• Archives of Pharmacal Research
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• v.22 no.5
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• pp.437-447
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• 1999

Type I diabetes, also known as insulin-dependent diabetes mellitus (IDDM) results from the destruction of insulin-producing pancreatic $\beta$ cells by a progressive $\beta$ cell-specific autoimmune process. The pathogenesis of autoimmune IDDM has been extensively studied for the past two decades using animal models such as the non-obese diabetic (NOD) mouse and the Bio-Breeding (BB) rat. However, the initial events that trigger the immune responses leading to the selective destruction of the $\beta$ cells are poorly understood. It is thought that $\beta$ cell auto-antigens are involved in the triggering of $\beta$ cell-specific autoimmunity. Among a dozen putative $\beta$ cell autoantigens, glutamic acid decarboxylase (GAD) has bee proposed as perhaps the strongest candidate in both humans and the NOD mouse. In the NOD mouse, GAD, as compared with other $\beta$ cell autoantigens, provokes the earliest T cell proliferative response. The suppression of GAD expression in the $\beta$ cells results in the prevention of autoimmune diabetes in NOD mice. In addition, the major populations of cells infiltrating the iselts during the early stage of insulitis in BB rats and NOD mice are macrophages and dendritic cells. The inactivation of macrophages in NOD mice results in the prevention of T cell mediated autoimmune diabetes. Macrophages are primary contributors to the creation of the immune environment conducive to the development and activation of $\beta$cell-specific Th1-type CD4+ T cells and CD8+ cytotoxic T cells that cause autoimmune diabetes in NOD mice. CD4+ and CD8+ T cells are both believed to be important for the destruction of $\beta$ cells. These cells, as final effectors, can kill the insulin-producing $\beta$ cells by the induction of apoptosis. In addition, CD8+ cytotoxic T cells release granzyme and cytolysin (perforin), which are also toxic to $\beta$ cells. In this way, macrophages, CD4+ T cells and CD8+ T cells act synergistically to kill the $\beta$ cells in conjunction with $\beta$ cell autoantigens and MHC class I and II antigens, resulting in the onset of autoimmune type I diabetes.

• Journal of fish pathology
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• v.20 no.2
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• pp.189-200
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• 2007

To investigate the innate immune response involved in early stage of anti-viral defence, carps were injected with UV-inactivated spring viraemia of carp virus (SVCV), poly inosinic:cytidylic acid (Poly I:C) and concanavalin A (Con A), respectively and examined lysozyme activity, serum complement activity and chemiluminescent (CL) response of leucocytes isolated from head kidney at 3 days post-injection. There was no significant difference in plasma lysozyme activities among all experimental groups. However, lysozyme activities of head kidney in the groups injected with antiviral activity inducers were significantly higher than those of the control injected with physiological saline. Bactericidal activities of serum of the groups injected with antiviral activity inducers were not significantly different from control group. However, the CL responses were significantly higher at lower dose of Poly I:C and Con A, whilst dose-dependent increase was shown in UV-inactivated SVCV-injected group. In the challenge test with 1×104 TCID50/fish of SVCV at 4 days post-injection, UV-inactivated SVCV- and Poly I:C-injected groups showed higher relative percent survival (RPS) than Con A-injected group. Furthermore, strong protection was observed in the group injected higher dose of Poly I:C although showed lower activities in lysozyme and CL response. These results suggested that Poly I:C might stimulate other factors belonging to non-specific immune system have induced protective immunity against the SVCV challenged.

• Journal of fish pathology
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• v.32 no.1
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• pp.9-20
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• 2019

The study investigated the dietary effects of medicinal herbs extract and multiple probiotics mixture on the growth performance, innate immune response and antibacterial activity of nile tilapia Oreochromis niloticus. Tilapia were divided in four groups. The first is a fish group fed a basal diet added with 40% medicinal herbs extract (MHE). The second is a fish group fed a basal diet supplied with $2{\times}10^8CFU/g$ of 2 Bacillus sp, 2 Lactobacillus sp and 2 Yeast sp, respectively (PB). The third group was fed with a mixture of probiotics (2 Bacillus sp, 2 Lactobacillus sp and 2 Yeast sp) with the medicinal herbs extract added in basal diet (MHE+PB). The fourth group was fed only a basal diet (C). In a non-specific immune parameters analysis, respiratory burst activity, lysozyme activity, phagocytic activity (PA), alternative complement pathway activity ($ACH_{50}$) and superoxide dismutase (SOD) activity were significantly (p<0.05) increased in the group MHE+PB compared to other groups. Both PB and MHE groups showed a significant (p<0.05) increase in respiratory burst activity, lysozyme activity compared to the control C group, whereas no significant differences were observed in PA, $ACH_{50}$ and SOD activity compared to the control group. In challenging test, fish were administered with Edwardsiella tarda (E. tarda) on 30 days after feeding with each experimental diet and viable E. tarda cell reduction was checked over 21 days post injection. MHE+PB group showed a significantly (p<0.05) reduced E. tarda cells compared to other groups. No significant antibacterial difference (p>0.05) was observed between PB and MHE only treated group. Compared to the control, a significant antibacterial difference (p<0.05) appeared in PB but not in MHE (p>0.05). The results suggest that the probiotics and MHE mixture could be utilized as an alternative to antibiotics in the control of fish diseases caused by E. tarda.

• Tuberculosis and Respiratory Diseases
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• v.46 no.2
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• pp.229-240
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• 1999

Background: The impact of the immune response on cancer gene therapy using viral vectors to deliver a "suicide gene" is currently unclear. A vigrous immune response targeted at viral proteins or transgene may enhance the efficacy of tumor destruction and even augment responses to tumor antigens. These responses may involve the release of cytokines and stimulation of tumor specific cytotoxic T-lymphocytes that enhance therapeutic efficacy. On the other hand, a vigorous rapid cellular immune response may destroy cells expressing the therapeutic gene and attenuate the response to therapy. Furthermore, development of neutralizing antibody responses may prevent readministration of virus, a potentially significant limitation. Evaluating the significance of these limitations in animal models and developing solutions are therefore of obvious importance. Methods: After retroviral transduction of mouse mesothelioma cell line(AB12) with Herpes Simplex Virus thymidine kinase (HSVtk) gene in vitro, subcutaneous flank tumors were established. To study the effect of intact immune system on efficacy of tumor erradication, the ability of the HSVtk/ganciclovir system to inhibit tumor growth was compared among normal Balb/c mice, immunodeficient Balb/c-nude and SCID mice, and Balb/c mice immunosuppressed with cyclosporin. Results: Ganciclovir treatment resulted in greater inhibition of tumor growth in Balb/c mice compared with immunodeficient Balb/c-nude mice and SCID mice(in immunodeficient mice, there were no growth inhibition by ganciclovir treatment). Ganciclovir treatment resulted in greater inhibition of tumor growth in noncyclosporin (CSA) treated Balb/c mice compared with CSA treated Balb/c mice. On day 8, mean ganciclovir-treated tumor volume were 65% of control tumor volume in Balb/c mice versus 77% control tumor volume in CSA-treated Balb/c mice. This effect was still evident during therapy (day 11 and 13). On day 13, non-CSA treated tumor volume was 35% of control tumor volume versus 60% of control tumor volume in CSA treated Balb/c mice. Duration of expression of HSVtk was not affected by the immunosuppression with CSA. Conclusion: These results indicate that the immune responses against retrovirally transduced cells enhance the efficacy of the HSVtk/ganciclovir system. These findings have important implications for clinical trials using currently available retrovirus vectors as well as for future vector design.

• The Journal of Pediatrics of Korean Medicine
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• v.12 no.1
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• pp.183-210
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• 1998

Cheonggisan(CGS) is well known for its effect on such allergic disease as urticaria and atopic dermatitis. Gagamcheonggisan(GCGS) was formulated by subtracting several herbs from CGS and adding several herbs to CGS. Even though it is being used frequently in the clinicai medicine for the treatment of above hypersensitivity diseases, basic study to make sure the mechanism of its action is rare. In this study the author tried to know the effect of CGS and GCGS on the vascular permeability, contact dermatitis, granular secretion from mast cells and function of macrophages. The results obtained in this study are as follows : 1. Administration of CGS and GCGS decreased the vascular permeability induced by serotonin and histamine. The decrease by serotonin is more typical and dose-dependent. 2. Administration of CGS and GCGS inhibited foot-pad and ear swelling responses induced by sheep red blood cells and picryl chloride respectively, the inhibition of foot-pad swelling responses is bigger than that of ear swelling responses and both of them are not dependent on the dose3. Treatment of peritoneal mast cells with CGS and GCGS water extract decreased the histamine release triggered by compound 48／80 in a dose dependent fashion 4. Administration of CGS and GCGS increased the phagocvtic activity of peritoneal macrophages and treatment of peritoneal macrophages with CGS activated phagocytic function in a dose dependent fashion. 5. Administration of CGS and GCGS enhanced such reactive oxygen intermediates(ROIs) as superoxide and hydrogen peroxide production from peritoneal macrophages. 6. Treatment of CGS and GCGS activated peritoneal macrophages for the production of ROIs. The above results show that CGS and GCGS decreased the hypersensitivity reactions by inhibiting non-specific inflammatory mediator release and vascular permeability without affecting general immune responsiveness.

• Fisheries and Aquatic Sciences
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• v.10 no.1
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• pp.1-7
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• 2007

The induction of cellular and humoral immunity and cytokine gene expression by synthetic CpG oligodexoynucleotides (CpG-ODNs) has not been investigated systematically in olive flounder Paralichthys olivaceus in vivo. We optimized the proper concentration of CpG-ODNs using an in vitro assay for the superoxide anion $(O_2^-)$. CpG-ODNs induced $O_2^-$ and nitric oxide (NO) production, lysozyme activity, and the proinflammatory cytokine gene expression of $IL-1{\beta}$ and $TNF-{\alpha}$ in olive flounder significantly in vivo, whereas non-CpG-ODNs did not produce these effects or produced them to a lesser extent. This implied that CpG-ODNs could stimulate cellular and humoral immunity and cytokine gene expression in olive flounder. This is the first evidence of NO production and the first study on the mRNA expression of the proinflammatory cytokine genes $IL-1{\beta}$ and $TNF-{\alpha}$ in olive flounder in response to CpG-ODNs. Comparison of the variation in NO production and lysozyme activity to that of other studies led us to postulate that a group-specific difference exists in the immune responses of olive flounder against CpG-ODNs. Furthermore, the detailed immunostimulatory spectrum of CpG-ODNs in olive flounder could be a useful index with which to analyze the effect of CpG-ODNs against the challenge test prior to field applications.

• Molecules and Cells
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• v.42 no.7
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• pp.503-511
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• 2019

As sessile organisms, plants have developed sophisticated system to defend themselves against microbial attack. Since plants do not have specialized immune cells, all plant cells appear to have the innate ability to recognize pathogens and turn on an appropriate defense response. The plant innate immune system has two major branches: PAMPs (pathogen associated molecular patterns)-triggered immunity (PTI) and effector-triggered immunity (ETI). The ability to discriminate between self and non-self is a fundamental feature of living organisms, and it is a prerequisite for the activation of plant defenses specific to microbial infection. Arabidopsis cells express receptors that detect extracellular molecules or structures of the microbes, which are called collectively PAMPs and activate PTI. However, nucleotidebinding site leucine-rich repeats (NB-LRR) proteins mediated ETI is induced by direct or indirect recognition of effector molecules encoded by avr genes. In Arabidopsis, plasmamembrane localized multifunctional protein RIN4 (RPM1-interacting protein 4) plays important role in both PTI and ETI. Previous studies have suggested that RIN4 functions as a negative regulator of PTI. In addition, many different bacterial effector proteins modify RIN4 to destabilize plant immunity and several NB-LRR proteins, including RPM1 (resistance to Pseudomonas syringae pv. maculicola 1), RPS2 (resistance to P. syringae 2) guard RIN4. This review summarizes the current studies that have described signaling mechanism of RIN4 function, modification of RIN4 by bacterial effectors and different interacting partner of RIN4 in defense related pathway. In addition, the emerging role of the RIN4 in plant physiology and intercellular signaling as it presents in exosomes will be discussed.

• IMMUNE NETWORK
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• v.22 no.6
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• pp.48.1-48.13
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• 2022

With the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, which are randomly mutated, the dominant strains in regions are changing globally. The development of preclinical animal models is imperative to validate vaccines and therapeutics against SARS-CoV-2 variants. The objective of this study was to develop a non-human primate (NHP) model for SARS-CoV-2 Delta variant infection. Cynomolgus macaques infected with Delta variants showed infectious viruses and viral RNA in the upper (nasal and throat) and lower respiratory (lung) tracts during the acute phase of infection. After 3 days of infection, lesions consistent with diffuse alveolar damage were observed in the lungs. For cellular immune responses, all macaques displayed transient lymphopenia and neutrophilia in the early stages of infection. SARS-CoV-2 Delta variant spike protein-specific IgM, IgG, and IgA levels were significantly increased in the plasma of these animals 14 days after infection. This new NHP Delta variant infection model can be used for comparative analysis of the difference in severity between SARS-CoV-2 variants of concern and may be useful in the efficacy evaluation of vaccines and universal therapeutic drugs for mutations.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6533-6535
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• 2013

Background: The purpose of this study was to evaluate a new type of tumor biomarker, eukaryotic elongation factor 2 (eEF2), in serum for the early diagnosis, confirmative diagnosis as well as assessment of treatment of non-small cell lung cancer (NSCLC). Methods: 130 patients with NSCLC and 50 healthy individuals undergoing physical examination in our hospital provided the observation and healthy control groups. An enzyme linked immune sorbent assay (ELISA) method was applied to determine serum eEF2 levels. Serum neuron specific enolase (NSE) and squamous cell carcinoma antigen (SCC) levels in the observation group were assessed with an automatic biochemical analyzer. Results: The median levels of eEF2 in the serum of NSCLC patients was found to be significantly higher than the healthy control group (p < 0.01) and it was markedly higher in stages III, IV than stages I, II (p < 0.05). eEF2 was higher with tumor size ${\geq}2$ cm than <2 cm (P< 0.01). Furthermore, two weeks after surgery patients showed a significant trend for eEF2 decrease (p < 0.05). Conclusions: The eukaryotic elongation factor 2 (eEF2) has certain clinical values for early diagnosis, verification, and prognosis as well as classification of lung cancer patients.

• Journal of Aquaculture
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• v.19 no.4
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• pp.247-253
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• 2006

This study was conducted to investigate the effects of dietary supplementation of ${\beta}-1,3$ glucan on growth and immune responses in juvenile olive flounder, Paralichthys olivaceus fed the white fish meal based diets for 6 weeks. Five experimental diets supplemented with ${\beta}-1,3$ glucan at 0, 0.01, 0.025, 0.05, 0.1 % (Control, $G_{0.01},\;G_{0.025},\;G_{0.05}\;and\;G_{0.1}$, respectively) of diet on a dry-matter basis. Five experimental diets were formulated to be isonitrogenous and isocaloric to contain 50.0% crude protein and 16.7 kJ available energy $g^{-1}$. Fish averaging $3.2{\pm}0.1\;g\;(mean{\pm}SD)$ were randomly distributed in each aquarium as triplicate groups of 15 fish. Weight gain (WG, %), specific growth rate (SGR, %), and feed efficiency (FE, %) of fish fed $G_{0.1}$ diet were found significantly higher than those of fish fed Control, $G_{0.01},\;G_{0.025}\;and\;G_{0.05}$ diets (P<0.05). However, there was no significant difference among the fish fed control, $G_{0.01},\;G_{0.025}$. Chemiluminescent responses (CL) of fish fed $G_{0.1}$ diet were significantly higher than those of fish fed the other diets. Serum lysozyme activities of fish fed $G_{0.05}$ and $G_{0.1}$ diets were higher than those of fish fed control, $G_{0.025}$ and $G_{0.05}$ diets. Fish fed $G_{0.1}$ diet showed a significantly lower cumulative mortality than did fish fed control diet throughout the challenge test (P<0.05). These results suggested that based on growth rate, feed efficiency, non-specific immunity and protection against microbial infections the optimum dietary ${\beta}-1,3$ gulcan could be greater than 0.05% but less than 1.0% in juvenile olive flounder, Paralichthys oilvaceus.