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Cells in innate immunity and their functions

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.

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Cells in innate immunity and their functions

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  1. 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

  2. Section I Tissue,cells and molecules of the innate immune system

  3. Innate Immunity Native Immunity Nonspecific Immunity Acquired Immunity Adaptive Immunity Specific Immunity Species development, formed evolutionally Possess from the time of birth，react rapidly Non-specific anti-infection immunity, also involved in specific immunity

  4. 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

  5. （二） Blood-brain barrier （三） blood –fetus barrier

  6. 二. Cells involved in innate immunity and their functions • Phagocute • Natural killer cells •  T cells • NKT cells • B1 cells

  7. 1. phagocytes Mononuclear phagocyte system neutrophils macrophage monocyte microglial cells, Kupffer,Osteoclast

  8. 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

  9. 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

  10. Phagocytes Biological functions surface receptors of phagocytes Mannitol, fucose, phosphatide receptor CR3, CR4 , CD14 C3bR FcγR Toll-like receptor scavenger Recognized molecules Corresponding carbohydrate and phosphatide LPS Antigens entrapped by C3b Antigens specially bound by IgG PAMP

  11. Phagocytes Biological functions Antimicrobial and cytotoxic activity Oxygen-dependent, Oxygen-independent Secretion of factors Cytokines, Inflammantory mediators Antigen presentation Intrinsic, Extrinsic Anti-tumour

  12. Antimicrobial and cytotoxic activity 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

  13. 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）

  14. Phagocytes Biological functions Anti-infection Anti-tumor:directly contact and fuse with the tumour cell membrane ; cytotoxic substance, proteinase, cytolysin, TNF-α,ADCC mediated by tumor specific antibody Antigen processing and presentation Immunoregulation

  15. 2. NK Cells 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＋

  16. NK cells Molecular recognition: killer activatory receptor(KAR) killer inhibitory receptor(KIR) KAR KAR recognize cell carbohydrate ligands →ITAM→transduce 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

  17. 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

  18. 3.  T cell Distributions:epithelia, mucosa surface markers:γδTCR, 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 γδTCR : same specificity of antigen recognition—response to common antigen Biological Function: anti-infection in skin and mucosa, anti-tumor, immunoregulation

  19. 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

  20. 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

  21. Other types of cells involved in the innate immunity: Dendritic cell Eosinophil granulocyte Basophilic granulocyte Mast cell

  22. 三. Innate effector molecules and their main function （一）complement system

  23. （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

  24. （三） Defensin （四） Lysozyme （五） β-Lysin

  25. Section 2 Phases of innate immune response Transient phase of innate immune response Early phase of innate immune response Induction Phase of adaptive immuneresponse

  26. Section 3 Characteristics of Innate Immune Response and Its Relationship with Adaptive Immune Response

  27. Ⅰ. Characteristics of innate immune response （一）Recognition features of innate immune cells 1. Pattern-recognition receptors (PRRs) and pathogen-associated molecular patterns (PAMPs)

  28. （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

  29. (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

  30. 2. Signal transduction mediated by PRRs（TLRs）

  31. 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 TLR5 TLR9 TLR6 TLR2 TLR1 CD14 TLR4 TLR3 MD2

  32. Ⅱ Features of Innate Immune Cell Response Various chemokine receptors on the surface Direct activation in the inflammation site Short-lived, without memory

  33. Ⅲ Relationship between Innate Immune Reponse and Adaptive Immune Response ⅰ Innate immune response initializes adaptive immune response ⅱ Innate immune response influences the type of adaptive immune response ⅲ Innate immune response assists adaptive immune response

  34. Non-specific immunityspecific immunity T, B, APC Cells involved epithelium mucosal cells, phagocyte, NK, NK1.1+T, B-1B, γδT instant～96h after 96h phase specific，exclusive antigen recognition， to take effect with requirement of clonal expansion and differentiation non-specific, broad spectrum of antigen recognition， to take effect without requirement of clonal expansion and differentiation features no immunological memory，short duration duration With immunological memory ，long duration

  35. Biological significances of innate immunity Participating and regulating the initiation of adaptive immune response Affecting the strength of adaptive immune response Affecting the type of adaptive immune response Affecting B cell memory , negative selection , self tolerance

  36. To master cell types participating the innate immune response • To master the significance of pattern recognition molecules and pathogen associated molecules • To master KAR/KIR and their modulation to NK cell killing effect • To master the main features of adaptive immunity and innate immunity • To be familiar with the kinds of phagocytes and the biological function • To be familiar with γδT cell and B-1B cell and their function • To understand function of the epithelial cells and their attachments • To understand the characteristics of various phagocytes

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