• 제목/요약/키워드: Immune activation

검색결과 964건 처리시간 0.033초

Harnessing NK cells for cancer immunotherapy: immune checkpoint receptors and chimeric antigen receptors

  • Kim, Nayoung;Lee, Dong-Hee;Choi, Woo Seon;Yi, Eunbi;Kim, HyoJeong;Kim, Jung Min;Jin, Hyung-Seung;Kim, Hun Sik
    • BMB Reports
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    • 제54권1호
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    • pp.44-58
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    • 2021
  • Natural killer (NK) cells, key antitumor effectors of the innate immune system, are endowed with the unique ability to spontaneously eliminate cells undergoing a neoplastic transformation. Given their broad reactivity against diverse types of cancer and close association with cancer prognosis, NK cells have gained considerable attention as a promising therapeutic target for cancer immunotherapy. NK cell-based therapies have demonstrated favorable clinical efficacies in several hematological malignancies but limited success in solid tumors, thus highlighting the need to develop new therapeutic strategies to restore and optimize anti-tumor activity while preventing tumor immune escape. The current therapeutic modalities yielding encouraging results in clinical trials include the blockade of immune checkpoint receptors to overcome the immune-evasion mechanism used by tumors and the incorporation of tumor-directed chimeric antigen receptors to enhance NK cell anti-tumor specificity and activity. These observations, together with recent advances in the understanding of NK cell activation within the tumor microenvironment, will facilitate the optimal design of NK cell-based therapy against a broad range of cancers and, more desirably, refractory cancers.

Mechanisms of immune tolerance to allergens in children

  • Kucuksezer, Umut C.;Ozdemir, Cevdet;Akdis, Mubeccel;Akdis, Cezmi A.
    • Clinical and Experimental Pediatrics
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    • 제56권12호
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    • pp.505-513
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    • 2013
  • Because the prevalence of allergic diseases has significantly increased in recent years, understanding the causes and mechanisms of these disorders is of high importance, and intense investigations are ongoing. Current knowledge pinpoints immune tolerance mechanisms as indispensable for healthy immune response to allergens in daily life. It is evident that development and maintenance of allergen-specific T cell tolerance is of vital importance for a healthy immune response to allergens. Such tolerance can be gained spontaneously by dose-dependent exposures to allergens in nature or by allergen-specific immunotherapy. Allergen-specific immunotherapy induces regulatory T cells with the capacity to secrete interleukin-10 and transforming growth factor-${\beta}$, limits activation of effector cells of allergic inflammation (such as mast cells and basophils), and switches antibody isotype from IgE to the noninflammatory type IgG4. Although allergen-specific immunotherapy is the only method of tolerance induction in allergic individuals, several factors, such as long duration of treatment, compliance problems, and life-threatening side effects, have limited widespread applicability of this immunomodulatory treatment. To overcome these limitations, current research focuses on the introduction of allergens in more efficient and safer ways. Defining the endotypes and phenotypes of allergic diseases might provide the ability to select ideal patients, and novel biomarkers might ensure new custom-tailored therapy modalities.

Dendritic Cell-Mediated Mechanisms Triggered by LT-IIa-B5, a Mucosal Adjuvant Derived from a Type II Heat-Labile Enterotoxin of Escherichia coli

  • Lee, Chang Hoon;Hajishengallis, George;Connell, Terry D.
    • Journal of Microbiology and Biotechnology
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    • 제27권4호
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    • pp.709-717
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    • 2017
  • Mucosal tissues are the initial site through which most pathogens invade. As such, vaccines and adjuvants that modulate mucosal immune functions have emerged as important agents for disease prevention. Herein, we investigated the immunomodulatory mechanisms of the B subunit of Escherichia coli heat-labile enterotoxin type IIa ($LT-IIa-B_5$), a potent non-toxic mucosal adjuvant. Alternations in gene expression in response to $LT-IIa-B_5$ were identified using a genome-wide transcriptional microarray that focused on dendritic cells (DC), a type of cell that broadly orchestrates adaptive and innate immune responses. We found that $LT-IIa-B_5$ enhanced the homing capacity of DC into the lymph nodes and selectively regulated transcription of pro-inflammatory cytokines, chemokines, and cytokine receptors. These data are consistent with a model in which directional activation and differentiation of immune cells by $LT-IIa-B_5$ serve as a critical mechanism whereby this potent adjuvant amplifies mucosal immunity to co-administered antigens.

지질다당류를 투여한 비장세포에서 4,4'-diaminodiphenyl sulfone (dapsone)의 항염증 효과: 염증 관련 사이토카인의 선택적 억제 (Anti-inflammatory effects of 4,4'-diaminodiphenyl sulfone (dapsone) in lipopolysaccharide-treated spleen cells: selective inhibition of inflammation-related cytokines)

  • 문선영;주홍구
    • 대한수의학회지
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    • 제55권3호
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    • pp.199-204
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    • 2015
  • 4,4'-diaminodiphenyl sulfone (dapsone) is a sulfone drug that has antibacterial effects on a variety of bacteria, especially Mycobacterium leprae; thus, it has been used to treat leprosy. Previous studies demonstrated that dapsone inhibits integrin-mediated adherence of neutrophils and production of prostaglandin $E_2$ by polymorphonuclear leukocytes. Hence, dapsone may act in immune cells and regulate cell-mediated inflammation processes. However, its anti-inflammatory effects remain unclear. The present study demonstrated that dapsone modulates the production of inflammation-related cytokines in immune cells. We employed the spleen cells of mice, which are major immune cells, and lipopolysaccharide (LPS) as a causative agent of inflammation for experiments. Dapsone induced a proportional change in splenocyte subsets and the apoptosis of spleen cells. Interestingly, dapsone decreased the production of tumor necrosis factor-alpha and interleukin (IL)-10, but not IL-6, in LPS-treated spleen cells. In other assays, we measured the dapsone-induced production of nitric oxide (NO) and the expression of activation markers of spleen cells. Dapsone decreased NO production in LPS-treated spleen cells. Taken together, our results demonstrate that dapsone has anti-inflammatory effects in immune cells and provide new insight into the potential uses of this agent.

밀리타리스 동충하초(Cordyceps militaris)의 인플루엔자백신 적응면역에 미치는 영향 (The Effect of Cordyceps militaris on Adaptive Immune Responses in DBA2 Mice Immunized with Influenza Vaccine)

  • 이환희;조효선
    • 약학회지
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    • 제59권1호
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    • pp.1-5
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    • 2015
  • Cordyceps militaris has shown to have various pharmacological activities including an immune-modulatory effect. Previously, we reported that anti-influenza effect of C. militaris in DBA/2 mice was mediated by increased IL-12 and the activation of NK cells. In this study, we investigated the effect of C. militaris on adaptive immune responses using DBA2 mice immunized with influenza vaccine. To determine the effect of C. militaris on antigen presentation capability, we treated RAW 264.7 cells with various concentrations of ethanol extract of C. militaris, which showed a significant upregulation of CD86 (B7.2), CD284 (TLR4), CD40, H-2k (MHC I) and I-Ad (MHC II). To examine the direct effect of C. militaris on adaptive immune responses, we immunized DBA2 mice with influenza vaccine in presence or absence of C. militaris. After 2 or 4 weeks, influenza-specific T cell proliferation, HAI titers and IFN-${\gamma}$ production were measured in plasma or PBMCs isolated from animals. Influenza-specific T cell proliferation and HAI titers were not considerably increased in immunized mice in presence of C. militaris. However, the production of IFN-${\gamma}$ was much greater in immunized mice with C. militaris as adjuvant than only immunized mice.

2주 동안의 율무 추출물 경구 투여가 복강대식세포의 사이토카인 $IL-1{\beta}$, IL-6, $TNF-{\alpha}$, IL-10 생성에 미치는 영향 (Effect of Job's Tear(Yul-Moo) Extracts on Mouse Oral Administration $IL-l{\beta}$, IL-6, $TNF-{\alpha}$, IL-10 Cytokine Production by Peritoneal Macrophage for Two Weeks)

  • 류혜숙
    • 한국식품영양학회지
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    • 제21권2호
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    • pp.204-209
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    • 2008
  • The present study examined the ex vivo effect of Job's tear on immune function. Seven to eight week old mice(Balb/c) were fed a chow diet ad libitum two different concentrations (50 and 500 mg/kg BW) of water extract of Job's tear were orally administ every other day for two weeks. The results indicated that macrophage activation had occurred in the mice receiving 50 mg/kg B. W. of Job's tear water extract. Overall, using a mouse model, this study demonstrated that Job's tear extract may enhance immune function by regulating the $IL-1{\beta}$, IL-6, $TNF-{\alpha}$ and IL-10 cytokine production capacity of activated macrophages in mice. This study may suggest that supplementation of Job's tear water extracts may enhance the immune function by regulating the enhancing the cytokine production by activated macrophage ex vivo.

식물체의 면역반응 기작 (Molecular Mechanism of Plant Immune Response)

  • 권택민;남재성
    • Journal of Plant Biotechnology
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    • 제32권2호
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    • pp.73-83
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    • 2005
  • Disease resistance in plants is often controlled by gene-for-gene mechanism in which avirulence (avr) gene products encoding by pathogens are specifically recognized, either directly or indirectly by plant disease resistance (R) gene products and sequential signal transduction pathways activating defense responses are rapidly triggered. As a results, not only exhibit a resistance against invading pathogens but also plants maintain the systemic acquired resistance (SAR) to various other pathogens. This molecular interaction between pathogen and plant is commonly compared to innate immune system of animal. Recent studies arising from molecular characterization of a number of R genes from various plant species that confer resistance to different pathogens and corresponding avr genes from various pathogens resulted in the accumulation of a wealth of knowledge on molecular mechanism of gene-for-gene interaction. Furthermore, new technologies of genomics and proteomics make it possible to monitor the genome-wide gene regulation and protein modification during activation of disease resistance, expanding our ability to understand the plant immune response and develop new crops resistant to biotic stress.

Interleukin-8 (IL-8) Expression in the Olive Flounder (Paralichthys olivaceus) against Viral Hemorrhagic Septicemia Virus (VHSV) Challenge

  • Kim, Kyung-Hee;Kim, Hyun Chul;Park, Choul-Ji;Park, Jong-Won;Lee, Young Mee;Kim, Woo-Jin
    • 한국발생생물학회지:발생과생식
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    • 제23권3호
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    • pp.231-238
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    • 2019
  • Interleukin-8 (IL-8) is an inflammatory cytokine that plays an important role in the inflammatory response through the activation of neutrophil cells. The expression of IL-8 was investigated in early developmental stages of the olive flounder and in tissues of 8-month-old individuals. The expression of IL-8 increased after the initiation of the immune system rather than at the early stage of development, and high expression was observed in the gills and spleen, the organs associated with immunity and metabolism. In addition, IL-8 expression after infection by viral hemorrhagic septicemia virus significantly increased in the fin, gill, muscles, and spleen. These results suggest that IL-8 is closely related to inflammation and immune regulation in the immune response of the olive flounder and may be used as a basis for studies on the immune systems of other fish.

Epigenetic memory in gene regulation and immune response

  • Kim, Min Young;Lee, Ji Eun;Kim, Lark Kyun;Kim, TaeSoo
    • BMB Reports
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    • 제52권2호
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    • pp.127-132
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    • 2019
  • Cells must fine-tune their gene expression programs for optimal cellular activities in their natural growth conditions. Transcriptional memory, a unique transcriptional response, plays a pivotal role in faster reactivation of genes upon environmental changes, and is facilitated if genes were previously in an active state. Hyper-activation of gene expression by transcriptional memory is critical for cellular differentiation, development, and adaptation. TREM (Transcriptional REpression Memory), a distinct type of transcriptional memory, promoting hyper-repression of unnecessary genes, upon environmental changes has been recently reported. These two transcriptional responses may optimize specific gene expression patterns, in rapidly changing environments. Emerging evidence suggests that they are also critical for immune responses. In addition to memory B and T cells, innate immune cells are transcriptionally hyperactivated by restimulation, with the same or different pathogens known as trained immunity. In this review, we briefly summarize recent progress in chromatin-based regulation of transcriptional memory, and its potential role in immune responses.

T Cell Immune Responses against SARS-CoV-2 in the With Corona Era

  • Ji-Eun Oh
    • 대한의생명과학회지
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    • 제28권4호
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    • pp.211-222
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    • 2022
  • After more than two years of efforts to end the corona pandemic, a gradual recovery is starting in countries with high vaccination rates. Easing public health policies for a full-fledged post-corona era, such as lifting the mandatory use of outdoor mask and quarantine measures in entry have been considered in Korea. However, the continuous emergence of new variants of SARS-CoV-2 and limitations in vaccine efficacy still remain challenging. Fortunately, T cells and memory T cells, which are key components of adaptive immunity appear to contribute substantially in COVID-19 control. SARS-CoV-2 specific CD4+/CD8+ T cells are induced by natural infection or vaccination, and rapid induction and activation of T cells is mainly associated with viral clearance and attenuated clinical severity. In addition, T cell responses induced by recognition of a wide range of epitopes were minimally affected and conserved against the highly infectious subsets of omicron variants. Polyfunctional SARS-CoV-2 specific T cell memory including stem cell-like memory T cells were also developed in COVID-19 convalescent patients, suggesting long lasting protective T cell immunity. Thus, a robust T-cell immune response appears to serve as a reliable and long-term component of host protection in the context of reduced efficacy of humoral immunity and persistent mutations and/or immune escape.