1,721,096 research outputs found
What we know (and don't know) about the biology and functions of mast cells and basophils
No full textBCR-ABL rearrangement and HLA antigens: a possible link to leukemia pathogenesis and immunotherapy
No full textRheostatic Functions of Mast Cells in the Control of Innate and Adaptive Immune Responses
Get PDFMast cells are evolutionarily ancient cells, endowed with a unique developmental, phenotypic, and functional plasticity. They are resident cells that participate in tissue homeostasis by constantly sampling the microenvironment. As a result of their large repertoire of receptors, they can respond to multiple stimuli and selectively release different types and amounts of mediator. Here, we present and discuss the recent mast cell literature, focusing on studies that demonstrate that mast cells are more than a switch that is turned 'off' when in the resting state and 'on' when in the degranulating state. We propose a new vision of mast cells in which, by operating in a 'rheostatic' manner, these cells finely modulate not only immune responses, but also the pathogenesis of several inflammatory disorders, including infection, autoimmunity, and cancer. New findings suggest that it is shortsighted to limit the classification of mast cells to two subtypes; indeed, each specific tissue has a unique mast cell type that differs significantly from those of other tissues.Mast cells continuously sample the microenvironment, working to maintain tissue homeostasis and contribute immediately to the immune response to non-self-antigens.A network of activating and inhibitory stimuli can modulate mast cell activity.A mast cell is more than a switch that is turned 'off' when in the resting state and 'on' when needed; instead, mast cells show a range of modulated responses that contribute to the fine-tuning of the immune response
Superantigenic characteristics of mouse mammary tumor viruses play a critical role in susceptibility to infection in mice
No full textMouse mammary tumor viruses (MMTV) are retroviruses that induce mammary carcinomas. An interesting feature of these viruses is the superantigen (SAg) encoded in an open reading frame within the 3' long terminal repeat. The mechanism by which ingestion of milk-borne virus results in infection of the host mammary tissue remains incompletely understood. However, a working model has been proposed in which the interaction between viral SAg, T-cell receptor and MHC class II I-E facilitates viral replication and hence infectivity. In this review we summarize current studies demonstrating the role of SAg stimulation in susceptibility to MMTV infection
Triggering of target of an antiproliferative antibody-1 (TAPA-1/CD81) up-regulates the release of tumour necrosis factor-alpha by the EBV-B lymphoblastoid cell line JY
No full textTarget of an antiproliferative antibody-1 (TAPA-1/CD81) has been shown to be non-covalently associated to HLA-DR antigens on the cell surface of B cells. In this study the authors report that triggering of CD81 by MoAb 5A6 or 1D6 significantly (P < 0.05) up-regulates the release of tumour necrosis factor-alpha (TNF-alpha) by the Epstein-Barr virus-positive (EBV)-B lymphoblastoid cell line JY. The accumulation of TNF-alpha in the culture medium of JY cells incubated with either anti-CD81 MoAb was found to be dose-dependent and similar to that obtained following crosslinking of HLA-DR antigens with MoAb L243. The effect of the combination of anti-CD81 and anti-HLA-DR MoAb on the release of TNF-alpha by JY cells was not synergistic or additive. In addition, the combination of anti-CD81 and anti-HLA-DR MoAb did not affect proliferation and homotypic aggregation of JY cells induced by each MoAb used alone. Both anti-CD81 or anti-HLA-DR MoAb induced protein tyrosine phosphorylation. However, different cytoplasmic proteins were phosphorylated following triggering of either molecule. Taken together, the data demonstrate that CD81 and HLA-DR antigens induce similar effector phenomena in the regulation of TNF-alpha release, homotypic aggregation and inhibition of JY cell proliferation
Crosslinking of HLA class II antigens upregulates TNF-a production by the B-Lymphoblastoid cell line JY
No full textIn addition to their functional role as peptide-binding proteins HLA class II Ag can also act as signal-transducing molecules. The present study showed that cross-linking of HLA class II Ag by the anti-HLA-DR mAb L243 or by the anti-HLA-DR,-DP mAb IVA12 significantly (p < 0.05) increased the release of TNF-alpha by the EBV-B lymphoblastoid cell line JY. In contrast, the anti-HLA-DR mAb 2.06 or the superantigens staphylococcal exotoxin toxic shock syndrome toxin-1 and staphylococcal enterotoxin B that bind to HLA-DR,-DQ Ag did not affect the release of TNF-alpha by JY cells. The accumulation of TNF-alpha in the culture medium of JY cells peaked at 24 h, decreased thereafter, and was found to be dependent on the dose of mAb L243 or mAb IVA12 used to cross-link HLA class II Ag. mAb L243 or staphylococcal exotoxin toxic shock syndrome toxin-1 enhanced the spontaneous homotypic aggregation of JY cells and mediated a dose-dependent inhibition of JY cell proliferation. These phenomena were not mediated by TNF-alpha released in response to cross-linking of HLA class II Ag; polyclonal anti-TNF-alpha neutralizing antibody did not affect JY cell aggregation and the inhibition of JY cell proliferation mediated by mAb L243. In contrast, TNF-alpha secreted by JY cells enhanced a nuclear factor-kB-like activity through the binding to the 75-kDa TNF-alpha receptor. These results demonstrate an additional role of HLA class II Ag as signal-transducing molecules regulating the production of bioactive TNF-alpha by EBV-B cells. The release of TNF-alpha after the triggering of HLA class II molecules could be relevant to different aspects of B cell biology and might play a role in the pathogenesis of human diseases in which antibodies cross-reactive to HLA class II Ag have been identified
Allergic responses and aryl hydrocarbon receptor novel pathway of mast cell activation.
No full textThe activation of the transcription factor aryl hydrocarbon receptor (AhR) is modulated by a wide variety of xenobiotics and ligands deriving from products of metabolism. The study of the contribution of AhR to allergic diseases has gained much interest in recent years. Here we discuss the role that environmental factors and metabolic products, particularly acting on AhR-expressing mast cells (MCs), could have in the development of local allergic/atopic response. Thus, this review will cover: a brief overview of the AhR mechanism of action in the immune system; a description of different AhR ligands and their effects to IgE-mediated MC activation in the allergic response, with particular attention to the role of IL-17; a discussion about the potential involvement of AhR in immune tolerance; and a conclusion on human diseases in which direct AhR activation of MC might have a major impact
The overlooked "nonclassical" functions of major histocompatibility complex (MHC) class II antigens in immune and nonimmune cells
No full textBesides their "classical" antigenic peptide-presenting activity, major histocompatibility complex (MHC) class II antigens can activate different cellular functions in immune and nonimmune cells. However, this "nonclassical" role and its functional consequences are still substantially overlooked. In this review, we will focus on these alternative functional properties of MHC class II antigens, to reawaken attention to their present and foreseeable immunobiologic and pathogenetic implications. The main issues that will be addressed concern 1) the role of MHC class II molecules as basic components of exchangeable oligomeric protein complexes with intracellular signaling ability; 2) the nonclassical functions of MHC class II antigens in immune cells; 3) the pathogenetic role of MHC class II antigens in inflammatory/autoimmune and infectious disease; and 4) the functional role of MHC class II antigens in solid malignancies
Regulatory B cells: Evidence, developmental origin and population diversity
No full textThe adaptive immune system has developed several highly effective mechanisms in order to avoid excessive or unwanted reactions and promote resolution of immune activation. An emerging, significant body of evidence indicates that B cells can actively modulate immune responses by mechanisms that do not directly involve the production of antibodies. B cells appear to have the capacity to both induce and suppress immune effector mechanisms and they exert these functions both by contact-dependent interactions and through the secretion of cytokines. In this review we will focus on the regulatory suppressive function of several recently described B cell populations, functionally defined "regulatory B cells" or Breg cells. We will first outline the evidence that has led to their identification and then we will summarize current hypotheses on their ontogeny and possible lineage relationship
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