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 ...
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…)
Allergen-specific immunotherapy is highly effective in the treatment of IgE-mediated allergy diseases such as rhinitis, conjunc ...
The precise mechanisms underlying the effects of Specific Immunotherapy are not well understood but several studies have shown ...
The specific treatment of allergy has previously relied upon allergen avoidance and sublingual immunotherapy. These approaches have ...
Allergen-specific immunotherapy aims to correct the underlying immune imbalance associated with specific immunotherapy allergic rhi ...
The immunologic mechanisms of sublingual immunotherapy are less established. In Cochrane analysis, the authors concluded that t ...
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…)
Regulatory T cells Treg (picture above) is the existence of suppressor cells, which limit ongoing immune responses and prevent ...
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 ...
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 ...
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 ...
Other humoral effectors and humoral factors have the ability to lyse microorganisms directly. The best studied of these are a class of small peptide antibiotics known as defensins, which in their active forms are all roughly 30 amino acids long (3,5 kilodaltons), positively charged, and protease-resistant. Each also has three internal disulfide bonds. They are classified as either α or β defensins based on the arrangement of the disulfides, but both classes have nearly the same compact, folded structure consisting of three strands of antiparallel β-pleated sheets. (more…)
Contact of pathogens with the innate immune system will most frequently occur at epithelia, and the biology of the airway epitheliu ...
The body's innate resistance to many pathogens is provided by enzymes and other proteins in the blood and tissue fluids. These ...
Innate immune responses are seen in a very broad range of tissues. Indeed, the Toll-like receptors (TLRs, one of the most important ...
While our primary concern is the impact that the innate immune system has on allergic disease, it is essential to recognize that al ...
A few of the best known humoral effectors of innate immunity are listed in Table 1 bellow, along with the types of target molec ...
Perhaps the most exciting recent advance in the cytokine signaling field has been the elucidation of the Jak/Stat pathway. The Janus kinase (Jak) family consists of four known enzymes (Jak1, Jak2, Jak3, and Tyk2), each of which associates specifically with the cytoplasmic tails of one or more cytokine receptor subunits. For example, IL-2R associates with both Jak1 and Jak3, which bind its α and γ subunits, respectively. Cytokine binding brings the receptor subunits together and allows the associated Jak proteins to phosphorylate and activate one another. The primary substrates of the activated Jaks are a family of transcription factors called the Stat (for signal transducers and activators of transcription) proteins. The Stat proteins contain SH2 domains and so are recruited to the vicinity of an activated receptor when its kinases become active. (more…)
The overlapping functions of cytokines largely reflect the properties of the cell surface receptors to which they bind. All cyt ...
The Ras-dependent pathway can be triggered by a variety of cytokine receptors, as well as by certain adhesion molecules and by ...
Hematopoietic progenitors depend on a variety of cytokines to control their growth and differentiation. These include several d ...
Although it is commonly imagined that hematopoiesis takes place in a liquid environment resembling the blood, with progenitors resp ...
Our understanding of hematopoiesis has advanced greatly in recent years with the isolation and characterization of hematopoietic st ...
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 ...
Some of the immediate sequelae of injury are uncomfortably familiar: Soon after an injury occurs, the affected site and its surrounding tissues become reddened, warm, swollen, and painful. These four signs which are probably the most useful and ubiquitous diagnostic clues in all of clinical medicine are hallmarks of acute inflammation, the body’s initial physiologic reaction to tissue distress. In its simplest form, inflammation is a response carried out by blood vessels and by the endothelial cells that line them. (more…)
The response to injury usually begins with dilatation of small blood vessels in and around the injured site (figure bellow). Th ...
Once it is tethered onto the venule wall, the neutrophil or other leukocyte comes into contact with a wide variety of inflammatory ...
Acute inflammatory response constitute the first line of defense against infection pathogenesis and how immune system works as ...
Nearly all tissues, organs, and serosal cavities harbor a population of resident phagocytes. Most contain only a diffuse scattering ...
Innate immune responses are seen in a very broad range of tissues. Indeed, the Toll-like receptors (TLRs, one of the most important ...
A few of the best known humoral effectors of innate immunity are listed in Table 1 bellow, along with the types of target molecules they recognize. Some are enzymes that can directly injure or kill microbial pathogens. An example is lysozyme, an endoglycosidase found in human saliva, mucus, tears, and other secretions, which attacks the protective cell wall encasing every bacterial cell. Lysozyme acts by digesting the peptidoglycan meshwork formed by long carbohydrate chains of alternating N-acetylmuramic acid and N-acetylglucosamine residues, crosslinked covalently by short oligopeptide sidechains which is a major constituent of all bacterial cell walls but is not found in mammalian tissues. (more…)
An especially elaborate and important type of innate antimicrobial enzymes defense is provided by a group of serum proteins tha ...
One especially favored target for immune recognition is bacterial lipopolysaccharide (LPS). This macromolecule is found only in ...
The body's innate resistance to many pathogens is provided by enzymes and other proteins in the blood and tissue fluids. These ...
With the exception of complement protein C3, most soluble mediators of innate immunity are found in relatively small amounts in ...
Although it is commonly imagined that hematopoiesis takes place in a liquid environment resembling the blood, with progenitors resp ...