Mast cells sensitization

IgE-medlated release of mast cell contents. Inset, Intact mast cell with histamine stored In granules. An IgE antibody molecule Is depicted adjacent to the mast cell. Two IgE molecules combine with a mast cell (sensitization). The attachment of an antigen (allergen) to the sensitized mast cell Initiates release of histamine (and other substances) from the mast cell. This degranulation can be prevented by such agents as isoproterenol, theophylline, epinephrine, and cromolyn sodium. H antihistamines do not interfere with degranulation but instead prevent actions of histamine at various pharmacological receptors. 

Insulin allergy, an immediate type hypersensitivity, is a rare condition in which local or systemic urticaria results from histamine release from tissue mast cells sensitized by anti-insulin IgE antibodies. In severe cases, anaphylaxis results. Because sensitivity is often to noninsulin protein contaminants, the human and analog insulins have markedly reduced the incidence of insulin allergy, especially local reactions. 

HOLLIDAY, M.R., COLEMAN, J.W., DEARMAN, R.J. KIMBER, I. (1993) Induction of mast cell sensitization by chemical allergens a comparative study. Journal of Applied Toxicology, 13,137-142. 

Mitchell GF, Humphrey JH, Williamson AR (1972) B cell tolerance induced by polymeric antigens I. Comparison of the dose and epitope density requirements for inactivation of primed and unprimed B cells in vivo. Eur J Immunol 5 361 Mota I (1964) The mechanism of anaphylaxis I. Production and biological properties of mast cell sensitizing antibody. Immunology 7 681 Neftel KA Waelti M Spengler H Von Felten A Weitzman SA Buergi H de Week AL (1981) Neutropenia after penicillins Toxic or immune-mediated Klin Wochenschr 59 877... 

Although the pathogenesis of exercise-induced allergy (EIA) is poorly understood, biopsy studies have demonstrated mast cell degranulation after exercise. Patient s with EIA who have specific foods as coprecipitating factors invariably have positive skin test reactions to these foods, thus specific IgE mast cell sensitization is indicated. A potential dysfunction in the autonomic nervous system has also been hypothesized. Differential diagnosis includes cholinergic urticaria. 

An allergen is usually an inert substance (e.g. pollen, house dust mite faeces) that in some individuals can trigger the generation of an (inappropriate) antigenic response. Mediated by TH2 lymphocytes, it causes B-Lymphocytes to produce lgE. Subsequent exposure of a sensitized individual to the allergen is therefore able to cross-link IgE antibodies on the surface of mast cells and trigger an immune response and histamine release. 

Foster B, Schwartz LB, Devouassoux G, Metcalfe DD, Prussin C Characterization of mast-cell try-ptase-expressing peripheral blood cells as basophils. J Allergy Clin Immunol 2002 109 287-293. Schwartz LB, Bradford TR, Rouse C, Irani AM, Rasp G, Van der Zwan JK, Van del Linden PW Development of a new, more sensitive immunoassay for human tryptase use in systemic anaphylaxis. J Clin Immunol 1994 14 190-204. 

TRPVl also plays a central role in intercellular pro-inflammatory feedback loops. An important example is mast cells and sensory nerves. Mast cells release tryptase that, in turn, activates the protease-activated receptor PAR-2 activation of PAR-2 then opens TRPVl via PKC [50]. In keeping with this, PAR-2 agonists reduce the heat activation threshold of TRPVl from 42 °C to below body temperature [51]. Excited nerve endings release SP that, as a positive feedback, binds to neurokinin NKl receptors on mast cells. Mast cells also express TRPVl [52]. Consequently, endovanilloids can act in concert to stimulate mast cells and activate capsaicin-sensitive nerve endings. Of relevance is the finding that PAR-2 is up-regulated in the bladder during experimental cystitis [53]. 

Facci L, Dal Toso R, Romanello S, Buriani A, Skaper SD, Leon A. Mast cells express a peripheral cannabinoid receptor with differential sensitivity to anandamide and palmitoylethanolamide. Proc Natl Acad Sci USA 1995 92 3376-3380. 

Hiiltner, L., Moeller, J., Schmitt, E., Jager, G., Reisbach, G., Ring, J. and Dormer, P. (1989) Thiol-sensitive mast cell lines derived from mouse bone marrow respond to a mast cell growth-enhancing activity different from both IL-3 and ILA. Journal of Immunology 142, 3440-3446. 

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. 

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