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  Authority of Polish Society of Allergology

vol 7. no 3. September 2002  

 Bronchial asthma
Molecular and immunological background of isocyanate-induced asthma: state of art
Waldemar Lutz, Cezary Pałczyński*

Zakład Immunotoksykologii, Instytut Medycyny Pracy im. Nofera w Łodzi, ul. Św. Teresy 8, 90-950 Łódź
*Klinika Chorób Zawodowych, Ośrodek Alergii Zawodowej i Środowiskowej, Instytut Medycyny Pracy im. Nofera w Łodzi, ul. Św. Teresy 8, 90-950 Łódź

Diisocyanates (DIC) are the most common chemicals that cause occupational asthma. They belong to the group of highly electrophilic, low molecular weight (LMW) compounds and are capable of making covalent binding with human proteins. The allergenic potential of diisocyanates may be associated with their ability to produce stable adducts with glutathione and thus to generate reactive oxygen forms. Despite the recent advances in immunologic patomechanisms leading to LMW-induced asthma, the significance of diisocyanate-modified proteins and protein-related reactive oxygen forms in the stimulation of immune response has not been adequately explained. It seems that the dendritic cells are the crucial elements that induce immune response to DIC in the lungs. Dendritic cells transform into mature forms after contact with DIC and DIC-modified proteins and migrate to peripheral lymph nodes where they present MHC-peptide-DIC complex to the naive T cells. The activation of T cells by dendritic cells requires interaction between TCR and MHC-peptide-DIC complex (signal 1) as well as additional interaction between CD28/CTLA-4 on lymphocytes and B7.1 or B7.2 molecules on the surface of dendritic cells (signal 2). According to the presentation of the modified peptide, either with MHC I or MHC II, different types of immune response – CD4 (Th) or CD8 (Tc) may develop. The response of Th lymphocytes can be categorised by the pattern of cytokine production – Th1 – IFNg and Th2 – IL-4, IL-5. It seems that the activation of lymphocytes requires additional signal 3 from the cells other than lymphocytes, e.g. the epithelial cells influenced by DIC. The signal 3 could be IL-10 and\or TGF-b and it may decide about the result of antigen recognition by the T cells, i.e. the development of either immune response or immune tolerance (T cell anergy).
Alergia Astma Immunologia, 2002, 7(3), 131-139

keywords: izocyjaniany, astma zawodowa, patogeneza molekularna, isocyanates, occupational asthma, molecular pathogenesis

pages: from 131 to 139

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