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The article reports on the findings of a study which suggests that BOB1 potentiates B cell receptor (BCR) signalling by regulating the expression of the microRNAs miR-146a and miR-210.

The article reports on a study which uncovers the unique population of T cells as receptors that recognize the lipids presented by the non-polymorphic antigen-presenting molecule CD1b.

The article presents a research which provides information that by the synchronous and well coordinated attack by innate and adaptive immune virus-specific CD8⁺ T cells, viral skin infection can be removed.

The article discusses research being done on effect of B-cell tolerance on systemic lupus erythematosus (SLE). It references separate studies by K. R. Kumar et al and P. Pisitkun et al, in a 2006 issue of "Science." Pisitkun et al. studied the Y-chromosome-linked autoimmune accelerator locus, an SLE-susceptibility locus in mice. Kumar et al investigated the SLE1 locus, known to be another SLE-susceptibility locus in mice.

The article discusses the study which determines the crucial role of mammalian target of rapamycin (mTOR) in the blending of the signals from the three factors to determine the effector versus memory CD8+ T cells responses. The researchers involve the antigen, co-stimulation for T cell activation and cytokine stimulation to determine the result. Researchers then show that mTOR is the crucial point of integration in CD8+ T cells for signals that programme effector versus memory differentiation.

The article offers information on cytokine thymic stromal lymphopoietin (TSLP) and B-cell homeostasis in the U.S. TSLP is similar to interleukin-7 and is expressed by epithelial cells. TSLP is also known to stimulate B-cells development and there is increasing evidence that it has a role in allergic disease.

The article discusses research being done on B cell receptor (BCR) signaling and internalization. It references a study by P. Hou et al., published in a 2006 issue of the journal "PLoS Biology." Details of how the study was conducted are given. The study shows that BCR signalling and internalization events are mutually exclusive. The authors also determine that a small fraction of surface BCR complexes were phosphorylated.

Discusses research being done on the distinctiveness of Igm memory B cells from the classical germinal-center-derived memory B cells. Reference to a study by S. Weller et al, published in the 2004 issue of "Blood"; Contribution of the cells to the regulation of T-cell independent responses; Similarity of the composition of the memory cells with the phenotypic characteristic of the cells located in the splenic marginal zone.

Discusses research being done on the role of B-cell-specific transcription repressor BACH2 during class-switch recombination (CSR) and somatic hypermutation. Reference to a study by A. Muto et al., published in a 2004 issue of "Nature"; Results of an immunohistochemical analysis of transcription-factor expression; Discussion on BACH2 as a regulator of CSR.

Discusses research being done on vitro methods for clonally expanding antigen-specific CD4+CD25+TReg cells that effectively suppress disease in a mouse model of autoimmune diabetes. Reference to a study by Jeffrey Bluestone and colleagues published in "The Journal of Experimental Medicine"; Expansion of CD4+CD25+TReg cells by Ralph Steinman and colleagues using dendritic cells isolated from nonobese diabetic mice and pulsed with specific autoantigen; Examination on the therapeutic capability of the two methods against autoimmune diabetes.

Discusses research being done on alternative mechanism involving impaired activation of antigen-presenting cells (APC) in resistant mouse strains. Reference to a study made by Kuchroo and colleagues, which was published in "The Journal of Clinical Investigation"; Comparison between SJL mice and 5B6 TCR-transgenic mice; Analysis of APC from the two mouse strains.

The article discusses research being done on mucosal immunology and dendritic cell (DC) biology. It references the study "Functional specialization of gut CD103+ dendritic cells in the regulation of tissue-selective T cell homing," by B. Johansson-Lindbom and colleagues in the 2015 issue. Topics discussed include the role of antigen-presenting cell (APC) in T cells imprinting, the crucial role of tissue of origin in determining DC behaviour, and the effects of DC103+ on T cells.

The article presents information on a research study on conventional dendritic cells (cDCs) conducted by researchers Caetano Reis e Sousa and colleagues, published in the journal "Cell." The study shows that the precursors of cDCs in mice can be traced by dendritic cell natural killer lectin group receptor 1. The researchers present a model that helps in identifying cDCs in mice on the basis of ontogeny.

Alveolar macrophages exist in a unique microenvironment and, despite historical evidence showing that they are in close contact with the respiratory epithelium, have until recently been investigated in isolation. The microenvironment of the airway lumen has a considerable influence on many aspects of alveolar macrophage phenotype, function and turnover. As the lungs adapt to environmental challenges, so too do alveolar macrophages adapt to accommodate the ever-changing needs of the tissue. In this Review, we discuss the unique characteristics of alveolar macrophages, the mechanisms that drive their adaptation and the direct and indirect influences of epithelial cells on them. We also highlight how airway luminal macrophages function as sentinels of a healthy state and how they do not respond in a pro-inflammatory manner to antigens that do not disrupt lung structure. The unique tissue location and function of alveolar macrophages distinguish them from other macrophage populations and suggest that it is important to classify macrophages according to the site that they occupy. [ABSTRACT FROM AUTHOR]

B cells are key components of the adaptive immune response. Their differentiation into either specific memory B cells or antibody-secreting plasma cells is a consequence of activation steps that involve the processing and presentation of antigens. The engagement of B cell receptors by surface-tethered antigens leads to the formation of an immunological synapse that coordinates cell signalling events and that promotes antigen uptake for presentation on MHC class II molecules. In this Review, we discuss membrane trafficking and the associated molecular mechanisms that are involved in antigen extraction and processing at the B cell synapse, and we highlight how B cells use cell polarity to coordinate the complex events that ultimately lead to efficient humoral responses. [ABSTRACT FROM AUTHOR]

Antibody production is an important feature of the vertebrate immune system. Antibodies neutralize and clear pathogens, thereby protecting against infectious diseases. Such humoral immunity has great longevity, often persisting for the host's lifetime. Long-lived humoral immunity depends on help provided by CD4+ T cells, namely T follicular helper (TFH) cells, which support the differentiation of antigen-specific B cells into memory and plasma cells. TFH cells are stringently regulated, as aberrant TFH cell activity is involved in immunopathologies such as autoimmunity, immunodeficiencies and lymphomas. The elucidation of the mechanisms that regulate TFH cell differentiation, function and fate should highlight targets for novel therapeutics. [ABSTRACT FROM AUTHOR]

The discovery of Toll-like receptors (TLRs) was an important event for immunology research and was recognized as such with the awarding of the 2011 Nobel Prize in Physiology or Medicine to Jules Hoffmann and Bruce Beutler, who, together with Ralph Steinman, the third winner of the 2011 Nobel Prize and the person who discovered the dendritic cell, were pioneers in the field of innate immunity. TLRs have a central role in immunity - in this Timeline article, we describe the landmark findings that gave rise to this important field of research. [ABSTRACT FROM AUTHOR]

The article presents a study that investigates the physiological significance of B cell in germinal B cell migration. As part of the study, the researchers have identified the mechanisms involved in B cell selection in germinal centers, and the importance of migration in dark and light zones. The study has also defined specific mechanism which govern B cell selection in germinal centers using a unique method with photoactivatable green fluorescent expression (PA-GFP).

The T cell protein cytotoxic T lymphocyte antigen 4 (CTLA4) was identified as a crucial negative regulator of the immune system over 15 years ago, but its mechanisms of action are still under debate. It has long been suggested that CTLA4 transmits an inhibitory signal to the cells that express it. However, not all the available data fit with a cell-intrinsic function for CTLA4, and other studies have suggested that CTLA4 functions in a T cell-extrinsic manner. Here, we discuss the data for and against the T cell-intrinsic and -extrinsic functions of CTLA4. [ABSTRACT FROM AUTHOR]

Presents information on research published in "Nature" which indicated that dendritic cells can distinguish antigens taken up in the presence of Toll-like receptor ligands from those taken up in the absence of such ligands. Importance of the study in the efforts of immunologists to understand how the immune system discriminates between self- and non-self antigens; Description on how dendritic cells work during an infection.

B cells are essential for humoral immunity, but the role that they have in regulating CD4(+) T cell responses remains controversial. However, new data showing that the transient depletion of B cells potently influences the induction, maintenance and reactivation of CD4(+) T cells, with the recent identification of antibody-independent functions of B cells, have reinvigorated interest in the many roles of B cells in both infectious and autoimmune diseases. In this Review, we discuss recent data showing how effector and regulatory B cells modulate CD4(+) T cell responses to pathogens and autoantigens. [ABSTRACT FROM AUTHOR]

In germinal centres, somatic hypermutation and B cell selection increase antibody affinity and specificity for the immunizing antigen, but the generation of autoreactive B cells is an inevitable by-product of this process. Here, we review the evidence that aberrant selection of these autoreactive B cells can arise from abnormalities in each of the germinal centre cellular constituents--B cells, T follicular helper cells, follicular dendritic cells and tingible body macrophages--or in the supply of antigen. As the progeny of germinal centre B cells includes long-lived plasma cells, selection of autoreactive B cells can propagate long-lived autoantibody responses and cause autoimmune diseases. Elucidation of crucial molecular signals in germinal centres has led to the identification of novel therapeutic targets. [ABSTRACT FROM AUTHOR]

Understanding how thymic selection imparts self-peptide-MHC complex restriction and a high degree of self tolerance on the T cell repertoire requires a detailed description of the parameters that shape the MHC ligand repertoire of distinct thymic antigen-presenting cells and of how these cells communicate with T cells. Several recent discoveries pertaining to cortex-specific pathways of antigen processing, the heterogeneity of thymic dendritic cells and the intercellular transfer of self antigens have uncovered surprising and unique aspects of antigen presentation in the thymic microenvironment. Here, we discuss these new findings in the context of how individual thymic stromal cell types support T cell selection in a cooperative rather than a redundant manner. [ABSTRACT FROM AUTHOR]

Human skin and its immune cells provide essential protection of the human body from injury and infection. Recent studies reinforce the importance of keratinocytes as sensors of danger through alert systems such as the inflammasome. In addition, newly identified CD103(+) dendritic cells are strategically positioned for cross-presentation of skin-tropic pathogens and accumulating data highlight a key role of tissue-resident rather than circulating T cells in skin homeostasis and pathology. This Review focuses on recent progress in dissecting the functional role of skin immune cells in skin disease. [ABSTRACT FROM AUTHOR]

Inflammation is a multicomponent response to tissue stress, injury and infection, and a crucial point of its control is at the level of gene transcription. The inducible inflammatory gene expression programme--such as that triggered by Toll-like receptor signalling in macrophages--is comprised of several coordinately regulated sets of genes that encode key functional programmes; these are controlled by three classes of transcription factors, as well as various transcriptional co-regulators and chromatin modifications. Here, we discuss the mechanisms of and the emerging principles in the transcriptional regulation of inflammatory responses in diverse physiological settings. [ABSTRACT FROM AUTHOR]

Hypoxia-inducible factor (HIF) is an important transcriptional regulator of cell metabolism and the adaptation to cellular stress caused by oxygen deficiency (hypoxia). Phagocytic cells have an essential role in innate immune defence against pathogens and this is a battle that takes place mainly in the hypoxic microenvironments of infected tissues. It has now become clear that HIF promotes the bactericidal activities of phagocytic cells and supports the innate immune functions of dendritic cells, mast cells and epithelial cells. In response to microbial pathogens, HIF expression is upregulated through pathways involving the key immune response regulator nuclear factor-kappaB, highlighting an interdependence of the innate immune and hypoxic responses to infection and tissue damage. In turn, HIF-driven innate immune responses have important consequences for both the pathogen and the host, such that the tissue microenvironment fundamentally influences susceptibility to infectious disease. [ABSTRACT FROM AUTHOR]

Autoreactive T cell responses have a crucial role in central nervous system (CNS) diseases such as multiple sclerosis. Recent data indicate that CNS autoimmunity can be mediated by two distinct lineages of CD4+ T cells that are defined by the production of either interferon-gamma or interleukin-17. The activity of these CD4+ T cell subsets within the CNS influences the pathology and clinical course of disease. New animal models show that myelin-specific CD8+ T cells can also mediate CNS autoimmunity. This Review focuses on recent progress in delineating the pathogenic mechanisms, regulation and interplay between these different T cell subsets in CNS autoimmunity. [ABSTRACT FROM AUTHOR]

The efficacy of vaccines depends on the presence of an adjuvant in conjunction with the antigen. Of these adjuvants, the ones that contain aluminium, which were first discovered empirically in 1926, are currently the most widely used. However, a detailed understanding of their mechanism of action has only started to be revealed. In this Timeline article, we briefly describe the initial discovery of aluminium adjuvants and discuss historically important advances. We also summarize recent progress in the field and discuss their implications and the remaining questions on how these adjuvants work. [ABSTRACT FROM AUTHOR]

A functional immune system depends on the appropriate activation of lymphocytes following antigen encounter. In this Review, we summarize studies that have used high-resolution imaging approaches to visualize antigen presentation to B cells in secondary lymphoid organs. These studies illustrate that encounters of B cells with antigen in these organs can be facilitated by diffusion of the antigen or by the presentation of antigen by macrophages, dendritic cells and follicular dendritic cells. We describe cell-surface molecules that might be important in mediating antigen presentation to B cells and also highlight the key role of B cells themselves in antigen transport. Data obtained from the studies discussed here highlight the predominance, importance and variety of the cell-mediated processes that are involved in presenting antigen to B cells in vivo. [ABSTRACT FROM AUTHOR]

Discusses research being done on the interaction between T cells and antigen-presenting cells (APC). Reference to a study by Matthias Gunzer et al published in a 2004 issue of "Blood"; Use of a three-dimensional collagen-matrix system and intravital imaging to show that T cells can interact with different APCs; Result of the comparison of the kinetics of T cell activation with different types of APC.

Discusses research being done on mature dendritic cells (DC). Reference to a study by M. Zhang et al, which appeared in a 2004 issue of "Nature Immunology"; Role of endothelial-like splenic stromal cells in the induction of mature DC proliferation; Main distinguishing characteristic of DC phenotype in vitro.

Presents the results of a study on the role of dendritic cells (DC) in ovarian tumors. Effect of β-defensin 29 expression on the tumors; Factors that contribute to the expression of the DC marker CD11c in the tumors; Significance of vascular endothelial growth factors to tumor vascularization.

Discusses research being done on the capability of certain polysaccharides processed with antigen-presenting cells to associate with major histocompatibility complex (MHC) class II molecules and induce cluster of differentiation T-cell responses. Reference to a study by B. A. Cobb, Q. Wang, A. O. Tzianabos and D. L. Kasper published in a 2004 issue of "Cell"; Investigation whether zwitterionic polysaccharide uses the conventional MHC class II antigen-presentation pathway; Discussion on the results of polysaccharide A taken up by antigen-presenting cells.

Discusses research being done on the role of B cells in immune responses. Reference to a study by M. E. Duddy et al which was published in "The Journal of Immunology"; Information on B-cell proliferation; Effect of B-cell receptor cross linking on immune responses.

Presents abstracts of several studies on immunology. "Induction of Protective IgA by Intestinal Dendritic Cells Carrying Commensal Bacteria," by A. J. Macpherson and T. Uhr; "Human Bone-Marrow Stromal Cells Inhibit Allogeneic T-cell Responses by Indoleamine 2, 3-Dioxygenase Mediated Tryptophan Degradation," by R. Meisel, et al.; "The STAT3 Isoforms α and β Have Unique and Specific Functions," by D. Maritano, et al.

Focuses on the T-cell recognition of antigen displayed by an antigen-presenting cell. Concept of the immunological synapse; Relation between antigen recognition and cytoskeletal changes; Function of Ezrin-Radixin-Moesin proteins.

Provides an overview of several studies concerning immunology published in various periodicals. "HSP70 Promotes Antigen-Presenting Cell Function and Converts T-Cell Tolerance to Autoimmunity in Vivo," by D. G. Miller, et al; "A Conserved Signal-Responsive Sequence Mediates Activation-Induced Alternative Splicing of CD45," by C. Rothrock, et al; "Use of a Small Molecule CCR5 Inhibitor in Macaques to Treat Simian Immunodeficiency Virus Infection or Prevent Simian-Human Immunodeficiency Virus Infection," by R. S. Veazey, et al.

The principal components of both MHC class I and class II antigen processing and presentation pathways are well known. In dendritic cells, these pathways are tightly regulated by Toll-like-receptor signalling and include features, such as cross-presentation, that are not seen in other cell types. However, the exact mechanisms involved in the subcellular trafficking of antigens remain poorly understood and in some cases are controversial. Recent data suggest that diverse cellular machineries, including autophagy, participate in antigen processing and presentation, although their relative contributions remain to be fully elucidated. Here, we highlight some emerging themes of antigen processing and presentation that we think merit further attention. [ABSTRACT FROM AUTHOR]

Discusses research being done on the role of plasmacytoid dendritic cells (pDC) in type I interferons after exposure to viruses. Reference to a study done by G. Jego et al., published in the 2003 issue of "Immunity"; Impact of pDC in plasma cell differentiation.

Investigates the potential involvement of CD3[sup-]CD4[sup+] cells in an immune response of antigen-specific CD4[sup+] T helper cells. Role of dendritic cells in T cell responses; Expression of the cells; Physiological presence of the cells; Details on CD antigens.

The realization that dendritic cells (DCs) orchestrate innate and adaptive immune responses has stimulated research on harnessing DCs to create more effective vaccines. Early clinical trials exploring autologous DCs that were loaded with antigens ex vivo to induce T-cell responses have provided proof of principle. Here, we discuss how direct targeting of antigens to DC surface receptors in vivo might replace laborious and expensive ex vivo culturing, and facilitate large-scale application of DC-based vaccination therapies. [ABSTRACT FROM AUTHOR]

Directing both innate and adaptive immune responses against foreign pathogens with correct timing, location and specificity is a fundamental objective for the immune system. Full activation of CD4+ T cells requires the binding of peptide-MHC complexes coupled with accessory signals provided by the antigen-presenting cell. However, aberrant activation of the T-cell receptor alone in mature T cells can produce a long-lived state of functional unresponsiveness, known as anergy. Recent studies probing both immune signalling pathways and the ubiquitin-proteasome system have helped to refine and elaborate current models for the molecular mechanisms underlying T-cell anergy. Controlling anergy induction and maintenance will be a key component in the future to mitigate unwanted T-cell activation that leads to autoimmune disease. [ABSTRACT FROM AUTHOR]

In recent years, there has been a shift from the perception of dendritic cells (DCs) solely as inducers of immune reactivity to the view that these cells are crucial regulators of immunity, which includes their ability to induce and maintain tolerance. Advances in our understanding of the phenotypical and functional plasticity of DCs, and in our ability to manipulate their development and maturation in vitro and in vivo, has provided a basis for the therapeutic harnessing of their inherent tolerogenicity. In this Review, we integrate the available information on the role of DCs in the induction of tolerance, with a focus on transplantation. [ABSTRACT FROM AUTHOR]

Most B cells in peripheral lymphoid tissues are produced in adult bone marrow and are referred to as B-2 cells. A minor B-cell population, known as the B-1-cell population, that is mainly involved in innate immune responses has been identified in mice. In contrast to B-2 cells, B-1-cell progenitors are produced most efficiently during fetal life. This Review focuses on the emergence of B-1-cell potential during embryogenesis, summarizes recent advances in the delineation of a fetal B-1-cell-specified progenitor, and discusses the possibility that distinct fetal and adult B-cell developmental programmes might be operative in humans. [ABSTRACT FROM AUTHOR]

To become activated, T cells must efficiently recognize antigen-presenting cells or target cells through several complex cytoskeleton-dependent processes, including integrin-mediated adhesion, immunological-synapse formation, cellular polarization, receptor sequestration and signalling. The actin and microtubule systems provide the dynamic cellular framework that is required to orchestrate these processes and ultimately contol T-cell activation. Here, we discuss recent advances that have furthered our understanding of the crucial importance of the T-cell cytoskeleton in controlling these aspects of T-cell immune recognition. [ABSTRACT FROM AUTHOR]

The developmental pathways that lead to the production of antigen-presenting dendritic cells (DCs) are beginning to be understood. These are the last of the pathways of haematopoiesis to be mapped. The existence of many specialized subtypes of DC has complicated this endeavour, as has the need to distinguish the DCs formed in steady state from those produced during an inflammatory response. Here we review studies that lead to the concept that different types of DC develop through different branches of haematopoietic pathways that involve different immediate precursor cells. Furthermore, these studies show that many individual tissues generate their own DCs locally, from a reservoir of immediate DC precursors, rather than depending on a continuous flux of DCs from the bone marrow. [ABSTRACT FROM AUTHOR]

B-cell memory is provided by populations of quiescent memory B cells and long-lived plasma cells. Whereas it is clear that both of these cell populations arise from germinal centres, the signals and circumstances that trigger germinal-centre B cells to enter and then persist in memory compartments are poorly defined. Here, I propose that germinal centres produce memory B cells and plasma cells throughout the immune response and that memory B cells arise by the emigration of B cells that are chosen at random from the pool available in the germinal centre. The ability of such emigrants to survive as memory B cells depends on their germinal-centre 'history', with the persistence of high-affinity B-cell variants being favoured. [ABSTRACT FROM AUTHOR]

The specificities of lymphocytes for antigen are generated by a quasi-random process of gene rearrangement that often results in non-functional or autoreactive antigen receptors. Regulation of lymphocyte specificities involves not only the elimination of cells that display 'unsuitable' receptors for antigen but also the active genetic correction of these receptors by secondary recombination of the DNA. As I discuss here, an important mechanism for the genetic correction of antigen receptors is ongoing recombination, which leads to receptor editing. Receptor editing is probably an adaptation that is necessitated by the high probability of receptor autoreactivity. In both B cells and T cells, the genes that encode the two chains of the antigen receptor seem to be specialized to promote, on the one hand, the generation of diverse specificities and, on the other hand, the regulation of these specificities through efficient editing. [ABSTRACT FROM AUTHOR]

For more than a quarter of a century, macrophage migration inhibitory factor (MIF) has been a mysterious cytokine. In recent years, MIF has assumed an important role as a pivotal regulator of innate immunity. MIF is an integral component of the host antimicrobial alarm system and stress response that promotes the pro-inflammatory functions of immune cells. A rapidly increasing amount of literature indicates that MIF is implicated in the pathogenesis of sepsis, and inflammatory and autoimmune diseases, suggesting that MIF-directed therapies might offer new treatment opportunities for human diseases in the future. [ABSTRACT FROM AUTHOR]

Epstein-Barr virus (EBV) is an extremely successful virus, infecting more than 90% of the human population worldwide. After primary infection, the virus persists for the life of the host, usually as a harmless passenger residing in B cells. However, EBV can transform B cells, which can result in the development of malignant lymphomas. Intriguingly, the three main types of EBV-associated B-cell lymphoma - that is, Burkitt lymphoma, Hodgkin lymphoma and post-transplant lymphomas - seem to derive from germinal-centre B cells or atypical survivors of the germinal-centre reaction in most, if not all, cases, indicating that EBV-infected germinal-centre B cells are at particular risk for malignant transformation. [ABSTRACT FROM AUTHOR]