5.3 Immunology of Asthma
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Review the mechanisms responsible for the four types of immune hypersensitivity reactions
What is allergic asthma and describe the role of genetic factors in the epidemiology of allergic asthma
Allergic asthma - occurs in previously sensitized individuals
What are environmental factors for allergic asthma?
- Housing design (rugs, bedding, humidity)
- Air pollution (vehicles, ozone, diesel)
- Diet (new foods, food processing)
What is atopy and describe the genetics of atopy, asthma and allergic rhinitis
Atopy - exaggerated tendency to form IgE to a variety of environmental antigens
What is the role of exposure to allergen in the development of allergic asthma?
- Antigens (allergens) are airborne
- Re-exposure to antigen can produce immediate response and a late reaction
What is the role of sensitization in the development of allergic asthma?
- Initial exposure to antigen (allergen) results in the production of specific antibody and isotype switching to IgE
- Subsequent exposure results in degranulation of mast cells through the cross-linking of 2 specific IgE molecules on its surface
What is the role of production of IgE antibodies in the development of allergic asthma?
IgE antibodies bind to a high affinity Fc receptors on mast cells
What is the role of binding of IgE antibodies to effector cells in the development of allergic asthma?
IgE molecules found on any mast cell can represent a variety of specificities
What is the role of release and activity of mediators in the development of allergic asthma?
Allergen must cross link 2 IgE molecules, both of which are specific for the epitopes on the allergen, to activate the cell
What is the role of synthesis and activity of late phase mediators in the development of allergic asthma?
- Starts 3-4 hours after initial challenge
- Occurs in about 50% of pts
- Lasts for 6-24 hours
- Endothelial adhesion molecules expressed (neutrophils, eosinophils and T cells migrate; edema develops, mucus secreted; mucosal inflammation major cause)
Describe the process of immunotherapy and the proposed mechanisms being induced
- Desensitization - infection w/ increasing doses of responsible allergen - induces immune deviation
- Peptide vaccination - induces T cell anergy
- Anti-IgE monoclonal antibody - binds Fc portion of IgE inhibiting binding to FcERI
What are the genes involved in immune response?
- IL-4, IL-4 receptor
- IgE receptor β chain
- MHC Class II
- T cell receptor α chain
- TIM gene family
What are the genes involved in systemic response?
- β2-adrenergic receptor
What are the mast cell mediators that are present in granules?
What are the mast cell mediators that are produced as a result of the activation of the cell?
- Arachidonic acid metabolites (prostaglandins, leukotrienes)
- Cytokines (IL-1,2,3,4,5,13; GM-CSF; IFN-γ; TNF-α)
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