Innate immunity

1
Innate immunity

• Part? overview of innate immunity
• Part? innate immune cells
• Part? functions of innate immunity

2
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

3
(No Transcript)
4
Innate immunity

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

5

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

6

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

7

• 2)  humoral factors
• complement
  lysozyme
• Cytokine

8
3)Cells of the innate immunity

• NK cells
• Phagocytes
• neutrophils
• monocytes, macrophages
• Others DC, basophils, mast cells eosinophils,
  ?dT cells, B1 cells,NKT cells

9
Hematopoietic Stem Cell
10
(No Transcript)
11
Part? innate immune cells -----Immunocytes
participating in innate immunity Phagocytes
(Macrophage) NK cells Other cells
12
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

13

Natural killer cells (NK)

• 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-?

14
1). Recognition (1). Direct recognition
receptors Recognizing tumor cell and virus-
infected cell(2). FcR Recognizing Ab-bound
target cell
15

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

16

• (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.

17

• (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

18

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

19
(2). FcR Recognizing Ab-bound target cellADCC
20
2. The mechanisms of killingperforin and
granuzyme Perforin creates pores in target cell
membranesgranzymes enzymes which enter through
perforin pores and induce apoptosis of target
cells. Fas-FasL pathway
21
NK cell
Target cell
22
(No Transcript)
23
(No Transcript)
24

Natural killer cells (NK)

• 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-?to enhance immune
  response

25
Monocyte/ macrophage
26
Mononuclear phagocytes
Macrophages are 5- to 10-fold larger than
monocytes and contain more organelles, especially
lysosomes
27
(No Transcript)
28
 

• Process of phagocytosis
• Recognization
• Endocytosis
• Killing and digestion

29
Mononuclear phagocytes
Macrophages are 5- to 10-fold larger than
monocytes and contain more organelles, especially
lysosomes
30
1) Recognition (1) pattern recognition
receptors (2) Opsonic receptor
31
Recognition(1) pattern recognition
receptors----- pathogen associated molecular
pattern, PAMP PAMPdistinct structures or
components that are common for many pathogens
e.g. LPS, proteoglycan, N-formylated peptides,
double RNA of viruses et al.
32

• 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.

33
(No Transcript)
34
(No Transcript)
35
(2) Opsonic receptor FcR the receptor for Fc
region of Ab CR the receptor for complement
component,C3b/4b
36
(No Transcript)
37
(No Transcript)
38
2) Endocytosis
39
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

40

• 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

41
(No Transcript)
42
(No Transcript)
43

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

44
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

45
(No Transcript)
46
(No Transcript)