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Asthma Inflammation & Remodeling of Airways

Asthma Inflammation & Remodeling of Airways. Anthony Shoukat Halima Zia Zahida Yaseen. Asthma. “Asthma is pulmonary disorder which is characterized by inflammation and remodeling of airway that leads to reversible airway obstruction”. Background and types. Background

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Asthma Inflammation & Remodeling of Airways

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  1. AsthmaInflammation & Remodeling of Airways Anthony Shoukat Halima Zia ZahidaYaseen

  2. Asthma “Asthma is pulmonary disorder which is characterized by inflammation and remodeling of airway that leads to reversible airway obstruction”

  3. Background and types Background • Environmental factors & genetic factors • Disease of Civilization • Dust, cool air and pollen etc. • Late night, early morning and after exercise • 10% of US (total population) Types • Extrinsic Asthma • Intrinsic Asthma

  4. Molecular Pathology of Asthma • Immune system • Evolutionary response -> allergens • Mast cell, eosinophil, basophiles & macrophages etc. in lung airway Hygiene Hypothesis • Differentiation of T Helper cells • Th1/Th2 Polarization

  5. Molecular Mechanism of T Helper cell’s Inflammatory Action in Asthma • Dendritic Cells => IL-10 => Th2 Th2 Cells response in two ways: • 1st Way: • Cytokines including IL-4, IL-5 and IL-13. IL-4 and IL-13 • Cytokines stimulates B-Cells and Plasma cells => IgE • IgE stimulate mast cells maturation • Maturation of mast cells => mediators (Histamine and Leukotriene) • 2nd Way: • IL-5 & IL-4 => mast cells => histamine, chymase, tryptase, cysteinyl & leukotriene. • IL-5 from these lymphocytes stimulates eosinophil. • They released (ECP), (MBP), Eosinophil Peroxidase and Eosinophil-derived Neurotoxin. • All of above collectively => hyperactivity & production of transmural edema.

  6. Dendritic Cells-> IL-12 => Th1. • Th1 cells -> Interferonᵞ (IFN-ᵞ), IL-2 and Lymph toxin • Neurophil Cells secrete Protease, Reactive oxygen species (ROS) and other inflammatory mediators • Antioxidant agent Dismutase => Mast cells • Neural Pathway and Inflammatory Pathway • Inflammatory response mainly comes from mast cells. • Neural Pathway • Noradrenergic and No cholinergic (NANC) system • Goblet Cell Hyperplasia • Collagen and elastic fibers => fibrosis and elastosis • Hypertrophy and hyperplasia • Transforming Growth Factor-β (TGF-β) • Mitogenic mediators like Epithermal and Fibroblast Growth Factors (EGF-FGF)

  7. Molecular Mechanism of T Helper cell’s Inflammatory Action in Asthma

  8. Genes involve in inflammatory action and remodeling of Airways • IL-17 • Kawaguchi et al =>His161Arg substitution • IL-21 • C5250T • P13K • SHIP • PTEN • INPP4a

  9. Genes involve in inflammatory action and remodeling of Airways • ADAM33 • DPP10

  10. References: • William, B.C. & Gregory, J. T. (2010). Essential Concept of Molecular Pathology. London UK: Elsevier Inc. • Introductory material is retrieved from Wikipedia. • Thomas, J. K., Barbara A. O & Richard A. G.(2006). Kuby: Immunology. US: Freeman, W. H. & Company • Amrendra, K., & Balaram, G.,(2009). Genetics of asthma: a molecular biologist perspective. Clinical and Molecular Allergy :1476-7961 • Image Links • http://www.drugs.com/health-guide/images/205198.jpg • http://www.nature.com/nrg/journal/v5/n5/images/nrg1326-i1.jpg • http://www.nhlbi.nih.gov/health/health-topics/images/asthma.jpg

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