Asthma - fccljohnson

Inflammation & Remodeling of
Anthony Shoukat
Halima Zia
Zahida Yaseen
“Asthma is pulmonary disorder which is characterized by
inflammation and remodeling of airway that leads to
reversible airway obstruction”
Background and types
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)
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
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
Kawaguchi et al =>His161Arg substitution
Genes involve in inflammatory
action and remodeling of Airways
• ADAM33
• DPP10
• 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
• Image Links

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