• Safety and Health at Work
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• 제13권2호
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• pp.248-254
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• 2022

Background: Occupational hazards in crop farms vary diversely based on different field operations as soil management, harvesting processes, pesticide, or fertilizer application. We aimed at evaluating the immunological status of crop farmers, as limited systematic investigations on immune alteration involved with crop farming have been reported yet. Methods: Immunological parameters including plasma immunoglobulin level, major peripheral immune cells distribution, and level of cytokine production from activated T cell were conducted. Nineteen grape orchard, 48 onion open-field, and 21 rose greenhouse farmers were participated. Results: Significantly low proportion of natural killer (NK) cell, a core cell for innate immunity, was revealed in the grape farmers (19.8±3.3%) in comparison to the onion farmers (26.4±3.1%) and the rose farmers (26.9±2.5%), whereas cytotoxic T lymphocyte proportion was lower in the grape and the onion farmers than the rose farmers. The proportion of NKT cell, an immune cell implicated with allergic response, was significantly higher in the grape (2.3±0.3%) and the onion (1.6±0.8%) farmers compared with the rose farmers (1.0±0.4%). A significantly decreased interferon-gamma:interleukin-13 ratio was observed from ex vivo stimulated peripheral blood mononuclear cells of grape farmers compared with the other two groups. The grape farmers revealed the lowest levels of plasma IgG1 and IgG4, and their plasma IgE level was not significantly different from that of the onion or the rose farmers. Conclusion: Our finding suggests the high vulnerability of workplace-mediated allergic immunity in grape orchard farmers followed by open-field onion farmers and then the rose greenhouse farmers.

• IMMUNE NETWORK
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• 제20권6호
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• pp.48.1-48.11
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• 2020

Hyperprogressive disease (HPD) is a distinct pattern of progression characterized by acceleration of tumor growth after treatment with anti-PD-1/PD-L1 Abs. However, the immunological characteristics have not been fully elucidated in patients with HPD. We prospectively recruited patients with metastatic non-small cell lung cancer treated with anti-PD-1/PD-L1 Abs between April 2015 and April 2018, and collected peripheral blood before treatment and 7-days post-treatment. HPD was defined as ≥2-fold increase in both tumor growth kinetics and tumor growth rate between pre-treatment and post-treatment. Peripheral blood mononuclear cells were analyzed by multi-color flow cytometry to phenotype the immune cells. Of 115 patients, 19 (16.5%) developed HPD, 52 experienced durable clinical benefit (DCB; partial response or stable disease ≥6 months), and 44 experienced non-hyperprogressive progression (NHPD). Patients with HPD had significantly lower progression-free survival (p<0.001) and overall survival (p<0.001). When peripheral blood immune cells were examined, the pre-treatment frequency of CD39⁺ cells among CD8⁺ T cells was significantly higher in patients with HPD compared to those with NHPD, although it showed borderline significance to predict HPD. Other parameters regarding regulatory T cells or myeloid derived suppressor cells did not significantly differ among patient groups. Our findings suggest high pre-treatment frequency of CD39⁺CD8⁺ T cells might be a characteristic of HPD. Further investigations in a larger cohort are needed to confirm our results and better delineate the immune landscape of HPD.

• Journal of Animal Science and Technology
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• 제45권6호
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• pp.957-966
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• 2003

면역반응중인 육계 병아리의 생산성과 단백질 및 에너지 이용성에 미치는 사료 중 크릴 밀의 영향을 조사하였다. 갓 부화(0 일령) 병아리(Avian)에 기초사료(크릴 밀 0.0%)와 기초 사료중 대두박 대신 0.5 또는 1.0%의 크릴 밀을 각각 대치한 사료(크릴 밀)를 급여하였다. 병아리 2 주령에 2일에 한 번씩 Salmonella typhymurium lipopolisacchaide(LPS)를 복강 내에 주입하여 자극한 면역반응시의 값을 멸균식염수(0.9%)을 주입한 것(대조)과 비교하였다. 대조 병아리에서 크릴 밀 사료는 생산성, 질소밸런스(NB), 뇨산 배설량, 및 ME 이용량에 영향을 미치지 않았다. 그러나, 면역반응은 사료 중 크릴 밀 함량에 관계없이 일당 증체량, 사료 섭취량과 NB를 대조에 비해서 유의하게(p〈0.05) 낮추었고, 뇨산 배설량과 간장 및 비장무게를 유의하게(p〈0.05) 높였다. 크릴 밀 1.0%사료는 사료효율을 유의하게 낮추고, 비장무게, g당 NB 또는 ME 이용량 및 사료 g당 ME값을 유의하게 높였다. 크릴 밀 사료는 면역 자극 후 회복중에는 간장과 비장무게를 감소 시켰다. 본 성적은 크릴 밀 사료가 면역반응중인 육계 병아리에서 단백질 분해는 증가시키나, 에너지 이용량은 높인다는 것을 나타내었다.

• 대한한방종양학회지
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• 제4권1호
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• pp.71-87
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• 1998

Even though appropriate immune response is necessary for the survival of the individual, excessive or insufficient immune Response might cause autoimmune or allergic disease. So the immune response must be controlled to the degree that is beneficial for the well being of the individual. This study was undertaken to know the effects of Gunleetang Gagambang on the immune system of the mouse. Gunleetang Gagambang has been used for cure of tumor as a traditional medicine without any experimental evidence to support the rational basis for its clinical use. This study was carried out to evaluate the possible therapeutic or antitumoral effects of Gunleetang Gagambang extract against tumor, and to carry out some mechanisms responsible for its effect. Some kinds of tumor were induced by the typical application of 3-methylcholanthrene(MCA) or by the implantation(s.c) of malignant tumor cells such as leukemia cells(3LL cells) or sarcoma cells(S180 cells). Treatment of the Gunleetang Gagambang on water-extract(dailly 1mg/mouse, i. p.) was continued for 7 days prior to tumor induction and after that the treatment was lasted for 20 days. Against squamous cell carcinoma induced by MCA, Gunleetang Gagambang decreased not only the frequency of tumor production but also the number and the weight of tumors per tumor bearing mice(TBM). Gunleetang Gagambang on also significantly suppressed the development of 3LL cell and S180 cell-implanted tumors in occurrence-frequency and their size. and some developed tumors were regressed by the continuous treatment of Gunleetang Gagambang extract into TBM. In vitro, treatment of Gunleetang Gagambang extract had no effect on the growth of some kinds of cell line such as FsaII, A431 strain but significantly inhibited the proliferation of 3LL, S180 cells and augmented the DNA synthesis of mitogen-activated lymphocytes. Gunleetang Gagambang also stimulated the migrative ability of leukocyte, the MIF and IL-2 production of T lymphocytes, but not IL 6 production of B cells. Gunleetang Gagambang administration to mice enhanced NK cells activities. These results demonstrated that Gunleetang Gagambang extract exhibited a significant prophylactic benefits against tumors and its antitumor activity was manifested depending on the type of tumor cells. And these results also suggested that effect of Gunleetang Gagambang might be chiefly due to nonspecitie enhancement of NK cell activities and cell-mediated immune responses.

• IMMUNE NETWORK
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• 제3권4호
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• pp.302-309
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• 2003

Background: CTLA4 (CD152), which is expressed on the surface of T cells following activation, has a much higher affinity for B7 molecules comparing to CD28, and is a negative regulator of T cell activation. In contrast to stimulating and agonistic capabilities of monoclonal antibodies specific to CTLA-4, CTLA4Ig fusion protein appears to act as CD28 antagonist and inhibits in vitro and in vivo T cell priming in variety of immunological conditions. We've set out to confirm whether inhibition of the CD28-B7 costimulatory response using a soluble form of human CTLA4Ig fusion protein would lead to persistent inhibition of alloreactive T cell activation. Methods: We have used CHO-$dhfr^-$ cell-line to produce CTLA4Ig fusion protein. After serum free culture of transfected cell line we purified this recombinant molecule by using protein A column. To confirm characterization of fusion protein, we carried out a series of Western blot, SDS-PAGE and silver staining analyses. We have also investigated the efficacy of CTLA4Ig in vitro such as mixed lymphocyte reaction (MLR) & cytotoxic T lymphocyte (CTL) response and in vivo such as experimental autoimmune encephalomyelitis (EAE), graft versus host disease (GVHD) and skin-graft whether this fusion protein could inhibit alloreactive T cell activation and lead to immunosuppression of activated T cell. Results: In vitro assay, CTLA4Ig fusion protein inhibited immune response in T cell-specific manner: 1) Human CTLA4Ig inhibited allogeneic stimulation in murine MLR; 2) CTLA4Ig prevented the specific killing activity of CTL. In vivo assay, human CTLA4Ig revealed the capacities to induce alloantigen-specific hyporesponsiveness in mouse model: 1) GVHD was efficiently blocked by dose-dependent manner; 2) Clinical score of EAE was significantly decreased compared to nomal control; 3) The time of skin-graft rejection was not different between CTLA4Ig treated and control group. Conclusion: Human CTLA4Ig suppress the T cell-mediated immune response and efficiently inhibit the EAE, GVHD in mouse model. The mechanism of T cell suppression by human CTLA4Ig fusion protein may be originated from the suppression of activity of cytotoxic T cell. Human CTLA4Ig could not suppress the rejection in mouse skin-graft, this finding suggests that other mechanism except the suppression of cytotoxic T cell may exist on the suppression of graft rejection.

• Journal of Chest Surgery
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• 제41권2호
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• pp.223-228
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• 2008

배경: 동물조직의 생체조직이식시 이종항원 물질인 알파-갈(${\alpha}$-Galactose) 항원결정인자에 대한 환자의 면역반응에 많은 관심이 높아지고 있다. 이에 이종 판막 이식 후 체내에서 ${\alpha}$-Galactose에 대하여 면역반응이 발현하는 것으로 알려져 있는 면역글로불린 G, M (IgG, IgM)의 변화를 일반적인 혈액 검사에 의한 혈중 농도를 측정하여 면역반응의 정도를 예측할 수 있는지 알아보고자 하였다. 대상 및 방법: 2006년 3월부터 2007년 1월까지, 개심술 환자를 대상으로 하여(이종 판막 이식 환자 (실험군, 10명), 이종 장기가 이식되지 않은 환자(대조군, 9명)) 전향적 연구를 시행하였다. 환자의 나이는 $10.3{\pm}9.1$세, 체중은 $31.4{\pm}20.3kg$이었다. 환자들에게서 수술 전, 수술 후 2일째, 수술 후 10일째에 일반적인 혈액 채취를 통하여 IgM, G의 혈중 농도를 측정하였다. 수술 이전에 이종 장기가 이식되어있던 환자들과 그렇지 않았던 환자들을 비교하여 면역 글로불린의 수술 전 기저치에 차이가 있는지, 그리고 이러한 이전의 상태가 수술 후 면역 글로불린의 혈중 농도 변화에 영향을 주었는지 통계학적으로 분석하였으며, 얻어진 혈중 농도로 두 군 간에 수술 후 면역 글로불린의 혈중 농도 변화와 정도에 차이가 있는지를 통계학적으로 분석하였다. 결과: 술전 이종 장기가 이식되어 있던 환자들과 그렇지 않은 환자들 사이에 면역글로불린의 혈중 농도에는 차이가 없었다(IgG; p-value=1.00, IgM; p-value=0.898). IgG, M 모두 실험군과 대조군 각 군 내에서 수술 전에 비하여 수술 후 2일째 혈중 농도가 감소하였다가 이후 다시 증가하는 일정한 변화의 경향을 보였고, 그 변화 정도가 시간에 따라 통계학적으로 의미 있게 달라졌다. 그러나 실험군과 대조군 사이에는 그 변화의 정도, 경향에 의미있는 차이가 없었다(IgG; p-value=0.393, IgM; p-value=0.193). 결론: 이종조직 판막이식 후 혈액 채취를 통해 얻은 혈중 농도 변화는 이종조직판막 이식을 하지 않는 수술을 받은 환자와 차이가 없었다. 이것은 면역 글로불린의 혈중 농도 변화 정도가 술 후 양 군 간에 차이가 없다기보다는, 일상적인 혈액 채취를 통한 면역 글로불린의 혈중 농도 측정으로는 면역 반응에 의한 면역 글로불린의 변화를 측정하기 어렵기 때문이라고 생각한다. 따라서 이종조직판막이식 후의 이종동물항원에 대한 면역반응의 체내 변화를 관찰하기 위해서는 직접적인 ${\alpha}$-Galactose에 대한 항체의 측정이 필요할 것으로 생각한다.

• BMB Reports
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• 제47권9호
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• pp.512-517
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• 2014

In this study, we showed that Mycobacterium abscessus MAB2560 induces the maturation of dendritic cells (DCs), which are representative antigen-presenting cells (APCs). M. abscessus MAB2560 stimulate the production of pro-inflammatory cytokines [interleukin (IL)-6, tumor necrosis factor (TNF)-${\alpha}$, IL-$1{\beta}$, and IL-12p70] and reduce the endocytic capacity and maturation of DCs. Using $TLR4^{-/-}$ DCs, we found that MAB2560 mediated DC maturation via Toll-like receptor 4 (TLR4). MAB2560 also activated the MAPK signaling pathway, which was essential for DC maturation. Furthermore, MAB2560-treated DCs induced the transformation of $na\ddot{i}ve$ T cells to polarized $CD4^+$ and $CD8^+$ T cells, which would be crucial for Th1 polarization of the immune response. Taken together, our results indicate that MAB2560 could potentially regulate the host immune response to M. abscessus and may have critical implications for the manipulation of DC functions for developing DC-based immunotherapy.

• BMB Reports
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• 제49권10호
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• pp.554-559
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• 2016

Mycobacterium abscessus, a member of the group of non-tuberculous mycobacteria, has been identified as an emerging pulmonary pathogen in humans. However, little is known about the protective immune response of antigen-presenting cells, such as dendritic cells (DCs), which guard against M. abscessus infection. The M. abscessus gene MAB1843 encodes ᴅ-alanyl-ᴅ-alanine dipeptidase, which catalyzes the hydrolysis of ᴅ-alanyl-ᴅ-alanine dipeptide. We investigated whether MAB1843 is able to interact with DCs to enhance the effectiveness of the host's immune response. MAB1843 was found to induce DC maturation via toll-like receptor 4 and its downstream signaling pathways, such as the mitogen-activated protein kinase and nuclear factor kappa B pathways. In addition, MAB1843-treated DCs stimulated the proliferation of T cells and promoted Th1 polarization. Our results indicate that MAB1843 could potentially regulate the immune response to M. abscessus, making it important in the development of an effective vaccine against this mycobacterium.

• 동의생리병리학회지
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• 제16권3호
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• pp.483-489
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• 2002

APA-01, which is an aqueous extract of five Chinese herbs, is a modified formula of Huoxiang-Zhengqi-San. The effect of new herb extract on immune response was investigated. The parameter examined to assess apparent immune response of APA-01 in mice included changes of body weight, relative weight of immune organs, cell proliferation and cytokine gene expression. The body weight and relative weight of immune organs were not significantly changed among the tested groups. In the spleen cell prolijeration assay, APA-01 increased the cell proliferation in a dose-dependent manner. Methotrexate (MTX), an agent of immune suppression, inhibited the spleen cell proliferation (IC/sub 50/: 800㎍/㎖). However, APA-01 significantly inhibited the suppression of mouse spleen cell proliferation. Therefore, it seems that APA-01 has a reducing effect of immune suppression. Immunomodulatory effect of APA-01 was further investigated using reverse transcription polymerase chain reaction (RT-PCR) in mouse spleen cells. In RT-PCR test, APA-01 enhanced the expression of cyclooxygenase-2 (COX-2) mRNA in a dose-dependent manner. In spite of immune suppression by MTX, COX-2 mRNA was induced by co-treatment with APA-01. These results suggest that APA-01 stimulates the proliferation of spleen cells, regulates the expression of COX-2 mRNA, and accelerates the recovery of inhibition of spleen cell proliferation induced by MTX, thus providing the immunological basis for clinical benefit of APA-01.

• 동의생리병리학회지
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• 제24권4호
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• pp.616-623
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• 2010

Three herbal formulas (Bangpungtongsung-san, Ohyaksungi-san, and Ojeok-san) for wind-cold and heat pain symptom were applied to investigate the immunological activities on antigen (Ag)-specific or Ag-non-specific immune responses in murine macrophage cell line (RAW 264.7) and ovalbumin (OVA)-immunized mice. This study was carried out in nitric oxide (NO) synthesis in RAW 264.7 cells and cellular proliferation in mouse splenocytes according to three herbal formulas. C57BL/6 mice were immunized intraperitonially with OVA/aluminium ($100\;{\mu}g/200\;{\mu}g$/mouse) on day 1, 8, and 15. Three herbal formulas were administrated to mice orally for 3 weeks from day 1. On day 22, OVA-, lipopolysaccharide (LPS)-, and concanavalin A (Con A)-stimulated splenocyte proliferation and antibodies (OVA-specific antibodies of the IgG, lgG1, and total IgM classes) in plasma were measured. Ohyaksungi-san increased NO synthesis in RAW 264.7 cells. Ojeok-san and Ohyaksungi-san significantly enhanced cellular proliferation by LPS and Con A in splenocytes from OVA-immunized mice (p<0.001). Three herbal formulas for wind-cold and heat pain symptom also significantly enhanced plasma OVA-specific IgG, IgG1, and total IgM levels compared with the OVA/Alum group. These results suggested that three herbal formulas for wind-cold and heat pain symptom could be used as stimulator of immune response.