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IMMUNOLOGY Immunology general Chen Weilin, Ph.D [email protected] 《医学免疫学》的主要研究内容: 免疫刺激剂 免疫系统(免疫器官、细胞、分子) 抗体 免疫调控 正常 抗 抗 自 肿 感 身 瘤 染 耐 受 致敏的淋巴细胞 细胞因子 补体 急性期蛋白等 免疫应答 应用 异常 肿 感 自 瘤 染 身 免 疫 病 免 疫 缺 陷 病 染 移 植 物 排 斥 变 态 反 应 性 疾 病 免 疫 学 诊 断 免 疫 学 预 防 免 疫 学 治 疗 Ⅰ Immunity and immunology Ⅱ Immunologic function Ⅲ Immune system Ⅳ Immune response Ⅴ Immunopathology Immunity 1.Immunity:refers to all mechanisms used by the body as protection against environmental agents that are foreign to the body. 2.Agents:microorganismor and their products, foods, chemicals, pollen,tumor cells, viruses… 3.Immune system: immune tissues and organs, immune cells, immune molecules 4.Immune response: benefits; damaging effects 5.Immunology:A science studying on organization and function of immune system Immunologic function Biological effects of immune system on antigens during immune responds physiological homeostasis effect---keeping normal pathological effect----resulting in diseases Physiological and pathological representation of immune response Function Physiological (advantageous) immune defense resist to pathogen Pathological (harmful) hypersensitivity/ immunologic deficiency disease immune homeostasis scavenge damaged Autoimmunne or senile cell disease immune surveillance Scavenge cells with Cancer misreplication/ virus persistent mutant cell infection Immune system dominate immune function execute immune effect comprise immune organs, immune cells and immune molecules 1 Immune organs center immune organs concept:places where immunocytes genesis, develop, differentiate and mature composition:bone marrow, thymus and bursa of Fabricius (which is one of Avian character) peripheral immune organs concept : places where mature T, B lymphocytes resident and contact with antigens and carry out immune response composition : lymphonode, spleen, mucosalassociated lymphoid tissue Bone marrow the place in which proliferation 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 1. 2. thymus gland 1.Cells:thymic stromal cells(TSC) thymocytes T cell (αβ+ ) monocytes,macrophage,TDC 2.Structure:cortex---immature thymocytes madulla---mature thymocytes Mø,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 The cellular organization of the human thymus 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 platelets spleen Downloaded from: StudentConsult (on 1 June 2006 02:08 PM) © 2005 Elsevier lymph node 1. 2. 3. Human:2-10mm in diameter round and kidney shaped Consists of : B-cell area(cortex) T-cell area(paracortex) central medulla lymph node Mucosal-associated lymphoid tissue(MALT) 1.non-encapsulated lymphoid tissue 2.in the lamina propria and submucosal areas of the gastrointestinal,respiratory and genitourinary tracts. 3.tonsil, appendix, Peyer’s patches 4.B cell IgA Mucosal-associated lymphoid tissue(MALT) Lymphocyte recirculation 1. 2. Lymphocytes leave the blood via high-walled endothelium of the post-capillary venules Lymphocyte trafficking exposes antigen to a large number of lymphocytes Lymphocyte recirculation 2 immunocytes all cells that participate in immune response and their precursors. cells participating in innate immune response NK, macrophage, granular leukocytes, monocyte, mast cell, B1-B cells participating in adaptive immune response T、B、APC Lymphocytes(T,B) NK cell eosinophil Dendritic cell Monocyte/macrophage basophil Mast cell Immunocytes neutrophil erythrocyte platelet 3 immune molecules immunoglobulin, MHC, complement, cytokine et al complement CR CKR cytokine Immune Response innate immune response natural immune response non-specific immune response adaptive immune response acquired immune response specific immune response Innate immunity mechanism of recognition Pathogen associated molecules patterns(PAMPs):LPS,DNA,RNA,Protein Danger-associated molecular patterns (DAMPS):DNA,HSP Pattern recognition receptors (PRR): Tolllike receptor(TLR) ,C-lectin recptor(CLR),RIG-I-Like recptor(RLR),NODlike Receptor(NLR) innate immunity Physiological barriers skin mucous membranes Phagocytosis polymorphonuclear leukocytes(PMN) macrophages Natural killer(NK) cell cytokines and inflammation Macrophages phagocytose and degrade foreign particles, bacteria and dead (and dying) host cells. Receptors on Macrophages: Toll-like receptors Fc receptors Mannose receptor Complement receptors IFNg receptor Chemokine receptors Scavenger receptors LPS receptor: CD14 toll-like receptor-4 CR3,4: Complement receptors (C3b) Scavenger receptor: sialic acid-bearing protein Mannose receptor: Binds mannose on bacteria, activates C’ Glycan receptor: Polysaccharides Localization and Removal of Foreign Substances Metabolic Destruction intracellular digestion, killing Oxygen independent: defensins and granular cationic proteins, lactoferrin, lysozyme, acid hydrolases Oxygen dependent: ROIs, RNIs; respiratory burst myeloperoxidase, hydrogen peroxide, superoxide anion, hydroxyl radicals, nitric oxide, peroxynitrite Macrophage Mediators Can Damage Host Tissues Bioactive Lipids ROI Activated Macrophage TNF-a IL-1 chemokines Proteolytic Enzymes RNI PH Reactive Oxygen Intermediates NADH NADPH H2O2 O2OH- Lipid Peroxidation Membrane, Protein and DNA Damage Innate defense is both preformed and inducible adaptive immunity The activation of lymphocytes antigen TCR(T cell receptor) BCR(B cell receptor) Proliferation and differentiation of lymphocytes B cell----cytokines T cell----Antigen-TCR;co-stimulatory signal Effective cell B cell----Antibody; T cell----CTL Memory cell adaptive immunity adaptive immunity Comparison between innate immunity and adaptive immunity Characteristics Cells Moleculars Phagocytes (PMNs and macrophages) Natural killer cells Master cells Dendritic cells Cytokines Complement Acute phase proteins T cells B cells Dendritic cells Antibodies Cytokines Innate immunity Generated little by little during long –term evolution Commonly owned by different germlines, herediable Responds rapidly Has some specificity No memory Adaptive immunity Stimulated by antigen Specially owned by some individuals, non-herediable but form immune memory Slow too start Highly specific Memory Adaptive immunity Humor immunity antibody cell immunity Bacterial component kill bacteria Target cell kill Mon/Mφ Active/attract IFNγ apoptosis chemokine Innate immunity Relationship between innate immunity and adaptive immunity Immunopathology Hypersensitivity - overactive immune response Immunodeficiency - ineffective immune response Autoimmunity - inappropriate reaction to self antigens •To master basic conceptions of immunity, immunology and immune function •To be familiar with the construction and function of immune organs and immunocytes •To understand differences of innate immunity and adaptive immunity