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Questions and Answers
What type of antibodies are primarily involved in Type II hypersensitivity reactions?
Which of the following is an example of a cytotoxic Type II hypersensitivity reaction with inflammation?
In non-cytotoxic Type II hypersensitivity reactions, the binding of antibodies influences which aspect of cell function?
Which mechanism is primarily responsible for cell destruction in cytotoxic Type II hypersensitivity reactions?
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Which condition is a classic example of a non-cytotoxic Type II hypersensitivity reaction?
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Which cytokines are primarily involved in amplifying the Th2 response?
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What is a significant drawback of the skin prick test for diagnosing type I hypersensitivity reactions?
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What role do eosinophils play in type I hypersensitivity reactions?
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What is the mechanism of action for humanized monoclonal anti-IgE antibodies in immunotherapy?
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Which of the following cytokines is associated with increasing cell adhesion molecule expression on endothelial cells?
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What is a key feature of the immediate early response in type I hypersensitivity?
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What is the main function of leukotrienes produced via the lipoxygenase pathway?
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Which test measures IgE levels in a patient's serum to diagnose allergies?
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Which cytokines are predominantly involved in the type 2 immune responses during the sensitization phase of type I hypersensitivity?
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What is the primary role of IgE antibodies in type I hypersensitivity reactions?
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Which of the following is NOT a typical environmental allergen that can trigger type I hypersensitivity reactions?
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Which phase of hypersensitivity reactions is characterized by the absence of symptoms upon initial exposure to the allergen?
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What triggers mast cells to release their chemical mediators during the allergic phase of type I hypersensitivity?
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What is the role of phospholipase A2 (PLA2) in the synthesis of newly synthesized lipid mediators during type I hypersensitivity?
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In diagnosing type II hypersensitivity diseases, which of the following tests is commonly used?
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Which immune cells are primarily involved in type I hypersensitivity reactions mediated by IgE?
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Study Notes
Hypersensitivity Reactions
- Type II hypersensitivity reactions are antibody-mediated and involve IgM or IgG antibodies directed against antigens on cells or extracellular matrix.
- These antibodies are tissue-specific and do not typically circulate systemically.
Type II Hypersensitivity Subtypes
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Cytotoxic Reactions: antibodies activate complement, mediate cell destruction through antibody-dependent cell-mediated cytotoxicity (ADCC), or opsonize cells.
- Examples: blood transfusion reactions, drug-induced hemolytic anemia, and hemolytic anemia of newborns.
- Drug-induced hemolytic anemia occurs when individuals produce antibodies against drugs or their metabolites attached to red blood cell proteins, leading to hemolysis.
- Rheumatic heart disease, characterized by antibodies attacking heart valve proteins, is an example of a type II hypersensitivity reaction with inflammation.
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Non-Cytotoxic Reactions: antibody binding to antigens affects cell function, either stimulating or inhibiting it.
- Examples: Graves’ disease and myasthenia gravis.
Type I Hypersensitivity Reactions (IgE-Mediated)
- Characterized by an exaggerated immune response against harmless environmental antigens (allergens), leading to tissue injury.
- Common allergens include plant pollens, drugs, dust, dust mites, animal dander, and food.
Pathogenesis
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Sensitization Phase:
- Antigen-presenting cells (APCs) engulf, process, and present allergens in association with MHC Class II molecules to naïve T helper cells.
- Naïve T helper cells differentiate into Th2 and Tfh cells in individuals with allergies.
- Th2 and Tfh cells secrete IL-4, IL-5, and IL-13, collectively known as type 2 immune responses.
- IL-4 induces B cell growth and switching from IgM to IgE isotype.
- IgE antibodies bind to high-affinity IgE receptors on mast cells and basophils.
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Allergic Phase:
- Upon re-exposure to the allergen, it cross-links sufficient IgE molecules, triggering mast cell degranulation and the release of chemical mediators.
Chemical Mediators
- Preformed Mediators: released immediately upon mast cell degranulation are involved in the immediate early response.
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Newly Synthesized Lipid Mediators: synthesis is controlled by activation of phospholipase A2 (PLA2), which hydrolyzes membrane phospholipids to generate arachidonic acid.
- Arachidonic acid is metabolized via the cyclooxygenase pathway (producing prostaglandins) or the lipoxygenase pathway (producing leukotrienes).
- Prostaglandins and leukotrienes are potent vasodilators, bronchoconstrictors, chemotactic factors for eosinophils, basophils, and Th2 cells, and stimulators of mucus secretion.
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Cytokines: IL-1, IL-3, IL-4, IL-5, IL-13, and TNF are released and contribute to late-phase reactions (2-8 hours).
- IL-4 and IL-13 amplify Th2 response, while IL-3 and IL-5 promote eosinophil production and activation.
Type I Hypersensitivity Responses
- Characterized by immediate early and late-phase responses.
- Early Response: occurs within minutes of allergen exposure due to mast cell degranulation and release of preformed and lipid mediators.
- Late-Phase Response: (2-8 hours) involves the recruitment of eosinophils, neutrophils, and Th2 cells due to cytokine release from mast cells, primarily TNF-α and IL-1.
Diagnosis of Type I Hypersensitivity Reactions
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Skin Prick Test: small amounts of potential allergens are introduced into the skin. A positive reaction (wheal and flare within 30 minutes) indicates an allergic response.
- Disadvantages: can sensitize individuals to new allergens, rarely induce systemic anaphylaxis, manifest late-phase reactions, and produce false-negative results in individuals taking antihistamines.
- IgE Test: measures IgE levels in serum.
Immunotherapy for Allergy
- Humanized monoclonal anti-IgE antibody: binds to the Fc portion of IgE and blocks its binding to IgE receptors on mast cells.
- Desensitization: repeated subcutaneous injections of small quantities of the antigen induce the production of IgG antibodies. This reduces the sensitivity to allergens by reducing the amount IgE antibodies in the system.
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Description
Test your knowledge on Type II hypersensitivity reactions, their mechanisms, and subtypes. This quiz covers cytotoxic and non-cytotoxic reactions, including examples like blood transfusion reactions and drug-induced hemolytic anemia. Assess your understanding of the antibody-mediated immune responses and their clinical implications.
