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1、Introduction and History of Immunology,Institute of immunology, ZJU,Lecture 1,History of Immunology Immune system Innate immunity Adaptive immunity,Text book: Medical Immunology 5th ed(金伯泉) References: Natural Review of Immunology Annual Review of Immunology,Immunity,Immunity: refers to all mechanis

2、ms used by the body as protection against environmental agents that are foreign to the body. The term “immunity” was first used in 1775 by Van Sweiten, a Dutch physician, as “immunitas” to describe the effects induced by an early attempt at variolization,Variolation,To induce immunity deliberately w

3、ere performed by the Chinese in the 1200 a technique called variolation Edward Jenner an English country doctor in 1798, took the scrab from Sarah Nelmes, a milkmaids and inserted into arm of James Phipps, a 8-year old boy. Eight weeks later, James was challenged with the deadly smallpox,Louis Paste

4、ur (1822-1895) Pasteur called the attenuated strain as “Vaccine”. The latin word “vacca=cow” in honor of Jenners work. Attenuated vaccines for cholera, anthrax, and rabies On July 4, 1886, 9-year-old Joseph Meister was bitten repeatedly by a rabid dog, Pasteur treated him with his attenuated rabies

5、vaccine two days later. Meister survived. Joseph Meister later become a gatekeeper for the Pasteur Institute. In 1940, when he was ordered by the German occupiers to open Pasteurs crypt, Joseph Meister refused and committed suicide,Robert Koch (1843-1910) German physician; also started to work on An

6、thrax in 1870s. Identified the spore stage. First time the causative agent of an infectious disease was identified. Discovered the tubercle bacillus and tuberculin. Detailed tuberculin skin test (DTH). Awarded 1905 Nobel Prize,Emil Adolf von Behring (1854 1917) A Student of Koch With Kitasato and We

7、rnike, discovered anti-toxin for Diphtheria and Tetanus and applied as therapy. Awarded first Nobel Prize in physiology, 1901,Paul Ehrlich (1854 1915) Developed a series of tissue-staining dyes including that for tubercle bacillus. Worked with Koch. Developed anti-toxin (Diphtheria) and hemalysis Si

8、de-chain theory of antibody formation: surface receptors bound by lock Ag stimulated receptors Shared 1908 Nobel Prize with Metchnikoff,Elie Metchnikoff (1845-1916) Embryologist studying starfish development. Found phagocytosis. Phagocytes from larva stuck on thorn from a tangerine tree. Later he fo

9、und a fungal spore attached to a phagocyte of Daphnia. Formed the basis of leukocyte phagocytosis. Birth of cellular immunology Shared Nobel Prize with Ehrlich in 1908,Sir Frank Macfarlane Burnet (1899-1985) Important work on influenza. Discovery of an influenza viral enzyme with the specificity for

10、 particular forms of neuramic acid. Used today for detection. Clonal selection theory to explain tolerance 1960 Nobel Prize for the discovery of acquired immunological tolerance. Rejection of donor grafts was due to an immunological reaction and that tolerance can be built up by injections into embr

11、yos,Gerald M. Edelman 1929,Rodney R. Porter 1917-1985,1972 Nobel Prize for their discoveries concerning the chemical structure of antibodies,BARUJ BENACERRAF,JEAN DAUSSET,GEORGE D. SNELL,Discovered genes that regulate immune responses (Ir gene), Now known ad the major histocompatibility antigens 198

12、0 Noble prize,Niels K. Jerne (1912-1994) Antibody avidity maturation Plaque forming assay Pre-existing repertoire (in host DNA) theory helped the formation of clonal selection theory. Host MHC is the driving force for the maturation and selection of T cells in the thymus. *Idiotype network Nobel Pri

13、ze, 1984, for theories concerning the specificity in development and control of the immune system and the discovery of the principle for production of monoclonal antibodies,Milstein (b. 1927) and Khler (1946-1995) Monoclonal antibody,Susumu Tonegawa (b. 1939) Cloning of the Immunoglobulin gene 1987

14、Nobel prize for his discovery of the genetic principle for generation of antibody diversity,Peter C. Doherty and Rolf M. Zinkernagel Two signals 1996 Nobel Prize for their discoveries concerning the specificity of the cell-mediated immune defense,Why we need to study immunology,New emerging diseases

15、 are close to us,Resurrection of 1918 Flu From Sequenced Fragments,HIV and AIDS,Autoimmunity,Allergy,Graft rejection,Skin co-stimulatory signal Effective cell B cell-Antibody; T cell-CTL Memory cell,adaptive immune response,adaptive immune response,Immune Response,Phagocytic cells,Monocytes/Macropha

16、ges functions:1 remove particulate antigens 2 take up,process and present antigenic peptides to T cells distribution:Kupffer cells in the liver microglial cells in the brain,Phagocytic cells,monocyte,Phagocytic cells,Neutrophils 1.neutrophils are short-lived phagocytic cells multilobed nucleus; 10-2

17、0m 2.neutrophils have a large arsenal(军火库,兵工厂) of antibiotic protein granules:lysosomes;lactoferrin;lysozyme,Neutrophil,Lymphocytes,1.Lymphocytes are wholly完全的 responsible for the specific immune recognition of pathogens, so they initiate adaptive immune responses. 2.Lymphocytes are derived from bon

18、e-marrow stem cells. 3.B lymphocytes develop in the bone marrow. T lymphocytes develop in the thymus,B Lymphocytes,BCR:a surface receptor specific for a particular antigen B cells antigen plasma cells secrete antibody humoral immunity,B Lymphocytes,T Lymphocytes,TCR:T-cell antigen receptor TCR+ 95%

19、TCR+ 15% CTL,cytotoxic T cells regulatory T cells helper T cells,Th CMI,cell mediated immunity,Antigen presenting cells,Macrophage: antigen processing high antigen presenting low Dentritic cell(DC):antigen presenting high,Antigen presenting cells,Natural killer cells(NK,15% of blood lymphocytes expr

20、ess neither T-cell nor B-cell antigen receptors,Components of blood,Tissues and organs of the immune system,Primary lymphoid organs the bone marrow the thymus gland Secondary lymphoid organs the spleen lymph nodes Mucosal-associated lymphoid tissue,Functions of lymphoid organs,the place in which pro

21、liferation of HSC take place the place in which development and maturation of B cells occur 3. The lymphoid progenitor cells are transported by circulating blood to the thymus and differentiate into fuctional T lymphocytes,Bone marrow,Thymus,1.Cells:thymic stromal cells(TSC) thymocytes T cell (+ ) m

22、onocytes,macrophage,TDC 2.Structure:cortex-immature thymocytes madulla-mature thymocytes M,TDC 3.Function:It is the site of T cell maturation; It determines the specificity of the TCR expressed on the T cells released to periphery,thymus gland,spleen,1. adult spleen:13*8cm 180-250g 2. the white pulp:lymphoid cells the red pulp venous sinuses cellular cords 3.function:a reservoiv for platelets, erythrocytes and granulocytes; destroy the Ag,aged pl

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