• 대한한방내과학회지
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• 제19권1호
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• pp.221-246
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• 1998

The aim of this experimental study was to evaluate the anti-tumor effects of Chungsimbohyeltang through investigation about viability of tumor cell by MTT assay, survival period of mice transplanted with L-1210 cells, growth inhibition on the tumor cell, body weight variation in mice transplanted with sarcoma-180 cells and its immunomodulatory effects through the investigation on delayed type hyper-sensitivity, the hemagglutinin and hemolysin titers for humoral immune response, the appearance of rosette forming cells for cell-mediated immune response, the natural killer cell activity, the transformation of lymphocyte, the productivity of Interleukin-2 and phagocytic index K was performed in immune-depressed ICR mice induced by methotrexate treatments. The results were as follows ; 1. $IC_{50}$ of Chungsimbohyeltang treated group was 5.85mg/ml in SNU-C4 cell, 1.38mg/ml in SNU-396 cell, 0.21mg/ml in SNU-1 cell, so it had low anti-tumor activity. 2. The both groups of Chungsimbohyeltang extract 10mg/kg and Chungsimbohyeltang extract 20mg/kg had no toxicity and the group of Chungsimbohyeltang 20mg/kg which was shown 120% in ILS had the effect of life prolongation in mice transplanted with L-1210 cells. 3. In the growth inhibition on the tumor cells, only the group of Chungsimbohyeltang extract 20mg/kg was noted and in the weight variation in mice transplanted with sarcoma-180 cells, both groups of Chungsimbohyeltang extract had a significant effect. 4. In the delayed type hypersensitivity and appearance of rosette forming cells, both groups of Chungsimbohyeltang extract didn't have any significant effect. 5. The hemagglutinin titers was slightly increased with no significance, and the hemolysin titers was significantly increased in the only group of Chungsimbohyeltang extract 20mg/kg. 6. The natural killer cell activity of the Chungsimbohyeltang extract groups was significantly increased in the ratio of 100:1 of effector and target cells, but it was not significantly increased in the ratio of 50:1, 10:1. 7. The transformation of lymphocyte and the productivity of Interleukin-2 were increased significantly and in dose-dependent manner in both group of Chungsimbohyeltang extract. 8. The phagocytic effect of macropage was significantly increased in both groups of Chungsimbohyeltang extract. Considering the results above, we could conclude that Chungsimbohyeltang have an indirect anti-tumor effect through the modulation of immunme response, although it had not toxicity on the tumor cell it self.

• Asian Pacific Journal of Cancer Prevention
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• 제16권12호
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• pp.4833-4837
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• 2015

Biomarkers for preclinical diagnosis of cancer are valuable tools for detection of malignant tumors at early stages in groups at risk and screening healthy people, as well as monitoring disease recurrence after treatment of cancer. However the complexity of the body's response to the pathological processes makes it virtually impossible to evaluate this response to the development of the disease using a single biomarker that is present in the serum at low concentrations. An alternative approach to standard biomarker analysis is called immunosignature. Instead of going after biomarkers themselves this approach rely on the analysis of the humoral immune response to molecular changes associated with the development of pathological processes. It is known that antibodies are produced in response to proteins expressed during cancer development. Accordingly, the changes in antibody repertoire associated with tumor growth can serve as biomarkers of cancer. Immunosignature is a highly sensitive method for antibody repertoire analysis utilizing high density peptide microarrays. In the present review we discuss modern methods for antibody detection, as well as describe the principles and applications of immunosignature in research and clinical practice.

• The Korean Journal of Physiology and Pharmacology
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• 제8권2호
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• pp.89-94
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• 2004

The arterial pressure is regulated by the nervous and humoral mechanisms. The neuronal regulation is mostly carried out by the autonomic nervous system through the rostral ventrolateral medulla (RVLM), a key area for the cardiovascular regulation, and the humoral regulation is mediated by a number of substances, including the angiotensin (Ang) II and vasopressin. Recent studies suggest that central interleukin-1 (IL-1) activates the sympathetic nervous system and produces hypertension. The present study was undertaken to elucidate whether IL-1 and Ang II interact in the regulation of cardiovascular responses to the stress of hemorrhage. Thus, Sprague-Dawley rats were anesthetized and both femoral arteries were cannulated for direct measurement of arterial pressure and heart rate (HR) and for inducing hemorrhage. A guide cannula was placed into the lateral ventricle for injection of IL-1 $(0.1,\;1,\;10,\;20\;ng/2\;{\mu}l)$ or Ang II $(600\;ng/10\;{\mu}l)$. A glass microelectrode was inserted into the RVLM to record the single unit spike potential. Barosensitive neurons were identified by an increased number of single unit spikes in RVLM following intravenous injection of nitroprusside. I.c.v. $IL-1\;{\beta}$ increased mean arterial pressure (MAP) in a dose-dependent fashion, but HR in a dose-independent pattern. The baroreceptor reflex sensitivity was not affected by i.c.v. $IL-1\;{\beta}$. Both i.c.v. $IL-1\;{\alpha}\;and\;{\beta}$ produced similar increase in MAP and HR. When hemorrhage was induced after i.c.v. injection of $IL-1\;{\beta}$, the magnitude of MAP fall was not different from the control. The $IL-1\;{\beta}$ group showed a smaller decrease in HR and a lower spike potential count in RVLM than the control. MAP fall in response to hemorrhage after i.c.v. injection of Ang II was not different from the control. When both IL-1 and Ang II were simultaneously injected i.c.v., however, MAP fall was significantly smaller than the control, and HR was increased rather than decreased. These data suggest that IL-1, a defense immune mediator, manifests a hypertensive action in the central nervous system and attenuates the hypotensive response to hemorrhage by interaction with Ang II.

• Asian-Australasian Journal of Animal Sciences
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• 제20권9호
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• pp.1453-1461
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• 2007

This study was conducted to test the hypothesis that dietary supplementation with an herbal extract of Acanthopanax senticosus (AS) enhances the immune response in weaned piglets. Sixty piglets weaned at 21 days of age were randomly assigned to 3 treatment groups representing the addition of 0 or 1 g/kg of the AS extract or 0.2 g/kg of colistin (an antibiotic) to maize- and soybean meal-based diets (n = 20 per group). On days 7, 14 and 28 after initiation of the addition, total and differential counts of leucocytes, proliferating activity of peripheral lymphocytes, serum levels of immunoglobulins (Ig) and cytokines and the spleen index were determined. The AS extract decreased (p<0.05) the number of neutrophils on days 7 and 28 in comparison with the control group and reduced (p<0.05) serum interleukin-$1{\beta}$ level on day 28 compared with the other 2 groups. Dietary supplementation with the AS extract increased (p<0.05) the lymphocyte/leukocyte ratio on day 28 compared with the control group and increased the proliferating activity of lymphocytes on days 14 and 28 compared with the other 2 groups. The AS extract increased (p<0.05) the serum content of IgG on day 7 and of IgG and IgM on day 28 compared with the other 2 groups, as well as increasing the serum content of tumor necrosis factor on day 7 and spleen index on days 7 and 28 compared with the control group. Collectively, these findings suggest that the AS extract as a dietary additive enhances the cellular and humoral immune responses of weaned piglets by modulating the production of immunocytes, cytokines and antibodies.

• Parasites, Hosts and Diseases
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• 제55권3호
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• pp.255-267
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• 2017

Malaria is an infectious disease affecting humans, which is transmitted by the bite of Anopheles mosquitoes harboring sporozoites of parasitic protozoans belonging to the genus Plasmodium. Despite past achievements to control the protozoan disease, malaria still remains a significant health threat up to now. In this study, we cloned and characterized the full-unit Plasmodium yoelii genes encoding merozoite surface protein 1 (MSP1), circumsporozoite protein (CSP), and Duffy-binding protein (DBP), each of which can be applied for investigations to obtain potent protective vaccines in the rodent malaria model, due to their specific expression patterns during the parasite life cycle. Recombinant fragments corresponding to the middle and C-terminal regions of PyMSP1 and PyCSP, respectively, displayed strong reactivity against P. yoelii-infected mice sera. Specific native antigens invoking strong humoral immune response during the primary and secondary infections of P. yoelii were also abundantly detected in experimental ICR mice. The low or negligible parasitemia observed in the secondary infected mice was likely to result from the neutralizing action of the protective antibodies. Identification of these antigenic proteins might provide the necessary information and means to characterize additional vaccine candidate antigens, selected solely on their ability to produce the protective antibodies.

• 한국어병학회지
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• 제27권2호
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• pp.85-89
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• 2014

Water temperature is a key environmental factor controlling the epizootics of viral diseases in fish. High water temperature is associated with the rapid spread of rock bream iridovirus (RBIV) disease and with high mortality of RBIV infected fish. Although protection of fish against iridoviral disease by active immunization has been reported, little information is available concerning whether fish survived from an epizootic of iridoviral disease can naturally acquire resistance against the viral disease. In the present study, we have demonstrated that juvenile rock bream, which survived from a natural epizootic of RBIV, acquired resistance against recurrence or reinfection of RBIV, and this resistance was established during the subsequent low water temperature period. Furthermore, the possible involvement of the adaptive humoral immune response in the resistance of the juvenile rock bream was suggested by in vivo neutralization experiment.

• 한국축산식품학회지
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• 제36권1호
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• pp.14-18
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• 2016

Oral administration of soluble antigen can induce peripheral tolerance to the antigen. This study was conducted to evaluate whether gamma-irradiated ovalbumin (OVA) can induce oral tolerance. To investigate this, we administrated intact or irradiated OVA to mice, induced allergic response using intact OVA and alum, then compared humoral and cellular immune responses. Mice treated with gammairradiated OVA had less OVA-specific IgE compared with those who were administered intact OVA. There was no difference in levels of OVA-specific IgG+A+M, IgG1, and IgG2a. Splenocytes of mice administered irradiated OVA showed similar OVA-specific T cell proliferation and secretion of IFN-γ and IL-4. However, there was an increase in IL-2 and a decrease of IL-6 secretion in mice treated with irradiated OVA. These results indicate that gamma-irradiated OVA have similar effects to intact OVA on antigen tolerance.

• 대한미생물학회지
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• 제14권1호
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• pp.79-87
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• 1979

Newcastle병(病) 바이러스(L-NDV)가 ICR 마우스의 세포성(細胞性), 체액성(體液性) 면역반응(免疫反應)에 미치는 영향(影響)을 알아보기 위(爲)하여 2-NDV($10^6$EID/mouse)를 SRBC($10^6$EID_{50}/mouse)로 면역(免疫)하기 전후(前後) 또는 동시(同時)에 미정맥내(尾靜脈內)로 감염(感染)시키고 면역(免疫) 4일(日)에 SRBC($10^8$세포/mouse)를 challenge하여 24시간후(時間後)에 족척종창반응(足蹠腫脹反應)을 검사(檢査)하였으며, 동시(同時)에 비장세포(脾臟細胞)의 로젤형성능(形成能), 말초순환(末梢循環) 혈액내(血液內)의 임파구(淋巴球)의 수(數), 그리고 SRBC에 대(對)한 응집항체가(凝集抗體價) 및 용혈항체가(溶血抗體價)를 측정(測定)하였다. 한편 NDV 감염(感染)으로 인(因)한 면역반응(免疫反應) 억제기전(抑制機轉)을 구명(究明)하기 위(爲)하여 L-NDV를 가온(加溫) 불활화(不活化)하거나(H-NDV), 자외선(紫外線)에 조사(照射)시켜(UV-NDV) 마우스에 투여(投與)하거나, L-NDV로 유도(誘導)한 마우스조제(粗製) interferon(C-IF)을 투여(投與)하여 발현(發現)되는 반응(反應)을 측정(測定), 비교(比較)하여 다음과 같은 결과(結果)를 얻었다. 족척종창반응(足蹠腫脹反應)을 SRBC로 면역전(免疫前) 오는 면역후(免疫後)에 L-NDV를 접종(接種)한 군(群)에서 모두 억제(抑制)되었으며 그 억제정도(抑制程度)는 바이러스 감염(感染)과 항원주사(抗原注射)와의 간격(間隔)이 길면 길수록 심(甚)하였다. 그러나 UV-NDV나 H-NDV를 접종(接種)한 군(群)에서의 족척종창반응(足蹠腫脹反應)은 대조군(對照群)에 비(比)하여 대체적(大體的)으로 경미(輕微)하거나 전혀 억제(抑制)가 인지(認知)되지 않았다. 한편 C-IF나 C-IF를 가온불활화(加溫不活化)한 C-IFh를 투여(投與)한 군(群)에서의 족척종창(足蹠腫脹)은 정도(程度)의 차이(差異)는 있으나 대조군(對照群)에 비(比)하여 현저(顯著)히 감소(減少)되었다. 비장세포(脾臟細胞)의 로젤형성율(形成率)은 바이러스 감염(感染)으로 현저(顯著)히 감소(減少)되었는데 그 감소(減少)의 정도(程度)는 면역전(免役前) 또는 면역(免疫)과 동시(同時)에 바이러스를 접종(接種)한 군(群)에서 면역후(免疫後) 바이러스를 감염(感染)시킨 군(群)보다 심(甚)하였다. 한편 UV-NDV나 H-NDV를 접종(接種)한 군(群)에서 비장세포(脾臟細胞)의 로젤형성률(形成率)은 L-NDV 접종군(接種群)에 비(比)하여 약간(若干) 경미(輕微)한 감소(減少)를 보이거나 또는 비슷한 양상(樣相)을 보여 대조군(對照群)보다는 현저(顯著)히 억제(抑制)된 결과(結果)를 보였다. 또한 마우스에 C-IF를 투여(投與)하면 비장세포(脾臟細胞)의 로젤형성률(形成率)은 억제(抑制)되었으나 C-IFh를 투여(投與)하면 오히려 로젤형성률(形成率)이 증가(增加)되었다. 체액성면역반응(體液性免疫反應)은 면역전(免疫前) 24 및 48시간(時間)에 L-NDV를 접종(接種)한 군(群)에서는 현저(顯著)히 억제(抑制)되었으나, 면역전(免疫前) 9시간(時間), 면역(免疫)과 동시(同時) 또는 면역후(免疫後)에 L-NDV를 접종(接種)한 대조군(對照群)과 유의(有意)한 차이(差異)를 보이지 않았다. 순환혈액내(循環血液內) 임파구수(淋巴球數)는 면역전(免疫前) 48 또는 24시간(時間)에 L-NDV를 접종(接種)하면 대조군(對照群)에 비(比)하여 현저(顯著)히 감소(減少)되었으나, 면역전(免疫前) 9시간(時間) 또는 면역(免疫)과 동시(同時)에 L-NDV를 접종(接種)하면 오히려 그 수(數)가 증가(增加)되었다. 이상(以上)의 실험결과(實驗結果) SRBC에 대(對)한 세포성(細胞性) 면역반응(免疫反應)의 억제(抑制)는 NDV가 afferent limb과 efferent limb를 모두 억제(抑制)하여 야기(惹起)되는 체액성(體液性) 면역반응(免疫反應)의 억제(抑制)는 NDV가 afferent limb만을 억제(抑制)하여 일어남을 알 수 있다. 또한 NDV 감염(感染)으로 인(因)한 면역반응억제(免疫反應抑制)는 interferon과 바이러스의 직접적(直接的)인 작용(作用)에 기인(基因)됨을 강력(强力)히 시사(示唆)한다.

• IMMUNE NETWORK
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• 제11권5호
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• pp.268-280
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• 2011

Background: Dengue virus, which belongs to the Flavivirus genus of the Flaviviridae family, causes fatal dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) with infection risk of 2.5 billion people worldwide. However, approved vaccines are still not available. Here, we explored the immune responses induced by alternating prime-boost vaccination using DNA vaccine, adenovirus, and vaccinia virus expressing E protein of dengue virus type 2 (DenV2). Methods: Following immunization with DNA vaccine (pDE), adenovirus (rAd-E), and/or vaccinia virus (VV-E) expressing E protein, E protein-specific IgG and its isotypes were determined by conventional ELISA. Intracellular CD154 and cytokine staining was used for enumerating CD4+ T cells specific for E protein. E protein-specific CD8+ T cell responses were evaluated by in vivo CTL killing activity and intracellular IFN-${\gamma}$ staining. Results: Among three constructs, VV-E induced the most potent IgG responses, Th1-type cytokine production by stimulated CD4+ T cells, and the CD8+ T cell response. Furthermore, when the three constructs were used for alternating prime-boost vaccination, the results revealed a different pattern of CD4+ and CD8+ T cell responses. i) Priming with VV-E induced higher E-specific IgG level but it was decreased rapidly. ii) Strong CD8+ T cell responses specific for E protein were induced when VV-E was used for the priming step, and such CD8+ T cell responses were significantly boosted with pDE. iii) Priming with rAd-E induced stronger CD4+ T cell responses which subsequently boosted with pDE to a greater extent than VV-E and rAd-E. Conclusion: These results indicate that priming with live viral vector vaccines could induce different patterns of E protein-specific CD4+ and CD8+ T cell responses which were significantly enhanced by booster vaccination with the DNA vaccine. Therefore, our observation will provide valuable information for the establishment of optimal prime-boost vaccination against DenV.

• 대한한방종양학회지
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• 제6권1호
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• pp.47-65
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• 2000

In order to investigate antitumor and immune response effect by Hyangsapyungwisan after Sarcoma-180 cells and methotrexate were treatred each other, the extract of Hyangsapyungwisan was orally administered to ICR mice for 14 days. To evaluate the effects of the Hyangsapyungwisan, 50% inhibition concentration($IC_{50}$), mean survival days, tumor weight for antitumor effects, hemagglutinin titer, hemolysin titer, rosette forming cells, natural killer cell activity and productivity of interleukin-2 for immune responses measured in ICR mice. The results were summarized as follows: 1. Mean survival time in Hyangsapyungwisan-treated group was slightly prolonged, as compared with control group(13.46%). 2. On the MTT assay, cell viability was significantly inhibited by $5{\mu}g/well,\;2.5{\mu}g/well,\;1.25{\mu}g/well,\;and\;0.625{\mu}g/well$ of Hyangsapyung-wisan concentration inhibited cell viability significantly. $IC_{50}$ for cell viability was $11.59{\mu}g/well$. 3. Tumor weight in Hyangsapyungwisan treated group was depressed, as compared with the control group(p<0.05). 4. Hemagglutinin titer in Hyangsapyungwisan-treated group was slightly increased with no significance, as compared with the control group. 5. Hemolysin titer in Hyangsapyungwisan-treated group was silightly increased, as compared with the control group(p<0.05). 6. Rosette forming cells in Hyangsapyungwisan-treated group was silightly increased, as compared with the control group(p<0.05). 7. Naural killer cell activity in Hyangsapyungwisan-treated group was significantly increased(p<0.05). 8. Production of interleukin-2 was significantly increased(p<0.05). According to the above results, Hyangsapygwisan had prominent antitumor effects, and enhance both cellular and humoral immunity in mice.