医学免疫学甲全套课程教学课件.ppt

1、 Introduction IMMUNOLOGY 曹雪涛主编 医学免疫学第六版 人民卫生出版社 2013 金伯泉主编 医学免疫学第五版 人民卫生出版社 2008 龚非力主编 医学免疫学第三版 科学出版社 2009 Abbas A K, et al. Cellular and Molecular Immunology. 7th ed. Elsevier Saunders, 2012 Janeway C A, et al. Immunobiology. 8th ed. Garland Science Publishing, 2012 References Immunology is on fron

2、tiers of life sciences Immunology is one of the main pillars for development of basic and clinical medicine Immunology is connected tightly with biotechnology and its industrialization A number of mysteries are under exploration in immunology Why study Immunology ?Why study Immunology ? Immunology i

3、s a difficult First, there are lots of details, and sometimes these details get in the way of understanding the concepts. A second difficulty in learning immunology is that there is an exception to every rule. The third difficulty in studying immunology is that our knowledge of the immune system is

4、still evolving. Introduction 1.Concept of Immunity 2.Immune Response 3.Immune Cells 4.Tissues and Organs of the Immune System 5.Immunopathology Immunity 1.Immunity: refers to all mechanisms used by the body as protection against environmental agents that are foreign to the body. (to recognize and el

5、iminate foreign substances) 2.Agents:microorganisms (viruses, bacteria etc) and their products, foods, chemicals, pollen, tumor cells, etc. 3.Immune system: immune tissues and organs, immune cells, immune molecules Introduction 4.Immune response: the coordinated reaction of the molecules and cells i

6、n the immune system to a foreign agent. Benefits: protect the host from diseases Damaging effects: cause tissue damage 5.Immunology is the study of the ways in which the body defends itself from infectious agents and other foreign substances in its environment. Three functions of immune system: (1)

7、immunologic defence (2) immunologic surveillance (3) immunologic homeostasis The Danger Model: A Renewed Sense of Self Polly Matzinger The Self-Nonself Models The Infectious-Nonself (INS) Model The Danger Model Introduction 1.Concept of Immunity 2.Immune Response 3.Immune Cells 4.Tissues and Organs

8、of the Immune System 5.Immunopathology 6.Brief history of Immune Response Immune Response Introduction Innate immune response natural immune response non-specific immune response Adaptive immune response acquired immune response specific immune response Innate immunity It refers to any inborn immuni

9、ty that is already present the first time a pathogen is encountered. It does not require prior exposure and is not modified significantly by repeated exposures to the pathogen over the life of an individual. Introduction Innate immune response Physiological barriers skin mucous membranes Phagocytosi

10、s polymorphonuclear leukocytes (PMN) monocytes/macrophages Natural killer (NK) cell Complement and acute phase proteins Introduction The principal mechanisms of innate and adaptive immunity Innate immunity mechanism of recognition Pathogen associated molecules patterns(PAMPs）: LPS, DNA, RNA, Protein

11、 Danger-associated molecular patterns (DAMPS): DNA, HSP Pattern recognition receptors (PRR): Toll-like receptor(TLR) ,C-lectin recptor(CLR),RIG- I-Like recptor(RLR),NOD-like Receptor(NLR) Toll-like receptor (TLR) TLR Many different types of blood cells participate in the immune response to microbes:

12、 Innate immune cells: phagocytes macrophage, neutrophils, dendritic cells Adaptive immune cells: lymphocytes T cells, B cells, APC Innate immune response Introduction (Lung) Macrophage Attacking E. coli Innate immune response Introduction Macrophage Attacking E.coli Although innate immunity can effe

13、ctively combat many infections, microbes that pathogenic for human have evolved to resist innate immunity. Defense against these infections are the task of the adaptive immune response, and this is why defects in the adaptive immune system result in increased susceptibility to infections. Adaptive i

14、mmune response Adaptive immune response The T cells and B cells in the body recognize the antigen and, in turn, become activated. The activated lymphocytes then proliferate and carry out their specific effector functions. Types of adaptive immunity Two types of adaptive immunity Humoral immunity: me

15、diated by B cells and defense against extracellular microbes. Cell-mediated immunity: mediated by T cells and defense against intracellular microbes. Cell-mediated immunity: Phagocytosis (cellular eating) cytotoxcity 细胞毒性(cellular killing) Humoral immunity: antibodies: (also called immunoglobulin) p

16、roteins secreted by B cells that bind directly and specifically to pathogens. Antibodies target pathogens by marking them for destruction by other components of the immune system. complement: group of serum proteins that can directly kill pathogens. Immune Effector Mechanisms 2005 Elsevier Types of

17、adaptive immunity. Adaptive immune response Introduction 1. The activation of lymphocytes antigen interacts with specific receptors: B cell- BCR (B cell receptor): membrane Ig T cell- TCR (T cell receptor), co-stimulatory signal 2. Proliferation and differentiation of lymphocytes B cell-cytokines (I

18、L-4,etc.) T cell-Antigen-TCR; co-stimulatory signal; cytokines(IL-2,IL-7,IL-15) 3. Effector cells and their functions B cell-Antibody; T cell-Th, CTL 4. Memory cells Adaptive immune response Introduction BCR (mIg) TCR The two-signal requirement for lymphocyte activation. Signal 1 is provided by anti

19、gen recognition. Signal 2 is provided by components of the microbes or substances produced during the innate immune response. Adaptive immune response Introduction 1. The activation of lymphocytes antigen interacts with specific receptors: B cell- BCR (B cell receptor): membrane Ig T cell- TCR (T ce

20、ll receptor), co-stimulatory signal 2. Proliferation and differentiation of lymphocytes B cell-cytokines 细胞因子(IL-4,etc.) T cell-Antigen-TCR; co-stimulatory signal共刺激信号; cytokines(IL-2,IL-7,IL-15) 3. Effector cells and their functions B cell-Antibody; T cell-CTL, Th 4. Memory cells Downloaded from: S

21、tudentConsult (on 31 May 2006 05:26 PM) 2005 Elsevier Downloaded from: StudentConsult (on 31 May 2006 05:26 PM) 2005 Elsevier Links between innate and adaptive immunity The innate and adaptive immune response Introduction Characteristics Cells Molecules Innate immunity Responds rapidly No memory No

22、or low specificity Physical barriers Phagocytes (PMNs and macrophages) Natural killer cells Humoral factors Complement Acute phase Proteins Cytokines Adaptive immunity Responds Slowly Memory Highly specific T cells B cells Dendritic cells Antibodies Cytokines Granzymes Individual B and T cells posse

23、ss the ability to make a specific receptor (each cell makes a different receptor molecule) Antigen binds to the cell surface receptor and activates the cell Process takes several days. Effector cells and memory cells are produced. Memory cells can thus be activated faster. Clonal selection theory Fr

24、ank M. Burnet The clonal selection hypothesis The Nobel Prize in Physiology or Medicine 1987 for his discovery of the genetic principle for generation of antibody diversity Susumu Tonegawa （利川根进）（利川根进） The genes encoding the T cell antigen receptor (TCR) are assembled by DNA rearrangement as T cells

25、 develop in the thymus TCR locus: structure in germline TCR locus: structure in T cells DNA rearrangement (rag1, rag2) transcription RNA splicing translation T cell V segmentsDJC The genes encoding the antigen receptors of T and B cells are assembled by DNA rearrangement as these cells develop. As a

26、 result of V(D)J recombination, every B and T cells expresses a unique version of the antigen receptor. Gene rearrangement of Ig Gene rearrangement of Ig Introduction 1.Concept of Immunity 2.Immune Response 3.Immune Cells 4.Tissues and Organs of the Immune System 5.Immunopathology 6.Brief history of

27、 Immune Response Immune Cells Introduction hematopoietic stem cell (HSC) Myeloid progenitor髓系祖细胞 Lymphoid progenitor Granulocytes (eosinophils 嗜酸,neutrophils中性, basophils嗜碱) Monocytes, macrophages Dendritic cell Erythrocyte红细胞 Megakaryocyte巨核细胞 T lymphocyte B lymphocyte NK cell Dendritic cell QuickT

28、ime?and aTIFF (LZW) decompressorare needed to see this picture.QuickTime?and aTIFF (LZW) decompressorare needed to see this picture. Most blood cells act to fight infection. Adaptive immunity Innate immunity Blood cells lineages. 1.Lymphocytes (except NK cells) are wholly responsible for the specifi

29、c immune recognition of pathogens, so they initiate adaptive immune responses. 2.Lymphocytes are derived from bone-marrow stem cells. 3.B lymphocytes develop in the bone marrow. T lymphocytes develop in the thymus. Introduction Lymphocytes Lymphocytes are extremely heterogeneous in lineage, function

30、 and phenotype and are capable of complex biologic responses and activities. Lymphocytes are often distinguished by surface proteins that may be identified by panels of monoclonal antibodies单克隆抗体. The standard nomenclature 术语for these proteins is the CD (cluster of differentiation) numerical designa

31、tion. B Lymphocytes BCR: a surface receptor (mIg) specific for a particular antigen B cells plasma cells antibody (the same specificity as the BCR) humoral immunity Introduction Ag secrete B Lymphocytes Introduction TCR: T-cell antigen receptor TCR+ 95% TCR+ 15% 1. Cytotoxic T cells (CTL) 2. helper

32、T cells: Th1, Th2, Th17 3. Regulatory T cells (Treg) and suppressor T cells (Ts) Introduction T Lymphocytes Properties of TH1, TH2, and TH17 subsets of CD4+ helper T cells. Introduction T Lymphocytes T lymphocyte Introduction T Lymphocytes Human T-lymphocyte Attacking Fibroblast Tumor Cells Speciali

33、zed cells that display antigens to T cells and provide second signal. Professional APCs include dendritic cells (DCs), macrophages (M) and B cells. Antigen presenting cells (APC) 1.Macrophage: powerful in antigen processing and destruction, but low in antigen presentation. 2.Dendritic cells (DC): su

34、ch as Langerhans cell (LC), powerful in antigen processing and presentation. Introduction Antigen presenting cells Introduction Natural killer cells (NK) 1. 10-15% of blood lymphocytes, LGL 2. express neither T-cell nor B-cell antigen receptors Introduction Phagocytic cells Monocytes (blood)/Macroph

35、ages (tissues) 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 Introduction Phagocytic cells Polymorphonuclear granulocytes 1.neutrophils; basophils; eosinophils 2.neutrophi

36、ls are short-lived phagocytic cells multilobed nucleus; 10-20 mm 3.neutrophils have a large arsenal of antibiotic proteins granules: lysosomes; lactoferrin Introduction Phagocytic cells Introduction Phagocytic cells Introduction monocyte neutrophil Phagocytic cells Introduction eosinophil neutrophil

37、 Phagocytic cells Introduction neutrophil activated erythrocyte platelet Introduction 1.Concept of Immunity 2.Immune Response 3.Immune Cells 4.Tissues and Organs of the Immune System 5.Immunopathology 6.Brief history of Immune Response Tissues of the immune system Primary (or central) lymphoid organ

38、s the bone marrow the thymus Secondary (or peripheral) lymphoid organs the spleen lymph nodes Cutaneous and mucosal immune system Introduction Generative lymphoid organs: the organs in which T and B lymphocytes mature and become competent to respond to antigens. Peripheral lymphoid organs: the organ

39、s in which adaptive immune responses to foreign antigens (such as microbes) are initiated. Maturation of lymphocytes. Mature lymphocytes leave the generative lymphoid organs and enter circulation and the peripheral lymphoid organs, where they respond to foreign antigens and from where they recircula

40、te in the blood and lymph. 1.the place in which proliferation of HSC takes place 2.the place in which development and maturation of B cells occur The lymphoid progenitor cells are transported by circulating blood to the thymus and differentiate into functional T lymphocytes Introduction Bone marrow

41、The thymus 1. Cells: thymic stromal cells (TSC) epithelial cells, monocytes (macrophage), TDC thymocytes T cell (+) 2. Structure: cortex-immature thymocytes medulla-mature thymocytes M, TDC 3. Function: It is the site of T cell maturation/selection; It determines the specificity of the TCR expressed

42、 on the T cells released to periphery Introduction The lymph node 1.Human:2-10mm in diameter 2.round and kidney shaped 3.Consists of : cortex (B-cell area) paracortex (T-cell area) central medulla (B-cell area) Introduction The lymph node Introduction Downloaded from: StudentConsult (on 1 June 2006

43、02:08 PM) 2005 Elsevier The morphology of lymph nodes. A.The structural organization and blood flow in a lymph node. B.Light micrograph shows a cross- section of a lymph node with numerous follicles in the cortex, some of them contain germinal centers, and the central medulla. 180-250g germinal cent

44、er (B) 1. the white pulp periarterial lymphatic sheath (T) the red pulp (B) 2. function: destroy the Ag, aged platelets immune response Introduction The spleen Introduction The spleen Downloaded from: StudentConsult (on 1 June 2006 02:08 PM) 2005 Elsevier The morphology of the spleen. a.A splenic ar

45、teriole surrounded by the periarteriolar lymphoid sheath (PALS) and the attached follicle containing a prominent germianl center. b.Light micrograph of a section shows an arteriole with the PALS and a secondary follicle. Within the peripheral lymphoid organs, T cells and B cells are segregated into

46、different anatomic compartments. Downloaded from: StudentConsult (on 31 May 2006 05:26 PM) 2005 Elsevier Segregation of T and B cells in different regions of peripheral lymphoid organs. A.The path by which na ve T and B cells migrate to different areas of a lymph node. B.Immunofluorescence shows that the B cells and T cells locate in the follicles and in the parafollicular cortex, respectively. Mucosal immune system (MIS)