Innate immunity Part Ⅰ overview of innate immunity Part Ⅱ innate immune cells Part Ⅲ functions of innate immunity

1. definition of innate immunity protection against infections that relies on the mechanisms that exist before infection and are capable of rapid response to pathogens.. Innate immunity is the first line of defence against infection

2.Characteristics set up at birth non –specific hereditable no immune memory Little individual difference Innate immunity

3.Composition Barriers Humoral factors Cells ----Phagocytes (neutrophils, macrophages) natural killer cells(NK)

1) Barriers mechanical defense : skin & mucous membrane Anatomic barrier.blood-brain barrier,.blood-placental barrier. Blood – thymus barrier Biological barrier: normal flora

2) humoral factors complement lysozyme Cytokine

3)Cells of the innate immunity NK cells Phagocytes: neutrophils monocytes, macrophages Others: DC, basophils, mast cells eosinophils, γδT cells, B1 cells,NKT cells

Hematopoietic Stem Cell

Part Ⅱ innate immune cells -----Immunocytes participating in innate immunity Phagocytes (Macrophage) NK cells Other cells

2. Natural killer( NK )cells in innate immunity Concept : large lymphocytes which can directly kill tumor cells and virus-infected cells without induction of antigens

 Source: Bone marrow, exist mainly in peripheral blood, spleen and liver.  Characteristics : contain cytotoxic substances  functions: 1) Fighting infection and cancer killing virus infected cells and tumor cells 2) Immunoregulation secreting INF-γ Natural killer cells (NK)

1). Recognition (1). Direct recognition receptors Recognizing tumor cell and virus- infected cell (2). FcR Recognizing Ab-bound target cell

(1). Direct recognition receptors HLA I molecules recognizing receptors Non-HLA I molecules recognizing receptors

(1). Direct recognition receptors HLA I molecules recognizing receptors 1 ） killer immunoglobulin-like receptor KIR2DL, KIR2DS; KIR3DL, KIR3DS 2 ） killer lectin-like receptor CD94/NKG2A, CD94/NKG2C recognize the MHC-I molecules on normal cells in normal condition, transduce inhibitory signals to inhibit the killing effect of NK cell.

(1). Direct recognition receptors 1 ） natural cytotoxicity receptors,NCR ） NKp30,NKp44,NKp46 2 ） NKG2D recognize the ligands on virus-infected cells and some tumor cells ----transduce active signals to kill target cells

Normal condition: HLA I molecules recognizing receptors (KIR,KLR) inhibition effect > activation effect killing effect of NK cell is inhibited Abnormal condition: Non-HLA I molecules recognizing receptors (NCR NKG2D) Activation effect > inhibition effect -----NK cells kill target cells

(2). FcR Recognizing Ab-bound target cell ADCC

2. The mechanisms of killing perforin and granuzyme Perforin: creates pores in target cell membranes granzymes : enzymes which enter through perforin pores and induce apoptosis of target cells. Fas-FasL pathway

NK cell Target cell

 Source: Bone marrow, exist mainly in peripheral blood, spleen and liver.  Characteristics : contain cytotoxic substances  functions: 1) Fighting infection and cancer killing virus infected cells and tumor cells 2) Immunoregulation secreting INF-γto enhance immune response Natural killer cells (NK)

Monocyte/ macrophage

Macrophages are 5- to 10-fold larger than monocytes and contain more organelles, especially lysosomes Mononuclear phagocytes

Process of phagocytosis Recognization Endocytosis Killing and digestion

Macrophages are 5- to 10-fold larger than monocytes and contain more organelles, especially lysosomes Mononuclear phagocytes

1) Recognition (1) pattern recognition receptors (2) Opsonic receptor

Recognition (1) pattern recognition receptors pathogen associated molecular pattern, PAMP PAMP: distinct structures or components that are common for many pathogens e.g. LPS, proteoglycan, N-formylated peptides, double RNA of viruses et al.

Pattern recognition receptors, PRR the receptors that can recognize pathogen associated molecular patterns, locating on the surface of macrophages e.g. mannose receptor, scavenger receptor, CD14, Toll like receptors et al.

(2) Opsonic receptor FcR the receptor for Fc region of Ab CR the receptor for complement component,C 3b/4b

2) Endocytosis

Activated macrophages kill phagocytosed microbes by producing microbicidal molecules in phagolysosome  Oxygen-dependent system.  Oxygen-independent system: ---Low pH(3.5-4), Lysozyme 3) killing and digestion

oxygen-dependent system: reactive oxygen intermediates, ROIs NADPH+ O 2 O 2 -,OH -, H 2 O 2, 1 O2 reactive nitrogen intermediates, RNIs: inducible nitric oxide synthase, NO oxygen-independent system Low PH ( ), lysozyme Digestion by various types of enzymes in phagocytes

Functions of monocyte/macrophage Phagocytosis Induction of inflammation Presentation of antigen

Part III functions of innate immunity 1. Fighting infection 2. Taking part in adaptive immunity 1)Innate immunity initiates adaptive immunity Presenting antigens Expressing B7 2)Innate immunity regulats adaptive immunity C3d Releasing cytokines