• Title/Summary/Keyword: MHC

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Cellular and Molecular Roles of $\beta$ Cell Autoantigens, Macrophages and T Cells in the Pathogenesis of Automimmune Diabetes

  • Yoon, Ji-Won;Jun, Hee-Sook
    • Archives of Pharmacal Research
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    • v.22 no.5
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    • pp.437-447
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    • 1999
  • Type I diabetes, also known as insulin-dependent diabetes mellitus (IDDM) results from the destruction of insulin-producing pancreatic $\beta$ cells by a progressive $\beta$ cell-specific autoimmune process. The pathogenesis of autoimmune IDDM has been extensively studied for the past two decades using animal models such as the non-obese diabetic (NOD) mouse and the Bio-Breeding (BB) rat. However, the initial events that trigger the immune responses leading to the selective destruction of the $\beta$ cells are poorly understood. It is thought that $\beta$ cell auto-antigens are involved in the triggering of $\beta$ cell-specific autoimmunity. Among a dozen putative $\beta$ cell autoantigens, glutamic acid decarboxylase (GAD) has bee proposed as perhaps the strongest candidate in both humans and the NOD mouse. In the NOD mouse, GAD, as compared with other $\beta$ cell autoantigens, provokes the earliest T cell proliferative response. The suppression of GAD expression in the $\beta$ cells results in the prevention of autoimmune diabetes in NOD mice. In addition, the major populations of cells infiltrating the iselts during the early stage of insulitis in BB rats and NOD mice are macrophages and dendritic cells. The inactivation of macrophages in NOD mice results in the prevention of T cell mediated autoimmune diabetes. Macrophages are primary contributors to the creation of the immune environment conducive to the development and activation of $\beta$cell-specific Th1-type CD4+ T cells and CD8+ cytotoxic T cells that cause autoimmune diabetes in NOD mice. CD4+ and CD8+ T cells are both believed to be important for the destruction of $\beta$ cells. These cells, as final effectors, can kill the insulin-producing $\beta$ cells by the induction of apoptosis. In addition, CD8+ cytotoxic T cells release granzyme and cytolysin (perforin), which are also toxic to $\beta$ cells. In this way, macrophages, CD4+ T cells and CD8+ T cells act synergistically to kill the $\beta$ cells in conjunction with $\beta$ cell autoantigens and MHC class I and II antigens, resulting in the onset of autoimmune type I diabetes.

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Immunogenicity of staphylococcal enterotoxin C mutant antigen in mice and dairy cows (포도상구균 장내 C 형 변이독소 (SEC mutant)의 면역원성에 대한 연구)

  • Chang, Byoung-sun;Joo, Yi-seok;Moon, Jin-san;Seo, Keun-seok;Yang, Soo-jin;Kim, So-hyun;Park, Yong-ho
    • Korean Journal of Veterinary Research
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    • v.41 no.2
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    • pp.177-188
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    • 2001
  • Mastitis is one of the most significant cause of economic loss to the dairy industry. Especially, Staphylococcus aureus is a major contagious mastitis-causing pathogen in dairy cattle. Because of its high transmission rate and resistance to antibiotic therapy, staphylococcal mastitis presents a constant threat to the dairy industry. Staphylococcal enterotoxin C(SEC) produced by S aureus has been known as one of superantigens which are able to stimulate a large proportion of T lymphocytes independently of their antigenic specificity. In this experiment, we have conducted preliminary studies with mice and lactating cows to evaluate the immunogenicity and safety of the experimental vaccine consists of SEC mutant antigen on controlling the bovine mastitis associated with S aureus infections. The average value of somatic cell counts in quarter milk, isolation rate of S aureus were consistently decreased in SEC-SER vaccinated groups, whereas antibody titers were highly increased in SEC-SER vaccinated groups. Peripheral blood were also collected from the lactating cows to determine the proportion of leukocyte subpopulation associated with humoral immunity(HI) and cell mediated immunity(CMI). Proportion of leukocyte subpopulation expressing $BoCD2^+$(total T lymphocyte), $BoCD4^+$(T helper cell), $BoCD8^+$(T cytotoxic/suppressor cell) and NonT/NonB lymphocyte which are involved in CMI in SEC-SER vaccinated groups were decreased for the initial stage after first vaccination and then increased from ten weeks after first vaccination maintaining elevated level till 14 weeks after vaccination. In contrast, proportion of monocyte, MHC class II and B lymphocyte which are associated with the production of primary immune response in SEC-SER vaccinated groups were increased for the initial period and then decreased from ten weeks after first vaccination. We present evidence that vaccination of SEC-SER mutant antigen in lactating cows induced a significant proliferation of bovine T lymphocytes. These results suggest that SEC-SER mutant antigen used in this experiment might be one of potential immunogen in developing innovative vaccine against bovine IMI associated with S aureus. Additional challenge trials should be carried out to evaluate substantial protection against S aureus under the commercial farm conditions.

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Modelling of Artificial Immune System for Development of Computer Immune system and Self Recognition Algorithm (컴퓨터 면역시스템 개발을 위한 인공면역계의 모델링과 자기인식 알고리즘)

  • Sim, Kwee-Bo;Kim, Dae-Su;Seo, Dong-Il;Rim, Kee-Wook
    • Journal of the Korean Institute of Intelligent Systems
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    • v.12 no.1
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    • pp.52-60
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    • 2002
  • According as many people use a computer newly, damage of computer virus and hacking is rapidly increasing by the crucial users. A computer virus is one of program in computer and has abilities of self reproduction and destruction like a virus of biology. And hacking is to rob a person's data in a intruded computer and to delete data in a Person s computer from the outside. To block hacking that is intrusion of a person's computer and the computer virus that destroys data, a study for intrusion detection of system and virus detection using a biological immune system is in progress. In this paper, we make a model of positive and negative selection for self recognition which have a similar function like T-cytotoxic cell that plays an important role in biological immune system. We embody a self-nonself distinction algorithm in computer, which is an important part when we detect an infected data by computer virus and a modified data by intrusion from the outside. And we showed the validity and effectiveness of the proposed self recognition algorithm by computer simulation about various infected data obtained from the cell change and string change in the self file.

Inhibitory Effects of Deer Antler Herbal-Acupuncture Solution on Cathepsin S and L Activity in RA Model Mice

  • Ahn, Hyung-Jun;Yoon, Jong-Hwa;Kim, Kyung-Ho;Lee, Seung-Deok;Kim, Kap-Sung
    • Journal of Acupuncture Research
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    • v.22 no.2
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    • pp.71-81
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    • 2005
  • Objective : Dear antler (Cervus korean TEMMINCK var. mantchuricus Swinhoe) used for traditional immunosuppressive and immuno-activating action. The effect of deer antler herbal-acupuncture(DAH) solution, prepared by water extract method, on cathepsin activities in bone tissues (cartilage and synovial) cells from mouse rheumatoid arthritis (RA) model was studied. The cysteine endoprotease cathepsin mediates degradation of the MHC class II invariant chain (Ii) in human and mouse antigen-presenting cells. The studies described here examine the functional significance of cathepsin inhibition on autoantigen presentation and organ-specific autoimmune diseases in a murine model for RA. Methods : An animal model for RA in BALB/c mice thymectomized 3 days after birth (3d-Tx) was constructed All 3d-Tx BALB/c mice developed autoimmune lesions in the bone tissue cells, starting at 3 weeks of age, and the disease mediated by CD4+ T cells was chronic and progressive. Significant inhibitory effects of DAH solution on cathepsin S and L were observed in each organ in a dose-dependent manner. Moreover, we confirmed that cathepsin S and L activity in each organ were clearly inhibited by DAB solution. When we examined the inhibitory effects of DAH solution against autoantigen-specific T cell responses in vitro, in regional lymph node cells, but not in spleens, from model mice, a significant inhibitory effect of DAB solution was observed in a dose-dependent manner. DAH solution do not block T cell proliferation to Con A, indicated that the dose of DAB solution 10 to $20\;{\mu}g/m{\ell}$ was sufficient to inactivate the autoantigen-specific T cell responses in vitro. In vivo therapeutic effects of DAB solution were examined in a murine model for RA, autoantigen-specific (C-II-specific) T cell response were significantly inhibited in LNCs from DAH solution-treated mice. Results : Iinhibition of cathepsin S and L in vivo alters autoantigen presentation and development of organ-specific autoimmunity in RA model. Conclusion : These data identify selective inhibition of cysteine protease cathepsin S and L as a potential therapeutic strategy for autoimmune disease process such RA. Thus, DAH solution will served as a potent anti-inflammatory and anti-arthritic agents for treatment of human RA.

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Comparison of Gene Expression Levels of Porcine Satellite Cells from Postnatal Muscle Tissue during Differentiation

  • Jeong, Jin Young;Kim, Jang Mi;Rajesh, Ramanna Valmiki;Suresh, Sekar;Jang, Gul Won;Lee, Kyung-Tai;Kim, Tae Hun;Park, Mina;Jeong, Hak Jae;Kim, Kyung Woon;Cho, Yong Min;Lee, Hyun-Jeong
    • Reproductive and Developmental Biology
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    • v.37 no.4
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    • pp.219-224
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    • 2013
  • Muscular satellite cell (SC), which is stem cell of postnatal pig, is an important for study of differentiation into adipogenesis, myogenesis, and osteoblastogenesis. In this study, we isolated and examined from pig muscle tissue to determine capacity in proliferate, differentiate, and expression of various genes. Porcine satellite cells (PSC) were isolated from semimembranosus (SM) muscles of 90~100 days old pigs according to standard conditions. The cell proliferation increased in multi-potent cell by Masson's, oil red O, and Alizarin red staining respectively. We performed the expression levels of differentiation related genes using real-time PCR. We found that the differentiation into adipocyte increased expression levels of both fatty acid binding protein 4 (FABP4) and peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$) genes (p<0.01). Myocyte increased the expression levels of the myosin heavy chain (MHC), myogenic factor 5 (Myf5), myogenic regulatory factor (MyoD), and Myogenic factor 4 (myogenin) (p<0.01). Osteoblast increased the expression levels of alkaline phosphatase (ALP) (p<0.01). Finally, porcine satellite cells were induced to differentiate towards adipogenic, myogenic, and osteoblastogenic lineages. Our results suggest that muscle satellite cell in porcine may influence cell fate. Understanding the progression of PSC may lead to improved strategies for augmenting meat quality.

Engraftment of Intraperitoneally Injected Bone Marrow Cells to Newborn Mice Injected with an Angiogenesis Inhibitor (혈관생성 억제제를 주사한 마우스 모델에서의 골수 세포의 복강 내 주입 후 생착)

  • Cho, Su-Jin;Ju, Sun-Young;Woo, So-Youn;Kang, Hyoung-Jin;Ahn, Hyo-Seop;Ryu, Kyung-Ha;Park, Eun-Ae
    • Neonatal Medicine
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    • v.15 no.1
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    • pp.22-31
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    • 2008
  • Purpose : Bronchopulmonary dysplasia (BPD) is characterized by arrested vascular and alveolar growth in the premature lung. Considering the consequences of arrested lung growth, the idea of administering bone marrow cells to enhance the inborn repair mechanism is promising as this may reduce the morbidity and mortality of BPD. We followed enhanced green fluorescent protein (EGFP)-labeled bone marrow cells (BMC) injected intraperitoneally into non-EGFP mice in order to determine their fate after transplantation. Methods : An angiogenesis inhibitor, SU1498, was injected subcutaneously on day 3 in non-EGFP C57BL/6 newborn mice to create a model of arrested alveolar development. On the following day, $1{\times}10^6$ BMCs isolated from major histocompatibility complex (MHC)- matched syngenic EGFP mice were injected intraperitoneally to non-EGFP BPD mice. Morphometric analysis, immunostaining, and confocal microscopy were performed to determine the fate of EGFP-positive stem cells in the injured lung. Results : SU1498 injection reduced alveolar surface area and mean alveolar volume in newborn mice. BMC injection resulted in recovery of lung structure comparable to controls. EGFP-positive BMCs were identified in the lungs of the recipient mice after intraperitoneal injection. The injected EGFP cells were co-stained with endothelial and epithelial cells of the developing lung as determined by confocal microscopy. Conclusion : Our results illustrated that EGFP-positive BMCs engrafted and trans-differentiated into epithelial and endothelial cells after intraperitoneal injection in a mouse model of arrested alveolar development.

Effects of soybean extracts fermented with Lactic acid bacteria on immune system activity (유산균을 이용한 대두 발효 추출물이 면역계 활성에 미치는 영향)

  • Park, Byung-Doo;Kim, Hye-Ja
    • Journal of Society of Preventive Korean Medicine
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    • v.16 no.3
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    • pp.139-153
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    • 2012
  • Objectives : NK cells are spontaneously cytotoxic lymphocytes. These are not only important parts in the first line of defence against bacterial and viral infections of outside, but they may also play a critical role in chronic viral diseases. NK cells kill their targets spontaneously, without the need for prior sensitization and class I MHC restriction by the regulation of cytolytic functions and secretion of a variety of cytokines, such as interleukin-12(IL-12), MCP-1, IL-6, TNF-${\alpha}$, IFN-${\gamma}$. In addition, macrophage and NK cells cooperate through the production of cell mediates. These cooperation and modulation are one of major factors to prevent for evading immune surveillance of cancer. Hence, it could be assumed that if any candidate to enhance activities of macrophage and NK cell, it is considered as a potentially useful agents against cancer. Methods : In our study, to investigate effect of fermented soybean extracts by Lactic acid bacteria (SFE, soybean fermented extracts) work on intestinal immune cell to maintain general immune modulating and anti-cancer activity. We analyzed NK cytotoxicity assay and gene expressions of cytokine related with macrophage and NK cell activity. Results : In vitro experiment, SFE was verified as safety material for cell toxicicty to tumor cell strain without any toxicity of tumor growth inhibition and various cell strain. Effects of macrophage activity stimulating directly by SFE measured induced cytokine. The studies showed that IL-12 production by stimulation of SFE depended on concentration from 0.16mg/mL to 0.63mg/mL with non toxicity to cell, and it was the best activity at 0.63mg/mL. Besides, the effective concentration of SFE producing TNF-${\alpha}$ is similar to IL-12, but it was the best activity at 1.25mg/mL. The level of MCP-1, IL-6 and IFN-${\gamma}$ depended on concentration from 0.16mg/mL to 10mg/mL, IFN-${\gamma}$ showed the best activity at the effective concentration of 0.63mg/mL. With the result of NK cell activity measurement, the spleen cell of mouse injected SFE had 1.5 times higher killing effect than non injected cell. Conclusions : The result of this studies is that Soybean fermetated extracts(SFE) has possibility to immune aided material for the function not only inhibition of microbial infection to macrophage but also activity of adaption immune and cellular immune system.

Effects of Corn Silage on Growth Performance, Carcass Characteristics, and Gene Expression of Longissimus dorsi Muscle Biopsy of Hanwoo Steers (옥수수 사일리지가 거세한우의 성장, 도체특성 및 등심 유전자 발현에 미치는 영향)

  • Kim, U.H.;Kang, D.H.;Park, B.H.;Jang, S.S.;Chung, K.Y.
    • Journal of Practical Agriculture & Fisheries Research
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    • v.24 no.1
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    • pp.41-48
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    • 2022
  • This study was conducted to investigate effects of corn silage on final fattening performance, carcass characteristics, and gene expression of Hanwoo Longissimus dorsi muscle biopsy. Twenty one steers with initial body weight of control 291.5±6.5kg, corn silage 291.7.0±17.3kg were used for 18 months of fattening period. Average daily gain of corn silage tended to increase compared to control in early fattening period(p=0.092). Feed conversion ratio of corn silage was higher than control in early fattening(p=0.005). The animals in corn silage increased A grade 23% in meat quantity than the control. Myogenic gene expression on the Longissimus dorsi biopsy were compared between corn silage and control. The level of myosin heavy chain(MHC) I, IIX mRNA were greater than the control in the whole period(p<0.05). The level of Peroxisome proliferator-activated receptor γ (PPAR γ) mRNA was greater than the corn silage(p<0.05). Inconclusion, corn silage will be possible to use as an alternative concentrate feeding system.

Effects of feeding high-energy diet on growth performance, blood parameters, and carcass traits in Hanwoo steers

  • Kang, Dong Hun;Chung, Ki Yong;Park, Bo Hye;Kim, Ui Hyung;Jang, Sun Sik;Smith, Zachary K.;Kim, Jongkyoo
    • Animal Bioscience
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    • v.35 no.10
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    • pp.1545-1555
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    • 2022
  • Objective: Our study aimed to investigate the effects of a 2% increase in dietary total digestible nutrients (TDN) value during the growing (7 to 12 mo of age) and fattening (13 to 30 mo of age) period of Hanwoo steers. Methods: Two hundred and twenty Hanwoo steers were assigned to one of two treatments: i) a control group (basal TDN, BTDN, n = 111 steers, growing = 70.5%, early fattening = 71.0%, late fattening = 74.0%) or high TDN (HTDN, n = 109 steers, growing = 72.6%, early = 73.1%, late = 76.2%). Growth performance, carcass traits, blood parameters, and gene expression of longissimus dorsi (LD) (7, 18, and 30 mo) were quantified. Results: Steers on the BTDN diets had increased (p≤0.02) DMI throughout the feeding trial compared to HTDN, but gain did not differ appreciably. A greater proportion of cattle in HTDN received Korean quality grade 1 (82%) or greater compared to BTDN (77%), while HTDN had a greater yield grade (29%) than BTDN (20%). Redness (a*) of LD muscle was improved (p = 0.021) in steers fed HTDN. Feeding the HTDN diet did not alter blood parameters. Steers fed HTDN diet increased (p = 0.015) the proportion of stearic acid and tended to alter linoleic acid. Overall, saturated, unsaturated, monounsaturated, and polyunsaturated fatty acids of LD muscle were not impacted by the HTDN treatment. A treatment by age interaction was noted for mRNA expression of myosin heavy chain (MHC) IIA, IIX, and stearoyl CoA desaturase (SCD) (p≤0.026). No treatment effect was detected on gene expression from LD muscle biopsies at 7, 18, and 30 mo of age; however, an age effect was detected for all variables measured (p≤0.001). Conclusion: Our results indicated that feeding HTDN diet could improve overall quality grade while minimum effects were noted in gene expression, blood parameters, and growing performance. Cattle performance prediction in the feedlot is a critical decision-making tool for optimal planning of cattle fattening and these data provide both benchmark physiological parameters and growth performance measures for Hanwoo cattle feeding enterprises.

Efficient Anti-Tumor Immunotherapy Using Tumor Epitope-Coated Biodegradable Nanoparticles Combined With Polyinosinic-Polycytidylic Acid and an Anti-PD1 Monoclonal Antibody

  • Sang-Hyun Kim;Ji-Hyun Park;Sun-Jae Lee;Hee-Sung Lee;Jae-Kyung Jung;Young-Ran Lee;Hyun-Il Cho;Jeong-Ki Kim;Kyungjae Kim;Chan-Su Park;Chong-Kil Lee
    • IMMUNE NETWORK
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    • v.22 no.5
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    • pp.42.1-42.20
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    • 2022
  • Vaccination with tumor peptide epitopes associated with MHC class I molecules is an attractive approach directed at inducing tumor-specific CTLs. However, challenges remain in improving the therapeutic efficacy of peptide epitope vaccines, including the low immunogenicity of peptide epitopes and insufficient stimulation of innate immune components in vivo. To overcome this, we aimed to develop and test an innovative strategy that elicits potent CTL responses against tumor epitopes. The essential feature of this strategy is vaccination using tumor epitope-loaded nanoparticles (NPs) in combination with polyinosinic-polycytidylic acid (poly-IC) and anti-PD1 mAb. Carboxylated NPs were prepared using poly(lactic-co-glycolic acid) and poly(ethylene/maleic anhydride), covalently conjugated with anti-H-2Kb mAbs, and then attached to H-2Kb molecules isolated from the tumor mass (H-2b). Native peptides associated with the H-2Kb molecules of H-2Kb-attached NPs were exchanged with tumor peptide epitopes. Tumor peptide epitope-loaded NPs efficiently induced tumor-specific CTLs when used to immunize tumor-bearing mice as well as normal mice. This activity of the NPs significantly was increased when co-administered with poly-IC. Accordingly, the NPs exerted significant anti-tumor effects in mice implanted with EG7-OVA thymoma or B16-F10 melanoma, and the anti-tumor activity of the NPs was significantly increased when applied in combination with poly-IC. The most potent anti-tumor activity was observed when the NPs were co-administered with both poly-IC and anti-PD1 mAb. Immunization with tumor epitope-loaded NPs in combination with poly-IC and anti-PD1 mAb in tumor-bearing mice can be a powerful means to induce tumor-specific CTLs with therapeutic anti-tumor activity.