Immunopathology Type 1, Allergies 2 Flashcards
Describe the mechanism of IgE-mediated hypersensitivity in terms of: IgE attachment to basophils or mast cells
IgE binds strongly to FcεR1 (receptors) on mast cell surface (association constant of 10^-10, CRAZY STRONG—that’s why IgE plasma levels are so low, all secreted IgE is immediately bound).
Describe the mechanism of IgE-mediated hypersensitivity in terms of: reaction to allergens
In response to an allergen, Th2-like Tfh helps B cells switch to IgE production.
Describe the mechanism of IgE-mediated hypersensitivity in terms of: mediator release
When 2 adjacent IgE molecules bound are cross-linked by allergen (must be at least divalent), the mast cell is signaled to release the contents of its granules, including histamine, heparin, enzymes and TNF. NOTE: normal people may have IgE on mast cells, but this IgE is the product of many weakly-activated clones, the chances of having 2 adjavent IgEs both specific for 2 epitopes on the same allergenic protein are small. Allergic person will have a few clones responding strongly, and be able to put 2 IgEs from the clones side by side.
Describe the mechanism of IgE-mediated hypersensitivity in terms of: effects of mediators on target tissues and cells.
This causes local OR systemic vasodilation, increase permeability, gut and bronchial smooth muscle contraction (rapid onset: 15 minutes). This phase can be blocked by anti-histamines (receptor antagonists)
Discuss the features that the various atopic diseases have in common which justify lumping them together
Atopic diseases are characterized by an abnormal IgE response to an environmental antigen. Allergies, unlike Type IV immunopathologies, are mediated by Th2 cells. There is also a lot of cross reaction, it: foods that cause OAS contain proteins that are similar to and cross react with proteins in pollen, person with T-cell mediated contact dermatitis to latex has symptoms of IgE-mediated oral allergy to avocados, bananas (which have cross reactive antigen).
ex. asthma, eczema, oral allergy syndrome, allergic rhinitis (seasonal)
Discuss the reasons for using glucocorticoids in asthma treatment
a. Asthma: reversible bronchoconstriction disease with progressive inflammation leading to fibrosis. Tested for with spirometry (measures air flow, the FEV1, volume of air forcibly exhaled from full lungs in 1 second). Measure at baseline, and after bronchodilator, a significant improvement after bronchodilation –> bronchoconstrictive disease.
b. Glucocorticoids (inhaled), inhibit the production of arachidonic acid from phospholipids and block both PG and LI synthesis. are used to treat asthma early to prevent the late-phase reactants and Th2 cells present in the lung that are pro-inflammatory.
Discuss intradermal skin tests with reference to procedure
An intradermal test is useful because it is easy. A drop of allergen extract is placed on the forearm and a needle is used to prick the epidermis through the drop. The results are observed at 15 to 20 minutes and the wheal/diameter of the central raised area is measured (5/15 mm).
Discuss intradermal skin tests with reference to safety
testing with buffer is necessary to control for skin hyperreactivity. Patients should be observed for 20-30 minutes after the test to make sure no problems result
Discuss intradermal skin tests with reference to specificity
A positive skin test does not necessarily mean symptoms are due to the allergen. Levels of sensitivity may be sub-clinical even with a positive test or symptoms might come from something that cross-reacts with the test extract
Discuss specific immunotherapy of allergic disease, considering duration of effect
“Allergy shots” are dilute solutions of allergen extracts, given subcutaneously once or twice a week with increases in the concentration as tolerated. When the maximal dose is reached shots are given monthly
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Discuss specific immunotherapy of allergic disease, considering risk of anaphylaxis
Discuss specific immunotherapy of allergic disease, considering percent of patients obtaining significant relief.
About 75% of people with seasonal rhinitis say they have an easier season after a course of immunotherapy.
Describe the immediate allergic reaction in terms of the time course of the reaction and mediators involved
Within 15 minutes of the intradermal injection of an allergen, a positive wheal-and-flare response (hives) is very obvious. Histamine, the most important granule released, has a half life in tissue of only a minute so it is very short lived.
Almost all of the IgE in the body (except in extremely allergic people ) is bound to mast cells via the receptor FcεRI.
Mast cells loaded with IgE are triggered to release the contents of their granules when two adjacent IgE molecules are cross-inked by allergen (must be divalent). The granules contain histamine, heparin, enzymes and TNF. These are all preformed so action is very rapid
Describe the late-phase reaction in terms of the time course of the reaction and mediators involved
Begins 4 to 10 hours after the immediate phase and is not affected by histamines.
In addition to releasing granules, the activated mast cell initiates a series of enzymatic steps causing phospholipase PLA2 to cleave arachidonic acid from membrane phospholipids. Arachidonic acid can then be cleaved to prostaglandins by cyclooxygenase and to leukotrienes by lipoxygenase. These compounds initiate inflammation and constrict bronchioles. The are together called the “eosinophil chemotactic factor of anaphylaxis” (ECF-A) b/c good at attracting eosinophils.
Late phase is not affected by histamines and instead depends on prostaglandins, leukotrienes and cytokines. Since histamines are not a big cause of the bronchoconstriction in asthma, anti-histamines do not play a major role in asthma. Eczema also seems to be more of a chronic late phase Type I immunopathology needing anti-inflammatory treatment rather than anti-histamines.
