Toll-like receptors (TLRs) act as receptors for numerous stimuli of immune cells, including bacterial cell wall constituents (lipopolysaccharide [LPS] from Gram-negative bacteria and lipopeptides from Gram-positive species), plasma proteins and extracellular matrix breakdown products. TLR2 and TLR4 bind lipopeptide and LPS respectively, mediating responses of alveolar macrophages and other immune cells to bacterial infection in the lungs. Exposure of lungs to LPS leads to pro-inflammatory responses of a number of cell types, including airway smooth muscle, which secretes a number of cytokines involved in leucocyte recruitment and the Th2 polarization of immune responses. Human airway smooth muscle cells were cultured with LPS in the absence and presence of peripheral blood mononuclear cells to determine direct and leucocyte-dependent TLR-mediated responses. (more…)
One especially favored target for immune recognition is bacterial lipopolysaccharide (LPS). This macromolecule is found only in ...
Airway hyper-responsiveness in asthma may involve smooth muscle growth, a manifestation of airway remodelling. The involvement ...
Innate immunity depends on both resident and recruited leukocytes. The macrophage without doubt plays an import- ant role in the de ...
Acetylcholine is a neurotransmitter of the nerve vagus, the functional effects mediated by binding to muscarinic receptors. Results ...
Eosinophil infiltration of the mucosa is a feature of asthmatic airways. Their adhesion to bronchial epithelial cells has been ...
Eosinophil infiltration of the mucosa is a feature of asthmatic airways. Their adhesion to bronchial epithelial cells has been proposed to lead to the generation of inflammation mediators which may contribute to asthma pathology. Bronchial epithelial cells (BEAS-2B cell line) and peripheral blood eosinophils were cultured alone or in combination and the production of an inflammatory cytokine, IL-6, was measured. IL-6 was produced principally by epithelial cells and the production was enhanced more than 10-fold in the presence of eosinophils. Significant augmentation of epithelial IL-6 production persisted even when eosinophils were fixed with paraformaldehyde. The eosinophil-induced IL-6 production was extensively inhibited by inhibitors of p38 mitogen-activated protein (MAP) kinase or nuclear factor ??B (NF??B). (more…)
Exacerbations of asthma are frequently associated with rhinoviral infection. Rhinoviruses infect respiratory epithelial cells, ...
Toll-like receptors (TLRs) act as receptors for numerous stimuli of immune cells, including bacterial cell wall constituents (l ...
Airway hyper-responsiveness in asthma may involve smooth muscle growth, a manifestation of airway remodelling. The involvement ...
Contact of pathogens with the innate immune system will most frequently occur at epithelia, and the biology of the airway epitheliu ...
Vascular Endothelial Growth Factor (VEGF), originally described as a vascular permeability factor generating tissue oedema, has be ...
Airway remodelling is considered to be of major importance in the pathology of asthma, with subepithelial basement membrane thickening in particular being indicative of early development of the disease and characteristic of its progression. Airway fibroblasts are central cells in the processes of remodelling: increased deposition of fibroblast-derived connective tissue proteins and differentiation of fibroblasts into contractile myofibroblasts are consistent observations in morphological studies of moderate to severe asthmatic airways. The secretory function of fibroblasts is under the control of locally produced growth factors such as vascular endothelial cell growth factor (VEGF, see below) and platelet-derived growth factor (PDGF). (more…)
Vascular Endothelial Growth Factor (VEGF), originally described as a vascular permeability factor generating tissue oedema, has be ...
Local micro environmental factors are crucial in determining both susceptibility to vascular remodeling and the extent of angio ...
Tumour Necrosis Factor is a pro-inflammatory cytokine implicated in the pathogenesis of asthmatic airway inflammation, hyper-react ...
Asthma is a continuing problem for healthcare, particularly in the industrialized world. Some 150 million people are estimated ...
Airway hyper-responsiveness in asthma may involve smooth muscle growth, a manifestation of airway remodelling. The involvement ...
A role for Leukotriene B4 in the induction of airway hyper-responsiveness was explored through the use of transgenic mice deficient in the BLT1 receptor for LTB4 . Ovalbumin challenge of sensitized wild-type mice resulted in the usual features of experimental asthma, including goblet cell hyperplasia, hyper-responsiveness to inhaled methacholine and elevated BAL fluid concentrations of the Th2 cytokine IL-13. In contrast, BLT1 –/– mice (i.e. genetically modified mice lacking the gene coding for the BLT1 receptor) exhibited significantly lower responses. BLT1 –/– mice also exhibited lower numbers of IL-13-positive T lymphocytes of both the helper (CD4 T Cells) and cytotoxic/suppressor (CD8 + ) types. (more…)
Vascular Endothelial Growth Factor (VEGF), originally described as a vascular permeability factor generating tissue oedema, has be ...
Airway hyper-responsiveness in asthma may involve smooth muscle growth, a manifestation of airway remodelling. The involvement ...
IgE plays an important role in allergic asthma. Reducing IgE in the airway mucosa should reduce airway inflammation. Omalizumab has ...
Some features seem to be common to severe asthma and Chronic Obstructive Pulmonary Disease with reversibility of airflow limita ...
Antihistamines have been shown to be effective in seasonal allergic rhinitis and chronic idiopathic urticaria. They improve qua ...
Treg cells or regulatory T cells constitute a large population of cellular infiltrate in atopic/allergic inflammation and a dysregulated immune response appears to be an important pathogenetic factor. Cardinal events during allergic inflammation can be classified as activation, organ-selective homing, survival and reactivation, and effector functions of immune system cells. T cells are activated by aeroallergens, food antigens, autoantigens, and bacterial exotoxins superantigens in allergic inflammation. They are under the influence of the skin, lung, or nose-related chemokine network and show organ-selective homing. (more…)
Allergen-specific immunotherapy is highly effective in the treatment of IgE-mediated allergy diseases such as rhinitis, conjunc ...
The induction of immune tolerance and specific immune suppression are essential processes in the control of immune responses. R ...
The intracellular forkhead winged transcription factor Foxp3 (forkhead box P3) appears to be specifically expressed by naturall ...
An emerging concept is that pro-inflammatory signals lead to loss of Regulatory T Cells (Treg) function. Pasare and Medzhitov ( ...
Regulatory T cells Treg (picture above) is the existence of suppressor cells, which limit ongoing immune responses and prevent ...
Allergen-specific immunotherapy is highly effective in the treatment of IgE-mediated allergy diseases such as rhinitis, conjunctivitis, asthma, and venom allergy hypersensitivity. It is the only treatment that leads to lifelong tolerance against previously disease-causing allergens due to restoration of the normal immunity. (more…)
Allergen-specific immunotherapy aims to correct the underlying immune imbalance associated with specific immunotherapy allergic rhi ...
Histamine is a low-molecular-weight monoamine that binds to four different G-protein-coupled receptors, and has recently been d ...
The precise mechanisms underlying the effects of Specific Immunotherapy are not well understood but several studies have shown ...
Treg cells or regulatory T cells constitute a large population of cellular infiltrate in atopic/allergic inflammation and a dys ...
The immunologic mechanisms of sublingual immunotherapy are less established. In Cochrane analysis, the authors concluded that t ...
The intracellular forkhead winged transcription factor Foxp3 (forkhead box P3) appears to be specifically expressed by naturally occurring Treg cells, particularly in mice, although in humans there is evidence of upregulation of Foxp3 in all T cells on activation. Foxp3 is required for the development and function of naturally occurring regulatory t cells (treg) and expression is sufficient to convert non-regulatory CD4+CD25T cells into cells with regulatory activity. Conversion of peripheral CD4+CD25 naive T cells to Foxp3+CD4+CD25 foxp3+ Treg cells can be induced by TGF-ß. In a murine asthma model, these TGF-ß-induced Treg prevented house-dust mite-induced allergic pathogenesis or infection pathogenesis in lungs. A single independent report has suggested that IL-4 and IL-13 also induce Foxp3+CD25+ Treg from CD4+CD25precursors. (more…)
Regulatory T cells Treg (picture above) is the existence of suppressor cells, which limit ongoing immune responses and prevent ...
An emerging concept is that pro-inflammatory signals lead to loss of Regulatory T Cells (Treg) function. Pasare and Medzhitov ( ...
Treg cells or regulatory T cells constitute a large population of cellular infiltrate in atopic/allergic inflammation and a dys ...
The induction of immune tolerance and specific immune suppression are essential processes in the control of immune responses. R ...
Allergen-specific immunotherapy is highly effective in the treatment of IgE-mediated allergy diseases such as rhinitis, conjunc ...
The induction of immune tolerance and specific immune suppression are essential processes in the control of immune responses. Regulatory T cells (Treg) play a central role in immune control in the periphery. Two broad categories of Treg have been described: naturally occurring Treg that are present in all individuals and antigen-induced Treg that secrete inhibitory cytokines such as interleukin (IL)-10 and/or transforming growth factor (TGF)-ß. (more…)
Regulatory T cells Treg (picture above) is the existence of suppressor cells, which limit ongoing immune responses and prevent ...
An emerging concept is that pro-inflammatory signals lead to loss of Regulatory T Cells (Treg) function. Pasare and Medzhitov ( ...
Treg cells or regulatory T cells constitute a large population of cellular infiltrate in atopic/allergic inflammation and a dys ...
The intracellular forkhead winged transcription factor Foxp3 (forkhead box P3) appears to be specifically expressed by naturall ...
Allergen-specific immunotherapy is highly effective in the treatment of IgE-mediated allergy diseases such as rhinitis, conjunc ...
A variety of proinflammatory cells, mediators, and cytokines orchestrate the development of airway hyperresponsiveness, which results in the episodic airflow obstruction characteristic of asthma. As a consequence, modulation of the underlying disease process with antii-nflammatory agents is firmly established as being the cornerstone of successful management. Inhaled corticosteroids are the most potent antiinflammatory agents available and satisfactorily suppress underlying airway inflammation in most individuals. (more…)
The cysteinyl leukotrienes (LTC 4 , LTD 4 and LTE 4 ) are lipid mediators produced from an arachidonic acid precursor following ...
Antihistamines have been shown to be effective in seasonal allergic rhinitis and chronic idiopathic urticaria. They improve qua ...
In the UK, Europe and the USA, montelukast is licensed for once-daily oral administration in adults and is also available as a ...
Leukotrienes can be found in the airway and urine following both spontaneous exacerbations of asthma and acute exposure to bron ...
Despite optimum drug delivery and good compliance with inhaled corticosteroids, many patients experience symptoms and exacerbat ...
Nearly all tissues, organs, and serosal cavities harbor a population of resident phagocytes. Most contain only a diffuse scattering of individual phagocytic cells that remain inconspicuous under normal conditions and are very similar to one another in appearance and function. In some tissues, however, phagocytes are especially abundant or have distinctive morphologic features and are known by specific names. Examples include the Kupffer cells that line sinusoids of the liver (and account for nearly 10% of total liver mass), osteoclasts in bone, or microglial cells of the brain (Table bellow). (more…)
Once it is tethered onto the venule wall, the neutrophil or other leukocyte comes into contact with a wide variety of inflammatory ...
Neutrophils make up an army of more-or-less identical circulating phagocytes that are poised to respond quickly and in vast numbers ...
Our understanding of hematopoiesis has advanced greatly in recent years with the isolation and characterization of hematopoietic st ...
The process by which blood cells grow, divide, and differentiate in the bone marrow is called hematopoiesis. Three general cl ...
Toll-like receptors (TLRs) act as receptors for numerous stimuli of immune cells, including bacterial cell wall constituents (l ...