F?s??? a??s?a ?p?d??e??-??tta?a-

1
F?s??? a??s?a?p?d??e??-??tta?a-µ??a??sµ??
e?e???p???s??
?etapt???a?? µ???µa ???s?????a?, ?µ?µa
???????a?, ?a?ep?st?µ?? ??????, ???µß???? 2014
??µ?t??? ?ast????? ?/??????, ???F? ??µ????t??
mastellos_at_rrp.demokritos.gr
2
???t?te? p?? ?a ?a??f????

• ??????s? f?s???? e?d???? a??s?a?
• ??e???t??? ???µa?s? a??s?p???t???? s?st?µat??
• ?eµf???tta????? ?p?d??e?? a?t??????
• ?p?d??e?? f?s???? a??s?a?(PRRs)
• PAMPs-?e???? ?a?a?t???st???-pa?ade??µata
• PRRs
• -???????µe??? ?p?d??e??
• -Yp?d??e?? e?d???tt???s??
• -?p?d??e?? µetaß?ßas?? s?µat??
• ?p?d??e?? Toll
• ?etaß?ßas? s?µat?? µ?s? ?p?d????? TLR
• TLR4-?p?d???a? LPS
• ???µ?s? ?d?? TLR
• ????? TLRs st? s??e??as?a f?s????-e?d???? a??s?a?
• ?LRs ?a? p?????t?ta ?-??tta????? ap????s?? (Th1
  ap????s?)

3
???s?p???t??? s?st?µa

• F?s??? ???s?a
• ??t?µ????ß?a?? pept?d?a
• fa????tta?a (µa???f??a, ??dete??f??a,
  µ?????tta?a, de?d??t??? ??tta?a)
• S?µp????µa-??s? µ????ß???
• ???µ?s? ?e?t??????? e?d???? a??s?a??? ap????s??

• ?p??t?t? ???s?a
• ?-?eµf???tta?a -a?t?s?µata
• T ?eµf???tta?a -??tta??t?????t?ta
• ?p????? ??????
• ?????s? ??tta???????
• ??e???p???s? ?-??tt????

4
??sd?????ta ta ???a a??µesa st? f?s??? ?a?
ep??t?t? a??s?ap????s??
Although natural killer (NK) cells have
traditionally been classified as cells of the
innate immune system, they share many
similarities with cytotoxic T lymphocytes. We use
a mouse model of cytomegalovirus infection to
show that, like T cells, NK cells bearing the
virus-specific Ly49H receptor proliferate
100-fold in the spleen and 1,000-fold in the
liver after infection. After a contraction phase,
Ly49H-positive NK cells reside in lymphoid and
non-lymphoid organs for several months. These
self-renewing memory NK cells rapidly
degranulate and produce cytokines on
reactivation. Adoptive transfer of these NK cells
into naive animals followed by viral challenge
results in a robust secondary expansion and
protective immunity. These findings reveal
properties of NK cells that were previously
attributed only to cells of the adaptive immune
system.
Nature Reviews Immunology 9, 302-303 (30 April
2009)
ORIGINAL RESEARCH PAPER Sun, J.C., Beilke, J.N.
Lanier, L.L. Adaptive immune features of
natural killer cells. Nature, 11 Jan 2009
5
??e???t??? ???µas? a??s?p???t???? s?st?µat??
F?s??? a??s?a
6
? f?s??? ?a? ep??t?t? (e?d????) a??s?ap????s?
d?af???p?????ta? st? ep?ped? t?? µ??a??sµ?? ?a?
?p?d????? p?? st?at??????? ??a t?? ep?te???
a??s???????? a?a?????s??
7

• ?p?d??e?? e?d???? a??s?a? (a?t???????? ?p?d??e??
  ?eµf???tt????) BCR, TCR
• ?a?????a t??a???, µ? ???????µ??µe???, ?e?et????
  a?as??d?asµ??
• ????µ??f??? de?aµe?? ?p?d????? a?t??????a?t?????p
  a???s?as???????? ep????? a??s?d?ast???? ??tta???
• ??sµe?s? a?t?a?t?????? ?a? pe??ßa????t????
  a?t?????? (a??e?????????) µp??e? ?a p???a??se?
  a?t????se? a?t?d??se?? ? a?ep???µ?te? a??e???e?
• ???a e??a? ta µ???a?? s?????a p?? ep?t??p??? st?
  a??s?p???t??? s?st?µa ?a ta?t?p???se? t??
  p????e?s? e??? a?t?????? ?a? ?a d?e??et?se? t??
  t??p? a??s?ap????s???

8
?p?d??e?? f?s???? a??s?a?(PRRs) ??a?????????
e?e???t??? s??t???µ??e? d?µ?? p??
?a?a?t??????? µe???e? ?at?????e?
µ???????a??sµ?? PAMPs-Pathogen Associated
Molecular Patterns PRRs-Pattern recognition
Receptors
9
?p?d??e?? f?s???? a??s?a?(PRRs) ??a?????????
e?e???t??? s??t???µ??e? d?µ?? st?? ep?f??e?a (?a?
t? es?te????) µ???????a??sµ?? p?? ?a?a?t??????ta?
ap? t?? pa???s?a s?st?????? epa?a?aµßa??µe???
d?µ???? µ?t?ß?? µe e?d??? t?p???af?a
(spacing) PAMPs -LPS (??p?p???sa??a??t??-ßa?
t???a?? t????µa) -pept?d???????e? -??p?te??????
??? -µa????e? -ßa?t???a?? DNA -dsRNA
(???) -???????e?
DAMPs
??????ta ??tta????? ?a??t??, s?????a ??tta?????
stress
10
?a?a?t???st??? t?? PAMPs

• ??e???t??? p??? s??t???µ??e? d?µ??
• ???s??t??e?ta? ap???e?st??? ap? pa????????
  µ???????a??sµ??? (ap??s?????? ap? t?? ?e??st?)
• -(d?????s? ?d???? ap? ???? a?t???????
  e????sµa)
• ?? d?µ?? PAMPs ?a???????? se µe???? ßa?µ? t??
  ep?ß??s? a??? ?a? t? µ???sµat???t?ta t??
  µ????ß??? µ?sa st?? ?e??st? t??
• ?a???s?????? ?e???e?µ??? ??f?as? se e??e?e?
  ?at?????e? pa??????? µ???????a??sµ??
• (p.?. LPS e?f?????? ??a ta gram(-) ßa?t???a??
  ste????)

11
?p?d??e?? f?s???? a??s?a? (PRRs)

• ?etaß?ß????ta? st? ???at???? ????d??µa
• -???????µ???t?ta
• ??f?????ta? se d?ast??? (effector) ??tta?a t??
  f?s???? a??s?ap????s?? ?a? sta ?ate?????
  a?t?????pa???s?ast??? ??tta?a p.?. µa???f??a,
  de?d??t??? ??tta?a, ?-?eµf???tta?a
• !! ?p??s?a ???????? ep?????? -??a ta ??tta?a t??
  ?d??? t?p?? p?? f????? PRRs ????? t?? ?d?a
  e?e?d??e?s? ?a? s?????e?a p??sdes?? ??a t?
  a?t?st???? µ???? PAMP
• !!! ? a????ep?d?as? PRR-PAMP ep??e? ?µes?
  a??s?ap????s? ap? t? a??s?d?ast??? ??tta?? ?????
  t? µes???ß?s? stad??? ep??tas??/p???ap?as?asµ??

12
?p?d??e?? f?s???? a??s?a? (PRRs)

• ??a??????ta? se
• ???????µe???? ?p?d??e??
• -??????e? -s?µp????µa
• ?p?d??e?? p?? ep????? e?d???t?s? (fa????tta?a,
  ?p?d??e?? scavenger)
• ?eµß?a????? ?p?d??e?? µetaß?ßas??
  e?d???tt????? s?µat?? (TLRs, PARs)
• ??d???tt????? ?p?d??e?? (NODs, NLRs)

13
?? s?st?µa t?? s?µp????µat?? pe???aµß??e? 30
d?a??t?? ?????p??te??e?, µeµß?a?????? ?a?
d?a??t??? ?p?d??e?? ?a? ???µ?st??? µ???a p??
s?µß?????? st?? e??e?? (f?s???) ?µ??a ??a?t?
pa??????? µ????ß???. ?a??e? s?µa?t??? ???? st??
epa???? ?a? ???µ?s? ?e?t??????? t?? ep??t?t??
a??s?ap????s?? µ?s? a????ep?d??se?? µe ?, ?-
?eµf???tta?a ?a??? ?a? µe ??tta?a p?? µet?????
st?? a?t?????pa???s?as? (de?d??t??? ??tta?a,
µa???f??a).
14
(No Transcript)
15
?d?? e?e???p???s?? s?µp????µat??
16
(No Transcript)
17
???????µe??? ?p?d??e?? f?s???? a??s?a? (PRRs)

• ?a????-desµe?t??? p??te???(MBL)
• Ko??e?t??e? (d?µ? ????a?????-pe????? ?e?t????)
• S?µp????µa-MBL??a??t???? s?µp???? e?e???p???s??
  ?d?? ?e?t????
• ?esµe?eta? se µ???a µa?????? ? f??????? st??
  ep?f??e?a µ????ß???

18
THE C3 Interactions
Other Proteins

• HHV-8
• HVA
• HVS

• HSVgC
• EBV
• Vaccinia

Pro MBP

• Schistosoma mansoni
• Babesia rodhani
• Trypanosoma cruzi

Fibronectin
Laminin
C. albicans
Virus
160kD, 70kD
Parasites
IL-2
C4bp
Foreign Proteins
CR1
C5
CR2
EBV
C3
CR3
B
Leismania
Receprors
Serum Proteins

P
Cell Surface Proteins
CR4
H
CR5
I
C3aR
?
MCP
Conglutinin
M-protein
DAF
Ecoviruses (6,7,12,25)
Measles Virus
19
??p???? ?e?t?????e? s?µp????µat??

• ??a?????s? ?d???-?????-PAMPs
• ???????p???s? pa??????? µ????ß??? ?a?
  ep?fa?e???-st????
• ??a??t?p???s?-ap?µ?????s? ep???µ???
  a??s?s?µp?e?µ?t??
• ???s????µ?s?-???a???? f?e?µ???d?? a?t?d??se??
  (????s? a?af??at?????? pept?d???)
• ??s? ??tt????st???? (µ?s? MAC)
• ?p?µ?????s? ??tta????? ?ata???p??-(p.?. p?????t??
  ap?pt?s?? ? ?????s?? ?st??)

20
?e?t?????e? t?? s?µp????µat?? se a?apt???a??
s?st?µata

• ??tta????? p??/s?asµ??-??t. a???s?-ep?ß??s?
• ???µ?s? e?d???tt????? ap?pt?t???? ?d??
• G???µ?p???s?-a?apa?a????
• ???pt???-ep?d?????s? ?e?????? ??S
• ?ste????es?
• ???pt??? a?µ?p???t???? ??tt????
• ??a?????s? ?st??

21
?? s?µp????µa st?? pa??f?s??????a f?e?µ???d??
??s??

• ? a?e???e??t? e?e???p???s? t?? s?µp????µat?? ??e?
  s?s?et?ste? µe t?? pa?????es? p?????
  a??s?e?f???st???? ??s?? (??e??? ?a? ???????)
• ?a?ade??µata
• ?e?µat?e?d?? a????t?da
• S?st?µat???? e????µat?d?? ?????
• ????ap?? s??????s?
• Spe??aµat??ef??t?de?
• ??µ???t??? a?a?µ?a
• ?s?a?µ??? ß??ß? µet? ap? epa?ad????s?
• ??e?a ap?????? µ?s?e?µat??
• S?pt??? ?atap????a

22
??a??t?? ?a? µeµß?a????? p??te??e? p?? ???µ?????
t?? e?e???p???s? t?? s?µp????µat??

• ??a??t?? p??te??e?
• C1 a?ast???a?
• C4bp
• pa?????ta? H
• pa?????ta? I
• p??pe?d???
• ?a?ß???pept?d?s? N/R
• S p??te???
• ??aste????
• SP-40,40

• ?eµß?a????? p??te??e?
• CR1
• MCP (CD46)
• DAF (CD55)
• CD59

23
???a??sµ?? ???µ?s?? s?µp????µat??
???a??sµ?? ?a??de??µa St???? 1. ??ast??e??
p??teas?? C1-INH C1r/C1s 2.
???te?se? ?a?ß???pept?d?se? C3a/C5a 3.
?p?t????s? ap?d?µ?s?? ???ße?tas?? DAF
(CD55) C3bBb 4. ?ata??t????
s?µpa?????te? MCP (CD46) C3b 5. ??ast???
s?µp????? d?e?sd?s?? µeµß????? CD59 C5b-9
MAC
24
??ad?p??s? (de?te??ta??? d?µ?) d?? d?ad??????
µ?t?ß?? SCR st? µ???? ???µ?st???? p??te???? t??
s?µp????µat??
25
??a??t?? ?a? µeµß?a????? p??te??e? ??? eµfa??????
d?µ???/?e?t??????? ?µ?????a µe t?? ???µ?st????
p??te??e? t?? s?µp????µat?? t?? ???????e?a? RCA
26
?a?t???a?? ste???? ????? t?? ??a??t?ta ?a
desµe???? st?? ep?f??e?a t??? t?? pa?????ta H ?a?
µe a?t?? t?? t??p? d?afe????? t?? a??s?a???
ap????s?? t?? ?e??st?
27
???s?e??s??t??? d??s? p?????t?? e?e???p???s??
t?? s?µp????µat??
HEL-C3d
2
Ca
HEL
0
10
100
1000
0.1
1
Concentration (nM)
Dempsey et al. (1996) Science 271, 348
Sensitivity of anti-HEL Ig-transgenic B cells to
HEL and HEL-C3d
28
?p?d??e?? PRR p?? ep????? fa????tt???s? pa???????
µ????ß???
Phagocytes bear different receptors that
recognize microbial components and induce
phagocytosis. These include -CD14 (LPS
Receptor) -CD11b/CD18 (CR3 CR) -Mannose
Receptor -Glucan Receptor -Scavenger receptors
29
Fa????tt???s?-pa???s?as? a?t??????
Macrophages ingest and degrade particulate
antigens through the use of long pseudopodia that
bind and engulf bacteria. The engulfed bacteria
are degraded when the phagosome fuses with a
vesicle containing proteolytic enzymes
(lysosome), forming the phagolysosome.
Specialized compartments also exist in the
macrophage to promote antigen processing for
presentation to antigen-specific T cells.
30
??tta?a t?? f?s???? a??s?ap????s??
31
??tta?a t?? f?s???? ?a? ep??t?t?? a??s?a?
32
Key innate immune effector cells Phagocytes
33
Phagocytes Neutrophils

• phagocytosis, intracellular killing (oxidative
  burst, Myeloperoxidase release, reactive O2
  species generation), inflammation and tissue
  damage
• characteristic nucleus, cytoplasm
• granules and CD67 membrane marker.

34
PhagocytesMacrophages

• phagocytosis, intracellular and extra-cellular
  killing, tissue repair, antigen presentation for
  specific immune response
• characteristic nucleus and CD14 membrane marker.

35
Granular leukocytes Eosinophils

• lt 5 of blood leukocytes, BM derived, stain red
  due to the presence of microscopic granules
  containing toxins.
• present in skin, gastrointestinal tract,
  respiratory system
• host defence against parasitic infections or
  allergic reactions, through release of their
  toxins or ADCC.
• eosinophilic toxins include ECP, MBP, EPO,
  oxygen radicals which harm parasites but can also
  induce tissue damage if uncontrolled (human
  asthma).

36
Granular leukocytes Basophils

• less than 1 of blood leukocytes, release
  compounds from basophilic granules to destroy
  bacteria and other pathogens.
• molecules released include histamine, serotonin,
  heparin, prostaglandins, leukotrienes.
• major role in allergic responses, particularly
  type I hypersensitivity reactions.
• very similar to mast cells-same type of
  leukocyte, basophils being the blood version and
  mast cells the tissue version.

37
S?te?t??? ??tta?a (mast cells)
38
Natural Killer (NK) cells

• also known as large granular lymphocytes (LGL)
• kill infected and malignant cells (granules in
  their cytoplasm contain proteins such as perforin
  and proteases known as granzymes)
• are identified by the presence of CD56 CD16 and
  absence of CD3
• activated by IL-2 and IFN-? to become LAK
  (Lymphokine Activated Killer) cells

39
Dendritic cells the bodys antigen sampling
machine in peripheral organsPresent antigens in
the context of MHC-peptide complexesInteract
with B-, T- cells, NK cells and NKT cells
National Cancer Institute (NCI), created by Don
Bliss, Sriram Subramaniam
40
NK-cell/DC interactions in the context of innate
immune responses at sites of injury or infection
41
...????? ??
42
?p?d??e?? Toll

• Hashimoto et al., Cell (1988)-?? ????d?? Toll
• ???µ??e? t?? p?????t?ta t?? p?os???p?s???? ????a
• st? p???µ? ?µß??? e?t?µ??
• ?? d??t?? µetaß?ßas?? s?µat?? µ?s? Toll s?µß???e?
  st?? f?s??? ?µ??a t?? e?t?µ?? ??a?t? pa???????
  µ???t?? (Lemaitre et al., Cell (1996)
• TLRs-???????e?a ?µ?????? ?p?d????? sta ???ast???
  (gt11 µ???)
• ?? TLRs a?????? st?? ?pe????????e?a ?p?d?????
  IL-1
• ?eµß?a????? ?????p??te??e? t?p?? 1

43
?p?d??e?? ???????e?a? Toll/IL-1R ?µ????? d?µ?
?????tt???? tµ?µa ?p?d???a TLR -?e?????? LRR
(Leucine Rich Repeats) -XLXXLXLXX- ?µ?????a
IL-1R/TLRs st? e?d???tt???? tµ?µa t?? ?p?d???a
pe????? TIR (Toll/IL-1R domain) (200 a.a.)-3
homology boxes ?e?????? Box1-3gt s?µß?????? st?
µetaß?ßas? t?? e?d???tt????? s?µat??
44
Innate immune recognition of bacterial cell wall
components by TLRs
Gram-positive bacteria
Gram-negative bacteria
45
Toll-like receptors and recognition of pathogens
LRR extracellular domain TIR domain inside
K. Takeda S. Akira, Cell. Microbiol. 5 143-53,
2003
46
Cellular location of TLRs
TLRs that recognize nucleic acids are localized
inside cells
47
???sd?te? (PAMPs) ?p?d????? TLR1-11
48
?eta???? s?µat?? µ?s? ?p?d????? TLR
-???sdes? PAMP -??µe??sµ?? ?p?d???a-a??a??
ste?e?d?aµ??f?s?? -???s????s? ep?te?est????
p??te???? st?? ?p?d???a MyD88 adaptor IRAKs
(????se?) TAK1 (TGF-b-activated kinase-1) TAB1,2
TRAF6 (TNF-receptor associated factor 6)
49
???te?????? a????ep?d??se?? sta ???a t??
??tta????? µeµß?????
50
???te?????? a?/ep?d??se?? s????e?a

• IRA?4gtf?sf??????s? t?? IRAK1gta?t?f?sf??????s?
  IRAK1 st? ?-te???? ????
• ???s????s? TRAF6 st? ?-te???? ???? t?? IRAK1
• ?p?µ?????s? s?µp???o? IRAK1/TRAF6 ap? ?p?d???a
  ?a? a????ep?d?as? µe s?µp???? TAB2/TAK1/TAB1
• ??e???p???s? TAK1 ????s?? (µ?s?
  TRAF6/UBC13-??µp?????t??????s??)

51
?etaß?ßas? s?µat?? TLR st?? p????a

• H ????s? TAK1 e?e???p??e? t? t??µe??? s?µp????
• t?? ???s
• ?? e?e??? s?µp???? IKKs ?ata??e? t? f?sf??????s?
  t?? a?ast???a t?? NF-kB, IkBgt ap????d?µ?s? IkB
  µ?s? Ub/p??teas?µat??
• ??e???p???s? d?µe??? p50/p65 (µeta??af???
  s?µp???? NF-kB) ?a? µetat?p?s? t??? st??
  p????agtgtµeta??af? ????d???-st????

52
?d?? µeta????? s?µat?? µ?s? ?p?d???a TLR4
(?p?d???a? LPS)
53
O ?p?d???a? TLR-4 a?a??????e? t??
??p?p???sa??a??t? LPS ?? s?????? ???d????
ßa?t???a??? ???µ???? st?? ?????f???a. ? LPS
desµe?eta? a????? st?? p??te??? t?? ??e?a? f?se??
LBP (LPS carrier) (LPS-Binding Protein) ?a? t?
s?µp???? a?a??????eta? ap? t?? ?p?d???a CD14 st??
ep?f??e?a t?? fa????tt????. ? a????ep?d?as?
LPS/LBP/CD14 p???a?e? t? s??e??? t?? ?p?d???a
CD14 µe t?? ?p?d???a TLR4 ?a? t? epa???????
µetaß?ßas? s?µat?? st?? p????a (NF-Kb). ?
?p?d???a? MD-2 a????ep?d?? µe t?? TLR4 ?a?
ep?t??pe? t? µeta???? s?µat?? µ?s? TLR4.
54
??e??t??p?sµ?? st? s?µat?d?t?s? µ?s? t?? ?p?d???a
TLR4

• MyD88-e?a?t?µe?? s?µat?d?t?s?
• ?pa???? ??f?as?? f?e?µ???d?? ??tta???????

• S?µat?d?t?s? ap??s?a MyD88
• ?pa???? IFN-ß ?a? µeta??af? ????d??? p??
  ep????ta? ap? IFNs

55
? p?e??t??p?sµ?? st? d??s? t?? TLRs ?fe??eta?
st?? p??sdes? d?af??et???? p??te????-adaptors

• ??aµes??aße?ta? ap? a????ep?d??se??
• TIR-TIR
• TLR Adaptors
• MyD88
• TIRAP
• TRIF
• TRAM

TLR-e?a?t?µe?? µeta??af? ????d??? p?? ep????ta?
ap? IFNs
56
???µ?s? ?d?? µeta????? s?µat?? µ?s? ?p?d?????
TLR µe a??d??µ? epa?at??f?d?t?s?

• ?a?atetaµ??? d???e?s? TLRs p???a?e? ?pe???f?as?
  ??tta???????gt??t??? a??s?d???e?s? p?? µp??e? ?a
  ?d???se? se e?d???s? pa?atetaµ???? f?e?µ???? ?a?
  ?e???e?µ???? a?af??a?t???? shock (p.?.
  s??a?µ?a)
• ????t???? t??p?p???t?? ?d?? TLR
• -IRAK-M (s?µp???? IRAK1/TRAF6)
• -SOCS1 (IRAK1?)
• -MyD88s (a?ta????st?? MyD88)
• -SIGIRR (TIR)
• -ST2 (TIR)

?eµß?a????? p??te??e?
57
S??e??as?a f?s???? ?a? e?d???? a??s?a? µ?s?
?p?d????? Toll ?a????sµ?? p?????t?ta? CD4
?-??tta????? ap????s??
58
?a?a?t???st??? ?h1/Th2 ap????s?? se µ????ß?a???
???µ??e??

• Th1 ap????s?
• ??d???tta???? pa?????a (PAMPs t?p?? 1 ßa?t???a,
  ???, µ???te?)
• ??af???p???s? ep??eta? ap? IL-12
• ?????s? ??tta????????FN-??L-2
• ?a?a???? a?t?s?µ?t?? IgG2
• ??e???p???s? µa???f????
• ?pe?e?a?s??s?a ep?ß?ad???µe??? t?p??

• Th2 ap????s?
• ?????tt???a pa?????a-PAMPS t?p?? 2 (p?????tta?a
  pa??s?ta, a??e???????a)
• ??af???p???s? ep??eta? ap? IL-4
• ?????s? ??tta???????IL-4IL-5IL-13
• ?a?a???? a?t?s?µ?t?? IgE
• ??e???p???s? ??s???f????, s?te?t???? ??tt????
• ??e?a (?µes?) ?pe?e?a?s??s?a

59
??a?????s? a?t?????? ap? ?-??tta?? µe t?
µes???ß?s? APC ??tt????
??t?????
CD4 T-??tta??
??d???t?s?
APC
?p?d???a? TCR
?ept?d??
MHC II
60
??e???p???s? ?-??tt???? ap? APCs ????? t??
?p?d????? TLR
61
NOD1 NOD2 (Nucleotide-Binding Oligomerization
Domain) proteins recognize peptidoglycan
substructures and promote innate immune responses
NOD1 and NOD2 are intracellular (cytosolic)
molecules and resemble some plant disease
resistance proteins Mutations in the NOD2 gene
increase susceptibility to Crohns disease (a
form of inflammatory bowel disease)
62
???a??sµ?? d??s?? t?? NOD p??te???? st?? epa????
f?s???? a??s?ap????s?? se ßa?t???a??? ???µ??e??
Martinon F. et al., Trends Immunol, 2005
63
PARs Protease-activated receptors as innate
immune sensors of microbial infections
-G-protein coupled receptors -Expressed on
various innate immune cells neutrophils,
monocytes, macrophages, DCs, mast cells
etc. -Activated via cleavage by serine proteases
released by microbes (activated by release of
cryptic receptor-tethered ligand)