Basophils sensitivity

Figure 10 Demonstration of histamine release of normal human basophils sensitized with other normal human smim (+) or scrum of a child with clinical anaphylaxis (o 1-ASP (4) following exposure to Increasing concentrations of 1-ASP. Data are expressed as percent of releasable histamine.

The current descriptions of sensitivity and maximal response are best applied to secretion of histamine. However, a more complete understanding will require further information about the same parameters in the context of lipid and cytokine release. Both of these mediators are critical determinants of the allergic inflammatory response, so that understanding the extent to which new therapeutics need to suppress basophil and mast cell responsiveness will be dependent on new information regarding the relative roles of each of the secreted mediators. Recent studies have indicated that basophil sensitivity is very similar when viewed from the secretion of each of three classes of mediators. This means that if cell surface antigen-specific IgE is present at a density sufficient to initiate only 50% of the maximum histamine release, approximately 50% of the maximal secretion of IL-4 and LTC4 will also be obtained. It remains to be determined whether the equivalent suppression of secretion for each of the three classes of mediators will lead to equivalent reductions for the functional endpoints of the three different mediator classes. 

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. 

Garda BE, Barber D, Salcedo G, Rihs HP, Raulf-Heimsoth M Basophil activation test and specific IgE measurements using a panel of recombinant natural rubber latex allergen to determine the latex allergen sensitization profile in children. Pediatr 52 Allergy Immunol 2006 17 148-156. 

There is no clinical disease state that is pathognomonic for lead exposure. The neurotoxic effects and hematopoietic effects of lead are well recognized. The primary biomarkers of effect for lead are EP, ALAD, basophilic stippling and premature erythrocyte hemolysis, and presence of intranuclear lead inclusion bodies in the kidneys. Of these, activity of ALAD is a sensitive indicator of lead exposure (Hemberg et al. 1970 Morris et al. 1988 Somashekaraiah et al. 1990 Tola et al. 1973), but the assay can not distinguish between moderate and severe exposure (Graziano 1994). Sensitive, reliable, well-established methods exist to monitor for these biomarkers however, they are not specific for lead exposure. Therefore, there is a need to develop more specific biomarkers of effect for lead. Recent data... 

Inhaled and intravenous histamine causes bronchoconstriction as one of the first recognized properties of histamine, which is inhibited by Hi antihistamines. As a manifestation of airway hyperresponsiveness, asthmatic individuals are more sensitive to the bronchoconstrictor effect of histamine than normal individuals. In addition, in vitro studies have shown increased histamine release in basophils and mast cells obtained from asthmatic subjects compared with... 

Despite the fact that a definite decrease in IgE antibody levels and IgE-mediated skin sensitivity normally requires several years of SIT, most patients are protected against bee stings already at an early stage of bee venom-SIT. The reason for this is that effector cells of allergic inflammation, such as mast cells, basophils and eosinophils. 

Mast Cells and Basophils. The chief sites of histamine storage are mast cells in the tissues and basophils in blood. These cells synthesize histamine and store it in secretory granules along with a heparin-protein complex. In response to specific antigens, mast cells or basophils are sensitized. Histamine is then secreted from the storage granules. Besides the histamine stores in mast cells and basophils, there is evidence of non-mast cell histamine in some tissues, particularly gastric and intestinal mucosa (60). 

Hematologic/Lymphatic Anemia hemolytic anemia thrombocytopenia thrombocytopenic purpura eosinophilia leukopenia granulocytopenia neutropenia bone marrow depression agranulocytosis reduction of hemoglobin or hematocrit prolongation of bleeding and prothrombin time decrease in WBC and lymphocyte counts increase in lymphocytes, monocytes, basophils, and platelets. Hypersensitivity Adverse reactions (estimated incidence, 1% to 10%) are more likely to occur in individuals with previously demonstrated hypersensitivity. In penicillin-sensitive individuals with a history of allergy, asthma, or hay fever, the reactions may be immediate and severe. 

By a negative feedback control mechanism mediated by H2 receptors, histamine appears to modulate its own release and that of other mediators from sensitized mast cells in some tissues. In humans, mast cells in skin and basophils show this negative feedback mechanism lung mast cells do not. Thus, histamine may act to limit the intensity of the allergic reaction in the skin and blood. 

Mechanism of type I hypersensitivity. Initial exposure to allergen (sensitization phase) leads to production of IgE by plasma cells differentiated from allergen-specific cells (not shown). The secreted IgE binds IgE-specific receptors (FcsR) on blood basophils and... 

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