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13 Cards in this Set
- Front
- Back
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Define Allergy
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IgE mediated immediate hypersensitivty reactions. They are the most frequent disorder of the immune system, affecting about 20% of population. Allergies have been increasing in industrialized societies. These are the most common disorder of the immune system.
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Define Atopy
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IgE mediated immediate hypersensitivty reactions. People with a strong propensity to develop these reactions are said to be atopic.
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Define Allergen
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Antigens that elicit immediate hypersensitivity reactions.
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Describe the role of the IgE Antibody in atopic disease
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IgE antibody produced in response to an allergen binds to high-affinity Fc receptors specific for the E heavy chain that are expressed on mast cells. In atopic individuals, mast cells are coated with IgE antibody that is specific for the antigens to which the individual is allergic.
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Sensitization
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The process of coating the mast cells with IgE. Called sensitization because coating with IgE specific for an antigen makes the mast cells sensitive to activation by subsequent encounter with that antigen.
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Briefly outline the steps involved in IgE production. Be sure to include the role of T cells and Cytokines.
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a. begins with Th2 cells and production of IgE antibodies in response to an Ag
b. binding of IgE to Fc receptors of mast cells c. then on subsequent exposure to Ag, cross-linking of the bound IgE by the Ag and release of mast cell mediators d. some mast cells cause rapid increase in vascular permeability and smooth muscle contractions, resulting in many of the symptoms of these reactions. e. this vascular and smooth muscle reaction may occur within minutes....hence why its called immediate hypersensitivity f. the late phase occurs because some mast cell mediators are cytokines that recruit neutrophils and eosinophils to the site of the reaction over several hours. this inflammatory component is called the late-phase reaction and it is mainly responsible for tissue injury that results from repeated bouts of immediate hypersensitivty |
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List the most important mast cell mediators of allergic reactions and their actions.
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a. IL 4 and IL 13 are cytokines secreted by Th2 cells
b. IL 4 stim B lymphocytes specfic for the foreign antigens to switch to IgE producing plasma cells c. IL 13 stim IgE d. atopic individuals produce large amounts of IgE antibody in response to Ag that normally would not produce IgE response. e. strong genetic basis for allergies f. atopic individuals have mast cells coated with IgE Ab specific for Ags g. process of coating mast cells with IgE is called sensitization because coating IgE specific for an antigen makes the mast cells sensitive to activation by subsequent encounter with that antigen i. in normal people, mast cells carry molecules of many specificities ii. normally, having only a few IgE specific for an Ag is not enough to elicit immediate hypersensitivity upon exposure h. mast cells present in all CT, usually adjacent to blood vessels i. route of entry of Ag determines where response is. i. inhaled Ag stimulates mast cells in bronchi ii. ingested Ag stimulates mast cells in intestines j. The most important mediators produced by mast cells are vasoactive amines and proteases stored in and released from granules, newly generated and secreted products of arachidonic acid metabolism and cytokines i. histamines - dilation of small blood vessels, increases vascular permeability, stimulates the transient contraction of smooth muscles ii. proteases - cause damage to local tissues iii. arachidonic acid metabolites (prostaglandins) cause vascular dilation iv. leukotrienes - stimulates prolonged smooth muscle contraction v. cytokines - induce local inflammation (late phase reaction), stimulate recruitment of leukocytes which cause late phase reaction vi. mast cells overall responsible for acute vascular and smooth muscle reactions and inflammation |
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Distinguish between the early and late phase allergic reactions and the mediators involved therein.
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a. cytokines produced by mast cells stimulate recruitment of leukocytes which cause late phase reaction
b. principal leukocytes are eosinophils, neutrophils, and Th2 cells c. Mast cell derived tumor necrosis factor (TNF) and IL4 promote neutrophil and eosinophil rich inflammation d. chemokines produced by mast cells and by epithelial cells also contribute to leukocyte recruitment e. eosinophils and neutrophils liberate preoteases causing tissue damage and Th2 cells may exacerbate the reaction by producing more cytokines f. eosinophils = prominent component of many allergic reactions and are important cause of tissue injury in these reactions...cells activated by cytokine IL5 produced by Th2 and mast cells g. immediate hypersensitivty reactions have diverse clinical and pathological features which are attributable to mediators produced by mast cells in diff amounts and in different tissues |
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Explain the pathogenesis of allergic rhinitis
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a. allergic rhinitis and sinusitis (common in hay fever) are reactions to inhaled Ags (protein of ragweed pollen)
b. mast cells in nasal mucosa produce histamine, while Th2 cells produce IL13 c. histamine and IL13 cause increased mucus production d. late phase reactions trigger more prolonged inflammation e. mast cell degranulation occurs and when Ags is ingested mast cell degranulation/released histamine causes increased peristalsis f. for inhaled Ags, bronchial mast cells release mediators (leukotrienes) which cause repeated bouts of bronchial constriction and airway obstruction g. treatment of immediate hypersensitivity is aimed at inhibiting mast cell degranulation, antagonizing the effects of mast cell mediators and reducing inflammation i. epinephrine for bronchial relaxation when anaphylaxis or asthma present ii. corticosteroids inhibit inflammation iii. small doses of the allergen can work by changing the T cell response away from the Th2 dominance and by inducing tolerance in allergen specific T cells or by stimulating regulatory T cells |
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Briefly summarize the epidemiology and impact of rhinitis in the United States
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a. Rhinitis affects 10 to 30 percent of children and adults in the United States
b. The overall prevalence of rhinoconjunctivitis in children aged 6 to 7 years and 13 to 14 years was 8.5 and 14.6 percent c. Prevalence in the industrialized world is increasing d. Risk factors - family history of atopy, male sex, birth during pollen season, first born, early use of antibiotics, maternal smoking exposure, indoor allergens, serum IgE >100 IU/mL before age 6 |
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Describe the primary symptoms associated with allergic rhinitis
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a. sneezing
b. rhinorrhea c. fatigue d. itching of palate and inner ear e. tearing/burning of eyes f. disturbed breathing g. may be associated with ADD, lower exam scores during pollen season for kids, poorer concentration, impaired athletic performance, lower self esteem, anxiety, depression, impaired sex performance, lower quality of life scores |
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List the major additional conditions associated with allergic rhinitis
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a. pt continually exposed to an allergen may have persistent nasal mucosal inflammation which results in continuous severe rhinitis symptoms
b. infraorbital edema and darkening due to subcutaneous venodilation c. accentuated lines or folds below the lower lids (suggests allergic conjunctivitis) d. transverse nasal crease caused by repeated rubbing and pushing the tip of the nose up with the hand e. allergic faces - typically seen in children with early-onset allergic rhinitis, consists of highly arched palate, open mouth due to mouth breathing and dental malocclusion f. allergic conjunctivitis g. sinusitis - nasal inflammation associated with allergic rhinitis can also cause obstruction of the sinus ostiomeatal complex h. asthma i. atopic dermatitis (eczema) j. oral allergy syndrome - itching or mild swelling of mouth /throat immediately following ingestion of certain uncooked fruits or veggies |
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Explain the mechanisms of skin tests and in vitro tests used for atopic diseases and describe positive results
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a. prick skin tests - quick, cost effective, safe way to identify presence of specific IgE. look for wheal and flare reaction
b. serum tests for allergy - immunoassays to detect allergen specific IgE Abs c. nasal cytology and direct inhalation challenge with allergen are uncommon tests d. sometimes patients may have suggestive history with negative testing |
