固有免疫细胞及功能英.ppt

,Cells in innate immunity and their functions,一. Tissue,cells and molecules of the innate immune system Phases of innate immune responses Characteristics of innate immune response and its relationship with adaptive immune response,Section I Tissue,cells and molecules of the innate immune system,Acquired Immunity Adaptive Immunity Specific Immunity,Innate Immunity Native Immunity Nonspecific Immunity,Species development, formed evolutionally Possess from the time of birth，react rapidly Non-specific anti-infection immunity, also involved in specific immunity,一. Tissue barriers and their effection,（一）The skin and mucosal surfaces provide protective barriers against infection Physical barriers: epithelial, cilia, mucus Chemical barriers: lactic acid, unsaturated fatty acid, gastric acid Biological barriers: microorganisms,（二） Blood-brain barrier （三） blood fetus barrier,二. Cells involved in innate immunity and their functions,Phagocute Natural killer cells T cells NKT cells B1 cells,1. phagocytes,Mononuclear phagocyte system,neutrophils,monocyte,macrophage,microglial cells, Kupffer,Osteoclast,Macrophage Long-lived( up to several months) Large, pleomorphism and rich in lysosomes in the cytoplasm. MHC-I/II and many adhension molecules Many receptors,Neutrophil Short-lived Small and round Large quantities, replaced rapidly Large amount of azurophil granule and neutrophil granule in the cytoplasm MHC-I and receptor of adhension molecules,surface receptors of phagocytes Mannitol, fucose, phosphatide receptor CR3, CR4 , CD14 C3bR FcR Toll-like receptor scavenger,Recognized molecules Corresponding carbohydrate and phosphatide LPS Antigens entrapped by C3b Antigens specially bound by IgG PAMP,Phagocytes Biological functions,Phagocytes Biological functions Antimicrobial and cytotoxic activity Oxygen-dependent, Oxygen-independent Secretion of factors Cytokines, Inflammantory mediators Antigen presentation Intrinsic, Extrinsic Anti-tumour,Oxygen-dependent killing mechanisms Reactive oxygen intermediates(ROIs) Neutrophil myeloperoxidase(MPO) Reactive nitrogen intermediates(RNIs) Oxygen-dependent killing mechanisms acid pH, lysozyme , lactoferrin, cationic protein, elastase,Antimicrobial and cytotoxic activity,Secretion of factors Released in appropriate or large quantities Cytokines：TNF-, IL-1, IL-6, IL-8, IL-12, MCP-1 Inflammation mediators：prostaglandin E, LTB4, PAF, phosphatidase, peroxidate Local inflammatory reaction（TNF-、IL-1、 LTB4） Fever and acute phase reaction（CRP、MBL） Immunoregulation（IL-1、IL-6、IL-12）,Phagocytes Biological functions Anti-infection Anti-tumor: directly contact and fuse with the tumour cell membrane ; cytotoxic substance, proteinase, cytolysin, TNF-,ADCC mediated by tumor specific antibody Antigen processing and presentation Immunoregulation,PBMC, Spleen Large amount of azurophil granule in the cytoplasma Kill the target cells directly with no needs of preactivation surface markers:CD3-, CD56, CD16,2. NK Cells,NK cells,Molecular recognition: killer activatory receptor(KAR) killer inhibitory receptor(KIR) KAR KAR recognize cell carbohydrate ligands ITAMtransduce activation signals KIR The extracellular region of KIR recognize MHC-I of self cells ITIM transduce inhibitory signals Regulation of NK cell killing effect by two receptors,NK cells Biological Functions Anti-infection：lysis, IFN- and TNF- Anti-tumor： directly contact and fuse with tumour cells membrane ADCC mediated by tumor specific antibodies Immunoregulation,3. T cell Distributions: epithelia, mucosa surface markers: TCR, CD2/3/16/25/45, LFA-1，DN Molecular recognition: Narrow spectrum of antigen recognition：HSP, CD1 complex, viral proteins (VP) The same group of cells express only one kind of TCR : same specificity of antigen recognitionresponse to common antigen Biological Function: anti-infection in skin and mucosa, anti-tumor, immunoregulation,4. NKT cells Distribution: liver, bone marrow, thymus surface marker: NK1.1, TCR-CD3 complex molecular recognition Narrow spectrum of antigen recognition ：CD1 complex，without MHC restriction Biological function: anti-infection, anti-tumor, involved in immunoregulation by secreting cytokines,5. B1 cell Distribution: abdomen, thoracic cavity，lamina propria of bowels walls Features: appear early in the ontogenesis，self-renewal Surface markers: CD5、CD11、mIgM，CD23 Molecular recognition Narrow spectrum of antigen recognition ： TI-2 polysaccharide antigen, TI-1 polysaccharide antigen（LPS）, self -antigen Features of response,Other types of cells involved in the innate immunity: Dendritic cell Eosinophil granulocyte Basophilic granulocyte Mast cell,三. Innate effector molecules and their main function,（一）complement system,（二）Cytokines 1. Cytokines to induce anti-viral ability 2. Cytokines to induce and promote Inflammatory reactions 3. Cytokines to induce and enhance anti-tumor abilities,（三） Defensin （四） Lysozyme （五） -Lysin,Transient phase of innate immune response Early phase of innate immune response Induction Phase of adaptive immune response,Section 2 Phases of innate immune response,Section 3 Characteristics of Innate Immune Response and Its Relationship with Adaptive Immune Response,. Characteristics of innate immune response,（一）Recognition features of innate immune cells 1. Pattern-recognition receptors (PRRs) and pathogen-associated molecular patterns (PAMPs),（1）Pattern-recognition Receptors, PRRs Expressed on the surface of innate immune cells with the ability of recognizing one or more PAMPs Lack of diversity, non-clonal expression, mediating rapid biological response Main types: Mannose-binding receptor, scavenger receptor, Toll-like receptor Biological functions: Opsonization, activation of complement system, phagocytosis, initializing cell activation and transduction of inflammatory signal, induction of apoptosis,(2) Pathogen Associated Molecular Patterns, PAMPs Some non-specific and highly conserved molecular structures shared by a class /group of specified microbial pathogens , that can be recognized by non-specific immune cells. For example: lipopolysaccharide (LPS), teichoic acid, peptidoglycan (PG), mannose, bacterial DNA/RNA. et al. Features: Commonly specific for pathogens Required for the microbes survival and pathogenicity Molecular basis for the pan-specific recognition of the host,2. Signal transduction mediated by PRRs（TLRs）,MD2,TLR6,TLR2,TLR1,CD14,TLR4,TLR3,TLR5,TLR9,Peptidoglycan , Teichoic acid（G） Bacterium lipoprotein LPS（leptospire） Cell walls of Mycobacterium Zymosan,LPS（G） teichoic acid （G） RSV F protein,dsDNA,Flagellin,Unmethylated CpGDNA, Features of Innate Immune Cell Response Various chemokine receptors on the surface Direct activation in the inflammation site Short-lived, without memory, Relationship between Innate Immune Reponse and Adaptive Immune Response, Innate immune response initializes adaptive immune response Innate immune response influences the type of adaptive immune response Innate immune response assists adaptive immune response,Non-specific immunity specific immunity,Cells involved,epithelium mucosal cells, phagocyte, NK, NK1.1+T, B-1B, T,T, B, APC,phase,instant96h after 96h,features,non-specific, broad spectrum of antigen recognition， to take effect without requirement of clonal expansion and differentiation,specific，exclusive antigen recognition， to take effect with requirement of clonal expansion and differentiation,duration,no immunological memory，short duration,With immunological memory ，long