Researchers develop a novel agent to treat extrinsic asthma. In a clinical trial, patients with moderate to severe asthma treated with this medication experience fewer exacerbations. They are found to have lower levels of serum IgE, even after exposure to triggering allergens. This medication helps improve asthma symptoms by binding and inhibiting the substance produced by sensitized Th2 cells in the airways that promotes immunoglobulin isotype switching in B lymphocytes. Which of the following is the most likely target of this medication?

Question

Researchers develop a novel agent to treat extrinsic asthma.  In a clinical trial, patients with moderate to severe asthma treated with this medication experience fewer exacerbations.  They are found to have lower levels of serum IgE, even after exposure to triggering allergens.  This medication helps improve asthma symptoms by binding and inhibiting the substance produced by sensitized Th2 cells in the airways that promotes immunoglobulin isotype switching in B lymphocytes.  Which of the following is the most likely target of this medication?

Quizplus · Accepted Answer

11ec160b_37dc_534c_9249_83475c1952b5_MD0001_00 There are 2 classes of CD4⁺ T-helper cells, Th1 cells and Th2 cells. Th1 cells contribute to cell-mediated adaptive immunity (targeting intracellular pathogens) and type IV (delayed-type) hypersensitivity reactions. On the other hand, Th2 cells play a prominent role in allergic response and type I hypersensitivity reactions. One hypothesis for the pathogenesis of asthma is an excess of Th2 cell activity relative to Th1 cell activity, resulting in excessive IgE production, an abnormal propensity for type I hypersensitivity reactions, and associated chronic eosinophilic bronchitis. In the asthma sensitization phase, inhaled antigens stimulate Th2 cells to secrete IL-4 and other lymphokines to stimulate B-cell antibody production as part of humoral adaptive immunity. Th2 cells also release IL-13, which, together with IL-4, promotes B-cell immunoglobulin class switching to IgE and leads to mast cell priming. Repeat exposure to inhaled antigens leads to mast cell degranulation of inflammatory substances (eg, histamine, leukotrienes) and further activation of eosinophils with release of tissue-damaging substances (eg, major basic protein). (Choice A) IL-1 is predominantly involved in the Th1 response and stimulates fever and acute inflammation. It also induces lymphokine secretion to recruit other leukocytes, including lymphocytes. (Choice B) IL-3 is secreted by both Th1 and Th2 cells and promotes the growth and differentiation of bone marrow stem cells. (Choice D) IL-5 is secreted by activated Th2 cells and stimulates the growth and differentiation of eosinophils. However, IL-5 promotes the class switching of B-cell immunoglobulin synthesis to IgA rather than to IgE and is a less important therapeutic target for asthma than IL-4. (Choice E) Interferon-gamma secreted by Th1 cells activates macrophages and, along with IL-2, stimulates CD8⁺ cytotoxic T cells. It also inhibits the differentiation of Th2 cells. (Choice F) Transforming growth factor-beta (TGF-β) is involved in tissue regeneration and repair. It can be produced by T lymphocytes, platelets, macrophages, endothelial cells, smooth muscle cells, fibroblasts, and keratinocytes. Educational objective: An excess of Th2 cell activity relative to Th1 cell activity may underlie the pathogenesis of asthma. In the asthma sensitization phase, inhaled antigens stimulate Th2 cells to secrete IL-4 and IL-13, which together promote B-lymphocyte class switching for IgE synthesis, leading to mast cell priming. Th2 cells also secrete IL-5, which activates eosinophils.

Researchers Develop a Novel Agent to Treat Extrinsic Asthma