin Immunol Source Type: research

Defining features of protective CD4 T cell responses to Mycobacterium tuberculosis.
Abstract CD4 T cells are critical for control of Mycobacterium tuberculosis (Mtb) infection and represent the best hope for vaccine-elicited protection. However, little is understood about the properties of Mtb-specific CD4 T cells that mediate control, and the lack of correlates of protection present a significant barrier to the rational development of new vaccination and therapeutic strategies which are sorely needed. Here we discuss the features of protective CD4 T cells including recent evidence for IFN-γ dependent and independent mechanisms of protection, poor protection by terminally differentiated cel...
Source: Current Opinion in Immunology - July 4, 2014 Category: Allergy & Immunology Authors: Sakai S, Mayer-Barber KD, Barber DL Tags: Curr Opin Immunol Source Type: research

Aging of the human innate immune system in HIV infection.
Abstract HIV infection is associated with a chronic inflammatory state arising from multiple factors, including innate immune recognition of HIV, increased microbial translocation, and release of endogenous ligands from damaged cells (such as CD4 T cells). In many respects, this heightened pro-inflammatory environment resembles that associated with aging in the absence of HIV infection, and evidence of dysregulated innate immune responses can be found in not only older HIV-negative adults, but also adults with HIV infection. While the study of innate immune aging in HIV infection is still in its early stages, it s...
Source: Current Opinion in Immunology - July 2, 2014 Category: Allergy & Immunology Authors: Zapata HJ, Shaw AC Tags: Curr Opin Immunol Source Type: research

Homeostasis between gut-associated microorganisms and the immune system in Drosophila.
Abstract The metabolic activities of a given gut bacterium or gut commensal community fluctuate in a manner largely depending on the physicochemical parameters within the gut niche. Recognition of the bacterial metabolic status in situ, by a sensing of the gut metabolites as a signature of a specific bacterial metabolic activity, has been suggested to be a highly beneficial means for the host to maintain gut-microbe homeostasis. Recently, analysis of Drosophila gut immunity revealed that bacterial-derived uracil and uracil-modulated intestinal reactive oxygen species (ROS) generation play a pivotal role in diverse...
Source: Current Opinion in Immunology - July 2, 2014 Category: Allergy & Immunology Authors: You H, Lee WJ, Lee WJ Tags: Curr Opin Immunol Source Type: research

An evolutionary perspective of how infection drives human genome diversity: the case of malaria.
Abstract Infection with malaria parasites has imposed a strong selective pressure on the human genome, promoting the convergent evolution of a diverse range of genetic adaptations, many of which are harboured by the red blood cell, which hosts the pathogenic stage of the Plasmodium life cycle. Recent genome-wide and multi-centre association studies of severe malaria have consistently identified ATP2B4, encoding the major Ca(2+) pump of erythrocytes, as a novel resistance locus. Evidence is also accumulating that interaction occurs among resistance loci, the most recent example being negative epistasis among alpha-...
Source: Current Opinion in Immunology - July 1, 2014 Category: Allergy & Immunology Authors: Mangano VD, Modiano D Tags: Curr Opin Immunol Source Type: research

Editorial overview: Immune senescence: Known knowns and unknown unknowns.
mery RR PMID: 24996928 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - July 1, 2014 Category: Allergy & Immunology Authors: Fülöp T, Montgomery RR Tags: Curr Opin Immunol Source Type: research

When genetics meets epigenetics: deciphering the mechanisms controlling inter-individual variation in immune responses to infection.
Barreiro LB Abstract The response of host immune cells to microbial stimuli is dependent on robust and coordinated gene expression programs involving the transcription of thousands of genes. The dysregulation of such regulatory programs is likely to significantly contribute to the marked differences in susceptibility to infectious diseases observed among individuals and between human populations. Although the specific factors leading to a dysfunctional immune response to infection remain largely unknown, we are increasingly appreciating the importance of genetic variants in altering the expression levels of immune...
Source: Current Opinion in Immunology - June 27, 2014 Category: Allergy & Immunology Authors: Pacis A, Nédélec Y, Barreiro LB Tags: Curr Opin Immunol Source Type: research

Genomics of host-pathogen interactions.
Abstract The study of immunity against infection can be framed in the context of genomics. First, long-term association with pathogens results in genomic signatures that result from positive selection. Evolutionary pressures tailor species or individual responses to pathogens, that may be associated with skewed patterns of immunity. Second, recent human population expansion carries an increasing burden of genetic mutation that can result in sporadic immunodeficiencies, and more generally, in diversity in susceptibility to infection. This review highlights current concepts and tools for the analysis of genomes and ...
Source: Current Opinion in Immunology - June 24, 2014 Category: Allergy & Immunology Authors: Rausell A, Telenti A Tags: Curr Opin Immunol Source Type: research

Impact of myeloid cells on the efficacy of anticancer chemotherapy.
Abstract Tumors are not immunologically silent but evolve and respond to therapy in the context of a continuous, bi-directional interaction with the host immune system. In line with this notion, several clinically successful chemotherapeutics have been shown to mediate antineoplastic effects as they (re)activate an anticancer immune response that is generally executed by lymphoid cells. Myeloid cells play a central role in this process, not only because they critically regulate the activity of T and B lymphocytes, but also because they exert direct tumoricidal effects, at least in some settings. Here, we discuss t...
Source: Current Opinion in Immunology - June 17, 2014 Category: Allergy & Immunology Authors: Senovilla L, Aranda F, Galluzzi L, Kroemer G Tags: Curr Opin Immunol Source Type: research

Cellular signaling in the aging immune system.
Abstract Causes for immunosenescence and inflamm-aging have to be established. Efficient function of the immune system requires homeostatic regulation from receptor recognition of antigenic challenge to cell responses and adaptation to its changing environment. It is reasonable to assume that one of the most important molecular causes of immunosenescence is alteration in the regulation of signaling pathways. Indeed, alterations in feed-forward and negative feedback (inhibitory) signaling have been highlighted in all cells involved in the immune response including short-lived (neutrophils) and long-lived (T lymphoc...
Source: Current Opinion in Immunology - June 13, 2014 Category: Allergy & Immunology Authors: Fulop T, Le Page A, Fortin C, Witkowski JM, Dupuis G, Larbi A Tags: Curr Opin Immunol Source Type: research

B cell function and influenza vaccine responses in healthy aging and disease.
Abstract Influenza vaccination is less effective in elderly as compared to young individuals. Several studies have addressed the identification of immune biomarkers able to monitor or predict a protective humoral immune response to the vaccine. In this review, we summarize these data, with emphasis on the effects of aging on influenza vaccine-specific B cell responses in healthy individuals and patients with Type-2 Diabetes, HIV and cardiovascular diseases. PMID: 24934648 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - June 13, 2014 Category: Allergy & Immunology Authors: Frasca D, Blomberg BB Tags: Curr Opin Immunol Source Type: research

Autophagy and the immune function in aging.
Abstract Just when you thought that you had heard it all about autophagy-the conserved cellular process that mediates turnover of cellular constituents in the lysosomes-studies keep coming out highlighting new types of autophagy, new functions for autophagy or even new autophagy-independent roles for the proteins associated with this process. The field of immunology has been riding the autophagic wave since the beginning of its revival; first due to its role in the host defense against pathogens, and more recently through the better understanding of the unique characteristics and functions of different autophagic ...
Source: Current Opinion in Immunology - June 11, 2014 Category: Allergy & Immunology Authors: Cuervo AM, Macian F Tags: Curr Opin Immunol Source Type: research

Human CNS immune senescence and neurodegeneration.
Abstract Microglial cells comprising the brain's immune system are essential for ensuring neuroprotection in the normal and pathological CNS. On the basis of histopathological observations in human brain, we believe that the ability of microglia to provide neuroprotection deteriorates as our brains get older and that such CNS immune senescence is a major factor contributing to the development of aging-related neurodegenerative diseases, notably Alzheimer's disease. The idea is consistent with the fact that immune senescence occurs naturally in the periphery, rendering the elderly people more susceptible to infecti...
Source: Current Opinion in Immunology - June 5, 2014 Category: Allergy & Immunology Authors: Streit WJ, Xue QS Tags: Curr Opin Immunol Source Type: research

Hematopoietic stem cell aging.
Abstract Aging is organized in a hierarchy, in which aging of cells results in aged tissues, ultimately limiting lifespan. For organ systems that also in the adult depend on stem cells for tissue homeostasis like the hematopoietic system that forms immune cells, it is believed that aging of the stem cells strongly contributes to aging-associated dysfunction. In this review, we summarize current aspects on cellular and molecular mechanisms that are associated with aging of hematopoietic stem cells, the role of the stem cell niche for stem cell aging as well as novel and encouraging experimental approaches to attenu...
Source: Current Opinion in Immunology - June 3, 2014 Category: Allergy & Immunology Authors: Geiger H, Denkinger M, Schirmbeck R Tags: Curr Opin Immunol Source Type: research

Discovery of single-gene inborn errors of immunity by next generation sequencing.
Abstract Many patients with clinical and laboratory evidence of primary immunodeficiency do not have a gene specific diagnosis. The use of next generation sequencing, particularly whole exome sequencing, has given us an extraordinarily powerful tool to identify the disease-causing genes in some of these patients. At least 34 new gene defects have been identified in the last 4 years. These findings document the striking heterogeneity of the phenotype in patients with mutations in the same gene. In some cases this can be attributed to loss-of-function mutations in some patients, but gain-of-function mutations in oth...
Source: Current Opinion in Immunology - May 30, 2014 Category: Allergy & Immunology Authors: Conley ME, Casanova JL Tags: Curr Opin Immunol Source Type: research

T cells and their cytokines in persistent stimulation of the immune system.
Abstract Age-dependent dysregulations of innate immunity impair effective priming of adaptive immunity. Alteration of helper functions of CD4 T cells during aging prevents them from sustaining cytotoxic responses of CD8 T cells against pathogens. The main characteristics of aged and/or differentiated T cells included telomere erosion, reduction of proliferation, decrease of IL-2 secretion and responsiveness, loss of CD28 and acquisition of cytotoxic properties. Phenotypic and functional modifications associated with aging affect development, differentiation, exhaustion/senescence status, migration, signalisation a...
Source: Current Opinion in Immunology - May 29, 2014 Category: Allergy & Immunology Authors: Kared H, Camous X, Larbi A Tags: Curr Opin Immunol Source Type: research

Human genome variability, natural selection and infectious diseases.
Abstract The recent availability of large-scale sequencing DNA data allowed researchers to investigate how genomic variation is distributed among populations. While demographic factors explain genome-wide population genetic diversity levels, scans for signatures of natural selection pinpointed several regions under non-neutral evolution. Recent studies found an enrichment of immune-related genes subjected to natural selection, suggesting that pathogens and infectious diseases have imposed a strong selective pressure throughout human history. Pathogen-mediated selection often targeted regulatory sites of genes belo...
Source: Current Opinion in Immunology - May 28, 2014 Category: Allergy & Immunology Authors: Fumagalli M, Sironi M Tags: Curr Opin Immunol Source Type: research

Complementary diversification of dendritic cells and innate lymphoid cells.
hy KM Abstract Dendritic cells (DCs) are professional antigen presenting cells conventionally thought to mediate cellular adaptive immune responses. Recent studies have led to the recognition of a non-redundant role for DCs in orchestrating innate immune responses, and in particular, for DC subset-specific interactions with innate lymphoid cells (ILCs). Recently recognized as important effectors of early immune responses, ILCs develop into subsets which mirror the transcriptional and cytokine profile of their T cell subset counterparts. DC diversification into functional subsets provides for modules of pathogen se...
Source: Current Opinion in Immunology - May 26, 2014 Category: Allergy & Immunology Authors: Briseño CG, Murphy TL, Murphy KM Tags: Curr Opin Immunol Source Type: research

A systems biology approach to the effect of aging, immunosenescence and vaccine response.
Abstract Aging can lead to immunosenescence, which dramatically impairs the hosts' ability to develop protective immune responses to vaccine antigens. Reasons for this are not well understood. This topic's importance is reflected in the increases in morbidity and mortality due to infectious diseases among elderly persons, a population growing in size globally, and the significantly lower adaptive immune responses generated to vaccines in this population. Here, we endeavor to summarize the existing data on the genetic and immunologic correlates of immunosenescence with respect to vaccine response. We cover how the ...
Source: Current Opinion in Immunology - May 9, 2014 Category: Allergy & Immunology Authors: Poland GA, Ovsyannikova IG, Kennedy RB, Lambert ND, Kirkland JL Tags: Curr Opin Immunol Source Type: research

Plasticity in the transcriptional and epigenetic circuits regulating dendritic cell lineage specification and function.
Abstract Dendritic cells (DC) are critical and functionally versatile innate immune sentinels. Here, we coarsely partition the adult DC lineage into three developmental subtypes and argue that pioneer transcription factors and chromatin remodeling are responsible for specification and plasticity between the DC subsets. Subsequently, intricate signaling-dependent transcription factor networks generate different functional states in response to pathogen stimuli within a specified DC subtype. To expand our understanding of lineage heterogeneity and functional activation states, we discuss the use of single cell genom...
Source: Current Opinion in Immunology - May 9, 2014 Category: Allergy & Immunology Authors: Paul F, Amit I Tags: Curr Opin Immunol Source Type: research

Shaping of NK cell subsets by aging.
Abstract NK cells are key players in the innate immune response against virus infection and tumors. Here we describe the current knowledge on age-associated changes in NK cells and the role of persistent CMV infection in configuring NK cell compartment in the elderly. Aging but not CMV causes a redistribution of NK cell subsets as shown by a decrease of CD56bright cells and an increase of CD56-CD16+ NK cells. On the contrary the changes in CD56dimCD16+ NK cells are compatible with the accumulation of CD57+ long-lived NK cells that can also be observed in young CMV-seropositive individuals. NK cell function and dyn...
Source: Current Opinion in Immunology - April 29, 2014 Category: Allergy & Immunology Authors: Solana R, Campos C, Pera A, Tarazona R Tags: Curr Opin Immunol Source Type: research

Effects of polymorphisms in immunity-related genes on the immune system and successful aging.
Abstract Aging is associated with the dysregulation of immune system. Despite a progressive decline in immune function resulting in hyporesponsiveness to infection and vaccination, aging is also characterized by a chronic, low-grade, pro-inflammatory condition. An elderly individual with a systemic inflammation is at an increased risk of age-related diseases. Polymorphisms in the genes coding for inflammatory or anti-inflammatory molecules associated with immune related processes can affect the balance between the pro-inflammatory and anti-inflammatory networks. An improved understanding of the interactions among ...
Source: Current Opinion in Immunology - April 26, 2014 Category: Allergy & Immunology Authors: Ruan Q, Qian F, Yu Z Tags: Curr Opin Immunol Source Type: research

Effect of aging on microRNAs and regulation of pathogen recognition receptors.
Abstract Immunosenescence is the multifactorial age-associated immune deteriorization that leads to increased susceptibility to infections and decreased responses to vaccines. Recent studies have shown a fundamental role for microRNAs (miRNAs) in regulating immune responses, and nearly all the miRNAs involved in immune regulation show modulation during aging. Aging-associated miRNAs are largely negative regulators of the immune innate response and target central nodes of aging-associated networks, in particular, NF-κB, the downstream effector of TLR signals that leads to induction of proinflammatory response...
Source: Current Opinion in Immunology - April 24, 2014 Category: Allergy & Immunology Authors: Olivieri F, Procopio AD, Montgomery RR Tags: Curr Opin Immunol Source Type: research

Immunosenescence: influenza vaccination and the elderly.
Abstract Aging is associated with a decline in the normal function of the immune system, both cellular and humoral, which often leads to a state of 'immunosenescence'. It is necessary that we understand the fundamental cellular and molecular basis of immune senescence and immune responsiveness to prevent age-related diseases, such as viral and bacterial infections, in order to develop appropriate preventative and novel therapeutic measures. Vaccination has been a highly effective prophylactic in protecting vulnerable populations worldwide from many pathogens. Novel vaccine research to enhance protection against th...
Source: Current Opinion in Immunology - April 24, 2014 Category: Allergy & Immunology Authors: Haq K, McElhaney JE Tags: Curr Opin Immunol Source Type: research

Expanding roles of neutrophils in aging hosts.
Abstract Neutrophils' role in the clearance of pathogens is well documented, but there is increasing appreciation that neutrophils can participate in the resolution of infection and inflammation. An obvious implication is that alteration of neutrophil functions with old age could significant impact both susceptibility of the host to infection and inflammatory conditions. Advances in recent years suggest additional chinks in the neutrophil antimicrobial arsenals in aged hosts, which render neutrophils less capable of killing pathogens. Moreover there is evidence that changes in neutrophil cross-talk with other immu...
Source: Current Opinion in Immunology - April 24, 2014 Category: Allergy & Immunology Authors: Tseng CW, Liu GY Tags: Curr Opin Immunol Source Type: research

Interleukin 33: a switch-hitting cytokine.
Abstract For many years IL-33 has been widely studied in the context of T helper type 2 (Th2)-driven inflammatory disorders. Interestingly, IL-33 has now emerged as a cytokine with a plethora of pleiotropic properties. Depending on the immune cells targeted by IL-33, it is reported to not only promote Th2 immunity, but also to induce T helper type 1 (Th1) immunity. Furthermore, recent studies have revealed that IL-33 can activate CD8(+) T cells. These new studies provide evidence for its beneficial role in antiviral and antitumor immunity. Here we review the evidence of IL-33 to drive protective T cell immunity pl...
Source: Current Opinion in Immunology - April 21, 2014 Category: Allergy & Immunology Authors: Villarreal DO, Weiner DB Tags: Curr Opin Immunol Source Type: research

Inflammation, ageing and chronic disease.
Abstract Acute inflammatory responses are essential for pathogen control and tissue repair but can also cause severe collateral damage. Tight regulation of the response is required to minimize host injury, but in the face of chronic infections and age-associated immune dysregulation, inflammatory processes may exert multiple detrimental effects on the organism. The signs of low level systemic inflammation commonly detectable in elderly people are associated with many chronic diseases of ageing and may even contribute to their causation. The purpose of this article is to review recent literature from the past two y...
Source: Current Opinion in Immunology - April 21, 2014 Category: Allergy & Immunology Authors: Pawelec G, Goldeck D, Derhovanessian E Tags: Curr Opin Immunol Source Type: research

Editorial overview: Lymphocyte activation and effector functions.
PMID: 24751355 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - April 18, 2014 Category: Allergy & Immunology Authors: Reynaud CA, Tangye S Tags: Curr Opin Immunol Source Type: research

Editorial overview: Vaccines: Vaccines for infectious diseases: are we there yet?
PMID: 24735901 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - April 12, 2014 Category: Allergy & Immunology Authors: Khader SA, Kolls JK Tags: Curr Opin Immunol Source Type: research

Commensal bacteria mediated defenses against pathogens.
Abstract Commensal bacterial communities residing within the intestinal lumen of mammals have evolved to flourish in this microenvironment. To preserve this niche, commensal bacteria act with the host to prevent colonization by invasive pathogens that induce inflammation and disrupt the intestinal niche commensal bacteria occupy. Thus, it is mutually beneficial to the host and commensal bacteria to inhibit a pathogen's ability to establish an infection. Commensal bacteria express factors that support colonization, maximize nutrient uptake, and produce metabolites that confer a survival advantage over pathogens. Fu...
Source: Current Opinion in Immunology - April 8, 2014 Category: Allergy & Immunology Authors: Abt MC, Pamer EG Tags: Curr Opin Immunol Source Type: research

Visualization and dynamic analysis of host-pathogen interactions.
Abstract To contain invading microbes, the immune system must efficiently recognize the presence of the invader, mobilize cells to the site of infection, and deploy effector function. Rare antigen-specific T cells must find small numbers of antigen-presenting cells, proliferate and differentiate in secondary lymphoid tissues, then traffic to the infected site and be activated by antigen again to contribute to host defense. Our understanding of the dynamic processes involved has benefited enormously from tools that enable the visualization of cell location and behavior in complex tissue environments. Here we summar...
Source: Current Opinion in Immunology - April 2, 2014 Category: Allergy & Immunology Authors: Mandl JN, Torabi-Parizi P, Germain RN Tags: Curr Opin Immunol Source Type: research

The imperfect control of self-reactive germinal center B cells.
Abstract Unlike T cells, B cells diversify their antigen receptor (BCR) binding specificities at two distinct stages of differentiation. Thus, in addition to initial variable region gene rearrangements, B cells recruited into T-dependent immune responses further modify their BCR specificity via iterative rounds of somatic hypermutation (SHM) within germinal centers (GCs). Although critical for providing the high-affinity antibody specificities required for long-term immune protection, SHM can also generate self-reactive B cells capable of differentiating into autoantibody-producing plasma cells. Recent data confir...
Source: Current Opinion in Immunology - March 27, 2014 Category: Allergy & Immunology Authors: Brink R Tags: Curr Opin Immunol Source Type: research

Clonal and cellular dynamics in germinal centers.
Abstract Germinal centers (GCs) are the site of antibody affinity maturation, a process that involves complex clonal and cellular dynamics. Selection of B cells bearing higher-affinity immunoglobulins proceeds via a stereotyped pattern whereby B cells migrate cyclically between the GC's two anatomical compartments. This process occurs in a timeframe that is well suited to analysis by intravital microscopy, and much has been learned in recent years by use of these techniques. On a longer time scale, the diversity of B cell clones and variants within individual GCs is also thought to change as affinity maturation pr...
Source: Current Opinion in Immunology - March 26, 2014 Category: Allergy & Immunology Authors: Victora GD, Mesin L Tags: Curr Opin Immunol Source Type: research

Vaccine approaches for multidrug resistant Gram negative infections.
Abstract Multidrug resistant (MDR) Gram negative bacterial infections are increasing in frequency and are associated with significant financial costs, morbidity and mortality. Current antibiotic therapies are associated with unacceptably poor clinical outcomes and toxicity. Unfortunately, the development of novel antimicrobials is stagnant leaving a significant clinical need for alternative treatments of MDR Gram negative rod infections. Recent preclinical studies have identified Th17 cells as critical mediators of broadly protective adaptive immunity, including protection against MDR infections. Studies of Th17 e...
Source: Current Opinion in Immunology - March 14, 2014 Category: Allergy & Immunology Authors: Campfield B, Chen K, Kolls JK Tags: Curr Opin Immunol Source Type: research

From the regulatory functions of B cells to the identification of cytokine-producing plasma cell subsets.
Abstract B lymphocytes have a unique role as antibody-producing cells. Antibodies are key mediators of humoral immunity against infections, and are thought to account for the protection afforded by successful vaccines. B cells can also secrete cytokines and subsequently regulate immune responses mediated by T and innate cells. Remarkably, recent studies identified plasma blasts/plasma cells as the main types of activated B cells producing the cytokines interleukin (IL)-10, IL-35, tumor necrosis factor (TNF)-α, IL-17, and GM-CSF in various contexts in mice. Here, we discuss these observations, which suggest t...
Source: Current Opinion in Immunology - March 13, 2014 Category: Allergy & Immunology Authors: Dang VD, Hilgenberg E, Ries S, Shen P, Fillatreau S Tags: Curr Opin Immunol Source Type: research

Eliciting broadly protective antibody responses against influenza.
Abstract Antibodies recognizing the hemagglutinin (HA) protein, which are elicited following infection or vaccination, confer protection against influenza virus infection. Although annual seasonal influenza vaccines provide some protection against currently circulating influenza strains, they lack efficacy against viruses expressing divergent globular head domains of HA. Moreover, antigenic drift within the globular head of circulating viruses necessitates frequent reformulation of the seasonal vaccine, a process that is both expensive and time-consuming. In this regard, vaccine strategies that generate antibodies...
Source: Current Opinion in Immunology - March 12, 2014 Category: Allergy & Immunology Authors: Kirchenbaum GA, Ross TM Tags: Curr Opin Immunol Source Type: research

Editorial overview: Lymphocyte development.
PMID: 24629726 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - March 11, 2014 Category: Allergy & Immunology Authors: Litman GW, Mauri C Tags: Curr Opin Immunol Source Type: research

Regulatory constraints in the generation and differentiation of IgE-expressing B cells.
Abstract B cells expressing antibodies of the immunoglobulin E (IgE) isotype are rare, yet are heavily implicated in the pathogenesis of allergies and asthma. This review discusses recent methodological advances that permit sensitive probing of IgE-expressing (IgE(+)) B cells in vivo and have accordingly clarified the basic behavior and fate of IgE(+) B cells during immune responses in mouse models. IgE antibody secreting plasma cells can arise from extrafollicular foci, germinal centers, and memory B cells. However, compared to B cells expressing other isotypes, IgE(+) B cells are susceptible to multiple addition...
Source: Current Opinion in Immunology - March 11, 2014 Category: Allergy & Immunology Authors: Yang Z, Robinson MJ, Allen CD Tags: Curr Opin Immunol Source Type: research

Editorial overview: Tumour immunology: New frontiers in cancer immunotherapy.
PMID: 24629727 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - March 10, 2014 Category: Allergy & Immunology Authors: Darcy PK, Ritchie DS Tags: Curr Opin Immunol Source Type: research

Invariant NKT cell development: focus on NOD mice.
Abstract Natural killer T (NKT) cells are non-conventional T lymphocytes expressing a TCRαβ and several NK cell markers. Once activated, they can rapidly secrete large amounts of cytokines such as IFN-γ and IL-4. As a result they can favor both Th1 and Th2 immune responses and play a critical role in anti-pathogenic immune responses as well as in regulation of autoimmune diseases. It has now been clearly established that iNKT cells can be subdivided into three subpopulations: iNKT1, iNKT2 and iNKT17 cells. Each of these populations is characterized by the expression of a particular transcription f...
Source: Current Opinion in Immunology - March 10, 2014 Category: Allergy & Immunology Authors: Ghazarian L, Simoni Y, Magalhaes I, Lehuen A Tags: Curr Opin Immunol Source Type: research

Innate immune memory: towards a better understanding of host defense mechanisms.
Abstract Innate immunity is classically defined as unable to build up immunological memory. Recently however, the assumption of the lack of immunological memory within innate immune responses has been reconsidered. Plants and invertebrates lacking adaptive immune system can be protected against secondary infections. It has been shown that mammals can build cross-protection to secondary infections independently of T-lymphocytes and B-lymphocytes. Moreover, recent studies have demonstrated that innate immune cells such as NK cells and monocytes can display adaptive characteristics, a novel concept for which the term...
Source: Current Opinion in Immunology - March 10, 2014 Category: Allergy & Immunology Authors: Quintin J, Cheng SC, van der Meer JW, Netea MG Tags: Curr Opin Immunol Source Type: research

Novel vaccine approaches for protection against intracellular pathogens.
Abstract Vaccination against intracellular pathogens requires generation of a pool of memory T cells able to respond upon infection and mediate either killing of the infected cell or induce killing mechanisms in the infected cell. T cell-inducing vaccines must aim to target the antigen to antigen-presenting cells (APCs) so that it can be presented on MHC molecules on the cell surface. Methods to do this include making use of vectors such as plasmid DNA or viruses, live attenuated pathogens or subunit vaccines targeted and enhanced using adjuvants. The choice of approach should be guided by the phenotype and locali...
Source: Current Opinion in Immunology - March 6, 2014 Category: Allergy & Immunology Authors: Griffiths KL, Khader SA Tags: Curr Opin Immunol Source Type: research

Regulation of the adaptive immune system by innate lymphoid cells.
Abstract Innate lymphoid cells (ILCs) are a group of lymphocytes that promote rapid cytokine-dependent innate immunity, inflammation and tissue repair. In addition, a growing body of evidence suggests ILCs can influence adaptive immune cell responses. During fetal development a subset of ILCs orchestrate the generation and maturation of secondary lymphoid tissues. Following birth, ILCs continue to modulate adaptive immune cell responses indirectly through interactions with stromal cells in lymphoid tissues and epithelial cells at barrier surfaces. In this review we summarize the current understanding of how ILCs m...
Source: Current Opinion in Immunology - March 1, 2014 Category: Allergy & Immunology Authors: Hepworth MR, Sonnenberg GF Tags: Curr Opin Immunol Source Type: research

Understanding Th17 cells through systematic genomic analyses.
Abstract Th17 cells are a subset of CD4+ T helper cells that play an important role in host defense and have been strongly associated with the pathogenesis of autoimmunity. The immense research effort on Th17 cells has benefited in recent years from major breakthroughs in genomic profiling technologies. The picture emerging from these studies has led us away from thinking about T cell differentiation in terms of rigid, separate pathways that give rise to canonical 'types'. Instead, it has encouraged us to understand T cell differentiation and function through a complex network of transcriptional regulators that ca...
Source: Current Opinion in Immunology - March 1, 2014 Category: Allergy & Immunology Authors: Peters A, Yosef N Tags: Curr Opin Immunol Source Type: research