• IMMUNE NETWORK
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• 제10권5호
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• pp.164-172
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• 2010

Background: We tested the hypothesis that dengue haemorrhagic fever (DHF) is associated with a $T_H1$-skewed immune response as opposed to dengue fever (DF). Methods: We estimated intracellular (in T-cells) and serum levels of designate $T_H1/T_H2$ cytokines [interferon-${\gamma}$ (IFN-${\gamma}$), interleukin-4 (IL-4), and tumor necrosis factor-${\alpha}$] and macrophage inflammatory protein-$1{\alpha}$ (MIP-$1{\alpha}$) at admission, 48h, and day 5 in 20 adults with dengue (DF=10, DHF=10) and 10 dengue-naive healthy controls. Results: At admission, intracellular IFN-${\gamma}$/IL-4 ratio in CD4+ T-cells and proportion of MIP-$1{\alpha}$-positive CD8+ T-cells were significantly higher in patients with DHF [7.21 (5.36~10.81) vs. 3.04 (1.75~4.02); p=0.011 and 6.2% (3.2~8.2%) vs. 2.4% (2.0~3.6%); p=0.023]. The latter showed a significant positive correlation with IFN-${\gamma}$/IL-4 ratio in CD4+ T-cells (Spearman's rho=0.64; p=0.003), percentage-change in haematocrit (rho=0.47; p=0.048), and serum alanine amino-transferase level (rho=0.61; p=0.009). Conclusion: We conclude that DHF is associated with a $T_H1$-skewed immune response. Further, MIP-$1{\alpha}$ in CD8+ T-cells is an important immunologic correlate of disease severity in dengue.

• Journal of Microbiology and Biotechnology
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• 제17권2호
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• pp.348-358
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• 2007

Metallothionein, a cysteine-rich stress response protein that is naturally induced by a variety of immunologic stressors, has been shown to suppress autoimmune disorders through mechanisms not yet fully defined. In the present study, we examined the underlying mechanisms by which metallothionein might mediate such regulation of autoimmunity. $Na\ddot{i}ve\;CD4^+$ T cells from metallothionein-deficient mice differentiated to produce significantly less IL-10, $TGF-{\gamma}$, and repressor of GATA, but more $IFN-{\gamma}$ and T-bet, when compared with those from wild-type mice. The levels of IL-4 and GATA-3 production were not different between the two groups of mice. Conversely, treatment with exogenous metallothionein during the priming phase drove $na\ddot{i}ve$ wild-type $CD4^+\;T$ cells to differentiate into cells producing more IL-10 and $TGF-{\beta}$, but less $IFN-{\gamma}$ than untreated cells. Metallothionein-primed cells were hyporesponsive to restimulation, and suppressive to T cell proliferation in an IL-10-dependent manner. Lymphocytes from metallothionein-deficient mice displayed significantly elevated levels of AP-1 and JNK activities in response to stimulation compared with those from wild-type controls. Importantly, transgenic mice overexpressing metallothionein exhibited significantly reduced susceptibility to collagen-induced arthritis and enhanced IL-10 level in the serum, relative to their nontransgenic littermates. Taken together, these data suggest that metallothionein is able to promote the generation of IL-10-and $TGF-{\beta}$-producing type 1 regulatory T-like cells by downregulating JNK-dependent AP-1 activity. Thus, metallothionein may play an important role in the regulation of Th1-dependent autoimmune arthritis, and may represent both a potential target for therapeutic manipulation and a critical element in the diagnostic assessment of disease potential.

• Journal of Gynecologic Oncology
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• 제29권6호
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• pp.93.1-93.11
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• 2018

The introduction of checkpoint inhibitors revolutionized immuno-oncology. The efficacy of traditional immunotherapeutics, like vaccines and immunostimulants was very limited due to persistent immune-escape strategies of cancer cells. Checkpoint inhibitors target these escape mechanisms and re-direct the immune system to anti-tumor toxicity. Phenomenal results have been reported in entities like melanoma, where no other therapy was able to demonstrate survival benefit, before the introduction of immunotherapeutics. The first experience in ovarian cancer (OC) was reported for nivolumab, a fully human anti-programmed cell death protein 1 (PD1) antibody, in 2015. While the data are extraordinary for a mono-immunotherapeutic agent and very promising, they do not match up to the revolutionary results in entities like melanoma. The key to exceptional treatment response in OC, could be the identification of the most immunogenic patients. We hypothyse that BRCA mutation could be a predictor of improved response in OC. The underlying DNA-repair-deficiancy should result in increased immunogenicity because of higher mutational load and more neoantigen presentation. This hypothesis was not tested to date and should be subject to future trials. The present article gives an overview of the immunologic background of checkpoint inhibition (CI). It presents current data on nivolumab and other checkpoint-inhibitors in solid tumors and OC specifically and depicts important topics in the management of this novel substance group, such as side effect control, diagnostic PD-1/programmed cell death-ligand 1 (PD-L1) expression assessment and management of pseudoprogression.

• Archives of Plastic Surgery
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• 제32권3호
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• pp.335-342
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• 2005

This study was undertaken to investigate possibility of the allogenic type I collagen inducing osteoinduction or osteoconduction at critical sized bone defect in the rabbit. Twenty Newzealand white rabbit, weighted from 2.8 kg to 3.5 kg, were used in this study. The skull was exposed and two bony defects were created with diameter of 10 mm. Group I(n=10), the bony defects was grafted from the other side bone. Group II(n=10), the bony defects was grafted by the allogenic type I collagen with bone morphogenic protein(BMP). Group III(n=10), the bony defects was grafted by the allogenic type I collagen only. Group IV(n=10), the bony defects was lefted with no grafts. The grafted bones and allogenic type I collagen were investigated with radiologic densitometry, histologic analysis and immunohistochemistry after 12 weeks. No major difference was observed in the gross finding between Group I, II, III, but dura mater was exposed in bony defect,the Group IV. The radiologic study demonstrated more bony opacity in the Group I, but the other groups did not demonstrate a significant difference. In the histologic study, grafted bone edge was completely consolidated with original bone in group I and new bone ingrew into the grafted allogenic type I collagen(group II, III),but there is no bone regeneration from the original bony edge in the group IV. The percent of the new bone formation by cross-sectional area was considered statistically significant at a p value of less than 0.05(p<0.05). In the immunohistochemistry study about BMP antibodies, the group IV demonstrated osteogenic activity in front of advancing original bone edge, in which the osteoblast stained strongly for BMP antibodies, but other group does not demonstrated any osteoblastic expression. There was no immunologic rejection. In conclusion, this results do not demonstrate that the allogenic type I collagen is useful for bone substitute, but the characters of the collagen, such as pliability, easy-handling, sponge-like structure, are useful in interpositional bone graft substitutes. The further evaluation of long term results about the resorption, immunologic tissue reaction, response of applied tissue growth factor to the allogenic collagen is needed.

• 미생물학회지
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• 제47권4호
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• pp.348-355
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• 2011

황색포도상구균은 사람에게서 염증을 동반한 다양한 형태의 국소적 또는 전신적 감염을 일으키는 주요 병원균이며, 황색포도상구균에서 풍부하게 발현되는 Staphylococcal protein A (SPA)는 염증의 활성화나 면역 반응의 회피와 관련된 균력인자로서 작용할 수 있다. 본 연구에서는 사람의 HaCaT 피부상피세포에서 재조합 SPA 단백질을 이용하여 염증반응에 대한 효과를 조사하기 위해서 pET-28a 발현벡터시스템을 이용하여 성공적으로 재조합 SPA 단백질을 제작하였고, 이 단백질(2 ${\mu}g$/ml)을 6, 12 및 24시간 처리한 HaCaT 피부상피세포에서 RT-PCR 및 ELISA를 이용하여 염증관련 부착인자 및 사이토카인의 발현을 분석하였다. SPA 처리 후 6시간에서 24시간까지 E-selectin, ICAM-1, MCP-1, IL-6 및 IL-8의 발현이 현저하게 증가함을 확인하였다. 또한 SPA는 HaCaT 피부상피세포에 대한 U937 단핵구의 부착력을 증진시켰다. 따라서, 본 연구의 결과는 SPA가 HaCaT 피부상피세포의 염증반응을 촉진시킨다는 사실을 보여주었으며, 황색포도상구균에 의한 피부염증질환에 있어서 중요한 병원성인자로서의 역할을 수행한다는 사실을 시사해준다.

• IMMUNE NETWORK
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• 제4권3호
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• pp.131-142
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• 2004

In recent years, adjuvants have received much attention because of the development of purified subunit and synthetic vaccines which are poor immunogens and require adjuvants to evoke the immune response. Therefore, immunologic adjuvants have been developed and testing for most of this century. During the last years much progress has been made on development, isolation and chemical synthesis of alternative adjuvants such as derivatives of muramyl dipeptide, monophosphoryl lipid A, liposomes, QS-21, MF-59 and immunostimulating complexes (ISCOMS). Biodegradable polymer microspheres are being evaluated for targeting antigens on mucosal surfaces and for controlled release of vaccines with an aim to reduce the number of doses required for primary immunization. The most common adjuvants for human use today are aluminum hydroxide and aluminum phosphate. Calcium phosphate and oil emulsions have been also used in human vaccination. The biggest issue with the use of adjuvants for human vaccines is the toxicity and adverse side effects of most of the adjuvant formulations. Other problems with the development of adjuvants include restricted adjuvanticity of certain formulations to a few antigens, use of aluminum adjuvants as reference adjuvant preparations under suboptimal conditions, non-availability of reliable animal models, use of non-standard assays and biological differences between animal models and humans leading to the failure of promising formulations to show adjuvanticity in clinical trials. The availability of hundreds of different adjuvants has prompted a need for identifying rational standards for selection of adjuvant formulations based on safety and sound immunological principles for human vaccines. The aim of the present review is to put the recent findings into a broader perspective to facilitate the application of these adjuvants in general and experimental vaccinology.

• Journal of Preventive Medicine and Public Health
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• 제32권3호
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• pp.347-354
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• 1999

Objective: This paper examines the possible toxicity to immune system in farmers chronically exposed to pesticides. Methods : We compared 43 male farmers exposed to pesticides with 29 male residents who had neither past nor current pesticides exposure. The selected variables for studying immunotoxicity were WBC, CD3, CD4, CD8, CD19, CD56, IgG, IgA, IgM, and IL-2. As part of the baseline questionnaires for the immunotoxicity, subjects were asked about kinds of farming, posticides exposure and medical history. Results : None of the variables for studying immunotoxicity showed statistically significant difference between the two groups. Although the results were not statistically significant, CD4 and the CD4/CD8 ratio decreased and CD8 increased. These effects showed a dose response change with exposure level. In the exposed group, the values of CD3, CD4, CD4/CD8 and CD19 decreased and those of the CD8 and CD56 increased compared to the non-exposed group. Also there was higher prevalence of self-reported disease in the exposed group compared to the non-exposed group. Conclusions: Although statistically significant differences in indices of immunotoxicity in farmers exposed to pesticides were not shown, the results suggest that pesticides may decrease immune function. More advanced test methods for immunotoxicity need to be developed and tested in larger population to detect immunotoxic effects of pesticides.

• Toxicological Research
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• 제34권1호
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• pp.7-12
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• 2018

Laboratory animal models have been developed to investigate preventive or therapeutic effect of medicinal products, or occurrence or progression mechanism of atopic dermatitis (AD), a pruritic and persistent inflammatory skin disease. The murine model with immunologic phenomena resembling human AD was introduced, which demonstrated skewedness toward predominance of type-2 helper T cell reactivity and pathophysiological changes similar as human AD following 2,4-dinitrochlorobenzene (DNCB) sensitization and challenge. Molecular mechanism on the DNCB-mediated AD was further evaluated. Skin tissues were collected from mice treated with DNCB, and each tissue was equally divided into two sections; one for protein and the other for mRNA analysis. Expression of filaggrin, an important protein for keratinocyte integrity, was evaluated through SDS-PAGE. Level of mRNA expression for cytokines was determined through semi-quantitative reverse transcriptase polymerase chain reaction. Expression of filaggrin protein was significantly enhanced in the mice treated with DNCB compared with the vehicle (acetone : olive oil = 4 : 1 mixture) treatment group or the normal group without any treatment. Level of tumor necrosis factor-alpha and interleukin-18 mRNA expression, cytokines involved in activity of type-1 helper T ($T_H1$) cell, was significantly downregulated in the AD group compared with other control groups. These results suggest that suppression of $T_H1$ cell-mediated immune response could be reflected into the skin tissue of mice treated with DNCB for AD induction, and disturbance of keratinocyte integrity might evoke a compensatory mechanism.

• 대한한방내과학회지
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• 제31권4호
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• pp.846-856
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• 2010

Objective : Allergic disease, a very common chronic illness that affects all ages of patients, has been well characterized as an IgE-dependent immunologic response. Recently, interest has grown about the late inflammatory reaction as well as the early one characterized by IgE and mast cells in allergic disease. The purpose of this study was to find the anti-inflammatory effect of Taeeumjowui-tang (Taiyintiaowei-tang) in allergic reaction. Methods : The experiment was performed using Raw 264.7 cells pretreated with Taeeumjowui-tang contents extracts. The results were measured for different concentrations of Taeeumjowui-tang extracts (100, 200, $300{\mu}g$/ml): the toxicity and proliferation of cells by MTT analysis, LPS-induced NO production using Griess reagent and IL-6/ TNF-${\alpha}$ production, which is a significant criteria for diagnosing allergic reaction. Results : No toxicity of Taeeumjowui-tang (100, 200, $300{\mu}g$/ml) on Raw 264.7 cells was found after 24 hours incubation. LPS-induced NO production was reduced after treatment with Taeeumjowui-tang (100, 200, $300{\mu}g$/ml)(P<0.001). IL-6 decreased only at $100{\mu}g$/ml(P<0.05). TNF-${\alpha}$ production decreased only at $300{\mu}g$/ml, but still statistically insignificant. There was no relationship between any components of Taeeumjowui-tang alone and inhibition of NO production. Conclusions : These data suggest that Taeeumjowui-tang has anti-inflammatory effects in allergic reaction.

• Archives of Plastic Surgery
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• 제32권4호
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• pp.408-415
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• 2005

Following a transverse rectus abdominis musculocutaneous(TRAM) flap breast reconstruction, denervated state of the flap causes the flap skin prone to thermal injury, calling for special attention. During the last 5 years, 69 breast reconstruction with 72 free TRAM flaps, were performed. Four out of thesse 69 patients sustained burn injury. Heat sources were a warm bag(n=2), heating pad(n=1) and warming light (n=1). The thermal injuries occured from 2 days to 3 months following the reconstruction. Three patients healed with conservative treatment, but one patient required debridement and skin graft. Initially 3 out of 4 patients with the burn had shown superficial 2nd degree burn with small blebs or bullae. However all 4 patients healed with scars. Mechanism of burn injuries of the denervated flap are known to be resulting from; 1) loss of behavioral protection due to denervation of flap with flap elevation and transfer, 2) loss of autonomic thermoregulatory control with heat dissipation on skin flap vasculature contributing to susceptibility of burn injury. 3) changes of immunologic and normal inflammatory response increasing thromboxane, and a fall in substance P & NGF (nerve growth factor). Including the abdominal flap donor site, sensory recovery of the reconstructed breast varies individually from 6 month even to 5 years postoperatively. During this period, wound healing is delayed, resulting in easier scarring compared to that observed in the sensate skin. Patients should be carefully informed and warned of possible burn injuries and taught to avoid exposure to heat source at least until 3 years postoperatively.