Hypersensitivities mediator release

Non-immune hypersensitivity via direct mediator release or direct activation of plasma-protein systems... 

It is a potentially lethal immediate hypersensitivity reaction, in whose pathomech-anism the main role is played by IgE antibodies. Mediators released in the process are responsible for tissue reactions, which may involve the respiratory system, gastrointestinal system, and the skin or cardiovascular system. 

Table 15.6 Mediators released by mast cells in type I hypersensitivity...

Topical cyclosporine A is an effective, safe, well-tolerated treatment option for severe or intractable VKC. An immunosuppressant, it affects and inhibits cell-mediated and immediate hypersensitivity reactions. It inhibits the release of interleukins, and it may prevent mediator release from mast cells. Relief is often noted after the first month of cyclosporine treatment, with continued results for up to 2 years. Some, however, have found a return of signs and symptoms 1 to 2 months after discontinuance of treatment. 

General — Work in the area of immediate hypersensitivity has continued to define the mechanism of mediator release stimulation by the interaction of antigen with specific cell bound immunoglobulin. Characterization of specific mediators such as slow reacting substance of anaphylaxis (SRS-A), eosinophil chemotactic factor of anaphylaxis (ECF-A) and histamine have appeared. ... 

The most important functional abnormality in asthma is increased resistance to airflow. This is the basis of most striking clinical manifestation of asthma, including breathlessness and wheezing. The mechanisms of increased airflow resistance include (1) decreased physical dimensions of the airways as a consequence of bronchoconstriction, (2) luminal narrowing due to airway wall edema, and (3) luminal obstruction resulting from h)q)ersecretion of mucus (McFadden, 1998). Those changes induced by the various inflammatory mediators released by mast cells as part of hypersensitivity reactions are reversible. Another functional abnormality... 

The IgE-mediated PCA reaction in the rat was one of the first in vivo animal models in which cromol5m was shown to be effective and has since been used extensively in screening for similar compounds. In this method, inflammatory mediators released by immediate hypersensitivity reactions in the skin produce a local increase in capillary permeability. 

In summary, current information suggests that the mechanism of airway narrowing during the early asthmatic response is an acute bronchoconstrictor response caused mainly by an IgE-dependent immediate hypersensitivity reaction. Of the preformed and newly synthesized mediators released from mast cells during these reactions, the cysteinyl leukotrienes appear to be the most important in the pathogenesis of the EAR. 

There are several possible routes whereby such responses can be affected. First, there is a neural response, as evidenced by the analogous symptoms of the cardiac and pulmonary chemoreflexes. Second, mediators released from the inflammatory cells in the lungs are carried by the blood directly to the heart. Of note, C3a and C5a which are released during anaphylaxis activate cardiac, but not limg mast cells (62). Third, antigens may penetrate the airway and alveolar epithelium and enter into the vasculature and directly interact with cardiac mast cells and basophils. This latter pathway is likely important when small molecules, such as sodium diisocyanate, are inhaled, as these molecules form albumin-isocyanate conjugates that may be related to the induction of toluene diisocyanate hypersensitivity (69). 

In type III or immunocomplex-mediated allergy, IgG antibodies form complexes with antigen. At low exposures, the body is able to remove diese complexes, but if there is a severe exposure, immunocomplexes release a variety of proinflammatory cytokines. The involvement of this mechanism is clearest in serum sickness. This mechanism is also considered to be most important in the development of extrinsic allergic alveolitis (hypersensitivity pneumonitis, especially... 

The rate of non-lgE-mediated immediate hypersensitivity reactions usually varies between 20 and 50% [1-7, 9], They are assumed to result from direct non-specific mast cell and basophil activation, which causes direct histamine release [19], Histamine release is predominantly found with the use of the benzylisoquinoUnes d-tubocurarine, atracurium and mivacurium, and the aminosteroid rapacuronium. Severe bronchospasm related to rapacuronium administration has been reported in children and adults. It might be related to the higher affinity of rapacuronium for M2 versus M3 muscarinic receptors [20]. Rapacuronium has been withdrawn from the market in the USA. 

IgE Mediates immediate hypersensitivity by causing release of mediators from mast cells and basophils upon exposure to antigen (allergen). Defends against worm infections by causing release of enzymes from eosinophils. Does not fix complement. Main host defense against helminthic infections. 

The answers are 25-e, 26-b, 27-a. (Hardmanr pp 67—68. Katzung, pp 30, 134.) Anaphylaxis refers to an acute hypersensitivity reaction that appears to be mediated primarily by immunoglobulin E (IgE). Specific antigens can interact with these antibodies and cause sensitized mast cells to release vasoactive substances, such as histamine. Anaphylaxis to penicillin is one of the best-known examples the drug of choice to relieve the symptoms is epinephrine. 

An immediate reaction occurs within seconds to minutes, resulting in the rapid release of preformed mediators and newly generated mediators from the arachidonic acid cascade. Mediators of immediate hypersensitivity include histamine, leukotrienes, prostaglandin, tryptase, and kinins. These mediators cause vasodilation, increased vascular permeability, and production of nasal secretions. Histamine produces rhinorrhea, itching, sneezing, and nasal obstruction. 

In sensitized asthmatic individuals, antigen challenge generally causes a Type I (IgE-mediated) immediate hypersensitivity response by release of preformed mediators, including histamine, and prostaglandins, which are responsible for bronchoconstric-tion and increased vascular permeability. Between 2 and 8 hours after the immediate response, asthmatics experience a more severe and prolonged (late phase) reaction that is characterized by mucus hyper-secretion, bronchoconstriction, airway hyperresponsiveness to a variety of nonspecific stimuli (e.g., histamine, methacholine), and airway inflammation characterized by eosinophils. This later response is driven by leukotrienes, chemokines and cytokines synthesized by activated mast cells and Th2 cells. Both proteins and haptens have been associated with these types of reactions. 

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