Fc receptor-mediated immunity against Bordetella pertussis

The relevance of specific Abs for the induction of cellular effector functions against Bordetella pertussis was studied. IgG-opsonized B. pertussis was efficiently phagocytosed by human polymorphonuclear leukocytes (PMN). This process was mediated by the PMN IgG receptors, FcγRIIa (CD32) and FcγRIIIb (CD16), working synergistically. Furthermore, these FcγR triggered efficient PMN respiratory burst activity and mediated transfer of B. pertussis to lysosomal compartments, ultimately resulting in reduced bacterial viability. Bacteria opsonized with IgA triggered similar PMN activation via FcαR (CD89). Simultaneous engagement of FcαRI and FcγR by B. pertussis resulted in increased phagocytosis rates, compared with responses induced by either isotype alone. These data provide new insights into host immune mechanisms against B. pertussis and document a crucial role for Ig-FcR interactions in immunity to this human pathogen.Centro de Investigación y Desarrollo en Fermentaciones Industriale

Fc receptor-mediated immunity against Bordetella pertussis

The relevance of specific Abs for the induction of cellular effector functions against Bordetella pertussis was studied. IgG-opsonized B. pertussis was efficiently phagocytosed by human polymorphonuclear leukocytes (PMN). This process was mediated by the PMN IgG receptors, FcγRIIa (CD32) and FcγRIIIb (CD16), working synergistically. Furthermore, these FcγR triggered efficient PMN respiratory burst activity and mediated transfer of B. pertussis to lysosomal compartments, ultimately resulting in reduced bacterial viability. Bacteria opsonized with IgA triggered similar PMN activation via FcαR (CD89). Simultaneous engagement of FcαRI and FcγR by B. pertussis resulted in increased phagocytosis rates, compared with responses induced by either isotype alone. These data provide new insights into host immune mechanisms against B. pertussis and document a crucial role for Ig-FcR interactions in immunity to this human pathogen.Centro de Investigación y Desarrollo en Fermentaciones Industriale

РАЗРАБОТКА НОВОГО РЕАГЕНТНОГО РЕЖИМА ФЛОТАЦИИ УГЛЕЙ ПАО "ДТЭК ДОБРОПОЛЬСКАЯ ЦОФ"

Совершенст- вование процесса флотации углей, поиск эффективных реагентов и оптималь- ных технологических режимов – один из главных факторов, от которых зависит технологическая и экономическая результативность флотационного обогаще- ния

Fc receptor binding of anti-CD3 monoclonal antibodies is not essential for immunosuppression, but triggers cytokine-related side effects

A major drawback to the use of OKT3, a mouse anti-CD3 monoclonal antibody (mAb), as an immunosuppressive agent is the associated cytokine release syndrome. We used a mouse model to elucidate the properties of anti-CD3 mAb responsible for these cytokine-related side effects. We have previously demonstrated that the hamster anti-CD3 mAb 145-2C11 induced strong cytokine release and morbidity in vivo, whereas two rat anti-CD3 mAb 17A2 and KT3 did not. In the current study, we show that the mitogenic capacity of soluble anti-CD3 mAb in vitro correlates with their induction of side effects in vivo. Mitogenesis in vitro and tumor necrosis factor-α (TNF-α) release in vivo induced by anti-CD3 mAb could be inhibited by the anti-FcγR mAb 2.4G2, indicating that FcγR binding of anti-CD3 mAb is responsible for their mitogenic properties and for their induction of side effects. Importantly, the two non-mitogenic rat anti-CD3 mAb were equally capable of suppressing skin allograft rejection as the mitogenic hamster anti-CD3 mAb, suggesting FcγR binding of anti-CD3 mAb is not essential for their immunosuppressive properties. This suggestion is reinforced by our demonstration that administration of 2.4G2 in vivo did not interfere with immunosuppression of skin allograft rejection by 145-2C11. These findings suggest that clinical use of non-mitogenic anti-CD3 mAb will result in effective immunosuppression without cytokine-related side effects

Crucial role of antibodies to pertactin in Bordetella pertussis immunity

Pertussis, a serious infectious disease of the respiratory tract caused by Bordetella pertussis, is reemerging in vaccinated populations. Efforts to curtail this disease are hampered by limited insight into the basis of protective immunity. Opsonophagocytosis was recently found to play a central role in cellular bactericidal activity against B. pertussis. In the present study, we studied the specificity of opsonic antibodies. Anti-pertactin antibodies, but not anti-pertussis toxin, anti-fimbriae, or anti-filamentous hemagglutinin antibodies, were found to be crucial for B. pertussis phagocytosis. These data are consistent with field studies showing that levels of antibodies to pertactin correlate with protection.Centro de Investigación y Desarrollo en Fermentaciones Industriale

Crucial role of antibodies to pertactin in Bordetella pertussis immunity

Pertussis, a serious infectious disease of the respiratory tract caused by Bordetella pertussis, is reemerging in vaccinated populations. Efforts to curtail this disease are hampered by limited insight into the basis of protective immunity. Opsonophagocytosis was recently found to play a central role in cellular bactericidal activity against B. pertussis. In the present study, we studied the specificity of opsonic antibodies. Anti-pertactin antibodies, but not anti-pertussis toxin, anti-fimbriae, or anti-filamentous hemagglutinin antibodies, were found to be crucial for B. pertussis phagocytosis. These data are consistent with field studies showing that levels of antibodies to pertactin correlate with protection.Centro de Investigación y Desarrollo en Fermentaciones Industriale

Testing relationships: ethical arguments for screening with HbA1C

Since the 1990s, glycated haemoglobin (HbA1C) has been the gold standard for monitoring glycaemic control in people diagnosed as having either type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM). Discussions are underway about diagnosing diabetes mellitus on the basis of HbA1C titres and using HbA1C tests to screen for T2DM. These discussions have focused on the relative benefits for individual patients, with some attention directed towards reduced costs to healthcare systems and benefits to society. We argue that there are strong ethical reasons for adopting HbA1C-based diagnosis and T2DM screening that have not yet been articulated. The rationale includes the differential impact of HbA1C-based diabetic testing on disadvantaged groups, and what we are beginning to learn about HbA1C vis-à-vis population health. Although it is arguable that screening must primarily benefit the individual, using HbA1C to diagnose and screen for T2DM may promote a more just distribution of health resources and lead to advances in investigating, monitoring and tackling the social determinants of health

Fc receptor-mediated immunity against Bordetella pertussis

The relevance of specific Abs for the induction of cellular effector functions against Bordetella pertussis was studied. IgG-opsonized B. pertussis was efficiently phagocytosed by human polymorphonuclear leukocytes (PMN). This process was mediated by the PMN IgG receptors, FcγRIIa (CD32) and FcγRIIIb (CD16), working synergistically. Furthermore, these FcγR triggered efficient PMN respiratory burst activity and mediated transfer of B. pertussis to lysosomal compartments, ultimately resulting in reduced bacterial viability. Bacteria opsonized with IgA triggered similar PMN activation via FcαR (CD89). Simultaneous engagement of FcαRI and FcγR by B. pertussis resulted in increased phagocytosis rates, compared with responses induced by either isotype alone. These data provide new insights into host immune mechanisms against B. pertussis and document a crucial role for Ig-FcR interactions in immunity to this human pathogen.Centro de Investigación y Desarrollo en Fermentaciones Industriale

PAS-positive lymphocyte vacuoles can be used as diagnostic screening test for Pompe disease

Screening of blood films for the presence of periodic acid-Schiff (PAS)-positive lymphocyte vacuoles is sometimes used to support the diagnosis of Pompe disease, but the actual diagnostic value is still unknown. We collected peripheral blood films from 65 untreated Pompe patients and 51 controls. Lymphocyte vacuolization was quantified using three methods: percentage vacuolated lymphocytes, percentage PAS-positive lymphocytes, and a PAS score depending on staining intensity. Diagnostic accuracy of the tests was assessed using receiver operating characteristic (ROC) curves. All three methods fully discerned classic infantile patients from controls. The mean values of patients with milder forms of Pompe disease were significantly higher than those of controls, but full separation was not obtained. The area under the ROC curve was 0.98 for the percentage vacuolated lymphocytes (optimal cutoff value 3; sensitivity 91%, specificity 96%) and 0.99 for the percentage PAS-positive lymphocytes and PAS score (optimal cutoff value 9; sensitivity 100%, specificity 98%). Our data indicate that PAS-stained blood films can be used as a reliable screening tool to support a diagnosis of Pompe disease. The percentage of PAS-positive lymphocytes is convenient for use in clinical practice but should always be interpreted in combination with other clinical and laboratory parameters