Transcript Innate immunity - Shandong University

Innate immunity
PartⅠ overview of innate immunity
 PartⅡ innate immune cells
 PartⅢ functions of innate immunity
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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
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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
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mechanical defense: skin & mucous membrane
Anatomic barrier
.blood-brain barrier,
.blood-placental barrier
. Blood – thymus barrier
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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
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)
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Source: Bone marrow, exist mainly in
peripheral blood, spleen and liver.
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Characteristics : contain cytotoxic
substances
functions:
1) Fighting infection and cancer
killing virus infected cells and tumor cells
2) Immunoregulation
secreting INF-γ
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1). Recognition
(1). Direct recognition receptors
Recognizing tumor cell and virus- infected
cell
(2). FcR
Recognizing Ab-bound target cell
(1). Direct recognition receptors
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HLA I molecules recognizing receptors
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Non-HLA I molecules recognizing
receptors
(1). Direct recognition receptors
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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
Natural killer cells (NK)
 Source: Bone marrow, exist mainly in peripheral blood, spleen and
liver.
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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
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,C3b/4b
2) Endocytosis
3) killing and digestion
Activated macrophages kill phagocytosed
microbes by producing microbicidal
molecules in phagolysosome
 Oxygen-dependent system.
 Oxygen-independent system:
---Low pH(3.5-4) , Lysozyme
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 immunity
1)Innate immunity initiates adaptive immunity
Presenting antigens
Expressing B7
2)Innate immunity regulats adaptive immunity
C3d
Releasing cytokines