Immunopathology Type I (Allergies) Flashcards
Discuss the roles of IgG, IgE, M2 macrophages, and eosinophils in helminth immunity.
IgG binds ova, activates complement, C3a and C5a attract neuts, and… nothing.
IgE: Worm sheds antigens which diffuses to nearby mast cells (loaded with anti-helminth IgE) –> degranulation & histamine release –> gut smooth muscle contracts –> shit out worm
ECF-A attracts eosinophils –> Fc receptors bind IgG on worm –> release granules, which include Major Basic Protein, which is highly toxic to helminths.
Th2 circulates to infection and attracts both eosinophils and macs. It makes, IL-4, IL-5 and IL-13, turn the macs into alternatively activated M2 macs, the cells that heal damage and wall off M1-resistant invaders
atopic / allergy / allergen
prone to develop any of the range of allergic syndromes
allergy is roughly the same as atopy. It is an atypical immune response to environmental antigens, eventually becomes characterized by increased reactivity of the end-organs to inflammatory mediators and irritants.
Antigen = allergen here
asthma
Asthma is both bronchoconstrictive ►and inflammatory, and no longer considered a mild disease.
hives, wheal-and-flare reaction
same thing. round red raised area
State the approximate incidence of atopic diseases in the general population, and in individuals with allergic parents.
US population: 20%
One parent: 35%
Two parents: 65%
Describe the mechanism of IgE-mediated hypersensitivity in terms of: IgE attachment to basophils or mast cells; reaction with allergens; mediator release; effects of mediators on target tissues and cells.
IgE binds strongly to FcεR1 receptors on the surface of mast cells.
When 2 adjacent IgE molecules so bound are cross-linked by allergen, the mast cell is signaled to release the contents of its characteristic granules, including histamine, which causes local or systemic vasodilation and increased permeability, and gut and bronchial smooth muscle contraction.
The activated mast cell also initiates a series of enzymatic steps: phospholipase PLA2 cleaves arachidonic acid from membrane phospholipids, and arachidonic acid can be converted by the cyclooxygenase pathway to prostaglandins, and by lipoxygenase to leukotrienes. These active compounds initiate inflammation, constrict bronchioles, and are together called “eosinophil chemotactic factor of anaphylaxis” or ECF-A, because they are particularly good at attracting eosinophils. Cytokines are also released by the mast cell.
Discuss the features that the various atopic diseases have in common which justify lumping them together.
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- Discuss the reasons for using glucocorticoids in asthma treatment.
Late-phase reactants and Th2 cells present in the lung are pro-inflammatory, and untreated chronic inflammation inevitably leads to fibrosis, which is mostly irreversible.
So, inhaled glucocorticoids are added early to the asthma treatment regimen; they are scarcely absorbed and can be used, with monitoring, in growing children without the serious side effects associated with systemic steroid treatment.
They inhibit the production of arachidonic acid from phospholipids and thus block both PG and LT synthesis. They also induce apoptosis in eosinophils.
- Discuss intradermal skin tests with reference to procedure, safety and specificity.
A drop of allergen extract is placed on the forearm or back and a fine hypodermic needle or special lancet is used to just prick the epidermis through the drop. The test areas are observed at 15 or 20 minutes and the results recorded as diameter of the central raised wheal/ diameter of the flare (e.g., 5/15 mm). Testing with buffer is necessary to control for skin hyperreactivity. All patients should be observed for 20-30 minutes after skin testing.
A positive skin test does not necessarily mean that your symptoms are due to that allergen; your level of sensitivity may be subclinical even with a positive test, or your symptoms may come from something else that cross-reacts with the test extract.
- Discuss specific immunotherapy of allergic disease, considering duration of effect,
risk of anaphylaxis, and percent of patients obtaining significant relief.
Glucocorticoids. Excellent when kept local, for example in pulmonary inhalers or as ointments; they are risky with multiple side effects when used systemically
Leukotriene inhibitors: superb additions to the treatment of asthma.
LABAs (long-acting beta-2 agonists) rapidly reduce bronchoconstriction. They are most often given in a combination with an inhalable steroid.
IgE blocker. a monoclonal antibody against IgE. There is so little IgE in the blood that it can all be effectively mopped up by the mAb, which is called omalizumab (Xolair). Costly.
Immunotherapy. “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. About 75% of people with seasonal rhinitis say they have an easier season after a course of immunotherapy. Shots are now available for insect venoms, too. Treatment may go on for several years. The mechanism is not clear; many think that the route of administration favors IgG production, and that the IgG effectively traps and clears the allergen before it can reach IgE-loaded mast cells. Others believe that repeated antigen exposure desensitizes mast cells. Lately, an increase in Treg has been observed.
