What is the immunologic evolution of mold allergy?

Updated: Dec 02, 2020
  • Author: Shih-Wen Huang, MD; Chief Editor: Harumi Jyonouchi, MD  more...
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Allergen-specific IgE produced by B cells mediate allergic diseases. The allergen sensitization begins with the processing of mold Ags by Ag-presenting cells (APC), such as dendritic cells. APCs present processed mold allergens to naive T-helper (Th) cells, which differentiate into the effector stage type 2 Th (Th2) cells and produce Th2 cytokines (interleukin [IL]-4, IL-5, and IL-13). IL-4 is essential for isotype switching to IgE and with additional signaling provided by the Th2 cells, B cells begin to produce IgE specific for allergens.

The Fc portion of IgE antibody binds to high-affinity Fcε receptors (FcεR) expressed on the cell surface of mast cells in tissue, which, in turn, stabilizes Fcε. IgE bound to FcεR is stable for several weeks. When allergens bind to adjacent 2 IgE molecules bound to FcεR (cross-linking), an activation signal is elicited, leading to the release of preformed and newly formed mediators from mast cells (mast-cell activation).

These mediators include histamine, leukotrienes, and prostaglandins, which cause acute tissue inflammation. Mast-cell activation also lead to release of various chemotactic factors, such as leukotriene B4, platelet-activating factor, and eosinophil chemotactic factor, resulting in an influx of eosinophils, neutrophils, and mononuclear cells into the site of mast-cell activation. Mast cells also produce IL-4, IL-5, and IL-13, further augmenting Th2 responses and IgE production.

Granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-3, and IL-5 derived from Th2 cells, mast cells, and other lineage cells induce the differentiation of eosinophil precursors in the bone marrow. IL-5 is thought to be crucial for eosinophil trafficking to the peripheral circulation, leading to eosinophilia. Various chemotactic factors, including chemokines, then recruit eosinophils to the site of allergen exposure. Thus, IgE-mediated immune reactions result in eosinophil-dominant inflammation. The initial inflammatory process initiated by mold allergens may be further compounded by the waves of inflammatory cell infiltration. Clinical features of mold allergy differ in the upper or lower respiratory tract that can also vary in each individual, influenced by age, genetic predisposition, exposure to other environmental allergens-irritants, etc.

Th2 responses are predominant to immune responses to mold allergens, but a type 1 T-helper (Th1) response characterized by cell-mediated immunity may also contribute to mold-induced inflammatory condition. The known clinical disorders related to immune reactions to molds are listed below.

Mold-induced respiratory symptoms may be notably delayed at the onset, and they may be associated with bacterial superinfection. This may reflect the fact that the concomitant microbial agents (and endotoxin) present in wild sources of mold growth, such as dusts from decomposing plant material, can compound the clinical manifestations.

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