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
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
I. Extrinsic Asthma
II. Intrinsic 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
• 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.
• 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)
Molecular Mechanism of T Helper cell’s
Inflammatory Action in Asthma
Genes involve in inflammatory action
and remodeling of Airways
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IL-17
Kawaguchi et al =>His161Arg substitution
IL-21
C5250T
P13K
SHIP
PTEN
INPP4a
Genes involve in inflammatory
action and remodeling of Airways
• ADAM33
• DPP10
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/nrg1326i1.jpg
• http://www.nhlbi.nih.gov/health/healthtopics/images/asthma.jpg