1、医学免疫学甲全册完整教学课件医学免疫学甲全册完整教学课件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 Ref
2、erences Immunology is on frontiers 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 st
3、udy Immunology ? Immunology is 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 knowl
4、edge of the immune system is 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 t
5、he body. (to recognize and eliminate 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
6、 of the molecules and cells in 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 fun
7、ctions of immune system: (1) 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.Immun
8、e Cells 4.Tissues and Organs 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 I
9、t refers to any inborn immunity 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
10、 mucous membranes Phagocytosis 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(P
11、AMPs）: LPS, DNA, RNA, Protein 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
12、 immune response to microbes: 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 Alth
13、ough innate immunity can effectively 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 susceptibil
14、ity to infections. Adaptive immune 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
15、immunity Humoral immunity: mediated 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: (
16、also called immunoglobulin) proteins 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 Mecha
17、nisms 2005 Elsevier Types of 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 ly
18、mphocytes B cell-cytokines (IL-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.
19、 Signal 1 is provided by antigen 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):
20、membrane Ig T cell- TCR (T cell 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. Me
21、mory cells Downloaded from: StudentConsult (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 R
22、esponds rapidly No memory No 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 I
23、ndividual B and T cells possess 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 faste
24、r. Clonal selection theory Frank 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
25、 DNA rearrangement as T cells 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
26、 as these cells develop. As a 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.Immun
27、opathology 6.Brief history of 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
28、NK cell Dendritic cell QuickTime?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 wholl
29、y responsible for the specific 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 heter
30、ogeneous in lineage, function 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 diffe
31、rentiation) numerical designation. 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. Cytot
32、oxic T cells (CTL) 2. helper 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 Fi
33、broblast Tumor Cells Specialized 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 presentatio
34、n. 2.Dendritic cells (DC): such 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 ce
35、lls Monocytes (blood)/Macrophages (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; basop
36、hils; eosinophils 2.neutrophils 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 Intro
37、duction eosinophil neutrophil 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 Primar
38、y (or central) lymphoid organs 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. Peripher
39、al lymphoid organs: the organs 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
40、and from where they recirculate 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 lymphocy
41、tes Introduction Bone marrow 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 spe
42、cificity of the TCR expressed 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: St
43、udentConsult (on 1 June 2006 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 me
44、dulla. 180-250g germinal center (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
45、of the spleen. a.A splenic arteriole 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
46、 B cells are segregated into 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.
