PBL Session 3

Rosshini Jagatheswaran

Describe the PATHOGENESIS of bronchial asthma

MUST KNOW Learning Outcome

How T helper cells work?

TH2 cells secrete cytokines IL-4, IL-5, IL-13

stimulate B cells to produce IgE and other

antibodies.

IL-4 stimulates the production of IgE

IL-5 activates locally recruited eosinophils

IL-13 stimulates mucus secretion from bronchial submucosal glands and also promotes IgE production by B cells

Sensitization to Allergen• Inhaled allergens• TH2– dominated response

• IgE productions• Eosinophil recruitment• Release of granules and mediators

Allergen-Triggered Asthma• Re-exposure• Ag-induced cross linking of IgE bound to IgE

receptors on mast cell• Mediators released – histamine, leukotrienes• Tight junctions between epithelial cells open• Antigen enter mucosa• Mucosal mast cells activated• Eosinophil release other mediators

• Leukotrienes - constriction of bronchi bronchospasm - increased mucus production mucosal

accumulation• Histamine

- increased vascular permeability swelling & redness edema

- increased mucus production mucosal accumulation• Eosinophilic chemotactic factor

- Chemotaxis of eosinophils accumulation of eosinophils

Late Phase• Recruited leukocytes

initiate late phase• Mediators release

from endothelium, epithelial cells, leukocytes

• Eosinophils MBP, ECP – damage epithelium

Comparison of a normal bronchiole with that in a patient with asthma

• Increase in the number of mucus-secreting goblet cells in the mucosa and hypertrophy of submucosal mucus glands Accumulation of mucus in the bronchial lumen

• Recruitment of eosinophils & macrophages intense chronic inflammation

• Thickened basement membrane • Hypertrophy & hyperplasia of smooth muscle

cells

POP-QUIZWhich T Helper Cell plays an important role in bronchial asthma?What happens after IgE binds to the mast cell in the first phase-sensitization phase?Leukotrienes causes …?Upon re-exposure of Ag, what happens after binding of IgE?

Some factors released by eosinophils in the late phase causes damage to the epithelium. Give 2 examples of the factors.

Give 2 differences of a normal bronchiole and bronchiole of an asthmatic patient.

THANK YOU