Eosinophils sensitization

Johnson, H.G., McNec, M.L. and Nugent, R,A. (1992). Canine in vivo tracheal chemotaxis of eosinophils to antigen in sensitized dogs inhibition by a steroid, a systemic lazaroid U-78517F, and several topical HI antihistamines. Am. Rev. Respir. Dis. 146, 621-625. 

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. 

The development of respiratory hypersensitivity requires an induction phase where exposures to the sensitizer lead to an interaction with immune cells and the eventual development of specific effecter immune molecules (e.g., antibodies) and cells (e.g., T lymphocytes) [5], The induction phase can require months to years of exposure before there is a detectable immune response and/or onset of symptoms typical of respiratory hypersensitivity, including asthma. Classic IgE mediated responses have been described as Th2 cell dominant responses. A subset of CD4+ T cells known as Th2 cells push the immune response to the development of IgE and IgG4 antibodies in humans along with secretion of cytokines that attract and activate inflammatory cells such as eosinophils. 

Nitric oxide and nitrite react with other peroxidase enzymes such as horseradish peroxidase (HRP) (138a,139), lactoperoxidase (138a) and eosinophil peroxidase (140) similarly. The rate constants for reaction of NO with compounds I and II in HRP were found to be 7.0 x 105M 1s 1 and 1.3 x 106M 1s 1, respectively (139). Catalytic consumption of NO as measured by an NO sensitive electrode in the presence of HRP compounds I and II is shown in Fig. 5 where accelerated consumption of NO is achieved even in deoxygenated solutions (140). 

Cell counts (lymphocytes, neutrophils, monocytes, eosinophils) were unaffected by u-hexane exposure. No reports of dermal sensitization after exposure to -hexane in humans were located. 

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. 

Hellings PW, Vandenberghe P, Kasran A, Coorevits L, Overbergh L, Mathieu C, et al Blockade of CTLA-4 enhances allergic sensitization and eosinophilic airway inflammation in genetically predisposed mice. Eur J Immunol 2002 32 585-594. 

Lambrecht BN. Salomon B. Klatzmann D. Pauwels RA Dendritic cells are required for the development of chronic eosinophilic airway inflammation in response to inhaled antigen in sensitized mice. J Immunol 1998 160 4090-4097. 

Treatment with omalizumab, the monoclonal humanized anti-IgE antibody, is reserved for patients with chronic severe asthma inadequately controlled by high-dose inhaled corticosteroid plus long-acting B-agonist combination treatment (eg, fluticasone 500 meg plus salmeterol 50 meg inhaled twice daily). This treatment reduces lymphocytic, eosinophilic bronchial inflammation and effectively reduces the frequency and severity of exacerbations. It is reserved for patients with demonstrated IgE-mediated sensitivity (by positive skin test or radioallergosorbent test [RAST] to common allergens) and an IgE level within a range that can be reduced sufficiently by twice-weekly subcutaneous injections. 

This type of immune response is unlike the other three in that antibodies are not involved, the response being initiated by sensitized TH1 cells. These are activated by contact with APCs. This stimulates them to secrete cytokines, which recruit macrophages, neutrophils, and eosinophils causing inflammation at the site of exposure. The cytokines also recruit and activate cytotoxic T cells, which can destroy the cell such as when an altered cell membrane is the antigen (Fig. 6.34). 

Ezeamuzie Cl, Philips E (2003) Positive coupling of atypical adenosine A3 receptors on human eosinophils to adenylyl cyclase. Biochem Biophys Res Commun 300 712-718 Feoktistov I, Biaggioni I (1995) Adenosine A2b receptors evoke interleukin-8 secretion in human mast cells. An enprofylline-sensitive mechanism with implications for asthma. J Clin Invest... 

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