Allergy, Asthma, and Inflammation
R&D Systems offers a wide variety of research reagents useful for the characterization of allergen-induced immune response pathways:
Allergy
Allergy is a hypersensitivity disorder characterized by an exaggerated immunologic response to an otherwise innocuous agent, called an allergen. Allergies can be caused by both host (race, gender, hereditary) and environmental factors (pollution, diet, infection). Exposure to inhaled allergens, such as pollen can initiate an acute immune response in allergen-sensitive individuals that leads to airway inflammation. Persistent inflammation is associated with allergen-induced asthma, a chronic respiratory disorder characterized by the production of IgE antibodies, airway hypersensitivity, and thickening of the airway wall.
Allergens are initially processed by dendritic cells which promote naïve T cells to differentiate into T helper type 2 cells (Th2). These Th2 cells produce cytokines, including IL-4 and IL-13 that, along with specific co-stimulatory molecules, induce B cells to produce allergen-specific IgE antibodies. IgE antibodies bind with high affinity to the Fc epsilon RI receptors found on mast cells, basophils, neutrophils, and eosinophils. Upon allergen re-exposure, allergen binding to IgE-Fc epsilon RI receptors on mast cells and basophils promotes receptor cross-linking and triggers the release of pro-inflammatory mediators, such as histamine and cysteinyl leukotrienes, that define the early phase asthmatic reaction. The late phase asthmatic reaction occurs several hours after the initial reaction and is characterized by eosinophil activation and leukocyte recruitment to the sites of allergen exposure. The release of cytokines and chemokines at these sites by infiltrating leukocytes plays a critical role in promoting chronic inflammation and airway remodeling.
The increase in allergic diseases in industrialized countries over the past decades has been attributed to a decline in infections during childhood, also known as the hygiene hypothesis.
Classification of the Allergic Response
The immunological allergic response is often thought of in terms of the Gell-Coombs classification which states that there are four main types of hypersensitivity:
- IgE mediated hypersensitivity, seen in food allergy and asthma.
- Antibody mediated hypersensitivity, seen in transfusion reactions.
- Immune complex mediated hypersensitivity, seen in arthritis.
- T-cell mediated (delayed hypersensitivity), seen in dermatitis.
Asthma
Asthma is a common chronic inflammatory disease of the respiratory system that affects approximately 22 million people in US. It has been classified as a complex genetic condition that is determined by the interaction of numerous genes along with environmental factors.
Asthma can be characterized by hyper-reactivity of the airways and the propensity of airways to constrict in response to various stimuli. This leads to symptoms such as shortness of breath, chest tightening, coughing and wheezing. Triggers of asthma 'attacks' include common colds, exercise, allergens (irritants such as smoke, fumes and dust, along with pollutants).
Cytokine signaling contributes greatly to asthma and the associated airway obstruction. Cytokines such as IL-4 cause the secretion of mucus and the onset of allergic inflammatory responses including the development of T helper cells. There are also numerous structural changes that occur in asthmatic airways and collectively lead to 'remodeling'. These include deposition of matrix proteoglycan and collagen in the submucosa, epithelial mucus metaplasia and a proliferation of microvessels and nerves.
Treatment for asthma includes bronchodilator therapy or anti-inflammatory drugs, particularly corticosteroid inhalation. Corticosteroids act by blocking the immune reaction to an allergen, decreasing inflammation by inhibiting cells such as mast cells, eosinophils and basophils.