Innate immunity Part overview of innate immunity n

Innate immunity PartⅠ overview of innate immunity n PartⅡ innate immune cells n PartⅢ functions of innate immunity n

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

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

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

1) Barriers n n mechanical defense: skin & mucous membrane Anatomic barrier . blood-brain barrier, . blood-placental barrier. Blood – thymus barrier n 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, B 1 cells, NKT cells

Hematopoietic Stem Cell

PartⅡ 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

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

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

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

(1). Direct recognition receptors n HLA I molecules recognizing receptors 1） killer immunoglobulin-like receptor KIR 2 DL, KIR 2 DS; KIR 3 DL, KIR 3 DS 2） killer lectin-like receptor CD 94/NKG 2 A, CD 94/NKG 2 C 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） NKp 30, NKp 44, NKp 46 2）NKG 2 D 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 NKG 2 D) Activation effect > inhibition effect -----NK cells kill target cells

(2). Fc. R 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-Fas. L pathway

NK cell Target cell

Natural killer cells (NK) Ø Source: Bone marrow, exist mainly in peripheral blood, spleen and liver. Ø Ø 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

Monocyte/ macrophage

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

Process of phagocytosis Recognization Endocytosis Killing and digestion

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

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

Recognition (1) pattern recognition receptors ----- pathogen associated molecular pattern, 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, CD 14, Toll like receptors et al.

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

2) Endocytosis

3) killing and digestion Activated macrophages kill phagocytosed microbes by producing microbicidal molecules in phagolysosome Ø Oxygen-dependent system. Ø Oxygen-independent system: ---Low p. H(3. 5 -4) , Lysozyme

oxygen-dependent system: reactive oxygen intermediates, ROIs NADPH+ O 2 - , OH- , H 2 O 2 , 1 O 2 reactive nitrogen intermediates, RNIs: inducible nitric oxide synthase, NO oxygen-independent system Low PH (3. 5 -4. 0), 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 B 7 2)Innate immunity regulats adaptive immunity C 3 d Releasing cytokines