scholarly journals IMMUNE MECHANISM OF PREECLAMPSIA

2015 ◽  
Vol 7 (2) ◽  
Author(s):  
John J. E. Wantania
Keyword(s):  
Immune Response ◽  
Nk Cells ◽  
Angiogenic Factors ◽  
Immune Mechanism ◽  
Single Factor ◽  
Immunological Factors ◽  
Maternal Immune Response

Abstrak: Sampai saat ini etiologi preeklamsi masih belum jelas. Faktor-faktor imun diduga terlibat dalam mekanisme terjadinya preeklamsi. Faktor-faktor tersebut berperan penting dalam terjadinya preeklamsi tidak sebagai penyebab tunggal tetapi sebagai bagian dalam jalur yang sangat rumit. Peran faktor imun paternal, respons imun dini maternal (terutama yang berhubungan dengan sel NK), korelasi antara faktor imun dan angiogenik terhadap peran autoantibodi (AT-1) merupakan hal-hal penting untuk ditelusuri lanjut. Pemahaman yang detil terhadap patomekanisme sangat bermanfaat dalam penatalaksanaan preeklamsi.Kata kunci: preeklamsi, faktor imun, mekanismeAbstract: The etiology of preeclampsia remains unclear so far. It seems immunological factors are involved in preeclampsia mechanism. These factors play some important roles in the mechanism, not as a single factor but as a part in a complex pathway. The role of paternal immunological factors, early maternal immune response (especially related to NK cells), the correlation between immunological and angiogenic factors to the role of autoantibodies (AT-1) are the important points that are needed to be explored further. Thorough understanding about the patho-mechanism would be very useful in the management of preeclampsia itself.Keywords: preeclampsia , immunological factors, mechanism

scholarly journals NLRP7 Promotes Choriocarcinoma Growth and Progression through the Establishment of an Immunosuppressive Microenvironment

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2999
Author(s):  
Deborah Reynaud ◽  
Roland Abi Nahed ◽  
Nicolas Lemaitre ◽  
Pierre-Adrien Bolze ◽  
Wael Traboulsi ◽  
...  
Keyword(s):  
Immune Response ◽  
Tumor Cells ◽  
Major Gene ◽  
Critical Role ◽  
Orthotopic Model ◽  
Independent Manner ◽  
Maternal Immune Response ◽  
The Impact

The inflammatory gene NLRP7 is the major gene responsible for recurrent complete hydatidiform moles (CHM), an abnormal pregnancy that can develop into gestational choriocarcinoma (CC). However, the role of NLRP7 in the development and immune tolerance of CC has not been investigated. Three approaches were employed to define the role of NLRP7 in CC development: (i) a clinical study that analyzed human placenta and sera collected from women with normal pregnancies, CHM or CC; (ii) an in vitro study that investigated the impact of NLRP7 knockdown on tumor growth and organization; and (iii) an in vivo study that used two CC mouse models, including an orthotopic model. NLRP7 and circulating inflammatory cytokines were upregulated in tumor cells and in CHM and CC. In tumor cells, NLRP7 functions in an inflammasome-independent manner and promoted their proliferation and 3D organization. Gravid mice placentas injected with CC cells invalidated for NLRP7, exhibited higher maternal immune response, developed smaller tumors, and displayed less metastases. Our data characterized the critical role of NLRP7 in CC and provided evidence of its contribution to the development of an immunosuppressive maternal microenvironment that not only downregulates the maternal immune response but also fosters the growth and progression of CC.

scholarly journals MITF induces escape from innate immunity in melanoma

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Luis Sánchez-del-Campo ◽  
Román Martí-Díaz ◽  
María F. Montenegro ◽  
Rebeca González-Guerrero ◽  
Trinidad Hernández-Caselles ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Nk Cells ◽  
Nk Cell ◽  
Luciferase Reporter ◽  
Damage Repair ◽  
Reporter Assays ◽  
Underlying Mechanisms ◽  
Nk Cytotoxicity

Abstract Background The application of immune-based therapies has revolutionized cancer treatment. Yet how the immune system responds to phenotypically heterogeneous populations within tumors is poorly understood. In melanoma, one of the major determinants of phenotypic identity is the lineage survival oncogene MITF that integrates diverse microenvironmental cues to coordinate melanoma survival, senescence bypass, differentiation, proliferation, invasion, metabolism and DNA damage repair. Whether MITF also controls the immune response is unknown. Methods By using several mouse melanoma models, we examine the potential role of MITF to modulate the anti-melanoma immune response. ChIP-seq data analysis, ChIP-qPCR, CRISPR-Cas9 genome editing, and luciferase reporter assays were utilized to identify ADAM10 as a direct MITF target gene. Western blotting, confocal microscopy, flow cytometry, and natural killer (NK) cytotoxicity assays were used to determine the underlying mechanisms by which MITF-driven phenotypic plasticity modulates melanoma NK cell-mediated killing. Results Here we show that MITF regulates expression of ADAM10, a key sheddase that cleaves the MICA/B family of ligands for NK cells. By controlling melanoma recognition by NK-cells MITF thereby controls the melanoma response to the innate immune system. Consequently, while melanoma MITFLow cells can be effectively suppressed by NK-mediated killing, MITF-expressing cells escape NK cell surveillance. Conclusion Our results reveal how modulation of MITF activity can impact the anti-melanoma immune response with implications for the application of anti-melanoma immunotherapies.

scholarly journals CMV-Specific Immune Response—New Patients, New Insight: Central Role of Specific IgG during Infancy and Long-Lasting Immune Deficiency after Allogenic Stem Cell Transplantation

2019 ◽  
Vol 20 (2) ◽  
pp. 271 ◽  
Author(s):  
Przemyslaw Zdziarski
Keyword(s):  
Immune Response ◽  
Nk Cells ◽  
Cellular Immune Response ◽  
Specific Immune Response ◽  
Primary Immune Response ◽  
Virus Reactivation ◽  
Allogenic Stem Cell Transplantation ◽  
Specific Igg ◽  
Cellular Immune

Although the existing paradigm states that cytomegalovirus (CMV) reactivation is under the control of the cellular immune response, the role of humoral and innate counterparts are underestimated. The study analyzed the host–virus interaction i.e., CMV-immune response evolution during infection in three different clinical situations: (1) immunodeficient CMV-positive human leukocyte antigen (HLA)-matched bone marrow recipients after immunoablative conditioning as well as immunocompetent, (2) adult, and (3) infant with primary immune response. In the first situation, a fast and significant decrease of specific immunity was observed but reconstitution of marrow-derived B and natural killer (NK) cells was observed prior to thymic origin of T cells. The lowest CMV-IgG (93.2 RU/mL) was found just before CMV viremia. It is noteworthy that the sole and exclusive factor of CMV-specific immune response is a residual recipient antibody class IgG. The CMV-quantiferon increase was detected later, but in the first phase, phytohemagglutinin (PHA)-induced IFN-γ release was significantly lower than that of CMV-induced (“indeterminate” results). It corresponds with the increase of NK cells at the top of lymphocyte reconstitution and undetected CMV-specific CD8 cells using a pentamer technique. In immunocompetent adult (CMV-negative donor), the cellular and humoral immune response increased in a parallel manner, but symptoms of CMV mononucleosis persisted until the increase of specific IgG. During infancy, the decrease of the maternal CMV-IgG level to 89.08 RU/mL followed by clinical sequel, i.e., CMV replication, were described. My observations shed light on a unique host-CMV interaction and CMV-IgG role: they indicate that its significant decrease predicts CMV replication. Before primary cellular immune response development, the high level of residual CMV-IgG (about >100 R/mL) from mother or recipient prevents virus reactivation. The innate immune response and NK-dependent IFN-secretion should be further investigated.

scholarly journals CD69 Deficiency Enhances the Host Response to Vaccinia Virus Infection through Altered NK Cell Homeostasis

2016 ◽  
Vol 90 (14) ◽  
pp. 6464-6474 ◽  
Author(s):  
Laura Notario ◽  
Elisenda Alari-Pahissa ◽  
Antonio de Molina ◽  
Pilar Lauzurica
Keyword(s):  
Immune Response ◽  
Infection Control ◽  
Vaccinia Virus ◽  
Nk Cells ◽  
Natural Killer ◽  
Host Response ◽  
Nk Cell ◽  
Innate Immune ◽  
Cell Numbers

ABSTRACTDuring the host response to viral infection, the transmembrane CD69 protein is highly upregulated in all immune cells. We have studied the role of CD69 in the murine immune response to vaccinia virus (VACV) infection, and we report that the absence of CD69 enhances protection against VACV at both short and long times postinfection in immunocompetent and immunodeficient mice. Natural killer (NK) cells were implicated in the increased infection control, since the differences were greatly diminished when NK cells were depleted. This role of NK cells was not based on an altered NK cell reactivity, since CD69 did not affect the NK cell activation threshold in response to major histocompatibility complex class I NK cell targets or protein kinase C activation. Instead, NK cell numbers were increased in the spleen and peritoneum of CD69-deficient infected mice. That was not just secondary to better infection control in CD69-deficient mice, since NK cell numbers in the spleens and the blood of uninfected CD69−/−mice were already augmented. CD69-deficient NK cells from infected mice did not have an altered proliferation capacity. However, a lower spontaneous cell death rate was observed for CD69−/−lymphocytes. Thus, our results suggest that CD69 limits the innate immune response to VACV infection at least in part through cell homeostatic survival.IMPORTANCEWe show that increased natural killer (NK) cell numbers augment the host response and survival after infection with vaccinia virus. This phenotype is found in the absence of CD69 in immunocompetent and immunodeficient hosts. As part of the innate immune system, NK lymphocytes are activated and participate in the defense against infection. Several studies have focused on the contribution of NK cells to protection against infection with vaccinia virus. In this study, it was demonstrated that the augmented early NK cell response in the absence of CD69 is responsible for the increased protection seen during infection with vaccinia virus even at late times of infection. This work indicates that the CD69 molecule may be a target of therapy to augment the response to poxvirus infection.

scholarly journals The Immunomodulatory Imbalance in Patients with Ketamine Cystitis

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Gang-Yi Fan ◽  
Juin-Hong Cherng ◽  
Shu-Jen Chang ◽  
Raju Poongodi ◽  
Adrienne Chang ◽  
...  
Keyword(s):  
Immune Response ◽  
Healthy Volunteers ◽  
Signaling Pathway ◽  
Chronic Inflammation ◽  
Immunoglobulin E ◽  
Serum Immunoglobulin ◽  
Immune Mechanism

The pathogenesis of ketamine cystitis (KC) has been recently linked with immune response to patients but the same has not yet been established. Hence, this study aims to propose a possible immune mechanism of irreversible bladder damage caused by KC. A total of 53 KC patients and 21 healthy volunteers as controls have been retrospectively assessed. The levels of serum immunoglobulin E (IgE), IL-6, and IFN-γ of KC patients were significantly higher than those of controls, whereas the TGF-β levels of KC patients substantially reduced but the IL-2 and IL-4 levels of KC patients were comparable to those of controls. Moreover, the KC patients had significantly higher counts of TH1, TH2, and TH17 cells than those of controls. The immune response of KC users may begin with the IL-6 production and differentiation of TH17 and may be followed by alternating between high expressions of TH1 and TH2. The IL-6 may further suppress the TREG cells which can aggravate chronic inflammation in KC patients and the imbalance in TH17 and TREG cells may involve the pathogenesis of KC. Further investigation is needed to define the role of IL-6 in TH1/TH2/TH17-regulated signaling pathway in ketamine-induced cystitis.

scholarly journals Role of natural killer cells in reproductive failure

2017 ◽  
Vol 66 (3) ◽  
pp. 143-156
Author(s):  
Alana O. Agnaeva ◽  
Olesya N. Bespalova ◽  
Dmitriy I. Sokolov ◽  
Sergey A. Selkov ◽  
Igor Yu. Kogan
Keyword(s):  
Nk Cells ◽  
Peripheral Blood ◽  
Recurrent Miscarriage ◽  
Communication Process ◽  
Modern World ◽  
Unknown Etiology ◽  
Sharp Change ◽  
Reproductive Losses ◽  
Immunological Factors

Reproductive losses are quite frequent in the modern world. They include: infertility, infertility of unknown etiology, multiple losses when IVF, recurrent implantation failure, miscarriage, recurrent miscarriage, both in the natural cycle and after ART management. It is important to note that the classification of some of these categories are not established yet. The etiology of reproductive losses is extremely diverse. Successful development of pregnancy at early terms is determined by genetic and immunological factors. Among the reproductive failures of unclear etiology, immunological causes are 50-80%. Over the past 20 years there are already known many different immunological factors that play role in the processes of fertilization. In this case, the evidence base on the role of each of them in the pathogenesis of reproductive failures is only being formed. Currently, the immunological relationship between mother and fetus is considered as a two-way communication process: the presentation of fetal antigens on the one hand, and on the other – the recognition and response to these antigens of the maternal immune system. Implantation of the embryo is accompanied by an increase in the production of proinflammatory cytokines followed by a sharp change in the cellular composition in the decidualizing endometrium, and the main population is NK cells. That is why this type of cells have a significant role in the normal development of pregnancy. The properties of NK cells in the uterus and peripheral blood are significantly different. To predict the onset and prolongation of pregnancy, peripheral blood NK (activity and quantity) is used. Evaluation of endometrial NK is often performed for the diagnosis of chronic endometritis. Currently, the definition of NK cells in peripheral blood in many clinics is proposed as a useful diagnostic test to address the issue of further appointment of immunoglobulins and evaluating the effectiveness of this therapy in patients with reproductive losses.

The potential role of the maternal immune response in autism

2010 ◽  
Vol 24 ◽  
pp. S66
Author(s):  
J. Van de Water ◽  
D. Braunschweig ◽  
P. Ashwood
Keyword(s):  
Immune Response ◽  
Potential Role ◽  
Maternal Immune Response

scholarly journals The Role of the Cytoskeleton in Regulating the Natural Killer Cell Immune Response in Health and Disease: From Signaling Dynamics to Function

2021 ◽  
Vol 9 ◽  
Author(s):  
Aviad Ben-Shmuel ◽  
Batel Sabag ◽  
Guy Biber ◽  
Mira Barda-Saad
Keyword(s):  
Immune Response ◽  
Nk Cells ◽  
Signaling Pathways ◽  
Natural Killer ◽  
Immunological Synapse ◽  
Nk Cell ◽  
Cell Immune Response ◽  
Effector Functions ◽  
Health And Disease

Natural killer (NK) cells are innate lymphoid cells, which play key roles in elimination of virally infected and malignant cells. The balance between activating and inhibitory signals derived from NK surface receptors govern the NK cell immune response. The cytoskeleton facilitates most NK cell effector functions, such as motility, infiltration, conjugation with target cells, immunological synapse assembly, and cytotoxicity. Though many studies have characterized signaling pathways that promote actin reorganization in immune cells, it is not completely clear how particular cytoskeletal architectures at the immunological synapse promote effector functions, and how cytoskeletal dynamics impact downstream signaling pathways and activation. Moreover, pioneering studies employing advanced imaging techniques have only begun to uncover the architectural complexity dictating the NK cell activation threshold; it is becoming clear that a distinct organization of the cytoskeleton and signaling receptors at the NK immunological synapse plays a decisive role in activation and tolerance. Here, we review the roles of the actin cytoskeleton in NK cells. We focus on how actin dynamics impact cytolytic granule secretion, NK cell motility, and NK cell infiltration through tissues into inflammatory sites. We will also describe the additional cytoskeletal components, non-muscle Myosin II and microtubules that play pivotal roles in NK cell activity. Furthermore, special emphasis will be placed on the role of the cytoskeleton in assembly of immunological synapses, and how mutations or downregulation of cytoskeletal accessory proteins impact NK cell function in health and disease.

scholarly journals The role of γδТ- and NK-сells in immune response

2010 ◽  
Vol 9 (5) ◽  
pp. 138-142 ◽  
Author(s):  
Ye. G. Churina ◽  
O. I. Urazova ◽  
V. V. Novitsky ◽  
I. O. Naslednikova ◽  
O. V. Voronkova
Keyword(s):  
Immune Response ◽  
Nk Cells ◽  
Inhibitory Effect ◽  
Antibacterial Action ◽  
Effector Functions

The article presents up-to-date literature data on the role of γδТ-cells and different NK-cells subpopulations in the immune response. Their origin, immunophenotypes, range of secreted cytokines as well as effector functions and factors having stimulating and inhibitory effect on γδТ- and NK-cells are described. Mechanisms of antibacterial action of this type of cells are analyzed. 

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