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Cellular Immunology

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https://www.readbyqxmd.com/read/28735814/tyrosine-kinase-inhibitors-as-modulators-of-trastuzumab-mediated-antibody-dependent-cell-mediated-cytotoxicity-in-breast-cancer-cell-lines
#1
Denis M Collins, Kathy Gately, Clare Hughes, Connla Edwards, Anthony Davies, Stephen F Madden, Kenneth J O'Byrne, Norma O'Donovan, John Crown
BACKGROUND: Trastuzumab is an anti-HER2 monoclonal antibody (mAb) therapy capable of antibody-dependent cell-mediated cytotoxicity (ADCC) and used in the treatment of HER2+ breast cancer. Through interactions with FcƴR+ immune cell subsets, trastuzumab functions as a passive immunotherapy. The EGFR/HER2-targeting tyrosine kinase inhibitor (TKI) lapatinib and the next generation TKIs afatinib and neratinib, can alter HER2 levels, potentially modulating the ADCC response to trastuzumab...
July 15, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28739077/t-bet-expressing-b-cells-during-hiv-and-hcv-infections
#2
James J Knox, David E Kaplan, Michael R Betts
T-bet-expressing B cells, first identified as perpetuators of autoimmunity, were recently shown to be critical for murine antiviral responses. While their role in human viral infections remains unclear, B cells expressing T-bet or demonstrating a related phenotype have been described in individuals chronically infected with HIV or HCV, suggesting these cells represent a component of human antiviral responses. In this review, we discuss the induction of T-bet in B cells following both HIV and HCV infections, the factors driving T-bet(+) B cell expansions, T-bet's relationship to atypical memory B cells, and the consequences of T-bet induction...
July 11, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28735813/atypical-memory-b-cells-in-human-chronic-infectious-diseases-an-interim-report
#3
Silvia Portugal, Nyamekye Obeng-Adjei, Susan Moir, Peter D Crompton, Susan K Pierce
Immunological memory is a remarkable phenomenon in which survival of an initial infection by a pathogen leads to life-long protection from disease upon subsequent exposure to that same pathogen. For many infectious diseases, long-lived protective humoral immunity is induced after only a single infection in a process that depends on the generation of memory B cells (MBCs) and long-lived plasma cells. However, over the past decade it has become increasingly evident that many chronic human infectious diseases to which immunity is not readily established, including HIV-AIDS, malaria and TB, are associated with fundamental alterations in the composition and functionality of MBC compartments...
July 11, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28712455/the-properties-of-the-unique-age-associated-b-cell-subset-reveal-a-shift-in-strategy-of-immune-response-with-age
#4
Susan L Swain, Olivia Kugler-Umana, Yi Kuang, Wenliang Zhang
In aged mice, conventional naive B cells decrease and a new population of age-associated B cells (ABC)(3) develops. When aged unprimed mice are infected with influenza virus, there is a reduced generation of helper CD4 T cell subsets and germinal center B cells, leading to limited production of IgG Ab and less generation of conventional long-lived plasma cells, compared to young. However, we find an enhanced non-follicular (GL7(-)) ABC response that is helper T cell-independent, but requires high viral dose and pathogen recognition pathways...
July 11, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28711152/functional-analysis-of-acquired-cd28-mutations-identified-in-cutaneous-t-cell-lymphoma
#5
Grzegorz B Gmyrek, Jeanette Pingel, Jaehyuk Choi, Jonathan M Green
CD28 is the major costimulatory receptor on T cells regulating proliferation, survival and effector function. Acquired mutations in the extracellular domain of CD28 have been identified in patients with cutaneous T cell lymphoma, angioimmunoblastic T cell lymphoma and other T cell neoplasms, suggesting it may contribute to disease pathogenesis. We used a heterologous system in which mutant human CD28 was expressed on primary murine T cells deficient in CD28 to ascertain how specific mutations identified in a genetic screen of patients with cutaneous T cell lymphoma affected normal T cell function...
July 10, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28705375/regulation-of-expression-and-trafficking-of-perforin-2-by-lps-and-tnf-%C3%AE
#6
Peng Xiong, Motoaki Shiratsuchi, Takamitsu Matsushima, Jiyuan Liao, Emi Tanaka, Yasuhiro Nakashima, Ryoichi Takayanagi, Yoshihiro Ogawa
Perforin-2 is constitutively expressed in macrophages that are required for bacterial control. In this study, we found that perforin-2 is expressed in human macrophages with two isoforms: full-length perforin-2a and a splice variant, perforin-2b. Two isoforms show different subcellular distributions. Perforin-2a was predominantly localized to the membrane of endosome-like vesicles by a C-terminal transmembrane domain. In contrast, the short isoform perforin-2b lacking the transmembrane domain failed to localize to the membrane of vesicles...
July 8, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28651742/strap-positively-regulates-tlr3-triggered-signaling-pathway
#7
Hyunbin D Huh, Eunhye Lee, Jinwook Shin, Boyoun Park, Sungwook Lee
Toll-like receptor (TLR) signaling drives the innate immune response by activating nuclear factor-κB (NF-κB) and interferon regulatory factor (IRF). We have previously shown that STRAP interacts with TAK1 and IKKα along with NF-κB subunit p65, leading to the activation of pro-inflammatory cytokines. However, the roles of STRAP in TRIF/TBK1-mediated TLR3 activation and the subsequent type I interferon (IFN) production are not fully elucidated. Here, we demonstrate that STRAP acts as a scaffold protein in TLR3-triggered signaling...
June 19, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28622785/comprehensive-long-non-coding-rna-expression-profiling-reveals-their-potential-roles-in-systemic-lupus-erythematosus
#8
Lian-Ju Li, Wei Zhao, Sha-Sha Tao, Jun Li, Shu-Zhen Xu, Jie-Bing Wang, Rui-Xue Leng, Yin-Guang Fan, Hai-Feng Pan, Dong-Qing Ye
Long non-coding RNAs can regulate gene transcription, modulate protein function, and act as competing endogenous RNA. Yet, their roles in systemic lupus erythematosus remain to be elucidated. We determined the expression profiles of lncRNAs in T cells of SLE patients and healthy controls using microarrays. Up to 1935 lncRNAs and 1977 mRNAs were differentially expressed. QRT-PCR showed downregulated uc001ykl.1 and ENST00000448942 in SLE patients. Expression of uc001ykl.1 correlated with erythrocyte sedimentation rate (ESR) and C-reactive protein, whereas ENST00000448942 level correlated with ESR and anti-Sm antibodies...
June 10, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28602279/an-elisa-immunoassay-employing-a-conserved-leishmania-hypothetical-protein-for-the-serodiagnosis-of-visceral-and-tegumentary-leishmaniasis-in-dogs-and-humans
#9
Ana Maria R S Carvalho, Lourena E Costa, Beatriz C S Salles, Thaís T O Santos, Fernanda F Ramos, Mariana P Lima, Miguel A Chávez-Fumagalli, Bruna T Silvestre, Áquila S B Portela, Bruno M Roatt, Julia A G Silveira, Denise U Gonçalves, Danielle F Magalhães-Soares, Mariana C Duarte, Daniel Menezes-Souza, Eduardo A F Coelho
In the present study, a conserved Leishmania hypothetical protein, namely LiHypA, was evaluated for the serodiagnosis of visceral and tegumentary leishmaniasis in dogs and humans. This protein showed a high amino acid sequence homology between viscerotropic and cutaneotropic Leishmania species. An enzyme-linked immunosorbent assay (ELISA) was developed using the recombinant antigen (rLiHypA), in addition to the A2 protein and two parasite antigenic preparations, which were used as controls. Regarding human diagnosis, results showed that rLiHypA was more sensitive and specific than ELISA-L...
June 8, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28651743/the-combination-of-nk-and-cd8-t-cells-with-ccl20-il15-armed-oncolytic-adenoviruses-enhances-the-growth-suppression-of-tert-positive-tumor-cells
#10
Jun-Feng Ye, Wen-Xi Qi, Ming-Yuan Liu, Yang Li
Adoptive immunotherapy and targeted gene therapy have been extensively used to eliminate tumor cells. The combination treatment is capable of efficiently generating an effective antitumor immune response and disrupting tumor-induced tolerance. Moreover, effective antitumor immune responses are dependent on coordinate interaction among various effector cells. This study focused on whether the combination of cytotoxic effector cell-based adoptive immunotherapy and CCL20/IL15-armed oncolytic adenoviruses could induce enhanced antitumor activity...
June 7, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28595857/direct-control-of-b-cells-by-tregs-an-opportunity-for-long-term-modulation-of-the-humoral-response
#11
REVIEW
Elizabeth Weingartner, Amit Golding
Tregs are believed to be important for maintaining self-tolerance and immune homeostasis. It is well established that Tregs maintain self-tolerance and immune homeostasis by directly suppressing and modulating the effector function of T cells. However, there are a small number of studies that suggest Tregs also directly suppress and modulate B cells. Herein we review the literature that has investigated direct action of Tregs on B cell effector function. This area of study is intriguing because it suggests Tregs may influence long-lived humoral immunity...
June 1, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28601359/osteopontin-exacerbates-pseudomonas-aeruginosa-induced-bacteremia-in-mice
#12
Zhenghao Piao, Haiying Yuan
Osteopontin (OPN) is a multifunctional protein involved in various pathophysiological processes. However, the role of OPN in Pseudomonas aeruginosa-related sepsis is not yet clear. Here, we found that OPN expression was elevated in plasma and spleen samples from P. aeruginosa-infected mice. To determine the function of OPN in sepsis, we used wild-type (WT) and OPN-knockout (KO) mice with P. aeruginosa-induced bacteremia. We found that OPN-KO mice exhibited reduced mortality compared with WT mice and that OPN exacerbated spleen bleeding and functional impairment...
May 30, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28645365/complexity-of-immune-responses-to-aav-transgene-products-example-of-factor-ix
#13
REVIEW
Roland W Herzog
After two decades of research, in vivo gene transfer with adeno-associated viral (AAV) vectors has now resulted in successful treatments and even cures for several human diseases. However, the potential for immune responses against the therapeutic gene products remains one of the concerns as this approach is broadened to more patients, diverse diseases, and target organs. Immune responses following gene transfer of coagulation factor IX (FIX) for the treatment of the bleeding disorder hemophilia B has been extensively investigated in multiple animal models...
May 29, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28669409/notch-signaling-pathway-regulates-the-growth-and-the-expression-of-inflammatory-cytokines-in-mouse-basophils
#14
Shuo-Yao Qu, Jia-Ji Lin, Jian Zhang, Li-Qiang Song, Xue-Min Yang, Chang-Gui Wu
Basophils (BAs) are the least common granulocytes of all leukocytes, but they play an important role in orchestrating of chronic allergic inflammation. The Notch signaling pathway is a highly conserved pathway that influences cell lineage decisions and differentiation during various stages of development. However, the relationship between Notch signaling and BA remains to be elucidate. Here, we report that several Notch signaling molecules were found to be expressed in BAs. γ-secretase inhibitor (GSI) treatment increase BAs apoptosis, and suppress BAs proliferation...
May 27, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28641866/t-bet-expressing-b-cells-novel-target-for-autoimmune-therapies
#15
Anatoly V Rubtsov, Philippa Marrack, Kira Rubtsova
Autoimmune diseases affect more than 23.5million Americans. Traditional therapies for autoimmune diseases involve immunosuppressive drugs that globally dampen immune responses or target and kill large populations of normal immune cells. Both approaches lead to severe dysfunction of the immune system increasing the risk of infections and cancer. Therefore, a more targeted approach, modulating only the pathogenic autoimmune response, would be tremendously beneficial for autoimmune patients. However, only some novel targets involved in pathogenic autoimmune response have been discovered and it is likely that more remain, currently unknown...
May 23, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28606360/sex-differences-in-regulatory-cells-in-experimental-stroke
#16
Hilary A Seifert, Gil Benedek, Jian Liang, Ha Nguyen, Gail Kent, Arthur A Vandenbark, Julie A Saugstad, Halina Offner
Stroke is the leading cause of disability in the United States. Sex differences, including smaller infarcts in females and greater involvement of immune-mediated inflammation in males may affect the efficacy of immune-modulating interventions. To address these differences, we sought to identify distinct stroke-modifying mechanisms in female vs. male mice. The current study demonstrated smaller infarcts and increased levels of regulatory CD19(+)CD5(+)CD1d(hi) B10 cells as well as anti-inflammatory CD11b(+)CD206(+) microglia/macrophages in the ipsilateral vs...
August 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28576260/regulation-of-bone-mass-by-the-gut-microbiota-is-dependent-on-nod1-and-nod2-signaling
#17
Claes Ohlsson, Giulia Nigro, Ivo Gomperts Boneca, Fredrik Bäckhed, Philippe Sansonetti, Klara Sjögren
Germ-free (GF) mice have increased bone mass that is normalized by colonization with gut microbiota (GM) from conventionally raised (CONV-R) mice. To determine if innate immune signaling pathways mediated the effect of the GM, we studied the skeleton of GF and CONV-R mice with targeted inactivation of MYD88, NOD1 or NOD2. In contrast to WT and Myd88(-/-) mice, cortical bone thickness in mice lacking Nod1 or Nod2 was not increased under GF conditions. The expression of Tnfα and the osteoclastogenic factor Rankl in bone was reduced in GF compared to CONV-R WT mice but not in Nod1(-/-) or Nod2(-/-) mice indicating that the effect of the GM to increase Tnfα and Rankl in bone and to reduce bone mass is dependent on both NOD1 and NOD2 signaling...
July 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28511921/myeloperoxidase-a-new-player-in-autoimmunity
#18
REVIEW
Anna Strzepa, Kirkwood A Pritchard, Bonnie N Dittel
Myeloperoxidase (MPO) is the most toxic enzyme found in the azurophilic granules of neutrophils. MPO utilizes H2O2 to generate hypochlorous acid (HClO) and other reactive moieties, which kill pathogens during infections. In contrast, in the setting of sterile inflammation, MPO and MPO-derived oxidants are thought to be pathogenic, promoting inflammation and causing tissue damage. In contrast, evidence also exists that MPO can limit the extent of immune responses. Elevated MPO levels and activity are observed in a number of autoimmune diseases including in the central nervous system (CNS) of multiple sclerosis (MS) and the joints of rheumatoid arthritis (RA) patients...
July 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28499490/frequent-inoculations-with-radiation-attenuated-sporozoite-is-essential-for-inducing-sterile-protection-that-correlates-with-a-threshold-level-of-plasmodia-liver-stage-specific-cd8-t-cells
#19
Hardik Patel, Naveen Yadav, Rajesh Parmar, Satish Patel, Agam P Singh, Neeta Shrivastava, Sarat K Dalai
Whole sporozoite vaccine (WSV) is shown to induce sterile protection that targets Plasmodium liver-stage infection. There are many underlying issues associated with induction of effective sterile protracted protection. In this study, we have addressed how the alterations in successive vaccine regimen could possibly affect the induction of sterile protection. We have demonstrated that the pattern of vaccination with RAS (radiation attenuated sporozoites) induces varying degrees of protection among B6 mice. Animals receiving four successive doses generated 100% sterile protection...
July 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28477840/leukotriene-receptor-expression-in-mast-cells-is-affected-by-their-agonists
#20
Justyna Agier, Sylwia Różalska, Karolina Wódz, Ewa Brzezińska-Błaszczyk
The effects of LTs are mediated by GPCRs: cysLTs interact with CYSLTR1, CYSLTR2, or GPR17, and LTB4 acts via BLT1R or BLT2R. Data relating to the presence of these receptors in mature tissue mast cells are not entirely known. By confocal microscopy with image analyses and flow cytometry, we established that native rat mast cells isolated from peritoneal cavity constitutively express all studied receptors. Moreover, we clearly documented that LTs by themselves can influence their own receptor expression. Low concentrations of LTs induce translocation of LT receptors from cell interior to plasma membrane, which can lead to increased mast cell responsiveness to LT stimulation...
July 2017: Cellular Immunology
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