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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
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