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

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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

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Symptoms of Asthma

Include:

• Coughing

• Wheezing

• Shortness of breath

• Chest tightness

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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

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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

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Causes of Asthma - Allergic Response

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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

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Causes of Symptoms

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• 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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