Pathophysiology of the inflammatory response.

Area of Science:

• Immunology
• Allergy Research
• Respiratory Medicine

Background:

• Airway allergic reactions involve diverse cells and mediators causing symptoms of allergic rhinitis and asthma.
• Studies in humans and animal models reveal a sequence of cellular events leading to airway inflammation in genetically predisposed individuals upon initial antigen exposure.

Purpose of the Study:

• To elucidate the cellular and molecular mechanisms underlying airway allergic inflammation, from initial sensitization to chronic symptoms.
• To highlight the roles of T(H)2 lymphocytes, immunoglobulin E (IgE), mast cells, and subsequent leukocyte recruitment in the pathogenesis of allergic airway diseases.

Main Methods:

• Review and synthesis of experimental data from in vitro studies, animal models, and human atopic subjects.
• Analysis of the sequential cellular activities and mediator releases involved in acute and late-phase allergic responses.

Main Results:

• Initial antigen exposure in susceptible individuals triggers T(H)2 lymphocyte differentiation and cytokine release, notably IL-4, promoting IgE production.
• IgE binding to mast cells primes them for activation upon re-exposure, leading to mediator release causing acute symptoms.
• Mast cell mediators also promote leukocyte adhesion and recruitment, initiating a late-phase response with further inflammation and potential for chronic changes.

Conclusions:

• Airway allergic inflammation is an orchestrated process initiated by T(H)2-dependent sensitization and amplified by mast cell activation and subsequent leukocyte infiltration.
• Chronic airway hypersensitivity and symptoms may result from repeated inflammatory cycles and the persistence of memory cells and eosinophils in the airway mucosa.