• Toxicological Research
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• v.33 no.4
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• pp.283-290
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• 2017

The host immune system is the first line of host defense, consisting mainly of innate and adaptive immunity. Immunity must be maintained, orchestrated, and harmonized, since overactivation of immune responses can lead to inflammation and autoimmune diseases, while immune deficiency can lead to infectious diseases. We investigated the regulation of innate and adaptive immune cell activation by Artemisia capillaris and its components (ursolic acid, hyperoside, scopoletin, and scopolin). Macrophage phagocytic activity was determined using fluorescently labeled Escherichia coli, as an indicator of innate immune activation. Concanavalin A (ConA)- and lipopolysaccharide (LPS)-induced splenocyte proliferation was analyzed as surrogate markers for cellular and humoral adaptive immunity, respectively. Neither A. capillaris water extract (WAC) nor ethanol extract (EAC) greatly inhibited macrophage phagocytic activity. In contrast, WAC suppressed ConA- and LPS-induced proliferation of primary mouse splenocytes in a dose-dependent manner. Similarly, EAC inhibited ConA- and LPS-induced splenocyte proliferation. Oral administration of WAC in mice decreased ConA- and LPS-induced splenocyte proliferation, while that of EAC suppressed LPS-induced splenocyte proliferation. Repeated administration of WAC in mice inhibited ConA- and LPS-induced splenocyte proliferation. Ursolic acid, scopoletin, and scopolin reduced ConA- and LPS-induced primary mouse splenocyte proliferation, while hyperoside did not show such activity. These results indicate that A. capillaris and its components, ursolic acid, scopoletin, and scopolin, suppress ConA- and LPS-induced adaptive immune cell activation. The results suggest that A. capillaris is useful as a regulator of adaptive immunity for diseases involving excessive immune response activation.

• IMMUNE NETWORK
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• v.11 no.5
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• pp.245-252
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• 2011

Antimicrobial peptides/proteins are ancient and naturally-occurring antibiotics in innate immune responses in a variety of organisms. Additionally, these peptides have been recognized as important signaling molecules in regulation of both innate and adaptive immunity. During mycobacterial infection, antimicrobial peptides including cathelicidin, defensin, and hepcidin have antimicrobial activities against mycobacteria, making them promising candidates for future drug development. Additionally, antimicrobial peptides act as immunomodulators in infectious and inflammatory conditions. Multiple crucial functions of cathelicidins in antimycobacterial immune defense have been characterized not only in terms of direct killing of mycobacteria but also as innate immune regulators, i.e., in secretion of cytokines and chemokines, and mediating autophagy activation. Defensin families are also important during mycobacterial infection and contribute to antimycobacterial defense and inhibition of mycobacterial growth both in vitro and in vivo. Hepcidin, although its role in mycobacterial infection has not yet been characterized, exerts antimycobacterial effects in activated macrophages. The present review focuses on recent efforts to elucidate the roles of host defense peptides in innate immunity to mycobacteria.

• Korean Journal of Poultry Science
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• v.35 no.3
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• pp.225-240
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• 2008

Marek's disease virus(MDV) is a highly cell-associated, lymphotropic $\alpha$-herpesvirus that causes paralysis and neoplastic disease in chickens. The disease has been controlled by vaccination which was provided the first evidence for a malignant cancer being controlled by an antiviral vaccine. Marek's disease pathogenesis is complex, involving cytolytic and latent infection of lymphoid cells and oncogenic transformation of $CD4^+$ T cells in susceptible chickens. MDV targets a number of different cell types during its life cycle. Lymphocytes play an essential role, although within them virus production is restricted and only virion are produced. Innate and adaptive immune responses develop in response to infection, but infection of lymphocytes results in immunosuppressive effects. Hence in MDV-infected birds, MDV makes its host more vulnerable to tumour development as well as to other pathogens. All chickens are susceptible to MDV infection, and vaccination is essential to protect the susceptible host from developing clinical disease. Nevertheless, MDV infects and replicates in vaccinated chickens, with the challenge virus being shed from the feather-follicle epithelium. The outcome of infection with MDV depends on a complex interplay of factors involving the MDV pathotype and the host genotype. Host factors that influence the course of MD are predominantly the responses of the innate and adaptive immune systems, and these are modulated by: age at infection and maturity of the immune system; vaccination status; the sex of the host; and various physiological factors.

• Journal of Life Science
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• v.29 no.7
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• pp.817-823
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• 2019

Immune system provides defense integrity of body against external invaders. In order to accomplish the important defending role immune system is composed of many different components which are regenerated continuously during lifespan. The key components are professional killing cells such as macrophage, neutrophil, natural killer cell, and cytotoxic T cell and professional blocking molecule, antibody, which is produced by plasma cell, the terminal differentiated B cell. Immune response is orchestrated harmoniously by all these components mediated through antigen presenting cells such as dendritic cells. Immune responses can be divided into two ways: innate immune response and adaptive immune response depending on induction mechanism. Aging is a broad spectrum of physiological changes. Likewise other physiological changes, the immune components and responses are wane as aging is progressing. Immune responses become decline and dysregulating, which is called immunosenescense. Immune components of both innate and adaptive immune response are affected as aging progresses leading to increased vulnerability to infectious diseases. Numbers of immune cells and amounts of soluble immune factors were decreased in aged animal models and human and also functional and structural alterations in immune system were reduced and declined. Cellular intrinsic changes were discovered as well. Recent researches focusing on aging have been enormously growing. Many advanced tools were developed to bisect aging process in multi-directions including immune system area. This review will provide a broad overview of aging-associated changes of key components of immunity.

• Genomics & Informatics
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• v.10 no.3
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• pp.153-166
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• 2012

A variety of ligands differ in their capacity to bind the receptor, elicit gene expression, and modulate physiological responses. Such receptors include Toll-like receptors (TLRs), which recognize various patterns of pathogens and lead to primary innate immune activation against invaders, and G-protein coupled receptors (GPCRs), whose interaction with their cognate ligands activates heterotrimeric G proteins and regulates specific downstream effectors, including immuno-stimulating molecules. Once TLRs are activated, they lead to the expression of hundreds of genes together and bridge the arm of innate and adaptive immune responses. We characterized the gene expression profile of Toll-like receptor 4 (TLR4) in RAW 264.7 cells when it bound with its ligand, 2-keto-3-deoxyoctonate (KDO), the active part of lipopolysaccharide. In addition, to determine the network communications among the TLR, Janus kinase (JAK)/signal transducer and activator of transcription (STAT), and GPCR, we tested RAW 264.7 cells with KDO, interferon-${\beta}$, or cAMP analog 8-Br. The ligands were also administered as a pair of double and triple combinations.

• IMMUNE NETWORK
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• v.4 no.4
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• pp.205-215
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• 2004

In the early host defense system, effector function of natural killer (NK) cells results in natural killing against target cells such as microbe-infected, malignant, and certain allogenic cells without prior stimulation. NK cell cytotoxicity is selectively regulated by homeostatic prevalence between a repertoire of both activating and inhibitory receptors, and the discrimination of untransformed cells is achieved by recognition of major histocompatibility complex (MHC) class I alleles through inhibitory signals. Although it is well known that the bipotential T/NK progenitors are derived from the common precusor, functional mechanisms in terms of the development of NK cells remain to be further investigated. NK cells are mainly involved in innate immunity, but recent studies have been reported that they also play a critical role in adaptive immune responses through interaction with dendritic cells (DC). This interaction will provide effector functions and development of NK cells, and elucidation of its precise mechanism may lead to therapeutic strategies for effective treatment of several immune diseases.

• IMMUNE NETWORK
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• v.15 no.1
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• pp.1-8
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• 2015

Innate immune cells survey antigenic materials beneath our body surfaces and provide a front-line response to internal and external danger signals. Dendritic cells (DCs), a subset of innate immune cells, are critical sentinels that perform multiple roles in immune responses, from acting as principal modulators to priming an adaptive immune response through antigen-specific signaling. In the gut, DCs meet exogenous, non-harmful food antigens as well as vast commensal microbes under steady-state conditions. In other instances, they must combat pathogenic microbes to prevent infections. In this review, we focus on the function of intestinal DCs in maintaining intestinal immune homeostasis. Specifically, we describe how intestinal DCs affect IgA production from B cells and influence the generation of unique subsets of T cell.

• BMB Reports
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• v.38 no.2
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• pp.121-127
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• 2005

Drosophila protects itself from infection by microbial organisms by means of its pivotal defense, the so-called innate immunity system. This is its sole defense as it lacks an adaptive immunity system such as is found in mammals. The strong conservation of innate immunity systems in organisms from Drosophila to mammals, and the ease with which Drosophila can be manipulated genetically, makes this fly a good model system for investigating the mechanisms of virulence of a number of medically important pathogens. Potentially damaging endogenous and/or exogenous challenges sensed by specific receptors initiate signals via the Toll and/or Imd signaling pathways. These in turn activate the transcription factors Dorsal, Dorsal-related immune factor (Dif) and Relish, culminating in transcription of genes involved in the production of antimicrobial peptides, melanization, phagocytosis, and the cytoskeletal rearrangement required for appropriate responses. Clarifying the regulatory interactions between the various pathways involved is very important for understanding the specificity and termination mechanism of the immune response.

• Journal of fish pathology
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• v.29 no.1
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• pp.13-23
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• 2016

Lectins play significant roles in the innate immune responses through binding to pathogen-associated molecular patterns (PAMPs) on the surfaces of microorganisms. In the present study, tissue distribution and expression analysis of olive flounder lectins were performed after viral hemorrhagic septicemia virus (VHSV) challenge. Fish egg lectin and serum lectin were found to be predominantly expressed in the gills and liver, these results indicate that the transcript expression of olive flounder lectins is concentrated in immune-related tissues. Following a VHSV challenge, an overall increase in the transcript levels of the genes was observed and the expression patterns were distinctly divided into early and later responses during VHSV infection. In conclusion, olive flounder lectins are specifically expressed in immune-related organs and induced in both the immediate and long-lasting immune responses to VHSV in the olive flounder. These results indicate that lectins may be play important roles in the host defense mechanism and involved in the innate and adaptive immune response to viruses in fish.

• Molecules and Cells
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• v.23 no.1
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• pp.1-10
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• 2007

Invading pathogens are recognized by diverse germline-encoded pattern-recognition receptors (PRRs) which are distributed in three different cellular compartments: extracellular, membrane, and cytoplasmic. In mammals, the major extracellular PRRs such as complements may first encounter the invading pathogens and opsonize them for clearance by phagocytosis which is mediated by membrane-associated phagocytic receptors including complement receptors. The major membrane-associated PRRs, Toll-like receptors, recognize diverse pathogens and generate inflammatory signals to coordinate innate immune responses and shape adaptive immune responses. Furthemore, certain membrane-associated PRRs such as Dectin-1 can mediate phagocytosis and also induce inflammatory response. When these more forefront detection systems are avoided by the pathogens, cytoplasmic PRRs may play major roles. Cytoplasmic caspase-recruiting domain (CARD) helicases such as retinoic acid-inducible protein I (RIG-I)/melanoma differentiation-associated gene 5 (MDA5), mediate antiviral immunity by inducing the production of type I interferons. Certain members of nucleotide-binding oligomerization domain (NOD)-like receptors such as NALP3 present in the cytosol form inflammasomes to induce inflammatory responses upon ligand recognition. Thus, diverse families of PRRs coordinately mediate immune responses against diverse types of pathogens.