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…)

Histamine Type-2 Receptor as Major Player in Peripheral Tolerance

histamine receptor
Histamine is a low-molecular-weight monoamine that binds to four different G-protein-coupled receptors, and has recently been demonstrated to regulate several essential events in the immune response. The histamine receptor type 2 (HR2) is coupled to adenylate cyclase and studies in different species and several human cells have demonstrated that inhibition of characteristic features of the cells by primarily cAMP formation dominates in HR2-dependent effects of histamine. (more…)

Sublingual Immunotherapy Mechanisms

sublingual immunotherapy
The immunologic mechanisms of sublingual immunotherapy are less established. In Cochrane analysis, the authors concluded that there was an increase in IgG4 but no stable effect on IgE levels in adults. In addition, the induction of allergen-specific IgA has been reported. There are conflicting data concerning lympho-proliferative responses. So far the evidence on changes in Th1/Th2/Treg activity induced by sublingual immunotherapy need to be confirmed. The effects on T-cell reactivity and cytokine secretion show strong variation in a number of studies. (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…)

Allergen-Specific Immunotherapy Mechanisms & The Involvement Of Treg Cells

allergen specific immunotherapy
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…)

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…)

Immunoglobulin E (IgE) Regulation and Biology

immunoglobulin e
Normally present at very low levels in plasma, antibodies of the immunoglobulin E (IgE) isotype were first discovered in 1967, decades after the description of IgA, IgG, and IM. IgE antibodies are produced primarily by plasma cells in mucosal-associated lymphoid tissue and their levels are uniformly elevated in patients suffering from atopic conditions like allergic rhinitis, asthma and atopic dermatitis. Production of allergen-specific IgE in atopic individuals is driven both by a genetic predisposition to the synthesis of this isotype as well as by environmental factors, including chronic allergen exposure. (more…)

Tumour Necrosis Factor Alpha in Symptomatic Corticosteroid-Dependent Asthma

Tumour Necrosis Factor Alpha
Tumour necrosis factor alpha (TNF-a) is a major therapeutic target in a range of chronic inflammatory disorders involving neutrophils and its excess production is characterized by a Th1-type immune response. Asthma is regarded as a Th2-type disorder when associated with atopy, (more…)

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