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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

AsthmaInflammation & Remodeling of Airways

Anthony Shoukat

Halima Zia

ZahidaYaseen

asthma
Asthma

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

background and types
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
molecular pathology of asthma
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
molecular mechanism of t helper cell s inflammatory action in asthma
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.
slide7

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