• Title/Summary/Keyword: 세포성면역반응

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Role of Tumor-associated Macrophage in Tumor Microenvironment (암미세환경에서 종양관련대식세포의 역할)

  • Min, Do Sik
    • Journal of Life Science
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    • v.28 no.8
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    • pp.992-998
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    • 2018
  • Cancer cells grow in an environment composed of various components that supports tumor growth. Major cell types in the tumor microenvironment are fibroblast, endothelial cells and immune cells. All of these cells communicate with cancer cells. Among infiltrating immune cells as an abundant component of solid tumors, macrophages are a major component of the tumor microenvironment and orchestrates various aspects of immunity. The complex balance between pro-tumoral and anti-tumoral effects of immune cell infiltration can create a chronic inflammatory microenvironment essential for tumor growth and progression. Macrophages express different functional programs in response to microenvironmental signals, defined as M1 and M2 polarization. Tumor-associated macrophages (TAM) secret many cytokines, chemokines and proteases, which also promote tumor angiogenesis, growth, metastasis and immunosuppression. TAM have multifaceted roles in the development of many tumor types. TAM also interact with cancer stem cells. This interaction leads to tumorigenesis, metastasis, and drug resistance. TAM obtain various immunosuppressive functions to maintain the tumor microenvironment. TAM are characterized by their heterogeneity and plasticity, as they can be functionally reprogrammed to polarized phenotypes by exposure to cancer-related factors, stromal factors, infections, or even drug interventions. Because TAMs produce tumor-specific chemokines by the stimulation of stromal factors, chemokines might serve as biomarkers that reflect disease activity. The evidence has shown that cancer tissues with high infiltration of TAM are associated with poor patient prognosis and resistance to therapies. Targeting of TAM in tumors is considered a promising therapeutic strategy for anti-cancer treatment.

The Optimal Activation State of Dendritic Cells for the Induction of Antitumor Immunity (항종양 면역반응 유도를 위한 수지상세포의 최적 활성화 조건)

  • Nam, Byung-Hyouk;Jo, Wool-Soon;Lee, Ki-Won;Oh, Su-Jung;Kang, Eun-Young;Choi, Yu-Jin;Do, Eun-Ju;Hong, Sook-Hee;Lim, Young-Jin;Kim, Ki-Uk;Jeong, Min-Ho
    • Journal of Life Science
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    • v.16 no.6
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    • pp.904-910
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    • 2006
  • Dendritic cells (DCs) are the only antigen presenting cells (APCs) capable of initiating immune responses, which is crucial for priming the specific cytotoxic T lymphocyte (CTL) response and tumor immunity. Upon activation by DCs, CD4+ helper T cells can cross-prime CD8+ CTLs via IL-12. However, recently activated DCs were described to prime in vitro strong T helper cell type 1 $(Th_1)$ responses, whereas at later time points, they preferentially prime $Th_2$ cells. Therfore, we examined in this study the optimum kinetic state of DCs activation impacted on in vivo priming of tumor-specific CTLs by using ovalbumin (OVA) tumor antigen model. Bone-marrow-derived DCs showed an appropriate expression of surface MHC and costimulatory molecules after 6 or 7-day differentiation. The 6-day differentiated DCs pulsed with OVA antigen for 8 h (8-h DC) and followed by restimulation with LPS for 24 h maintained high interleukin (IL)-12 production potential, accompanying the decreased level in their secretion by delayed re-exposure time to LPS. Furthermore, immunization with 8-h DC induced higher intracellular $interferon(IFN)-{\gamma}+/CD8+T$ cells and elicited more powerful cytotoxicity of splenocytes to EG7 cells, a clone of EL4 cells transfected with an OVA cDNA, than immunization with 24-h DC. In the animal study for the evaluation of therapeutic or protective antitumor immunity, immunization with 8-h DC induced an effective antitumor immunity against tumor of EG7 cells and completely protected mice from tumor formation and prolonged survival, respectively. The most commonly used and clinically applied DC-based vaccine is based on in vitro antigen loading for 24 h. However, our data indicated that antigen stimulation over 8 h decreased antitumor immunity with functional exhaustion of DCs, and that the 8-h DC would be an optimum activation state impacted on in vivo priming of tumor-specific CTLs and subsequently lead to induction of strong antitumor immunity.

Yangkyuksanhwa-Tang Attenuates Ischemic Brain Injury in a Focal Photothrombosis Stroke Model (뇌허혈 마우스모델에서 양격산화탕이 뇌 손상 완화에 미치는 효과)

  • Han, Do-Kyung;Pak, Malk-Eun;Kwon, Ok-Sun;Choi, Byung-Tae
    • Journal of Life Science
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    • v.29 no.11
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    • pp.1258-1266
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    • 2019
  • Yangkyuksanhwa-Tang (YKSH), consisting of nine different herbs, is commonly used in Soyangin-type individuals with stroke, based on the Sasang Constitution Theory in Korea. However, no evidence has yet confirmed a beneficial effect of YKSH in ischemic stroke treatment. In this study, we investigated the effects of YKSH on ischemic brain injury in a mouse model of cerebral ischemia. Focal cerebral ischemia in mice was induced by photothrombosis, and behavioral recovery was evaluated. Infarct volume, inflammation, and newly generated cells were evaluated by histology and immunochemistry. YKSH treatment resulted in a significant recovery from the motor impairments induced by focal cerebral ischemia, as determined with wire grip and rotarod tests. YKSH treatment also decreased the infarct volume and the number of cells positive for tumor necrosis factor-${\alpha}$ and myeloperoxidase when compared with a vehicle-treated control group. By contrast, YKSH treatment considerably increased the number of cells positive for glial fibrillary acidic protein and ionized calcium-binding adapter molecule 1, as well as the number of cells doubly positive for Ki67/doublecortin when compared with the vehicle-treated group. These results suggest that YKSH treatment attenuated the infarct size by anti-inflammatory action, astrocyte and microglia activation, and neuronal proliferation, thereby facilitating neurofunctional recovery from a cerebral ischemic assault. YKSH could therefore be a potential treatment for neurofunctional restoration of the injured brains of patients with stroke.

Expression of Myelin-Associated Glycoprotein (MAG) in the Aged Rat Cerebrum (노화된 흰쥐대뇌 에서 Myelin-Associated Glycoprotein (MAG)의 발현)

  • Cho, Ik-Hyun;Park, Chang-Hyun;Lee, Jong-Hwan;Bae, Chun-Sik;Ye, Sang-Kyu;Lee, Beob-Yi;Park, Seung-Hwa;Koh, Ki-Seok;Kim, Jin-Suk;Chang, Byung-Joon
    • Applied Microscopy
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    • v.36 no.2
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    • pp.101-108
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    • 2006
  • Myelin-associated glycoprotein (MAG) has been known to have a crucial role to the formation of myelin sheath during initial stage of myelination. In the present study, we investigated the aging-related expressional changes of MAG in the rat cerebrum. MAG expression was markedly decreased in cerebral cortex by aging. In the adult rat cerebrum, MAG-positive rolls were process-bearing cells with large nucleus, and extensively distributed. However, in the aged rat brain, MAG-positive cells showed small and round morphology with little cytoplasm and few processes. MAG was co-expressed with galatocerebroside, but not with Iba-1, or GFAP. These results suggest that the expressional change of MAG-positive cells is associated with degeneration of oligodendrocyte-myelin system by aging, and that MAG is likely to be a reliable marker for the mature oligodendrocytes in the aged rat brain.

DISTRIBUTION OF NITRIC OXIDE SYNTHASE ISOFORMS IN PERIORAL EXOCRINE GLANDS IN RATS (흰쥐 구강주위 외분비선에서 산화질소 합성동위효소의 분포)

  • Jeong, Jong-Cheol;Kim, Sun-Hun;Ryu, Sun-Youl
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.26 no.3
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    • pp.284-292
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    • 2000
  • 내인성 산화질소는 산화질소 합성효소에 의하여 합성되며 여러 분비선에서 다양한 기능을 하리라 추측되고 있다. 구강주위 외분비선은 형태적으로 유사하나 분비물의 성분과 분비량은 서로 달라 이들 조직에서 산화질소 동위효소의 분포와 기능을 추론함은 흥미 있는 일이다. 또한 구강주위 외분비선과 분비선의 지배신경의 산화질소동위효소의 분포에 관한 보고는 희박하다. 본 연구는 흰쥐구강 주위 외분비조직, 즉 3대 타액선, 혀의 소타액선, 누선 그리고 구강점막의 피지선과 지배신경 및 신경절에서 eNOS와 nNOS의 분포를 면역조직화학 방법에 의하여 관찰하여 다음의 결과를 얻었다. nNOS는 악하선신경절, 대타액선의 분비도관 주위의 신경절후신경섬유, 혀의 소타액선 주위의 신경절후섬유, 누선에서 강한 양성반응을 보였다. nNOS는 대타액선과 근상피세포에서 중등도의 양성반응을 보였고 이중 이하선에서 반응이 가장 약하였으며, 피지선의 분비관에서 약한 반응을 보였다. 그러나 상교감신경절과 삼차신경절, 소타액선의 분비관 및 대,소 타액선의 선포에서는 반응이 매우 미약하거나 관찰되지 않았다. eNOS는 혈관의 내피세포와 대타액선의 분비관, 누선의 분비관 및 선포에서 강한 양성 반응을 보였고, 근상피세포에서 중등도의 반응을, 피지선에서 약한 반응을 보였다. 모든 신경절과 신경섬유에서 eNOS의 반응은 음성이었고 타액선의 일부 선포에서는 미약한 면역반응을 보였다. 이상의 결과 eNOS에 의해 합성된 NO는 악안면영역의 외분비선에서 혈류량의 조절과 분비도관의 기능 조절에 관여하고, nNOS에 의한 NO는 외분비선의 자율신경계에서 신경전달물질로의 기능과 분비도관에서의 분비기능 조절에 관여함을 시사하였다.

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Ultrastructural Antigenic Localization in the Tissues of Echinostoma hortense Observed by Immunogold Labeling Method (면역황금표식법을 이용한 호르텐스극구흡충의 조직내 항원성 부위에 관한 연구)

  • Yoon-Kyung Jo;Yong-Suk Ryang;Kyu-Je Lee;Insik Kim;Jang-Keun Ryu;Mi-Sook Song
    • Biomedical Science Letters
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    • v.5 no.2
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    • pp.155-165
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    • 1999
  • This study involved applying rat sera (control, infected and immunized) to adult worm tissue in order to measure the antigenic response. A serum was obtained from rats infected with E. hortense metacercaria for 4 weeks. Another immunized serum was taken from rats given a muscle injection with crude adult worm antigen. The detection of antigenic response in E. hortense tissue was made by immunogold labeling method and measured through gold particles impregnated in the tissue. The antigenic sites, those with the highest density of gold particles, were the tegmental syncytium, vitelline cells, seminal receptacle and cecum.

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Immunomodulatory activities of polysaccharides extracted from Cudrania tricuspidata fruits in macrophage (꾸지뽕(Cudrania tricuspidata) 열매에서 분리된 조다당의 큰포식세포 면역 활성 조절)

  • Cho, Eun-Ji;Kim, Yi-Eun;Byun, Eui-Hong
    • Korean Journal of Food Science and Technology
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    • v.50 no.5
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    • pp.511-516
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    • 2018
  • Macrophages play a crucial role in the host immune defense system. The current study investigated immunomodulatory activities induced by polysaccharides extracted from Cudrania tricuspidata (CTPS) fruits in murine macrophages and their role in signaling pathways. In macrophages, CTPS predominantly induced nitric oxide (NO), tumor necrosis factor-a, and interleukin-6 production. In addition, CTPS significantly up-regulated expression of the macrophage surface marker (CD80/86 and MHC class I/II). These results indicate that polysaccharides extracted from CTPS may potentially play an immunomodulatory role in macrophages via mitogen-activated protein kinases and nuclear factor-B signaling. These findings may be useful in the development of immune enhancing adjuvant materials obtained from natural sources.

The Effects of Scutellaria baicalensis GEORGI on Allergic contact dermatitis induced by DNCB in Mice (황금(黃芩) 추출물(抽出物)이 DNCB로 유발(誘發)된 생쥐의 Allergy성(性) 접촉피부염(接觸皮膚炎)에 미치는 영향(影響))

  • Jun, Jae-Hong;Kang, Yoon-Ho
    • The Journal of Dong Guk Oriental Medicine
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    • v.7 no.1
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    • pp.119-133
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    • 1998
  • This study was performed to investigated the effects of an immunosuppression and a mitigation of inflammation of Scutellaria baicalensis GEORGI on Allergic contact dermatitis. In order to study, after oral administration of Scutellaria baicalensis GEORGI extract, contact hypersensitivity assay, general morphologic change of skin, sulfated acid mucosubstance, mast cell, IL-2R, ICAM-1 and CD11b were observed in BALB/C mouse induced allergic contact dermatitis by the contact sensitizing DNCB. Ear swelling in contact hypersensitivity assay was decreased in the Scutellaria baicalensis GEORGI extracts administered(HEGT) group, compared with DNCB painted group. In the general morphologic change of skin, hyperplasia of keratinocytes, increase of lymphocytes and inflammatory cell, increase of vasculogenesis and epidermal lymphocytes infiltration, increase of cell damage in epidermal basal layer and prickle layer were decreased in the HEGT group, compared with DNCB painted group. Increase of sulfated acid mucosubstance, mast cell, IL-2R positive cell, ICAM-1 positive cell, CD11b positive cell were decreased in the HEGT group, compared with DNCB painted group.

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The Purification and Immunogenicity of TB-14 Recombinant Protein of Mycobacterium tuberculosis (결핵균 특이 TB-14 재조합 단백질의 분리 및 세포성 면역반응에 미치는 영향)

  • Song, Ho-Yeon;Kim, Young-Hee;Kim, Chang-Hwan;Min, Young-Ki;Kim, Dae-Joong;Ko, Kwang-Kjune
    • Tuberculosis and Respiratory Diseases
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    • v.61 no.3
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    • pp.239-247
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    • 2006
  • Background: Culture filtrate proteins secreted by mycobacteria are thought to play an important role in inducing protective immunity and to develop new methods for diagnosing tuberculosis. Methods: A culture filtrate protein of M. avium that was strongly reactive with goat antiserum against M. intracellulare was constructed. Its homologous protein (TB-14) in M. tuberculosis was cloned, expressed and purified. The inductions of IFN-${\gamma}$ stimulated with $10{\mu}g$ of TB-14 recombinant protein and $10{\mu}g$ PPD were estimated by using whole bloods from seven PPD (-) subjects, seven PPD (+) healthy volunteers and nine tuberculosis patients. Results: M. avium culture filtrate protein was confirmed as a hypothetical protein that was termed contig 116. A novel 14-kDa recombinant protein (TB-14) of M. tuberculosis was composed of 148 amino acids, including 30 amino acids of the signal peptide, and it showed 78% homology with M. avium. In the PPD (+) healthy volunteers, recombinant TB-14 protein strongly induced the secretion of IFN-${\gamma}$ in whole blood cultures. Conclusion: These results suggest that TB-14 recombinant protein might play an important role in inducing cell-mediated immunity against tuberculosis. Furthermore, TB-14 protein antigen and its antiserum will be available for the development of new diagnostic tools for tuberculosis.

Study on the Production and Management of Aquatic Animal : Application of ELISPOT-Assay for the Detection of Antibody Secreting Cells in Flounder, Paralichthys olivaceus (수산생물의 생산과 관리에 관한 기초연구 : ELISPOT 기법을 이용한 넙치의 항체생성 세포분석)

  • HA Jai Yi;PARK Jun-Hyo;KIM Myoung Sug;CHUNG Joon-Ki;JEONG Hyun Do
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.32 no.4
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    • pp.420-426
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    • 1999
  • We examined the immune response in flounder, Paralichthys olivaceus, with immunization of formalin killed Edwardsiella tarda as an antigen. The ELISPOT-assay (enzyme-linked immunospot assay) was optimized technically and applied to count the number of total and specific antibody secreting cells (TASC and SASC) in lymphocytes of different lymphatic organs. Incubation of lymphocytes on 96 well plate for more than 2.5hrs came out enough time in ELISPOT-assay for counting the antibody secreting cells in the anterior kidney and spleen. However, too much of plate-coated antigen or rabbit anti-flounder immunoglobulin for SASC or TASC counting, respectively, was appeared to decrease the sensitivity of the assay system. Specificity of the system was also confirmed by the absence of TASC in lymphocytes treated with cycloheximide to prevent protein synthesis. The peak numbers of SASC appeared at wk 3 post immunization after that there was a sharp decrease and reached to almost zero at wk 7. In the spleen and kidney, the timing and numbers of SASC on peak response were concurrent without preferential organ distribution. The specific antibody level in the sera increased rapidly between wk 2 and 3 after immunization, i.e. like the specific cellular response found with ELISPOT-assay on that period, However, the remained high level of specific serum antibody from wk 5 after immunization until the end of experiment was clearly distinguishable from the kinetics of SASC response decreased sharply.

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