innate immunity part Ⅰ overview of innate immunity part Ⅱ innate immune cells part Ⅲ functions...

Innate immunityInnate immunity

Part overview of innate immunityⅠ Part innate immune cellsⅡ Part functions of innate immunityⅢ

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 l

ysozyme 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 innate immune cells Ⅱ-----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 t

o 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 granuzymePerforin: creates pores in target cell membranesgranzymes : 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 cell

s 2) Immunoregulation secreting INF-γto enhance immune respo

nse

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 patte

rn, 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, PRRthe 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,C3b/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+ O2 O2- ,OH- , H2O2 ,

1O2

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 immunity1)Innate immunity initiates adaptive immunity Presenting antigensExpressing B7 2)Innate immunity regulats adaptive immunit

yC3dReleasing cytokines