Chronic hepatitis B virus infection is a major health problem, with over 245 million chronic carriers worldwide. This persistent infection is thought to be associated with inefficient innate and adaptive immune responses. Natural killer cells (NK cells) and plasmacytoid dendritic cells (pDCs) are the major innate immune cells which respond to viral infection at the early phase and are considered major components of the antiviral immune response. In this review, we summarize recent findings regarding the role of NK cells, pDCs, and their cross-talk in HBV infection and its chronicity. Although the data regarding the biological function of pDCs and NK cells in HBV infection is still controversial, many studies show that in chronic HBV infection, the cytotoxicity of NK cells is retained, while their capacity to secrete cytokines is strongly impaired. In addition, interferon-α production by pDCs is impaired during chronic HBV infection, and the virus interferes with pDC-NK cell interaction.
Imagery instructions specifying mucosal immunity should alter mucosal immunoglobulin A (m-IgA) levels in high absorbers, whose intent concentration evokes intense physiological responses. After screening for health status, 121 high or low absorbers were randomly assigned to either Relaxation Alone (R), Relaxation with Mucosal Immune Imagery (RI), or Vigilance Task control (VT). Before and after one 60-min intervention, subjects reported theory-relevant psychological variables and provided 5 ml whole saliva, which was immediately frozen and assayed later en masse with enzyme-linked immunoabsorbence (ELISA). MANOVA analysis of psychological variables replicated past research. ANOVA on residualized m-IgA found Time x Absorption interaction and Condition main effects. High more than low absorbers responded to relaxation with mucosal immune imagery by producing higher m-IgA. High absorbers appear able to locate where their immune systems will respond. Individual differences like absorption level need to be emphasized in diagnosis and treatment responsiveness.
Humanized monoclonal antibodies (mAbs) against HER2 including trastuzumab and pertuzumab are widely used to treat HER2 overexpressing metastatic breast cancers. These two mAbs recognize distinct epitopes on HER2 and their combination induces a more potent blockade of HER2 signaling than trastuzumab alone. Recently, we have reported characterization of a new chimeric mAb (c-1T0) which binds to an epitope different from that recognized by trastuzumab and significantly inhibits proliferation of HER2 overexpressing tumor cells. Here, we describe humanization of this mAb by grafting all six complementarity determining regions (CDRs) onto human variable germline genes. Humanized VH and VL sequences were synthesized and ligated to human γ1 and κ constant region genes using splice overlap extension (SOE) PCR. Subsequently, the humanized antibody designated hersintuzumab was expressed and characterized by ELISA, Western blot and flow cytometry. The purified humanized mAb binds to recombinant HER2 and HER2-overexpressing tumor cells with an affinity comparable with the chimeric and parental mouse mAbs. It recognizes an epitope distinct from those recognized by trastuzumab and pertuzumab. Binding of hersintuzumab to HER2 overexpressing tumor cells induces G1 cell cycle arrest, inhibition of ERK and AKT signaling pathways and growth inhibition. Moreover, hersintuzumab could induce antibody-dependent cell cytotoxicity (ADCC) on BT-474 cells. This new humanized mAb is a potentially valuable tool for single or combination breast cancer therapy.
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