搜索
您的当前位置:首页正文

2011诺贝尔奖免疫学研究的突破及意义

来源:爱够旅游网
    储以微,教授、博士生导师。毕业于上海医科大学临床医疗系,后攻读免疫学专业研究生,分获硕士、博士学位。曾赴美国University of Washington医学院肿瘤中心作访问 学者,美国EACRI肿瘤研究中心作访问教授。现任复旦大学上海医学院免疫学系副主任(主持工作),复旦大学生物治疗研究中心主任及复旦大学医学学位与研究生教育管理办

公室主任。中国免疫学会理事,上海市免疫学会理事兼感染免疫专业主任委员。

    主要从事肿瘤免疫及免疫调节在自身免疫性疾病中的作用机制研究,作为课题负责人及骨干,承担国家973项目、“十一五”国家重大专项、国家自然科学基金、上海市科委重点项目及上海市曙光学者研究基金等。研究成果发表在Journal of Immunology,Cancer Research,Cell Death and Differentiation,Arthritis and Rheumatism,Cancer Immuno Immunotherapy等杂志上。担任《中国免疫学杂志》、《中国肿瘤生物治疗杂志》、《国际免疫学杂志》等杂志编委,并为Plos One,Rheumatology等杂志审稿。负责复旦大学上海医学院博士生《现代免疫学》、八年制《医学免疫学》以及全英语课程Medical Immunology的授课及课程建设。主编教育部“十一五”规划教材《免疫学与病原生物学》,参编Tumor Immunology Cancer Vaccines (Kluwer Academic Publishers,New York)和《实用内科学》等专著。

2011诺贝尔奖:免疫学研究的突破及意义

储以微

复旦大学上海医学院免疫学系-复旦大学生物治疗研究中心 上海200032

[摘要]  2011年的诺贝尔生理学或医学奖授予了3位从事免疫学研究的科学家,以表彰他们在树突状细胞和固有免疫分子方面的重要研究发现。基于他们的研究,人们逐渐明确了固有免疫细胞,特别是树突状细胞在抗原识别,进而启动适应性免疫应答方面的作用及其分子机制。本文对上述3位科学家及其团队的研究工作及他们所开创的研究领域的进展进行了系统回顾,并作一综述。

树突状细胞;Toll样受体;诺贝尔奖

10.3969/j.issn. 1672-8467.2011.06.001

2011 Nobel Prize:The breakthrough in immunology 

CHU Yi-wei 

万方数据472

万方数据万方数据473

@[ 1 ]  Steinman RM,Cohn ZA. Identification of a novel cell 

       type in peripheral lymphoid organs of mice. Ⅰ. 

       Morphology, quantitation, tissue distribution [J ]. J 

       Exp Med ,1973,137(1) :1142 - 1162.

@[ 2 ]  Steinman RM, Cohn ZA. Identification of a novel cell 

       type in peripheral lymphoid organs of mice. Ⅱ.

       Functional properties in vitro[J]. J Exp Med, 1974,

       139(2) :380 - 397.

@[3]  Steinman RM, Kaplan  G, Witmer  MD, et  al. 

       Identification of a novel cell type in peripheral        lymphoid organs of mice. V. Purification of spleen 

       dendritic cells,new surface markers, and maintenance 

       in vitro[J]. J Exp Med ,1979,149(1) :1 - 16.

@[ 4 ]  Steinman RM, Witmer MD. Lymphoid dendritic cells 

       are potent stimulators of the primary mixed leukocyte 

       reaction in mice[J]. Proc Natl Acad Sci USA, 1978,

       75(10) :5132 - 5136.

@[ 5 ]  Nussenzweig MC, Steinman RM, Gutchinov B, et al.

       Dendritic cells are accessory cells for the development 

       of anti-trinitrophenyl cytotoxic T lymphocytes[J]. J 

       Exp Med, 1980,152(4) : 1070 - 1084.

@[6]  Inaba K, Steinman RM, Van Voorhis WC, et al.

       Dendritic cells are critical accessory cells for thymus

       dependent antibody responses in mouse and in man 

       [J]. Proc Natl Acad Sci USA, 1983, 80 (19):       6041 - 6045.

@[ 7 ]  Schuler G, Steinman RM. Murine epidermal Langerhans        cells mature into potent immunostimulatory dendritic cells 

       in vitro[J]. J Exp Med, 1985,161(3) :526 - 546.

@[ 8 ]  Romani N,Koide S, Crowley M, et al. Presentation of        exogenous protein antigens by dendritic cells to T cell 

       clones. Intact protein is presented best by immature, 

万方数据        epidermal Langerhans cells[J]. J Exp Med , 1989,169

        (3) :1169 - 1178.

@@[ 9 ]  Liu K,Iyoda T, Saternus M, et al. Immune tolerance         after delivery of dying cells to dendritic cells in situ 

        [J]. J Exp Med ,2002,196(8) :1091 - 1097.

@@[10]  Hawiger D,Inaba K, Dorsett Y, et al. Dendritic cells 

        induce peripheral T cell unresponsiveness under 

        steady state conditions in vivo[J]. J Exp Med, 2001,

        194(6) :769 - 779.

@@[11]  Zhang M,Tang H, Guo Z, et al. Splenic stroma drives         mature dendritic cells to differentiate into regulatory 

        dendritic cells [J]. Nat Immunol, 2004, 5 ( 11 ) :

        1124- 1133.

@@[12]  Janeway CJ. Approaching the asymptote? Evolution         and revolution in immunology[J]. Cold Spring Harb 

        Symp Quant Biol, 1989,54 (Pt 1) : 1 - 13.@@[13]  Lemaitre B, Nicolas E, Michaut L, et al.  The 

        dorsoventral regulatory gene cassette spatzle/Toll/ 

        cactus controls the potent antifungal response in 

        Drosophila adults[J]. Cell, 1996,86 (6) : 973 - 983.@@[ 14]  Hashimoto C, Hudson KL, Anderson KV. The Toll gene         of Drosophila, required for dorsal-ventral embryonic 

        polarity,appears to encode a transmembrane protein 

        [J]. Cell, 1988,52(2) :269 - 279.

@@[15]  Shelton CA, Wasserman SA. Pelle encodes a protein 

        kinase required to establish dorsoventral polarity in 

        the Drosophila embryo [ J ]. Cell, 1993, 72 ( 4 ) :

        515 - 525.

@@[16]  Morissto D, Anderson KV. Signaling pathways that 

        establish the dorssl-ventral pattern of the Drosophila 

        embryo[J]. Annu Rev Genet, 1995,29:371 - 399.@@[17]  SiebenlistU, Franzoso  G, Brown  K.  Structure, 

        regulation and function of NF-kappa B[J]. Annu Rev 

        Cell Biol, 1994,10 :405- 455.

@@[18]  Lemaitre B, Reichhart JM, Hoffmann JA. Drosophila 

        host defense: differential induction of antimicrobial         peptide genes after infection by various classes of 

        microorganisms[J]. Proc Natl Acad Sci USA, 1997,

        94(26) : 14614 - 14619.

@@[19]  Poltorak A, He X, Smirnova I, et al. Defective LPS 

        signaling in C3H/HeJ  and C57BL/10ScCr mice:

        mutations in Tlr4 gene[J ]. Science, 1998,282 (5396) :

        2085 - 2088.

@@[20]  Kawai T, Akira  S. Toll-like  receptors and  their 

        crosstalk with other innate receptors in infection and 

        immunity[J]. Immunity, 2011,34 (5) : 637 - 650.@@[21]  Park BS, Song DH, Kim HM, et al. The structural 

        basis of lipopolysaccharide recognition by the TLR4 

        MD-2 complex [ J ]. Nature, 2009, 458 ( 7242 ) :

        1191 - 1195.

@@[22]  Wilgenhof S, Van Nuffel AM, Corthals J, et al.

@   @   @    @   @   @    @  @          Therapeutic vaccination with an autologous mRNA 

        electroporated dendritic cell vaccine in patients with 

        advanced melanoma[J]. J Immunother ,2011,34(5) :

        448 - 456.

@@[23]  Steele JC,Rao A,Marsden JR, et al. Phase Ⅰ/Ⅱ trial of 

        a dendritic cell vaccine transfected with DNA encoding 

        melan A and gp100 for patients with metastatic 

        melanoma[J]. Gene Ther,2011,18(6) :584 - 593.@@[24]  BerntsenA, Trepiakas  R, Wenandy  L, et  al.

        Therapeutic dendritic cell vaccination of patients with 

        metastatic renal cell carcinoma: a clinical phase 1/2 

        trial[J]. J Immunother,2008,31(8) :771 - 778.@@[25]  Tanimoto T,  Hori   A,  Kami   M.  Sipuleucel-T 

        immunotherapy for castration-resistant prostate cancer 

        [J]. N Engl J Mead ,2010,363(20) : 1966 - 1968.@@[26]  PrinsRM, Soto H, Konkankit V, et al.  Gene 

        expression profile correlates with T-cell infiltration         and  relative  survival  in  glioblastoma  patients 

        vaccinated with dendritic cell immunotherapy [J].

        Clin Cancer Res ,2011,17(6) :1603 - 1615.

@@[27]  Cannon MJ,Goyne H, Stone PJ, et al. Dendritic cell 

        vaccination against ovarian cancer-tipping the Treg/ 

        TH17 balance to therapeutic advantage? [J]. Expert 

        Opin Biol Ther,2011,11(4) :441 - 445.

@@[28]  Delluc' S, Hachem P, Rusakiewicz S, et al. Dramatic 

        efficacy improvement of a DC-based vaccine against 

        AML by CD25 T cell depletion allowing the induction         of a long-lasting T cell response[J]. Cancer Immunol 

        Immunother,2009,58(10) : 1669 - 1677.

@@[29]  Delamarre L,Mellman I. Harnessing dendritic cells for 

        immunotherapy[J]. Semin Immunol, 2011,23 ( 1 ) :

        2- 11.

@@[30]  Farag MM, Hoyler B, Encke J, et al. Dendritic cells 

        can effectively be pulsed by HBVsvp and induce 

        specific immune reactions in mice[J]. Vaccine, 2010, 

        29(2) :200 - 206.

@@[31]  Chen W,Shi M, Shi F, et al. HBcAg-pulsed dendritic 

        cell vaccine induces Thl polarization and production of 

万方数据        hepatitis B virus-specific cytotoxic T lymphocytes[J].

        Hepatol Res, 2009,39 (4) : 355 - 365.

@@[32]  Burdek M, Spranger S, Wilde S, et al. Three-day         dendritic cells for  vaccine development: antigen 

        uptake, processing and presentation [ J ]. J Transl 

       Med ,2010,8:90.

@@[33]  Navabi H,Jasani B, Reece A, et al. A clinical grade 

        poly Ⅰ: C-analogue (Ampligen) promotes optimal DC 

        maturation and Thl-type T cell responses of healthy 

        donors and cancer patients in vitro [J]. Vaccine,

        2009,27(1) :107- 115.

@@[34]  Spranger S,Javorovic M, Büdek M, et al. Generation 

        of Thl-polarizing dendritic cells using the TLR7/8 

        agonist CL075 [J ]. J Immunol, 2010, 185 (1):

        738- 747.

@@[35]  Zhang Y, Luo F, Cai Y, et al. TLR1/TLR2 agonist 

        induces tumor regression by reciprocal modulation of         effector and regulatory T cells[J]. J Immunol,2011, 

        186(4) : 1963 - 1969.

@@[36]  Alizadeh D, Zhang L, Brown CE, et al. Induction of         anti-glioma natural killer cell response following 

        multiple low-dose intracerebral CpG therapy[J]. Clin 

       Cancer Res ,2010,16(13) :3399 - 3408.

@@[37]  Zhao D,Alizadeh D, Zhang L, et al. Carbon nanotubes 

        enhance  CpG  uptake  and  potentiate  antiglioma         immunity [ J ]. Clin Cancer Res, 2011, 17 ( 4 ) :

        771 - 782.

@@[38]  Brody JD, Ai WZ, Czerwinski DK, et al. In situ 

        vaccination with a TLR9 agonist induces systemic         lymphoma regression:a phase Ⅰ/Ⅱ study[J]. J Clin 

       Oncol,2010,28(28) :4324 - 4332.

@@[39]  Prins RM, Soto  H, Konkankit  V, et  al. Gene 

        expression profile correlates with T-cell infiltration         and  relative  survival  in  glioblastoma  patients 

        vaccinated with dendritic cell immunotherapy [J].

        Clin Cancer Res ,2011,17(6) :1603 - 1615.

2011-10-17

2011诺贝尔奖:免疫学研究的突破及意义

作者:作者单位:刊名:英文刊名:年,卷(期):

储以微, CHU Yi-wei

复旦大学上海医学院免疫学系-复旦大学生物治疗研究中心 上海200032复旦学报(医学版)

Fudan University Journal of Medical Sciences2011,38(6)

本文链接:http://d.g.wanfangdata.com.cn/Periodical_shykdxxb201106001.aspx

因篇幅问题不能全部显示,请点此查看更多更全内容

Top