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Introduction:This page is still being prepared. It will provide a brief general account on occupational, and other environmental sensitisation. An outline of the mechanisms responsible for this will be provided. It will address prevention and management and will link to other pages on this site providing more detailed accounts on specific conditions.Mechanisms:Immune mechanisms: Type I:Type I immune reactions (immediate hypersensitivity) can result in Occupational Asthma, Angio-oedema and/or urticaria. You may wish to refer to a case-study. In classical Type I hypersensitivity the exogenous agent may be a complete antigen. Its initial chemical interaction is with antigen presenting cells such as dendritic cells. The allergic asthmatic response is mediated by CD4+ T lymphocytes with the type 2 helper (Th2) cell profile of cytokine secretion (Interleukins 4,5,6 and 13). It eventually results in specific reaginic antibody (almost invariably IgE, although rarely it might be IgG4). Subsequent exposure to the chemical substance will result in a second chemical interaction - this time with the specific antibody to it which resides mainly on the surface of pulmonary mast cells, and thus sets off the biological cascade resulting in asthma as we know it. The following image shows the location of mast cells inside the lung. The cells are demonstrated immunohistochemically by a 'sandwich' technique in which they are revealed by virtue of the Immunoglobulin E (IgE) binding to their cell surface and appear stained brown. In the left hand side of the image the mast cells are shown in the bronchial epithelium, closely apposed to the basement membrane. On the right hand side of the image they are shown in the septa between the alveoli.    Many low molecular weight asthmagens are not complete antigens but behave as haptens or partial antigens. In these cases their first chemical interaction is with a native human macromolecule, such as albumen. Immunologically recognisable epitopes would then be formed, or exposed as a result of covalent reaction with native carrier proteins. Thence the subsequent chemical interactions are essentially identical to the ones outlined above. Thus the first interaction is with the surface of antigen presenting cells where the type of MHC class II proteins is probably an important host determinant of the interaction.Subsequently this leads to specific antibody formation, and finally the reaction of the antigenic complex with cell surface antibody. Immune mechanisms: Type IV:Type IV immune reactions(delayed hypersensitivity) in the skin are manifest as Occupational Allergic Dermatitis . In this condition there are some fundamental differences from those
described above for Type I reactions which lead to asthma and urticaria.
In the Type IV immune response, the lymphocytes with aTh1 profile (Type
1 helper cells) are activated and correspondingly different cytokines are
manifest. The resultant immune response is i.e. without freely circulating
antibodies. The symptoms follow a slower time course.
Other mechanisms:A number of very important occupational asthmagens such as diisocyanates and resin acids (abietic acid from colophony,and other related compounds) have revealed only limited and inconsistent evidence of being mediated by classical type I hypersensitivity. In sensitisation to these or other low molecular weight asthmagens a chemical reaction with some as yet undefined cell surface component or chemical activation of a transcription factor activation may well be a crucial step in asthmagenesis. There is evidence for an isocyanate T-cell HLA class II molecule interaction, and that diisocyanates result in the production of histamine-releasing factors and other mediators in pathways distinct from Type I immune responses.
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References:Occupational Asthma |
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