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…)

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…)

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…)

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…)

CD14 Tobacco Gene–Environment Interaction Modifies Asthma Severity & Immunoglobulin E Levels

CD14 gene
CD14 is part of the receptor complex for endotoxin, which is a component of tobacco smoke. The CD14 gene is located on chromosome 5q, a region previously demonstrated to be linked to asthma when stratified for smoke exposure. This study was designed to extend these findings by determining whether polymorphisms in the CD14 gene are related to this gene–environment interaction on asthma. Puerto Rican (n = 362 trios) and Mexican (n = 259 trios) families ascertained through a child with asthma were studied. (more…)

T-Cell Immunoglobulin Mucin 1 Genetic Variants And Associated With Asthma In An African-American Population

T-Cell Immunoglobulin
The Tcell Ig domain and mucin domain (TIM) proteins, the genes for which are located on chromosome 5q, have been suggested to be involved in allergic disease. This study examined allergies genetic association of sequence variants of the TIM1 and TIM3 genes in an African-American population. Case–control and family based association analyses were performed for three SNPs each in the TIM1 and TIM3 genes, and an insertion/deletion polymorphism in Tcell Ig domain and mucin domain 1. (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…)

Primary Immunodeficiencies: Antibody Deficiency and Immunoglobulin Replacement Therapy

Primary immunodeficiencies occur with a frequency approaching that of cystic fibrosis (1:2500 live births). However, because they are perceived to be very rare and usually present with common infections, they are under-diagnosed. Often the diagnosis is not considered until substantial end-organ damage has occurred, by which time definitive treatment is only partially successful in preventing further infections. (more…)

SAP Gene Defects In Male Patients Diagnosed With Common Variable Immunodeficiency

The molecular basis of Common Variable Immunodeficiency (CVID) is unknown and the diagnosis requires the exclusion of other diseases known to cause primary antibody deficiency syndromes, such as X-linked lymphoproliferative disease (XLP). XLP is a rare primary immunodeficiency disease in which severe immune dysregulatory phenomena occur, typically after exposure to Epstein–Barr virus (EBV). The defective gene in XLP is SAP (SLAM associated protein, where SLAM is signalling lymphocyte activation molecule), a small SH2 domain containing protein involved in signal transduction events downstream of the SLAM family of receptors. (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…)

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