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The Biochemistry of Asthma
Candice Biback, Kristen Conte, Sarah James, Man Yen Ng
October 27, 2015
PHM142 Fall 2015Coordinator: Dr. Jeffrey HendersonInstructor: Dr. David Hampson
Interactive Activity
2
What is Asthma?
Definition:
• Chronic illness that leads to inflammation and narrowing of the airways
Causes:
Many contributors not well understood:
• Genetic, environmental and immune factors
Triggers include: exercise, allergens, irritants
3
Symptoms of Asthma
Include:
• Coughing
• Wheezing
• Shortness of breath
• Chest tightness
4
Initiation of Allergic Response
• Allergen binds antigen-presenting cell
• Antigen is presented to naive T cell
• Interaction between antigen-presenting cell and naive T cell leads to differentiation into T-helper (Th2) cells
5
Primary Allergic Response Pathway
• B cells are stimulated by
IL-4 and IL-13
• B cell releases IgE
antibodies
• IgE antibodies bind to
Mast cells
6
Causes of Asthma - Allergic Response
7
Review: PG Synthesis
• Liberation of AA from membrane phospholipids by phospholipase A2 in response to inflammatory stimuli
• AA converted to PGH2, a common precursor of several PGs
• PGD2 is a major product of COX-catalyzed reactions in a variety of cells, including T cells, macrophages, mast cells, and platelets
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Role of PGD2 in Asthma
9
Causes of Symptoms
10
• Mediators released by leukocytes ultimately responsible for symptoms
• Histamine
• Leukotrienes
• Chronic Inflammation
Possible Treatments• Inhaled corticosteroids
provide an anti-inflammatoryresponse (example, Flovent)
Advair
• Combination drug
• Both corticosteroid and long-acting β2 adrenergic agonist
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Summary Slide
Definition: Chronic illness that leads to inflammation and narrowing of the airways
Symptoms: Coughing, Wheezing, Shortness of breath, Chest tightness
Pathway:1. Allergen binds antigen-presenting cell 2. Antigen presented to naive T cell3. Interaction between antigen-presenting cell and naive T cell leads to differentiation into T-helper (Th2) cells 4. IL-4 and IL-13 stimulate B cells 5. B cells releases IgE antibodies 6. IgE antibodies bind to Mast cells 7. Mast cells release mediators, i.e., histamine, leukotrienes and prostaglandin D2 (PGD2)
Causes of Symptoms: PGD2 → promotes chemotaxis, upregulates cytokine and interleukin productionHistamine → increased mucus secretion, increased bronchoconstriction, inflammation Leukotrienes → smooth muscle contraction, increased vascular permeability of small blood vessels
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ReferencesAsthma Facts and Figures. (n.d.). Retrieved October 26, 2015, from https://www.aafa.org/display.cfm?id=8&sub=14
Asthma Symptoms. (2015, January 2). Retrieved October 26, 2015, from http://acaai.org/asthma/symptoms
Barnes, P.J. and Adcock, I.M. (2003). How do corticosteroids work in asthma? Annals of Internal Medicine, 139, 359-71.
Holgate, S.T. (2008). Pathogenesis of asthma. Clinical and Experimental Allergy, 38, 872-97.
Ishmael, F.T., (2011). The inflammatory response in the pathogenesis of asthma. Inflammatory Response in the Pathogenesis of Asthma, 111, Supplement 7, S11-17.
Masafumi, A. and Takeshi, F. (2011). Prostaglandin D2 and TH2 Inflammation in the Pathogenesis of Bronchial Asthma, Korean J Intern Med, 26:8-18.
Schleimer, R.P., Kato, A., Kern, R., Kuperman, D. and Avila, P.C. (2007). Epithelium: At the interface of innate and adaptive immune responses. J Allergy Clin Immunol, 120(6), 1279-84.
Van der velden, V.H.J. (1998). Glucocorticoids: mechanisms of action and anti-inflammatory potential in asthma. Mediators of Inflammation, 7:229-37.
What Is Asthma? (2014, August 4). Retrieved October 26, 2015, from http://www.nhlbi.nih.gov/health/health-topics/topics/asthma/
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