• Title/Summary/Keyword: Cell-mediated Immunity

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Disseminated life-threatening viral skin rash in a child with atopic dermatitis

  • Astrid Herzum;Corrado Occella;Ehab Garibeh;Lodovica Gariazzo;Gianmaria Viglizzo
    • Clinical and Experimental Vaccine Research
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    • v.12 no.2
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    • pp.176-178
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    • 2023
  • We report the case of a toddler, with a history of mild atopic dermatitis (AD) since early infancy, presented to the Giannina Gaslini, a pediatric polyclinic hospital, 14 days after measles-mumps-rubella (MMR) vaccination, for the occurrence of a disseminated vesico-pustular rash, accompanied by general malaise, fever, restlessness, and anorexia. Eczema herpeticum (EH) was diagnosed clinically and confirmed by laboratory examinations. The exact pathogenesis of EH in AD is still debated and possibly involves an inter-play between altered cell-mediated and humoral immunity, failure to up-regulate antiviral proteins, and exposure of viral binding sites through the dermatitis and an epidermal barrier failure. We hypothesize that in this particular case, MMR vaccination might have played an additional important role in the alteration of innate immune response, facilitating the manifestation of herpes simplex virus type 1 in the form of EH.

Generation of Renal Cell Carcinoma-specific CD4+/CD8+ T Cells Restricted by an HLA-39 from a RCC Patient Vaccinated with GM-CSF Gene-Transduced Tumor Cells

  • Jun, Do Youn;Moutner, Joseph;Jaffee, Elizabeth
    • IMMUNE NETWORK
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    • v.3 no.2
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    • pp.96-102
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    • 2003
  • Background: Granulocyte-macrophage colony-stimulating factor (GM-CSF) gene-transduced tumor cell vaccines induce very potent systemic anti-tumor immunity in preclinical and clinical models. Our previous phase I clinical trial in patients with metastatic renal cell carcinoma (RCC) has demonstrated both immune cell infiltration at vaccine sites and T cell-mediated delayed-type hypersensitivity (DTH) response to whole tumor cell vaccines. Methods: To investigate the immune responses to autologous genetically- modified tumor cell vaccines, tumor-specific $CD8^+$ T cell lines were generated from peripheral blood lymphocytes (PBL) of a RCC patient 1.24 by repeated in vitro stimulation with either B7.1-transduced autologous RCC tumor cells or B7.1-transduced autologous tumor cells treated with interferon gamma ($IFN{\gamma}$), and cloned by limiting dilution. Results: Among several RCC-specific cytotoxic T lymphocytes (CTLs), a $CD4^+/CD8^+$ double positive T cell clone (17/A2) appeared to recognize $IFN{\gamma}$-treated autologous RCC restricted by HLA-B39. The 17/A2 also recognized other HLA-B39 positive RCC tumor cells after $IFN{\gamma}$ treatment. Conclusion: These results demonstrate that autologous RCC vaccination successfully generates the tumor-specific CTL 17/A2, and suggest that the presentation and recognition of the tumor antigen by the 17/A2 might be upregulated by $IFN{\gamma}$.

Immunological Studies on Oriental Pharmaceutical Preparations (I) (한약제제(漢藥製劑)의 면역학적(免疫學的) 연구(硏究) (제 1 보)(第 1 報))

  • Kim, Byong-Kak;Chung, Kyeong-Soo;Choi, Eung-Chil;Kim, Hye-Ryung;Park, Hee-Ju;Cho, Pil-Hyoung
    • Korean Journal of Pharmacognosy
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    • v.14 no.3
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    • pp.125-129
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    • 1983
  • To examine effects of oriental pharmaceutical preparations on immunity, four of such preparations which are currently being used were examined. After their fluid extracts were injected intraperitoneally to ICR mice, the counts of total cell number, PMN and macrophage in the peritoneal cavity were made by using non-specific esterase staining method, and plaque-forming cells (PFC) were measured by using the modified method of Cunningham and Jerne. The results showed that 'Bo-Jung-Ik-Ki-Tang', 'Ih-Jung-Tang', 'Ohn-Kyeong-Tang' and 'Ke-Ji-Bok-Ryeong-Hwan-Ka-Dae-Hwang' increased both the macrophages and the total cells of the peritoneal cavity and that these preparations increased the number of PFC in the spleen. Therefore the data indicate that they potentiate both of the cell­mediated and humoral immunities in the mice.

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New trends of vaccine development: Recombinant vaccinia viruses (expression vectors) as vaccines (Vaccine개발(開發)의 새로운 동향(動向) : Vaccinia virus를 발견(發見) vector로 이용하는 재조합(再組合) 생(生)vaccine의 작성(作成))

  • Kim, Uh-ho
    • Korean Journal of Veterinary Research
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    • v.29 no.3
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    • pp.407-416
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    • 1989
  • The prospect of live vaccines consisting of genetically modified vaccinia virus expressing foreign genes is exciting, but important issues concerning safety and efficacy need to resolved. Vaccinia virus (VV) is an efficient expression vector with broad host range infectivity and large DNA capacity. This vector has been particularly useful for identifying target antigens for humoral and cell-mediated immunity. The WHO smallpox eradication program, involving the extensive use of VV vaccines, resulted in the late 1970s in the elimination of one of the world's most feared diseases. This achievement is a triumph for preventive medicine and for international collaboration in public health. In 1980, WHO recommended that the routine use of smallpox vaccine should be stopped. Against this background, the prospect of li ve vaccines consisting of genetically modified VV expressing foreign antigens arising from the work of Moss, and Paoletti and their colleagues in 1982 has been greeted with enthusiasm. These investigators have shown that genes coding for immunogenic proteins can be inserted into VV DNA without impairing the ability of the virus to grow in cell culture. Moreover experimental animals infected with VV recombinants containing genes coding for a variety of immunizing proteins have been shown to be protected against challenge infection with the corresponding infectious agent. In this communication, I describe current progress in the construction of a novel plasmid vector that facilitate the insertion and expression of foreign genes in VV as well as the selection of recombinants.

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

  • Lee, Hwan Hee;Cho, Hyosun
    • YAKHAK HOEJI
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    • v.59 no.1
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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.

Influenza Virus-Derived CD8 T Cell Epitopes: Implications for the Development of Universal Influenza Vaccines

  • Sang-Hyun Kim;Erica Espano;Bill Thaddeus Padasas;Ju-Ho Son;Jihee Oh;Richard J. Webby;Young-Ran Lee;Chan-Su Park;Jeong-Ki Kim
    • IMMUNE NETWORK
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    • v.24 no.3
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    • pp.19.1-19.15
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    • 2024
  • The influenza virus poses a global health burden. Currently, an annual vaccine is used to reduce influenza virus-associated morbidity and mortality. Most influenza vaccines have been developed to elicit neutralizing Abs against influenza virus. These Abs primarily target immunodominant epitopes derived from hemagglutinin (HA) or neuraminidase (NA) of the influenza virus incorporated in vaccines. However, HA and NA are highly variable proteins that are prone to antigenic changes, which can reduce vaccine efficacy. Therefore, it is essential to develop universal vaccines that target immunodominant epitopes derived from conserved regions of the influenza virus, enabling cross-protection among different virus variants. The internal proteins of the influenza virus serve as ideal targets for universal vaccines. These internal proteins are presented by MHC class I molecules on Ag-presenting cells, such as dendritic cells, and recognized by CD8 T cells, which elicit CD8 T cell responses, reducing the likelihood of disease and influenza viral spread by inducing virus-infected cell apoptosis. In this review, we highlight the importance of CD8 T cell-mediated immunity against influenza viruses and that of viral epitopes for developing CD8 T cell-based influenza vaccines.

The Study of MHC class I Restricted CD8+ T Cell Mediated Immune Responses against Mycobacterium tuberculosis Infection: Evidence of M. tuberculosis S pecific CD8+ T Cells in TB Patients and PPD+ Healthy Individuals (MHC class I 분자들에 의해 제시되는 Epitope을 인지하는 CD8+ T 림프구의 결핵균 감염에 대한 면역반응의 연구: 결핵 환자와 PPD+ 건강개체에 존재하는 결핵균 항원에 특정한 CD8+ T세포)

  • Cho, Jang-Eun;Lee, Kyung Wha;Park, Seung Kyu;Cheon, Seon-Hee;Cho, Sang-Nae;Cho, Sungae
    • IMMUNE NETWORK
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    • v.3 no.3
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    • pp.235-241
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    • 2003
  • Background: The protective immunity against tuberculosis (TB) involves both CD4+ T cells and CD8+ T cells. In our previous study, we defined four Mycobacterium tuberculosis derived peptide epitopes specific for HLA-$A^*0201$ restricted CD8+ T cells ($ThyA_{30-38}$, $RpoB_{127-135}$, $85B_{15-23}$, $PstA1_{75-83}$). In this study, we investigated the immune responses induced by these peptide specific CD8+ T cells in latently and chronically infected people with TB. Methods: We characterized these peptide specific CD8+ T cell population present in PBMC of both TB patients and PPD+healthy people using IFN-${\gamma}$elispot assay, intracellular staining and HLA-A2 dimer staining. Results: The frequency of peptide specific CD8+ T cell was in the range of 1 to 25 in $1.7{\times}10^5$ PBMC based on ex vivo IFN-${\gamma}$ elispot assay, demonstrating that these peptide specific CD8+ T cell responses are induced in both TB patients and PPD+ people. Short term cell lines (STCL) specific for these peptides proliferated in vitro and secreted IFN-${\gamma}$ upon antigenic stimulation in PPD+ donors. Lastly, HLA-$A^*0201$ dimer assays indicated that $PstA1_{75-83}$ specific CD8+ T cell population in PPD+ healthy donors is heterogeneous since approximately 25~33% of $PstA1_{75-83}$ specific CD8+ T cell population in PPD+ healthy donors produced IFN-${\gamma}$ upon peptide stimulation. Conclusion: Our results suggest that MHC class I restricted CD8+ T cell mediated immune responses to M. tuberculosis infection are induced in both TB patients and PPD + people; however, the CD8+ T cell population is functionally heterogeneous.

Immunization of Mice with Recombinant Brucella abortus Organic Hydroperoxide Resistance (Ohr) Protein Protects Against a Virulent Brucella abortus 544 Infection

  • Hop, Huynh Tan;Reyes, Alisha Wehdnesday Bernardo;Simborio, Hannah Leah Tadeja;Arayan, Lauren Togonon;Min, Won Gi;Lee, Hu Jang;Lee, Jin Ju;Chang, Hong Hee;Kim, Suk
    • Journal of Microbiology and Biotechnology
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    • v.26 no.1
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    • pp.190-196
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    • 2016
  • In this study, the Brucella abortus ohr gene coding for an organic hydroperoxide resistance protein (Ohr) was cloned into a maltose fusion protein expression system (pMAL), inserted into Escherichia coli, and purified, and its immunogenicity was evaluated by western blot analysis using Brucella-positive mouse sera. The purified recombinant Ohr (rOhr) was treated with adjuvant and injected intraperitoneally into BALB/c mice. A protective immune response analysis revealed that rOhr induced a significant increase in both the IgG1 and IgG2a titers, and IgG2a reached a higher level than IgG1 after the second and third immunizations. Additionally, immunization with rOhr induced high production of IFN-γ as well as proinflammatory cytokines such as TNF, MCP-1, IL-12p70, and IL-6, but a lesser amount of IL-10, suggesting that rOhr predominantly elicited a cell-mediated immune response. In addition, immunization with rOhr caused a significantly higher degree of protection against a virulent B. abortus infection compared with a positive control group consisting of mice immunized with maltose-binding protein. These findings showed that B. abortus rOhr was able to induce both humoral and cell-mediated immunity in mice, which suggested that this recombinant protein could be a potential vaccine candidate for animal brucellosis.

Milk Yield and Immune Response of Periparturient and Early Lactation Friesian Cows Fed Diets Supplemented with a High Level of Amino-acid Chelated Chromium

  • Terramoccia, S.;Bartocci, S.;Lillini, E.
    • Asian-Australasian Journal of Animal Sciences
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    • v.18 no.8
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    • pp.1098-1104
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    • 2005
  • The trial was carried out on twenty-one Friesian cows at the end of eight months gestation, nine multiparous and twelve primiparous; allocated into three groups (1 control, 2 and 3 experimental). The same diet was administred to all three groups before partum (12.8 kg DM/head/day) and after partum (18.8 kg DM/head/day). The cows in groups 2 and 3 received two different daily quantities of amino-acid chelated chromium (0.6 and 1.2 mg Cr/kg DM) from 4 weeks prior to presumed parturition to 6 weeks after. The milk yield control was carried out at 15, 30, 42 and 60 days. All animals were immunised two weeks prior to the presumed parturition and two weeks after with the following antigens: ovalbumin and brucellergene. Blood samples were collected weekly to monitor humoral and cell-mediated immune responses. When analysing the results of antibody immunity (ovalbumin) in the sixth blood collection both treated groups significantly increased compared to group 1 (0.5230 and 0.4536 vs. 0.1812 OD; p<0.05). The results of the cell-mediated immune response (brucellergene) had significant differences (p<0.10) in correspondence to the third (between group 2 and control) and the fifth (between groups 3 and 2) blood collection. Significant differences in fat corrected milk were observed at 42 days between group 3 and the other two groups (31.01 vs. 26.99 and 28.66 kg/d, p<0.05) and at 60 days between group 3 and control (30.88 vs. 26.69 kg/d, p<0.05). Before partum and at partum a positive immune response was obtained with a lower dose of chromium. After partum a positive immune response, anti-OVA indicator, was obtained with the higher dose of chromium while, $\gamma$-IFN indicator, with the lower dose. A significant increase of the milk yield resulted at both 42 and 60 days with the highest level of chromium.

Construction and Preliminary Immunobiological Characterization of a Novel, Non-Reverting, Intranasal Live Attenuated Whooping Cough Vaccine Candidate

  • Cornford-Nairns, R.;Daggard, G.;Mukkur, T.
    • Journal of Microbiology and Biotechnology
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    • v.22 no.6
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    • pp.856-865
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    • 2012
  • We describe the construction and immunobiological properties of a novel whooping cough vaccine candidate, in which the aroQ gene, encoding 3-dehydroquinase, was deleted by insertional inactivation using the kanamycin resistance gene cassette and allelic exchange using a Bordetella suicide vector. The aroQ B. pertussis mutant required supplementation of media to grow but failed to grow on an unsupplemented medium. The aroQ B. pertussis mutant was undetectable in the trachea and lungs of mice at days 6 and 12 post-infection, respectively. Antigen-specific antibody isotypes IgG1 and IgG2a, were produced, and cell-mediated immunity [CMI], using interleukin-2 and interferon-gamma as indirect indicators, was induced in mice vaccinated with the aroQ B. pertussis vaccine candidate, which were substantially enhanced upon second exposure to virulent B. pertussis. Interleukin-12 was also produced in the aroQ B. pertussis-vaccinated mice. On the other hand, neither IgG2a nor CMI-indicator cytokines were produced in DTaP-vaccinated mice, although the CMI-indicator cytokines became detectable post-challenge with virulent B. pertussis. Intranasal immunization with one dose of the aroQ B. pertussis mutant protected vaccinated mice against an intranasal challenge infection, with no pathogen being detected in the lungs of immunized mice by day 7 post-challenge. B. pertussis aroQ thus constitutes a safe, non-reverting, metabolite-deficient vaccine candidate that induces both humoral and cell-mediated immune responses with potential for use as a single-dose vaccine in adolescents and adults, in the first instance, with a view to disrupting the transmission cycle of whooping cough to infants and the community.