Requirement for Leukotriene B4 Receptor 1 in Allergen-Induced Airway Hyper-Responsiveness

Airway Hyper-Responsiveness
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…)

Leukotriene Receptor Antagonists & 5-Lipoxygenase Inhibitors


Two main strategies have been developed to block the effects of cysteinyl leukotrienes in the airway. One method is to use drugs that prevent their synthesis (using a 5-lipoxygenase inhibitor) and the other involves interfering with the binding of cysteinyl leukotrienes to their cellular receptor using a leukotriene receptor antagonist (LTRA). (more…)

Treg Cells In Allergen-Specific Immunotherapy

treg cells
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…)

Regulatory T Cells (Treg) Therapeutic Application

treg
An emerging concept is that pro-inflammatory signals lead to loss of Regulatory T Cells (Treg) function. Pasare and Medzhitov (2003) demonstrated that activation of DCs through TLRs led to the production of signals, including IL-6, which blocked the suppressive effect of CD4+CD25+ Treg. Subsequent studies support these observations. For example in a mouse model of allergic airway disease, IL-6 is proposed to act via two mechanisms to promote disease: direct enhancement of Th2 responses and by overcoming the suppressive function of CD4+CD25+ Treg. Tumor necrosis factor (TNF) as well as IL-7 and IL-15 have also been proposed to overcome regulatory activity in other human immunologic diseases. (more…)

Foxp3 Forkhead Winged Transcription Factor & Mechanisms Of Suppression

foxp3
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…)

Allergic Responses Prevention: Regulatory T Cells (Treg)

Regulatory T Cells
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…)

Vascular Endothelial Growth Factor (VEGF) & Induces Muscle Hyperflasia Enhances TH2-Mediated Sensitization

Vascular Endothelial Growth Factor (VEGF), originally described as a vascular permeability factor generating tissue oedema, has been found to exert a range of angiogenic actions, including epithelial cell proliferation, blood vessel formation and endothelial cell survival. Elevated levels of Vascular Endothelial Growth Factor have been detected in bronchial tissues and secretions of asthmatic bronchial individuals, raising questions regarding its possible pathogenetic role in asthma. Using transgenic mice in which local over expression of VEGF could be induced in the lungs by administration of a tetracycline antibiotic demonstrated induction of an asthma-like phenotype with airway inflammation and oedema, hyper-responsiveness and remodelling (airway, parenchymal and vascular). Antigen-induced airway inflammation was accompanied by VEGF production by epithelial cells and TH2 cells, with production by Th1 cells markedly lower. (more…)

Effects Of Treatment With Anti-Immunoglobulin E Antibody Omalizumab

IgE plays an important role in allergic asthma. Reducing IgE in the airway mucosa should reduce airway inflammation. Omalizumab has significant anti-inflammatory effect and reduces serum and airway IgE, but IgE or eosinophils may not be causally linked to airway bronchial hyperresponsiveness to methacholine in mild to moderate asthma. (more…)

Allergic Reactions To Penicillin and Skin Test Evaluation via Intradermal Injection

Intradermal Injection
This study compared the diagnostic value of intradermal tests and patch tests in 20 patients with non-immediate reactions to penicillin (none had IgE antibodies to benzylpenicillin or amoxicillin detectable using a commercial RAST [radioallergosorbent test] method), using 30 patients tolerant to penicillin as controls. Intradermal tests assessed reactivity to injection of major and minor determinants of benzylpenicillin, amoxicillin and ampicillin. Allergy patch testing involved the same hapten solutions used for intradermal testing, either embedded in a patch disk or mixed with petrolatum. (more…)

Allergen Vaccine and Allergenic Source of Material

Allergen Vaccine
Being an immunological disease, the characteristics of allergy are those of specificity and memory. Regardless of whether the clinical manifestation is rhinoconjunctivitis, rhinitis, or asthma, the underlying immunological response disorder is based on the adverse reactions of cells in the immune system upon contact with allergens. These cells are specific for epitopes that are structural parts of allergens present in the allergenic source material. Two types of cells (i.e., T cells and B-cells) produce receptor molecules (i.e., T-cell receptors and immunoglobulin [IgE] antibodies) that, through high-affinity interactions with the allergen, efficiently catalyze the presence of even minute amounts of allergens into clinical symptoms, the extreme consequence of which may be life-threatening to the patient. (more…)

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