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 ...
More severe asthma can persist from childhood into adulthood without remission. Another important tendency in the natural history is for symptoms to remit in adolescence only to return again in adulthood. In general, the amount of wheezing in early adolescence seems to be a guide for severity in early adult years, with 73% of those with few symptoms at age 14 years continuing to have little or no asthma progression at age 28 years. Similarly 68% of those with frequent wheezing at 14 years still suffered from recurrent asthma at age 28 years. Most subjects with frequent wheezing at 21 years continued to have comparable asthma at 28 years. In addition to the importance of symptoms in childhood, childhood degree of bronchial responsiveness in combination with a low FEV-1 were also related to the outcome of asthma in adulthood. (more…)
In the Tucson CRS study, about 50% of young children experienced a period of recurrent wheezing and/or coughing in the first 6 ...
Exposure and allergic sensitization to cockroach was associated with a significantly greater risk of asthma hospitalization and ...
With the help of well-trained and experienced pulmonary function technicians, children as young as 4 to 5 years of age should b ...
Asthma is a complex syndrome rather than a single disease entity. Different phenotypes with varying prognosis and determinants have ...
It is clear from the results of large epidemiologic studies that while atopy is a major risk factor for asthma, it is usually n ...
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 ...
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…)
Allergen-specific immunotherapy aims to correct the underlying immune imbalance associated with specific immunotherapy allergic rhi ...
The precise mechanisms underlying the effects of Specific Immunotherapy are not well understood but several studies have shown ...
The increasing prevalence of allergic disease in the Western world has led to the concept of the ‘allergic march’ to describe t ...
Allergen-specific immunotherapy is highly effective in the treatment of IgE-mediated allergy diseases such as rhinitis, conjunc ...
Histamine is a low-molecular-weight monoamine that binds to four different G-protein-coupled receptors, and has recently been d ...
Regulatory T cells Treg (picture above) is the existence of suppressor cells, which limit ongoing immune responses and prevent autoimmune disease, was postulated over 30 years ago. The recent phenotypic and functional characterization of these cells has led to a resurgence of interest in their therapeutic application in a number of immune-mediated diseases. Two broad subsets of CD3+CD4+ suppressive or Treg cells have been described: constitutive or naturally occurring versus adaptive or inducible Treg. (more…)
An emerging concept is that pro-inflammatory signals lead to loss of Regulatory T Cells (Treg) function. Pasare and Medzhitov ( ...
The intracellular forkhead winged transcription factor Foxp3 (forkhead box P3) appears to be specifically expressed by naturall ...
The induction of immune tolerance and specific immune suppression are essential processes in the control of immune responses. R ...
Treg cells or regulatory T cells constitute a large population of cellular infiltrate in atopic/allergic inflammation and a dys ...
Allergen-specific immunotherapy is highly effective in the treatment of IgE-mediated allergy diseases such as rhinitis, conjunc ...
Neutrophils make up an army of more-or-less identical circulating phagocytes that are poised to respond quickly and in vast numbers wherever tissue injury has occurred. The mature cells, which are also known as segmented neutrophils (segs) or polymorphonuclear leukocytes (polys, or PMNs), can easily be identified by their characteristic multilobed nucleus and by the abundant storage granules in their cytoplasm (Figure bellow). (more…)
The process by which blood cells grow, divide, and differentiate in the bone marrow is called hematopoiesis. Three general cl ...
Once it is tethered onto the venule wall, the neutrophil or other leukocyte comes into contact with a wide variety of inflammatory ...
Although it is commonly imagined that hematopoiesis takes place in a liquid environment resembling the blood, with progenitors resp ...
Nearly all tissues, organs, and serosal cavities harbor a population of resident phagocytes. Most contain only a diffuse scattering ...
Acute inflammatory response constitute the first line of defense against infection pathogenesis and how immune system works as ...
One especially favored target for immune recognition is bacterial lipopolysaccharide (LPS). This macromolecule is found only in the outer lipid bilayer that surrounds the cell walls of gram-negative bacteria, such as Neisseria, Salmonella, and Escherichia coli. Each molecule of bacterial lipopolysaccharide consists of a core carbohydrate linked on one side to a phospholipid (called lipid A) that is anchored in the bilayer and on the other side to a long polysaccharide chain (called the O sidechain) that extends outward from the bacterial surface (Figure 1 bellow). The sequence of sugars making up the O sidechain is species-specific and highly variable, even within a single bacterial genus: For example, more than 1000 variants in Salmonella are known. (more…)
Toll-like receptors (TLRs) act as receptors for numerous stimuli of immune cells, including bacterial cell wall constituents (l ...
Bacteria cause allergic disease because of toxicity, invasiveness, immunopathology, or lends of these three mechanisms. Thus much ...
Exotoxins are noxious proteins secreted by many bacteria. These toxins are often heat-labile and thus can be heat-inactivated f ...
A few of the best known humoral effectors of innate immunity are listed in Table 1 bellow, along with the types of target molec ...
Breast milk contains a variety of bioactive substances, among them soluble CD14 (sCD14), which plays an important role in innat ...
The overlapping functions of cytokines largely reflect the properties of the cell surface receptors to which they bind. All cytokine receptors function as multiprotein complexes made up of two or more integral membrane polypeptides, called subunits (Figure 1 bellow). A typical subunit polypeptide has an extracellular domain that participates in cytokine binding, a transmembrane region, and an intracellular domain (also called a cytoplasmic tail gp41) involved in signal transduction the molecular events that transmit signals to the cell interior and induce specific cellular responses when the receptor binds its appropriate cytokine ligand. Some receptors (eg, EPO-R) function as homodimers of a single type of subunit; others (eg, GM-CSFR) function as heterodimers, and still others (eg, IL-2R) as heterotrimers. (more…)
Perhaps the most exciting recent advance in the cytokine signaling field has been the elucidation of the Jak/Stat pathway. The ...
The Ras-dependent pathway can be triggered by a variety of cytokine receptors, as well as by certain adhesion molecules and by ...
Adenosine is a nucleoside and consists of adenine in glycosidic linkage with ribose. Most adenosine is derived from cleavage of ade ...
One especially favored target for immune recognition is bacterial lipopolysaccharide (LPS). This macromolecule is found only in ...
Although it is commonly imagined that hematopoiesis takes place in a liquid environment resembling the blood, with progenitors resp ...
Once it is tethered onto the venule wall, the neutrophil or other leukocyte comes into contact with a wide variety of inflammatory mediators that may either be expressed by the activated endothelium or simply diffuse into the blood from the injured tissue. Among these mediators are a diverse subset of intermediaries known as leukocyte chemotactic factors which bind to receptors on the leukocyte surface and trigger the second, activation phase of margination. (more…)
Neutrophils make up an army of more-or-less identical circulating phagocytes that are poised to respond quickly and in vast numbers ...
Nearly all tissues, organs, and serosal cavities harbor a population of resident phagocytes. Most contain only a diffuse scattering ...
Acute inflammatory response constitute the first line of defense against infection pathogenesis and how immune system works as ...
Some of the immediate sequelae of injury are uncomfortably familiar: Soon after an injury occurs, the affected site and its sur ...
Although it is commonly imagined that hematopoiesis takes place in a liquid environment resembling the blood, with progenitors resp ...
The Ras-dependent pathway can be triggered by a variety of cytokine receptors, as well as by certain adhesion molecules and by many other surface receptors when they contact appropriate ligands. Signaling in this pathway can be initiated by cytosolic proteins called Src-family kinases, so named because they bear regions of sequence homology to the oncoprotein Src. These Src-like kinases contain specialized protein domains, termed SH2 domains (for Src-homology region 2), that enable them to bind other proteins containing phosphorylated tyrosine residues. When a cytokine receptor binds ligand, subunits of the receptor become phosphorylated and can immediately be bound by a Src-family kinase. (more…)
Perhaps the most exciting recent advance in the cytokine signaling field has been the elucidation of the Jak/Stat pathway. The ...
The overlapping functions of cytokines largely reflect the properties of the cell surface receptors to which they bind. All cyt ...
Although it is commonly imagined that hematopoiesis takes place in a liquid environment resembling the blood, with progenitors resp ...
The process by which blood cells grow, divide, and differentiate in the bone marrow is called hematopoiesis. Three general cl ...
Our understanding of hematopoiesis has advanced greatly in recent years with the isolation and characterization of hematopoietic st ...