• Title/Summary/Keyword: MHC-class I

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Human Cytomegalovirus Inhibition of Interferon Signal Transduction

  • Daniel M. Miller
    • Korean Journal of Microbiology
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    • v.38 no.4
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    • pp.203-203
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    • 2002
  • Cytomegalovirus (CMV), a beta-herpesvirus with worldwide distribution, exhibits host persistence, a distinguishing characteristic of all herpesviruses. This persistence is dependent upon restricted gene expression in infected cells as well as the ability of productively infected cells to escape from normal cell-mediated anti-viral immunosurveillance. Type I (IFN-α/β) and type II (IFN-γ) interferons are major components of the innate defense system against viral infection. They are potent inducers of MHC class I and II antigens and of antigen processing proteins. Additionally, IFNS mediate direct antiviral effects through induction effector molecules that block viral infection and replications such as 2′, 5-oligoadenylate synthetase (2, 5-OAS). IFNS function through activation of well-defined signal transduction pathways that involve phosphorylation of constituent proteins and ultimate formation of active transcription factors. Recent studies have shown that a number of diverse viruses, including CMV, EBV, HPV mumps and Ebola, are capable of inhibiting IFN-mediated signal transduction through a variety of mechanisms. As an example, CMV infection inhibits the ability of infected cells Is transcribe HLA class I and II antigens as well as the antiviral effector molecules 2, 5-OAS and MxA I. EMSA studies have shown that IFN-α and IFN-γ are unable to induce complete signal transduction in the presence of CMV infection, phenomena that are associated with specific decreases in JAKl and p48. Viral inhibition of IFN signal transduction represents a new mechanistic paradigm for increased viral survival, a paradigm predicting widespread consequences in the case of signal transduction factors common to multiple cytokine pathways.

Human Cytomegalovirus Inhibition of Interferon Signal Transduction

  • Miller, Daniel M.;Cebulla, Colleen M.;Sedmak, Daniel D.
    • Journal of Microbiology
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    • v.38 no.4
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    • pp.203-208
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    • 2000
  • Cytomegalovirus (CMV), a beta-herpesvirus with worldwide distribution, exhibits host persistence, a distinguishing characteristic of all herpesviruses. This persistence is dependent upon restricted gene expression in infected cells as well as the ability of productively infected cells to escape from normal cell-mediated anti-viral immunosurveillance. Type I (IFN-$\alpha$/$\beta$) and type II (IFN-γ) interferons are major components of the innate defense system against viral infection. They are potent inducers of MHC class I and II antigens and of antigen processing proteins. Additionally, IFNS mediate direct antiviral effects through induction effector molecules that block viral infection and replications such as 2', 5-oligoadenylate synthetase (2, 5-OAS). IFNS function through activation of well-defined signal transduction pathways that involve phosphorylation of constituent proteins and ultimate formation of active transcription factors. Recent studies have shown that a number of diverse viruses, including CMV, EBV, HPV mumps and Ebola, are capable of inhibiting IFN-mediated signal transduction through a variety of mechanisms. As an example, CMV infection inhibits the ability of infected cells Is transcribe HLA class I and II antigens as well as the antiviral effector molecules 2, 5-OAS and MxA I. EMSA studies have shown that IFN-$\alpha$ and IFN-γ are unable to induce complete signal transduction in the presence of CMV infection, phenomena that are associated with specific decreases in JAKl and p48. Viral inhibition of IFN signal transduction represents a new mechanistic paradigm for increased viral survival, a paradigm predicting widespread consequences in the case of signal transduction factors common to multiple cytokine pathways.

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Effect of bee pollen extract on activation of dendritic cells and induction of Th1 immune response (꿀벌 꽃가루 열수 추출물의 수지상 세포 활성화 및 Th1 반응에 미치는 효과)

  • Cho, Eun-Ji;Kim, Yi-Eun;Byun, Eui-Hong
    • Korean Journal of Food Science and Technology
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    • v.50 no.4
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    • pp.444-450
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    • 2018
  • Dendritic cells (DCs) are potent antigen-presenting cells that play a pivotal role in modulating both innate and adaptive immunity. This study examined the immunomodulatory activities of hot-water extracts of bee pollen (BPW) in bone-marrow derived DCs (BMDC) and mice splenocytes. BMDCs isolated from mice were treated with 250 and $500{\mu}g/mL$ BPW for 24 h. BPW, up to $500{\mu}g/mL$, did not display any cellular toxicity against BMDCs. In fact, it functionally induced BMDC activation via augmentation of CD80, CD86, and major histocompatibility complex (MHC) class I/II expression and pro-inflammatory cytokine (tumor necrosis factor; $TNF-{\alpha}$, interleukin; IL-6, and $IL-1{\beta}$) production. Interestingly, BPW treatment significantly increased the production of interferon $(IFN)-{\gamma}$ in splenocytes, suggesting its possible contribution to Th1 polarization in immune response. Taken together, these findings suggest that BPW may regulate innate and adaptive immunity via DC activation and Th1 polarization in immune responses.

Advance Understanding and New Treatment of Alopecia Areata (원형탈모증(alopecia areata)의 최신 이해와 치료)

  • Kang, Kyung-Hwa
    • Journal of Life Science
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    • v.26 no.11
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    • pp.1345-1354
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    • 2016
  • Alopecia areata (AA) is a common and tissue-specific autoimmune disease of hair follicle resulting in the loss of hair on the scalp and elsewhere on the body. Hair follicles is a unique organ because it has its own immune system and hormonal milieu and has a different immune state at each hair cycle stage. The collapses of anagen-dependent hair follicle immune privilege arise autoimmune attack, inducing ectopic MHC class I expression in the hair follicle epithelium and autoantigen presentation to autoreactive CD8+T cells, which results in AA. Clinical and experimental studies have pointed that psychological stress may also influence the hair follicle immune/hormone systems and contribute to the induction of AA. The key pathogenesis of AA is associated with immune privilege guardians (including ACTH, ${\alpha}-MSH$, and $TGF-{\beta}$), natural killer group 2D-positive (NKG2D+) cells (including NK and CD8+T cells), and stress hormones (including CRH and substance P). Effective treatments for AA are still demanded. One of the future targets of treatment will be the modification of hair follicle immune privilege including stress. Recent studies have reported that JAK inhibitors and immunomodulators used in other autoimmune disease, such as psoriasis, atopic dermatitis, and rheumatoid arthritis, Tregs, platelet-rich plasma therapy, statins, and prostaglandin anaolgues are effective for AA. Here the article reviews the recent understanding in the pathogenesis associated with perifollicular endocrine/immunology and new treatments of AA.

Purification of Recombinant CTP-Conjugated Human prostatic acid phosphatase for activation of Dendritic Cell (수지상세포 활성화를 위한 세포투과 펩타이드가 결합된 재조합 전립성 산성 인산분해효소의 정제)

  • Yi, Ki-Wan;Ryu, Kang
    • KSBB Journal
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    • v.24 no.1
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    • pp.80-88
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    • 2009
  • Human prostatic acid phosphatase (PAP), with comprehensive homology to glandular kallikrein, are representative serum biomarkers of prostate cancer. Dendritic cell (DC), which is the potent antigen-presenting cells(APC) in the immune system, can induce strong T cell responses against viruses, microbial pathogens, and tumors. Therefore, the immunization using DC loaded with tumor-associated antigens is a powerful method for inducing anti-tumor immunity. The CTP (Cytoplasmic Transduction Peptide) technology developed by Creagene which can transport attached bio-polymers like nucleic acids or proteins into the cell with high permeation efficiency. As the active forms of PAP can mediate apoptotic processing, we used multimer forms of PAP as an inactive form for antigen pulsing of DCs. In this study, multimeric forms of CTP-rhPAP was obtained according to the advanced purification process and subsequently confirmed by gel filtration chromatography, western blot and Dynamic Light Scattering. Therefore, CTP-conjugated PA multimers transduced into the cytoplasm were efficiently presented on the cell surface without any harm effect on cells via MHC class I molecules and result in induction of a large number of effector cell.

Immunomodulatory activities of crude polysaccharide fraction separated from Perilla frutescens Britton var. acuta Kudo (자소엽(Perilla frutescens Britton var. acuta Kudo) 조다당류 추출물의 면역활성 효과)

  • Byun, Eui-Hong
    • Korean Journal of Food Science and Technology
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    • v.49 no.5
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    • pp.559-566
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    • 2017
  • This aim of this study was to examine the immunomodulatory activities of crude polysaccharides from Perilla frutescens Britton var. acuta Kudo (PCP) in mouse bone marrow-derived dendritic cells (BMDC) and splenocytes. The immunomodulatory activity was determined by cell viability, nitric oxide (NO) production, cell surface marker expression (CD 80/86 and MHC class I/II), and cytokine production in BMDC, and cell viability, and cytokine production in splenocytes. Cell proliferation and cytokine production (tumor necrosis factor; TNF-${\alpha}$, interleukin (IL)-6, IL-$1{\beta}$, and IL-12) tested in BMDC were significantly increased by PCP treatment. Additionally, the cell surface markers (CD 80/86, MHC class I/II) were highly increased by PCP treatment. For cytokine production in splenocytes, PCP treatment significantly increased the production of Th 1 cytokines [IL-2 and interferon (IFN)-${\gamma}$], but not Th 2 cytokines (IL-4). Therefore, PCP can induce immune cell activation and is a potential candidate for the development of nutraceuticals to boost the immune system.

Polymorphisms in Exon 2 of MHC Class II DRB3 Gene of 10 Domestic Goats in Southwest China

  • Zhao, Yongju;Xu, Huizhong;Shi, Lixiang;Zhang, Jiahua
    • Asian-Australasian Journal of Animal Sciences
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    • v.24 no.6
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    • pp.752-756
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    • 2011
  • Polymorphism of the second exon of the caprine leukocyte antigen-DRB3 gene (CLA-$DRB3^*02$) was investigated in this study. The 285 bp PCR product of 258 individuals from 10 domestic goat breeds in Southwest China was digested with restriction endonucleases PstI and HaeIII and then genotyped. Three alleles and 4 restriction digestion profiles were distinguished by digestion of the PCR fragment by PstI, and 8 alleles and 13 genotypes by HaeIII. For HaeIII restriction enzyme sites, the Chi-square ($X^2$) test showed that all goat breeds in this study did not fit with the Hardy-Weinberg equilibrium (p<0.01 or p<0.05). The highly polymorphic nature of CLA-$DRB3^*02$ was demonstrated and the ranges of gene heterozygosity (He) and polymorphism information content (PIC) were 0.36-0.63 and 0.32-0.55, respectively. Clustering analysis showed that the 10 goat breeds clustered into two groups and Dazu Black goat had a close genetic relationship with Chengdu Grey, Jintang Black and Nanjiang Yellow goats.

In vitro response of rat microglia and human polymorphonuclear cells (PMN) to immunoactive compounds

  • Lombardi, Valter RM;Eetcheverria, Ignacio;Fernandez-Novoa, Lucia;Diaz, Joaquin;Seoane, Silvia;Cacabelos, Ramon
    • Advances in Traditional Medicine
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    • v.5 no.3
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    • pp.216-230
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    • 2005
  • Although the field of study in immune enhancing compounds is relatively new, natural products from plants represent a rich and promising source of novel molecules with immunomodulating properties, Microglial cells, the main immune effector cells of the brain, usually display a ramified morphology and low expression levels of immunologically relevant antigens such as MHC class I and class II. Since any compound which participates in activation of phagocytic cells contributes to the production of potentially toxic factors, the search for convenient in vitro test-systems and study of mechanisms of action of these agents are of great interest. Human blood polymorphonuclear (PMN) cells and primary microglial cells isolated from Sprague-Dawley rats were used as cellular screening tests for study of phagocytosis-stimulating action of immunomodulating agents. Numbers of phagocytic activity were evaluated by the phagocyte ingestion of yeast cells and NO-synthase activity, nitrite production, and nitroblue tetrazolium test were determined after phagocyte stimulation. It was possible to demonstrate that indexes of phagocytic activity can be used as quantitative indicators for measurement immunomodulating activity. As a positive control, Zymosan A-induced phagocytosis in both PMN cells and primary microglial cells was used. $IFN-{\gamma}$ (0.1 -1 U/ml) stimulated phagocytosis in PMN cells 1.2 times after 2 - 3 h incubation, although at higher concentrations (10 - 100 U/ml) it strongly inhibited phagocytosis. In a similar way, at higher concentrations, $IFN-{\gamma}$ (100 - 500 U/ml) suppressed phagocytosis in zymosan-A stimulated microglial cells. When Polypodium leucotomus, cambricum and vulgare extracts were tested alone, increased levels of phagocytosis were observed in PMN. In addition, microglial cells showed both increased phagocytosis and MHC class-II antigen expressions. Surprisingly, when PMN and microglia were treated with a combination of Polypodium and $IFN-{\gamma}$, phagocytosis was not inhibited. We did not find changes in NO-synthase activity and nitrite production in both microglia and PMN cells activated by different immunomodulating agents. These results indicate that primary microglial cell cultures as well as human PMN cells can provide reproducible quantitative results in screening phagocytic activity of different immunoactive compounds. Furthermore, both inhibitory or activation mechanisms might be studied using these in vitro experimental approaches.

Immunological Synergistic Effects of Combined Treatment with Herbal Preparation (HemoHIM) and Red Ginseng Extracts (마우스세포를 이용한 홍삼추출물과 생약복합추출물의 병용 처리에 따른 면역활성 효과)

  • Byun, Myung-Woo;Byun, Eui-Hong
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.44 no.2
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    • pp.182-190
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    • 2015
  • This present study demonstrates the immunological synergistic effects of herbal preparation (HemoHIM) and red ginseng powder granule in various immune cell models (bone marrow-derived macrophages, dendritic cells, and mouse splenocytes) from mice. Both herbal preparation and red ginseng extracts were treated to bone-marrow derived macrophages, dendritic cells, and mouse splenocytes, and there was no cytotoxicity at a dose below $200{\mu}g/mL$. Cell proliferation and cytokine [tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-6, and IL-12] production tested in bone marrow-derived macrophages and dendritic cells significantly increased upon combined treatment. Cell surface marker (CD 80/86, MHC class I/II)-mediated immune cell activation was highly elevated by combined treatment. For cytokine production in splenocytes, combined treatment significantly increased production of Th 1 type cytokines [IL-2 and interferon (IFN)-${\gamma}$] but not Th 2 type cytokines (IL-4 and IL-10). Therefore, combined treatment with HemoHIM and red ginseng extracts is an effective method to establish powerful immunological synergy in immune cells.

The Emerging Role of Natural Killer Cells in Innate and Adaptive Immunity

  • Kim, Eun-Mi;Ko, Chang-Bo;Myung, Pyung-Keun;Cho, Daeho;Choi, Inpyo;Kang, Hyung-Sik
    • IMMUNE NETWORK
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    • v.4 no.4
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    • pp.205-215
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    • 2004
  • In the early host defense system, effector function of natural killer (NK) cells results in natural killing against target cells such as microbe-infected, malignant, and certain allogenic cells without prior stimulation. NK cell cytotoxicity is selectively regulated by homeostatic prevalence between a repertoire of both activating and inhibitory receptors, and the discrimination of untransformed cells is achieved by recognition of major histocompatibility complex (MHC) class I alleles through inhibitory signals. Although it is well known that the bipotential T/NK progenitors are derived from the common precusor, functional mechanisms in terms of the development of NK cells remain to be further investigated. NK cells are mainly involved in innate immunity, but recent studies have been reported that they also play a critical role in adaptive immune responses through interaction with dendritic cells (DC). This interaction will provide effector functions and development of NK cells, and elucidation of its precise mechanism may lead to therapeutic strategies for effective treatment of several immune diseases.