면역학 Coico, R., Sunshine, G., (2009) Immunology : a short course, 6 th Ed., Wiley-Blackwell Immunology Prof. H. J. Kim
CHAPTER 1 Introduction & Overview 1. 2. 3. 4. 5. 정의 면역이란? 면역학의발달사면역반응의생리적기능 Kinds of Immunity Immune System 6. 면역공학 2
면역 / 免疫 / Immunology Immunitas ; 세금, 죄, 군복무등의면제를받는다는 의미의라틴어. 법률용어 immunity ( 의학적으로특정질환으로부터의보호 ) 3
10세기중국에서천연두 ( 마마 ) 를예방하기위해상처의딱지를가루로만들어바늘에묻혀찌르는방법을사용. 14세기 Ibn Khatima와 Ibn al-khatib가 전염성실체 (theory of germ) 존재기록 (Turkey, 1369). 16세기 Girolam Fracastoro (Italy, 1546) 에의해전염성포자 (spore) 혹은씨앗과같은질병의실체기록. (discovered syphillis [ 매독 ]) Portrait of Girolamo Fracastoro by Titian, This is a file from the Wikimedia Commons 4
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Year Who Achievements 1798 1880 1881 1882 1890 1894 1899 1905 1925 1953 1958 1959 1961 1969 1975 1982 1984 1886 1974 1987 1990s Jenner Kock Pasteur Metchnikoff Behring & Kitasato Pfeiffer & Bordet Bordet Carrel & Guthric Lewis Medawar Dausset & Snell Porter & Edelman Nowell Benaceraf Kohler & Milstein Allison & Kappler Hedrick & Davis - - Steinman & Cohn Tonagawa Cowpox( 두창 ) vaccination : 동물바이러스를이용한질병예방 Tuberculosis ( 결핵 ) : cell-mediated rabies vaccine ( 광견, 공수병 ) : killed & attenuated vaccine Phagocytosis (1908) * cellular immunity Diphtheria toxin injection : Serum antibody discovery Bacteriolysis : (antibody & complement :1919) Complement organ transplantation chemical mediators of inflammation Immune tolerance Histocompatibility antigens (1980) structure of antibody (1972) Mitogenic activation of lymphocytes. genetic control of immune response (1980) Hybridoma : monoclonal antibody generation T cell receptor T cell receptor gene The 1 st FDA approved therapeutic monoclonal Ab (OKT3) The 1 st humanized monoclonal Ab produced Discovery of dendritic cells (2011) somatic rearrangement of immune response gene Development of safer vaccines & Immune Engineerings 7
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Steinman, R. M. and Cohn, Z. A., J. Exp. Med. 1974. 139: 380 397. 9
결핵장티푸스천연두광견병황열병홍역소아마비이하선염풍진수두 장티푸스페스트백일해소아마비진드기매개뇌염 디프테리아파상풍백일해 B 형간염라임병인간유두종 폐렴 수막구균 10
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기능刺戟抗原 ( 예 ) 기능亢進時기능低下時 防禦機能外因性 ( 세균, 미생물 ) 알레르기면역기능저하 恒常性維持機能 外因性, 內因性 ( 노화세포 ) 自家면역질환 監督機能 ( 변이세포 ) 악성종양질환 12
선천성면역 (innate/native immunity) Natural barriers Phagocytes NK cells Complements - low specificities - rapid response - no memory 후천성면역 (acquired/adaptive immunity) Lymphocytes (B/T) - Immunization Active immunization Passive immunization Adoptive immunization - high specificity - slow response - memory 13
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Immunity Innate Immunity ( 선천성면역능 ) Acquired Immunity ( 후천성면역능 ) Humoral Immunity 체액성면역계 Cellulal Immunity ( 세포성면역계 ) Antibody (B Lymphocyte) Helper T Lymphocyte Cytotoxic T Lymphocyte (killer T cells) 16
5-1. Cells of the Immune System Immune Cells (1) 선천성면역계의세포들 Phagocytes : monocyts, macrophage, dendritic cell 등 (professional APC) Granulocytes : neutrophil, eosinophil, basophil 등 NK cell, mast cell 등 (2) 후천성면역계의세포들 B Lymphocyte : T Lymphocyte : helper T, regulatory T cell, cytotoxic T cell (3) Antigen Presenting Cells ( 항원제시세포, Target cells, APC) Professional APC : Phagocytes (Mφphage, DC, B cell) APC : all the cells those infected or mutated 17
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5-2. Humoral Immunity and Cellular Immunity (BCR) Humoral immunity Cellular immunity By B cells T cells Mediator Immunoglobulin Granules, cytokines Function Antigen tagging Complement activation ADCC B cell help Inflammatory effects Cytotoxic effects Regulatory effects Cytokine effects 19
Antibody ( 항체 ) : humoral immunity Fig. 1.2. Typical antibody molecule composed of two heavy(h) and two light (L) chains. Immunoglobulin (Ig) Antibody (secreted form) B cell Receptor (membrane form) 20
면역담당세포 B 세포 T 세포항원제시세포 항체공학맞춤면역치료면역기능조절 백신약물전달항체치료 암치료자가면역치료장기이식 알레르기 AIDS 치매 21
6-1. Antibody Engineering (1) 22
6-1. Antibody Engineering (2) 23
6-1. Antibody Engineering (3) 24
6-1. Antibody Engineering (4) Chimeric Antibody (Genetic engineering) 25
6-2. Antibody Engineering Human antibody from xeno-mouse Construction of human antibody producing Transgenic Mouse 26
6-3. Antigen Engineering Approaches to enhance antigen targeting to antigenpresenting cells for improved immunization. 27
6-4. APC Engineering 29
Strategies for Designing & Optimizing New Generation Vaccines