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The maternal immune system during pregnancy
Published in Hung N. Winn, Frank A. Chervenak, Roberto Romero, Clinical Maternal-Fetal Medicine Online, 2021
uNK cells are considered to be poorly cytotoxic, yet potent cytokine producers, in contrast to classic NK cells that display higher levels of cytotoxicity but are poor cytokine producers. A small fraction of uNK cells (10–15%) contain surface CD16 detectable by flow cytometry (65). CD16 is an antibody receptor, and only CD16+ cells exhibit cytotoxicity, and thus most uNK cells lack cytotoxic capability (66). All uNK cells remain at the implantation site in high numbers during early gestation, decrease after 20 weeks of gestation, and are practically absent in term decidua (67–69).
Opsonization of Actinobacillus actinomycetemcomitans by LPS-Directed IgG Antibodies in Sera of Juvenile Periodontitis Patients
Published in Helmut Brade, Steven M. Opal, Stefanie N. Vogel, David C. Morrison, Endotoxin in Health and Disease, 2020
Phagocyte recognition of IgG-opsonized targets is mediated by membrane receptors for the Fc region of the IgG molecule (FcγR). Three main classes of FcγR are presently recognized (48,49), differing in their cellular distribution as well as their affinity and specificity for human IgG subclass antibodies. FCγRI (CD64) is primarily expressed on mononuclear phagocytes, but can be induced on neutrophils through exposure to interferon gamma or granulocyte colony-stimulating factor. This receptor exhibits high affinity (Ka, 108–109 M−1) for monomeric human IgGl and IgG3 and moderate affinity for human IgG4. Affinity of FCγRI for IgG2 is at least two orders of magnitude lower than for IgGl and IgG3. FCγRII (CD32) and FCγRIII (CD16) are low-affinity receptors (Ka, 1–3 × 107 M−1), which bind to IgG in complexed (or polymeric), but not monomeric, form. FCγRIII, the most abundant class of IgG Fc receptors expressed on mononuclear and polymorphonuclear phagocytes, only binds human IgGl and IgG3.
Phenotypic and Functional Characteristics of Human A-NK Cells
Published in Ronald H. Goldfarb, Theresa L. Whiteside, Tumor Immunology and Cancer Therapy, 2020
Nikola L. Vujanovic, Theresa L. Whiteside
When freshly separated A-NK cells were studied by two-color flow cytometry for phenotypic characteristics, it appeared that they differed from NA-NK cells in expression of different surface molecules. In Table 1, the phenotypic profiles of A-NK cells and NA-NK cells are compared. It is clear from the data in Table 1 that A-NK cells are homogenous in expression of CD56 antigen: they are all CD56dim cells. In contrast, NA-NK cells and resting (not activated) NK cells (R-NK) contain both CD56bnght and CD56dlm subsets of NK cells. The CD16 antigen is either expressed dimly or not at all expressed on A-NK cells, in contrast to NA-NK cells, which are mainly CD16bnght or CD16-. By two-color flow cytometry, it was possible to demonstrate that CD56brightCD16- subset of NK cells was absent in the A-NK cell subset. Instead, A-NK cells contained significantly more CD56dimCD16- cells than either NA-NK or R-NK cells. One of the most important findings was that A-NK cells uniformly expressed the β2 integrins CD18, CD11a and, particularly, CD11b at high levels of surface density. In contrast, NA-NK cells had a dim and heterogeneous expression of the 62 integrins.
Recalcitrant Herpes Zoster Ophthalmicus in a Patient Discovered to Have Underlying Functional Natural Killer Cell Deficiency
Published in Ocular Immunology and Inflammation, 2022
Brent J. Deibert, Kurtis C. Johnson, Luke W. Desilet, Andrew C. Rorie
NK cells account for approximately 5–15% of lymphocytes in peripheral blood.6 The cytotoxic effects of NK cells occur by one of two identified mechanisms: antibody-dependent cellular cytotoxicity (ADCC) and an antibody-independent pathway known as “NK cell cytotoxicity.”6,7 NK cells possess an activating surface receptor, CD16 (FcR), that binds the Fc region of preformed antibodies. CD16 allows recognition and ADCC destruction of opsonized target cells by the NK cells.7 The ADCC response is therefore dependent on prior adaptive immune response by B cells for cell destruction. It is known that NK cells can also act without a prior antibody response denoting their role in the innate immune system targeting tumor cells, transplanted cells, and virally infected cells.6,7
New nonchemotherapy treatment options for cutaneous T-cell lymphomas
Published in Expert Review of Anticancer Therapy, 2021
AFM13 is a tetravalent bispecific anti-CD30/CD16A antibody that recruits NK cells to tumors expressing CD30[52]. CD16A is an activating receptor for the IgG Fc domain predominantly expressed on NK cells and macrophages. The antibody recruits and activates NK cells to induce cytotoxic effects against CD30+ cells. A phase Ib/IIa trial evaluated antibody efficacy in patients with relapsed or refractory CD30+ lymphoma with cutaneous presentation, including transformed and untransformed MF and c-ALCL[53]. Three doses were used, the most intensive being 7 mg/kg continuous IV over 5 days weekly. Overall, 4 out of 8 assessed patients responded to AFM13. Responders showed increased expression of the activation marker CD69 on NK cells and increased infiltration of CD56+ NK cells into tumors compared to non-responders. Infusion-related reactions occurred in 4 out of 9 patients. Because AFM13 is a chimeric antibody, it may face neutralizing activity from patient-generated antidrug antibodies (ADA)[52]. In a phase I dose escalation study in relapsed or refractory CD30+ Hodgkin Lymphoma, 15 out of 28 patients had detectable ADAs of which 8 had neutralizing potential.
Margetuximab for the treatment of HER2-positive metastatic breast cancer
Published in Expert Opinion on Biological Therapy, 2021
Paolo Tarantino, Stefania Morganti, Jacopo Uliano, Federica Giugliano, Edoardo Crimini, Giuseppe Curigliano
More in detail, CD16A is encoded by two alleles differing in the codon for amino acid 158: a higher-affinity valine (V) variant and a lower-affinity phenylalanine (F) variant [13]. The increase in affinity to both the allotypes of CD16A ultimately leads to a greater antibody-dependent cellular cytotoxicity (ADCC) activation, namely the killing of targeted cells by activated effector cells (NK lymphocytes, macrophages, neutrophils), which has been previously demonstrated to be a relevant player in the context of targeting HER2 [14,15]. Preclinical studies demonstrate that the optimized Fc domain confers enhanced ADCC against all HER2+ tumor cell tested compared with trastuzumab, including in trastuzumab resistant and HER2 low expressing cells, defined as those with an HER” immunohistochemical score of 1+ or 2+ with a negative in-situ hybridization test [12,16]. Of note, the greatest improvement in ADCC activation occurred in presence of the CD16A-158 F, the low-binding allele [12].