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Host adaptive immune receptors recognizing influenza hemagglutinin (HA) primarily comprise B-cell receptors (BCRs) and T-cell receptors (TCRs) that specifically bind to the HA surface glycoprotein of the influenza virus (Krammer, 2020). HA is essential for viral entry, as it binds to sialic acid on host cells and facilitates membrane fusion; thus, it is the primary target for neutralizing immune responses (Whittle et al., 2011). BCRs recognize specific epitopes on the HA globular head or the more conserved stem region, and upon activation, differentiate into plasma cells that secrete antibodies to block viral infection. TCRs recognize HA-derived peptides presented by MHC molecules, providing the necessary signals for B-cell maturation and direct clearance of infected cells (Grant et al., 2013). These receptors are the functional targets of all current influenza vaccines, which seek to induce long-lasting and broad-spectrum immunity (Schmidt et al., 2015). Challenges in targeting these receptors include original antigenic sin, where prior exposure to influenza antigens can bias the immune response toward older strains, potentially reducing the efficacy of vaccines against new, drifted variants (Zhang et al., 2019).
Antigen-mediated activation of specific B and T cell receptors to elicit protective immunity and immunological memory.
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