scholarly journals NK Cells Influence Both Innate and Adaptive Immune Responses after Mucosal Immunization with Antigen and Mucosal Adjuvant

2010 ◽  
Vol 184 (8) ◽  
pp. 4327-4337 ◽  
Author(s):  
Lindsay J. Hall ◽  
Simon Clare ◽  
Gordon Dougan
Keyword(s):  
Immune Responses ◽  
Nk Cells ◽  
Mucosal Immunization ◽  
Adaptive Immune Responses ◽  
Mucosal Adjuvant ◽  
Adaptive Immune

Engaging the NKG2D Receptor with a Novel Bispecific Protein (ULBP2-antiCD138) Activates NK Cells and Has Potent Antitumor Activity Against Human Multiple Myeloma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5157-5157
Author(s):  
Elke Pogge von Strandmann ◽  
Michael Hallek ◽  
Andreas Engert
Keyword(s):  
Multiple Myeloma ◽  
Immune Responses ◽  
Nk Cells ◽  
Clinical Investigation ◽  
Human Peripheral Blood ◽  
Malignant Cells ◽  
Adaptive Immune Responses ◽  
Nude Mouse Model ◽  
Ifn Gamma ◽  
Adaptive Immune

Abstract NK cells, a component of the innate immune system, attack virus-infected and malignant cells without prior antigen stimulation, mediate cellular cytotoxicity and produce cytokines such as interferon gamma (IFN-gamma) upon stimulation. There is growing evidence that NK cells also participate directly in adaptive immune responses, mainly by cross-talk with dendritic cells. One key factor responsible for the activation of innate and adaptive immune responses is NKG2D, a stimulatory receptor expressed on natural killer cells that binds to cellular ligands on malignant cells. Therefore we designed a recombinant NK receptor ligand (ULBP2) fused to an antibody (BB4) detecting the tumor antigen CD138 which is overexpressed on a variety of malignancies including multiple myeloma (MM). The major findings were that (1) ULBP2-BB4 bound both NK cells and tumor cells, (2) triggered NK-mediated cell lysis of CD138+ malignant cell lines and primary MM cells in the allogenic and autologous setting, (3) activated IFN-gamma secretion of NK cells exposed to immobilized protein, and (4) the co-therapy with ULBP-BB4 and human peripheral blood lymphocytes abrogated the tumor growth in a nude mouse model with subcutaneously growing MM cells. This is the first report on the design, expression, purification and functional pre-clinical investigation of a recombinant NKG2D ligand. The results suggest not only a potential clinical use of this novel construct in patients with MM, but might also offer an innovative therapy approach which is based on NKG2D engagement transferable to other malignancies.

NK cells in autoimmune diseases: Linking innate and adaptive immune responses

2018 ◽  
Vol 17 (2) ◽  
pp. 142-154 ◽  
Author(s):  
Elena Gianchecchi ◽  
Domenico Vittorio Delfino ◽  
Alessandra Fierabracci
Keyword(s):  
Immune Responses ◽  
Autoimmune Diseases ◽  
Nk Cells ◽  
Adaptive Immune Responses ◽  
Adaptive Immune

scholarly journals IFN-gamma, Produced by NK Cells that Infiltrate Liver Allografts Early After Transplantation, Links the Innate and Adaptive Immune Responses

2005 ◽  
Vol 5 (9) ◽  
pp. 2094-2103 ◽  
Author(s):  
Hideaki Obara ◽  
Kazuhito Nagasaki ◽  
Christine L. Hsieh ◽  
Yasuhiro Ogura ◽  
Carlos O. Esquivel ◽  
...  
Keyword(s):  
Immune Responses ◽  
Nk Cells ◽  
Adaptive Immune Responses ◽  
Ifn Gamma ◽  
Adaptive Immune

scholarly journals Activating receptors promote NK cell expansion for maintenance, IL-10 production, and CD8 T cell regulation during viral infection

2009 ◽  
Vol 206 (10) ◽  
pp. 2235-2251 ◽  
Author(s):  
Seung-Hwan Lee ◽  
Kwang-Sin Kim ◽  
Nassima Fodil-Cornu ◽  
Silvia M. Vidal ◽  
Christine A. Biron
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Viral Infection ◽  
Nk Cells ◽  
Cell Expansion ◽  
Nk Cell ◽  
Cd8 T Cell ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Activating Receptors

Natural killer (NK) cells have the potential to deliver both direct antimicrobial effects and regulate adaptive immune responses, but NK cell yields have been reported to vary greatly during different viral infections. Activating receptors, including the Ly49H molecule recognizing mouse cytomegalovirus (MCMV), can stimulate NK cell expansion. To define Ly49H's role in supporting NK cell proliferation and maintenance under conditions of uncontrolled viral infection, experiments were performed in Ly49h−/−, perforin 1 (Prf1)−/−, and wild-type (wt) B6 mice. NK cell numbers were similar in uninfected mice, but relative to responses in MCMV-infected wt mice, NK cell yields declined in the absence of Ly49h and increased in the absence of Prf1, with high rates of proliferation and Ly49H expression on nearly all cells. The expansion was abolished in mice deficient for both Ly49h and Prf1 (Ly49h−/−Prf1−/−), and negative consequences for survival were revealed. The Ly49H-dependent protection mechanism delivered in the absence of Prf1 was a result of interleukin 10 production, by the sustained NK cells, to regulate the magnitude of CD8 T cell responses. Thus, the studies demonstrate a previously unappreciated critical role for activating receptors in keeping NK cells present during viral infection to regulate adaptive immune responses.

2B4 co-stimulation: NK cells and their control of adaptive immune responses

2005 ◽  
Vol 42 (4) ◽  
pp. 419-423 ◽  
Author(s):  
Erika Assarsson ◽  
Taku Kambayashi ◽  
Catrine M. Persson ◽  
Hans-Gustaf Ljunggren ◽  
Benedict J. Chambers
Keyword(s):  
Immune Responses ◽  
Nk Cells ◽  
Adaptive Immune Responses ◽  
Adaptive Immune

scholarly journals A detailed analysis of innate and adaptive immune responsiveness upon infection with Salmonella enterica serotype Enteritidis in young broiler chickens

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Nathalie Meijerink ◽  
Robin H. G. A. van den Biggelaar ◽  
Daphne A. van Haarlem ◽  
J. Arjan Stegeman ◽  
Victor P. M. G. Rutten ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Nk Cells ◽  
Salmonella Enterica ◽  
Broiler Chickens ◽  
Immune Modulation ◽  
Adaptive Immune Responses ◽  
Activation Markers ◽  
Adaptive Immune ◽  
Adaptive Immune Cells

AbstractSalmonella enterica serotype Enteritidis (SE) is a zoonotic pathogen which causes foodborne diseases in humans as well as severe disease symptoms in young chickens. More insight in innate and adaptive immune responses of chickens to SE infection is needed to understand elimination of SE. Seven-day-old broiler chickens were experimentally challenged with SE and numbers and responsiveness of innate and adaptive immune cells as well as antibody titers were assessed. SE was observed in the ileum and spleen of SE-infected chickens at 7 days post-infection (dpi). At 1 dpi numbers of intraepithelial cytotoxic CD8+ T cells were significantly increased alongside numerically increased intraepithelial IL-2Rα+ and 20E5+ natural killer (NK) cells at 1 and 3 dpi. At both time points, activation of intraepithelial and splenic NK cells was significantly enhanced. At 7 dpi in the spleen, presence of macrophages and expression of activation markers on dendritic cells were significantly increased. At 21 dpi, SE-induced proliferation of splenic CD4+ and CD8+ T cells was observed and SE-specific antibodies were detected in sera of all SE-infected chickens. In conclusion, SE results in enhanced numbers and activation of innate cells and we hypothesized that in concert with subsequent specific T cell and antibody responses, reduction of SE is achieved. A better understanding of innate and adaptive immune responses important in the elimination of SE will aid in developing immune-modulation strategies, which may increase resistance to SE in young broiler chickens.

scholarly journals Chemokine Receptor Expression on Normal Blood CD56+NK-Cells Elucidates Cell Partners That Comigrate during the Innate and Adaptive Immune Responses and Identifies a Transitional NK-Cell Population

2015 ◽  
Vol 2015 ◽  
pp. 1-18 ◽  
Author(s):  
Margarida Lima ◽  
Magdalena Leander ◽  
Marlene Santos ◽  
Ana Helena Santos ◽  
Catarina Lau ◽  
...  
Keyword(s):  
Immune Responses ◽  
Nk Cells ◽  
Chemokine Receptors ◽  
Nk Cell ◽  
Cxcr4 Expression ◽  
Receptor Expression ◽  
Normal Blood ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Cd56 Expression

Studies of chemokine receptors (CKR) in natural killer- (NK-) cells have already been published, but only a few gave detailed information on its differential expression on blood NK-cell subsets. We report on the expression of the inflammatory and homeostatic CKR on normal bloodCD56+lowCD16+andCD56+high  CD16-/+lowNK-cells. ConventionalCD56+lowandCD56+highNK-cells present in the normal PB do express CKR for inflammatory cytokines, although with different patternsCD56+lowNK-cells are mainly CXCR1/CXCR2+and CXCR3/CCR5−/+, whereas mostlyCD56+highNK-cells are CXCR1/CXCR2−and CXCR3/CCR5+. Both NK-cell subsets have variable CXCR4 expression and are CCR4−and CCR6−. The CKR repertoire of theCD56+lowNK-cells approaches to that of neutrophils, whereas the CKR repertoire of theCD56+highNK-cells mimics that of Th1+T cells, suggesting that these cells are prepared to migrate into inflamed tissues at different phases of the immune response. In addition, we describe a subpopulation of NK-cells with intermediate levels of CD56 expression, which we namedCD56+intNK-cells. These NK-cells are CXCR3/CCR5+, they have intermediate levels of expression of CD16, CD62L, CD94, and CD122, and they are CD57−and CD158a−. In view of their phenotypic features, we hypothesize that they correspond to a transitional stage, between the well-knownCD56+highandCD56+lowNK-cells populations.

scholarly journals Human natural killer cells mediate adaptive immunity to viral antigens

2019 ◽  
Vol 4 (35) ◽  
pp. eaat8116 ◽  
Author(s):  
Rana Nikzad ◽  
Laura S. Angelo ◽  
Kevin Aviles-Padilla ◽  
Duy T. Le ◽  
Vipul K. Singh ◽  
...  
Keyword(s):  
Immune Responses ◽  
Nk Cells ◽  
Natural Killer ◽  
Adaptive Immunity ◽  
Human Memory ◽  
Humanized Mice ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Human Volunteers

Adaptive immune responses are defined as antigen sensitization–dependent and antigen-specific responses leading to establishment of long-lived immunological memory. Although natural killer (NK) cells have traditionally been considered cells of the innate immune system, mounting evidence in mice and nonhuman primates warrants reconsideration of the existing paradigm that B and T cells are the sole mediators of adaptive immunity. However, it is currently unknown whether human NK cells can exhibit adaptive immune responses. We therefore tested whether human NK cells mediate adaptive immunity to virally encoded antigens using humanized mice and human volunteers. We found that human NK cells displayed vaccination-dependent, antigen-specific recall responses in vitro, when isolated from livers of humanized mice previously vaccinated with HIV-encoded envelope protein. Furthermore, we discovered that large numbers of cytotoxic NK cells with a tissue-resident phenotype were recruited to sites of varicella-zoster virus (VZV) skin test antigen challenge in VZV-experienced human volunteers. These NK-mediated recall responses in humans occurred decades after initial VZV exposure, demonstrating that NK memory in humans is long-lived. Our data demonstrate that human NK cells exhibit adaptive immune responses upon vaccination or infection. The existence of human memory NK cells may allow for the development of vaccination-based approaches capable of establishing potent NK-mediated memory functions contributing to host protection.

scholarly journals The Impact of Ly49-NK Cell-Dependent Recognition of MCMV Infection on Innate and Adaptive Immune Responses

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Michal Pyzik ◽  
Eve-Marie Gendron-Pontbriand ◽  
Silvia M. Vidal
Keyword(s):  
Immune Responses ◽  
Nk Cells ◽  
Cell Biology ◽  
Cell Activation ◽  
Nk Cell ◽  
Adaptive Immune Responses ◽  
Mcmv Infection ◽  
Adaptive Immune ◽  
Innate Lymphocytes ◽  
The Impact

Clinical and experimental data indicate that a subset of innate lymphocytes, natural killer (NK) cells, plays a crucial role in the response against herpesviruses, especially cytomegaloviruses (CMV). Indeed, in mice, NK cells, due to the expression of germline encoded Ly49 receptors, possess multiple mechanisms to recognize CMV infection. Classically, this results in NK cell activation and the destruction of the infected cells. More recently, however, this unique host-pathogen interaction has permitted the discovery of novel aspects of NK cell biology, implicating them in the regulation of adaptive immune responses as well as in the development of immunological memory. Here, we will concisely review the newly acquired evidence pertaining to NK cell Ly49-dependent recognition of MCMV-infected cell and the ensuing NK cell regulatory responses.

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