中科院细胞与分子免疫学课程chapter

Cellular and Molecular Immunology,主讲教师：刘利新,Email address: ,使用教材：,The Main Immunology Journal,Cell: 36.2EMBO J. : 14.0Lancet: 10.2Nature: 29.5Nature Medicine: 26.6New England Journal of Medicine: 28.9PNAS: 10.3Science: 24.6,Autoimmunity: 1.1Cancer Immunology Immunotherapy: 2.3Cellular Immunology: 2.3Clinical and Experimental Allergy: 2.7European Journal of Immunology: 5.6Human Immunology: 2.6Immunity: 20.6Immunogenetics: 2.9Immunology: 2.6,Immunopharmacology : 1.4Infection and Immunity : 4.2International Archives of Allergy and Applie Immunology : 1.9International Immunology :2.9Journal of Allergy and Clinical Immunology: 4.6Journal of Autoimmunity: 2.2Journal of Clinical Immunology: 2.4Journal of Experimental Medicine: 15.7,Journal of Immunology: 7.1Journal of Immunological Methods: 1.9Journal of Immunotherapy: 3.1Journal of Reproductive Immunology: 1.5Molecular Immunology: 2.1Parasite Immunology: 2.0Scandinavian Journal of Immunology: 1.7Tissue Antigens: 3.0Transplantation: 3.5Vaccine: 3.2,Introduction to Immunology,Q: Interesting?,A: Of Course,Example1:,Allergen and desensitization therapy,The nude mouse cannot mount an immune response,The nude mouse has a defect in its immune system, and can only live if protected from pathogens. The mouse has a transplant of rabbit skin, and cant reject the foreign tissue. Mice with immune deficiencies are very useful in cancer research because human cancer cells can grow into tumors allowing new ways to test cancer therapy,Example 2:,Introduction to Immunology,Q: Worthy?,A: Very Worthy!,免疫学对人类的贡献,I Vaccine of infectious diseases such as smallpox,Smallpox,An Inquiry into the causes and effects of the Variolae Vaccinae, a disease discovered in some of the western counties of England, particularly Gloucestershire, and known by the name of the cow-pox,Baxby D. 1999. Edward Jenners Inquiry; a bicentenary analysis. Vaccine. 1999 Jan 28;17(4):301-7.,II Blood group antigen and blood transfusion reaction,III Histocompatibility antigen and organ transplantation,Joseph E. Murray 1919,幸运的莫雷,Joseph E. Murray 1919,The 1990 Nobel Prize in Physiology or Medicine,Organ transplantationImmunosuppression ( ionizing irradiation and cytotoxic drugs ),IV Allergen and desensitization therapy,V The fourth pattern tumor therapy -BRM（生物反应调节）,VI The diagnosis and therapy of immunodeficiency diseases,Severe combined immunodeficiency (SCID),Bubble-boy (XSCID),chain of IL-2 receptor is deficient in XSCID.Gene therapy,Rheumatoid Arthritis，RA,TNF-a and IL-1 cause excessive inflammatory reaction in RA.Inhibitors of TNF-a for therapy,Autoimmunity:,Autoimmunity: Systemic lupus erythematosus,Influenza,Sars,New Appearance of Virus,（猪繁殖与呼吸综合征，PRRS）,Porcine Reproductive and Respiratory Syndrome,美国全力保持其分子免疫学的领先地位，因为分子免疫学可使人们更好的理解和认知生命科学，解决医学问题，应用于药物研制，有效地防治疾病，带来更大的经济效益。NIH基金中，有15用于免疫学研究。,国际分子免疫学发展：,3. Nobel Prize in Immunology,1997 S.B. Prusiner USA prions1999 G. Blobel USA signal transduction.,Introduction to Immunology,Q: Difficult?,A: A Little.,So many cells, molecular and mechanisms were involved in Immunologic response,Schedule,Section I ( 2 chapter )Introduction to Immunology Chapter 1General Properties of Immune Responses Chapter 2Cells and Tissues of the Immune System,Section II -1( 4 chapter )Recognition of Antigens,Chapter 3 Antibodies and Antigens Chapter 4 The Major Histocompatibility Complex,Chapter 5Antigen Processing and Presentation to T Lymphocytes Chapter 6Antigen Receptors and Accessory Molecules of T Lymphocytes,Section II-2 ( 4 chapter )Maturation, Activation, and Regulation of Lymphocytes Chapter 7Lymphocyte Maturation and Expression of Antigen Receptor Genes Chapter 8Activation of T Lymphocytes,Chapter 9B Cell Activation and Antibody Production Chapter 10Immunologic Tolerance,Section II-3 ( 5 chapter )Effector Mechanisms of Immune Responses Chapter 11Cytokines Chapter 12Innate Immunity,Chapter 13Effector Mechanisms of Cell-Mediated Immunity Chapter 14Effector Mechanisms of Humoral ImmunityChapter 15 Immunity to Microbes,Section III ( 5 chapter )The Immune System in Disease,Chapter 16Transplantation Immunology Chapter 17Immunity to Tumors,Chapter 18 Diseases Caused by Immune Responses: Hypersensitivity and Autoimmunity Chapter 19Immediate Hypersensitivity Chapter 20 Congenital and Acquired Immunodeficiencies,Section I Introduction to Immunology,Chapter 1 General Properties of Immune Responses,Definition:,immunity: the Latin word immunitas, which referred to the protection from legal prosecution offered to Roman senators during their tenures in office. Immunity: Historically, protection from disease and, more specifically, infectious disease.,Immunity: A reaction Foreign substancesIncluding microbes, macromolecules (such as proteins and polysaccharides), regardless of the physiologic or pathologic consequence of such a reaction.,A more inclusive definition:,Immunology: the study of the cellular and molecular events that occur after an organism encounters microbes and other foreign macromolecules.Immune system: The cells and molecules responsible for immunity.Immune response: The collective and coordinated response to the introduction of foreign substances,Innate and Adaptive Immunity,Innate immunity:,Principal components of innate immunity Physical and chemical barriers, such as epithelia and antimicrobial substances produced at epithelial surfaces; Phagocytic cells (neutrophils, macrophages) and NK (natural killer) cells; Blood proteins, including members of the complement system and other mediators of inflammation; Proteins called cytokines that regulate and coordinate many of the activities of the cells of innate immunity.,CharacterAlso called natural or native immunity consists of cellular and biochemical defense mechanisms that are in place even before infection and posed to respond rapidly to infections. These mechanisms react only to microbes and not to noninfectious substances, and they respond in essentially the same way to repeated infections.,Adaptive immunity,Adaptive immunity,The components of adaptive immunity Lymphocytes and their products Antigens,Character,Be acquired by exposure to infectious agents.Specificity：Exquisite specificity for distinct molecules, an extraordinary capacity to distinguish among different, even closely related, microbes and molecules.Memory：An ability to remember and respond more vigorously to repeated exposures to the same microbe .4. Self-limitation: Antibody levels decline with time after each immunization 5. Nonreactivity to self.,Specificity, memory, and self-limitation of immune responses,Table 1-2. Features of Innate and Adaptive Immunity,上堂课回顾：,免疫：机体对微生物，大分子物质如蛋白、多糖等外界物质所发生的生理或病理上的反应。根据机体对外界物质反应时所参与的细胞和分子的不同，免疫分为：天然免疫：是多细胞生物普遍具有的最古老的防御机制，在个体出生时就具备，可对外来病原体迅速应答，产生非特异抗感染免疫作用。参与天然免疫反应的成份：吞噬细胞（巨噬细胞，中性粒细胞）自然杀伤细胞,Two important links between innate immunity and adaptive immunity:The innate immune response to microbes stimulates adaptive immune responses and influences the nature of the adaptive responses. Adaptive immune responses use many of the effecter mechanisms of innate immunity to eliminate microbes, and they often function by enhancing the antimicrobial activities of the defense mechanisms of innate immunity.,Types of Adaptive Immune Responses,Two types: humoral immunity and cell-mediated immunity,Humoral immunity Be mediated by molecules in the blood and mucosal secretions, called antibodies, that are produced by cells called B lymphocytes. Antibodies recognize microbial antigens, neutralize the infectivity of the microbes, and target microbes for elimination by various effecter mechanisms. Humoral immunity is the principal defense mechanism against extracellular microbes and their toxins because secreted antibodies can bind to these microbes and toxins and assist in their elimination.,Cell-mediated immunityBe mediated by T lymphocytes (also called T cells). Eliminate intracellular microbes, such as viruses and some bacteria, survive and proliferate inside phagocytes and other host cells, where they are inaccessible to circulating antibodies. Defense against such infections is a function of cell-mediated immunity, which promotes the destruction of microbes residing in phagocytes or the killing of infected cells to eliminate reservoirs of infection.,Protective immunity against a microbe may be induced by the hosts response to the microbe or by the transfer of antibodies or lymphocytes specific for the microbe: active immunity and passive immunity.,Active immunity,Active immunity: The form of immunity that is induced by exposure to a foreign antigen because the immunized individual plays an active role in responding to the antigen. Naive : Individuals and lymphocytes that have not encountered a particular antigen.Immune: Individuals who have responded to a microbial antigen and are protected from subsequent exposures to that microbe.,Passive immunityPassive immunity: By transferring serum or lymphocytes from a specifically immunized individual, the recipient of such a transfer becomes immune to the particular antigen without ever having been exposed to or having responded to that antigen. A useful method for conferring resistance rapidly, without having to wait for an active immune response to develop. fetus and severe infection.,Through passive immunity, we know what cells and molecules that are responsible for acquired immunity.,Emil Adolf von BehringGermanyMarburg University Marburg, Germany b. 1854d. 1917,Karl Landsteiner Austria Rockefeller Institute for Medical Research New York, NY, USA b. 1868d. 1943,Elie Metchnikoff (1845-1916) Found phagocytosis.,Shared Nobel Prize with Ehrlich in 1908,Identified an apparent link between acidophilus-type bacteria and extended lifespan for humans. Acidophilus is a nutritional supplement product, which contains a given bacteria. Also, along with P.P. Roux, they researched the affects of using calomel(绿化亚汞） ointment to treat syphilis.,生产商：法国合生元制药（中国）有限公司 益生菌概念是从诺贝尔奖获得者Elie Metchnikoff首次提出的理论发展而来。健康儿童体内有多种益生菌，它们定植在肠道内壁，击活免疫细胞，提高肌体免疫力，并形成起保护作用的菌膜，阻止有害物质通过肠道进入体内，提高免疫力。,ChinaRen社区首页通版闲聊区,详细描述 ：婴幼儿的肠内菌丛状况在两岁后才会和成人一样，此时宝宝体内有益菌缺少后就会引起胃肠功能紊乱，便秘、腹泻、偏食、厌食，免疫力下降，反复感冒、体内毒素淤积 现代医学证明，健康儿童体内有多种益生菌，它们定植在肠道内壁，激活免疫细胞，提高机体免疫力，并形成有保护作用的菌膜，阻止有害物质通过肠道进入体内。-诺贝尔奖获得者Elie Metchnikoff,Cellular Components of the Adaptive Immune System,The principal cells of the immune system are lymphocytes, antigen-presenting cells, and effecter cells.,B lymphocytes are the only cells capable of producing antibodies. They recognize extracellular (including cell surface) antigens and differentiate into antibody-secreting cells, thus functioning as the mediators of humoral immunity. T lymphocytes, the cells of cell-mediated immunity, recognize the antigens of intracellular microbes and function to destroy these microbes or the infected cells.,Classes of lymphocytes,Helper T cells: Secrete cytokines, whose function is to stimulate the proliferation and differentiation of the T cells themselves, as well as other cells, including B cells, macrophages, and other leukocytes. Cytotoxic T lymphocytes (CTLs): CTLs kill cells that produce foreign antigens, such as cells infected by viruses and other intracellular microbes Regulatory T cells: Mainly to inhibit immune responses,Antigen-presenting cells (APCs): Macrophage, DC.Effector cells: activated T lymphocytes, mononuclear phagocytes and other leukocytes.,Phases of Adaptive Immune Responses,Adaptive immune responses may be divided into distinct phases:The recognition of antigenThe activation of lymphocytesThe elimination of antigen Homeostasis and the maintenance of memory,The recognition of antigen,The Nobel Prize in Physiology or Medicine 1984for theories concerning the specificity in development and control of the immune system”,Niels K. Jerne Denmark Basel Institute for Immunology Basel, Switzerland b. 1911 d. 1994,Sir Frank Macfarlane Burnet Peter Brian MedawarAustralia United Kingdom Walter and Eliza Hall Institute for Medical Research Melbourne, Australia b. 1899 d. 1985,University College London, United Kingdom b. 1915 d. 1987,Clonal selection theory: MacFarlane Bu