Toll-like receptors (TLRs) act as receptors for numerous stimuli of immune cells, including bacterial cell wall constituents (lipopolysaccharide [LPS] from Gram-negative bacteria and lipopeptides from Gram-positive species), plasma proteins and extracellular matrix breakdown products. TLR2 and TLR4 bind lipopeptide and LPS respectively, mediating responses of alveolar macrophages and other immune cells to bacterial infection in the lungs. Exposure of lungs to LPS leads to pro-inflammatory responses of a number of cell types, including airway smooth muscle, which secretes a number of cytokines involved in leucocyte recruitment and the Th2 polarization of immune responses. Human airway smooth muscle cells were cultured with LPS in the absence and presence of peripheral blood mononuclear cells to determine direct and leucocyte-dependent TLR-mediated responses. (more…)
One especially favored target for immune recognition is bacterial lipopolysaccharide (LPS). This macromolecule is found only in ...
Airway hyper-responsiveness in asthma may involve smooth muscle growth, a manifestation of airway remodelling. The involvement ...
Innate immunity depends on both resident and recruited leukocytes. The macrophage without doubt plays an import- ant role in the de ...
Acetylcholine is a neurotransmitter of the nerve vagus, the functional effects mediated by binding to muscarinic receptors. Results ...
Eosinophil infiltration of the mucosa is a feature of asthmatic airways. Their adhesion to bronchial epithelial cells has been ...
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…)
Vascular Endothelial Growth Factor (VEGF), originally described as a vascular permeability factor generating tissue oedema, has be ...
Airway hyper-responsiveness in asthma may involve smooth muscle growth, a manifestation of airway remodelling. The involvement ...
IgE plays an important role in allergic asthma. Reducing IgE in the airway mucosa should reduce airway inflammation. Omalizumab has ...
Some features seem to be common to severe asthma and Chronic Obstructive Pulmonary Disease with reversibility of airflow limita ...
Antihistamines have been shown to be effective in seasonal allergic rhinitis and chronic idiopathic urticaria. They improve qua ...
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 is highly effective in the treatment of IgE-mediated allergy diseases such as rhinitis, conjunc ...
The induction of immune tolerance and specific immune suppression are essential processes in the control of immune responses. R ...
The intracellular forkhead winged transcription factor Foxp3 (forkhead box P3) appears to be specifically expressed by naturall ...
An emerging concept is that pro-inflammatory signals lead to loss of Regulatory T Cells (Treg) function. Pasare and Medzhitov ( ...
Regulatory T cells Treg (picture above) is the existence of suppressor cells, which limit ongoing immune responses and prevent ...
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…)
Allergen-specific immunotherapy aims to correct the underlying immune imbalance associated with specific immunotherapy allergic rhi ...
Histamine is a low-molecular-weight monoamine that binds to four different G-protein-coupled receptors, and has recently been d ...
The precise mechanisms underlying the effects of Specific Immunotherapy are not well understood but several studies have shown ...
Treg cells or regulatory T cells constitute a large population of cellular infiltrate in atopic/allergic inflammation and a dys ...
The immunologic mechanisms of sublingual immunotherapy are less established. In Cochrane analysis, the authors concluded that t ...
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…)
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 intracellular forkhead winged transcription factor Foxp3 (forkhead box P3) appears to be specifically expressed by naturall ...
Allergen-specific immunotherapy is highly effective in the treatment of IgE-mediated allergy diseases such as rhinitis, conjunc ...
Nearly all tissues, organs, and serosal cavities harbor a population of resident phagocytes. Most contain only a diffuse scattering of individual phagocytic cells that remain inconspicuous under normal conditions and are very similar to one another in appearance and function. In some tissues, however, phagocytes are especially abundant or have distinctive morphologic features and are known by specific names. Examples include the Kupffer cells that line sinusoids of the liver (and account for nearly 10% of total liver mass), osteoclasts in bone, or microglial cells of the brain (Table bellow). (more…)
Once it is tethered onto the venule wall, the neutrophil or other leukocyte comes into contact with a wide variety of inflammatory ...
Neutrophils make up an army of more-or-less identical circulating phagocytes that are poised to respond quickly and in vast numbers ...
Our understanding of hematopoiesis has advanced greatly in recent years with the isolation and characterization of hematopoietic st ...
The process by which blood cells grow, divide, and differentiate in the bone marrow is called hematopoiesis. Three general cl ...
Toll-like receptors (TLRs) act as receptors for numerous stimuli of immune cells, including bacterial cell wall constituents (l ...
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 ...
With the exception of complement protein C3, most soluble mediators of innate immunity are found in relatively small amounts in the serum under normal conditions. The concentrations of several of these proteins, however, can increase as much as 1000-fold during serious infections or other crises, as part of a coordinated protective reaction called the acute-phase response. In this response, the liver temporarily increases its synthesis of more than 30 different serum proteins, often called acute-phase proteins (Table bellow). Many of these, such as complement factors C3 and B, MBL, LBP, C-reactive protein, and serum amyloid protein P, participate in antimicrobial defense. (more…)
Acute phase proteins are plasma proteins, the synthesis and the circulating concentrations of which are adaptively regulated in res ...
Most acute phase proteins are synthesized in the liver, although the genes for some are also expressed in cells and tissues els ...
There is considerable diversity among acute phase proteins with respect to the concentrations attained, their structures, and their ...
Acute phase proteins and the acute phase response in general arc stably conserved in evolution and are universal within each specie ...
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 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 ...