Cutaneous Immunology

SU RV E ILLANCE
RMA L TISSUE SCF ligation induces
NO MCp to MC TC
CCR3 (Trypase/Chymase)
CD34+ Mast Cell SCF R SCF
CD13+ Precursor VLA-4 VCAM-1

& Infectious Disease

PSGL-1 E-Selectin C5aR C3aR

Mast Cell
(MCTC)
CRIg Th2 VLA-4
Type II
Macrophage SCF R
E-Selectin TLR1 TLR2
P-Selectin PSGL-1
HSPG Basal lamina
CCR4
The response to infection is crucial for the survival of an organism. It includes a complex cascade of immunological events involving an array of cell types and the integration of a multitude of biochemical signals. This illustration depicts early CCL22/MDC VE-Cadherin
inflammatory processes that accompany insult of the epidermis by a sliver contaminated with the bacteria, Staphylococcus aureus. This is shown in contrast to normal tissue surveillance and the accompanying cellular migration patterns that CCR3 CD99 VE-Cadherin
Th2 CD99
enable the immune system to detect the introduction of pathogens. CCL17/TARC ICAM-2
CCR4 PSGL-1 JAM-A ICAM-2

Immature PECAM-1 JAM-A

Dermal DC PECAM-1
IMMUNE CELL MARKERS
Type I Type II 6-Sulfo LacNAc Inflammatory Monocyte-derived Immature Dermal Mature Dermal
Macrophage Macrophage Dendritic Cell Classic Monocyte 2 Monocyte 3 Langerhans Cell Dendritic Cell Dendritic Cell Dendritic Cell
(IL-4-induced) (Slan DC) 1 (Mono-DC) (DDC) (DDC)
γδ T Cell CXCR4
CD1a– CD1c+ 6-Sulfo LacNAc+ CCR1+ CCR2– Birbeck granule+ CD1a+ CD1a – CCR2+

CD1c– CD14+/– C5aR+ CCR2+ CCR5+ CCR6+ CD11c+ CD1c+ CD1a+ HSPG PECAM-1
Vδ1
CD14 + CD80 +/–
CD1a +
CD14 +
CD11c +
CD1a +
CD14low CD83 –
CD1c +
γδ T Cell
CXCL12/SDF-1
CD71 + CD86+ CD1c– CD16– CD14– DC-SIGN/CD209– CD86+ DC-LAMP/CD208– CD83+ CXCR4

Integrin aVb5+ CD11c+ CD64+ CD16+ E-Cadherin+ DC-SIGN/CD209+ FXIIIa+ CXCR4+ Fibroblast
CD80+
CD86+ MMR/CD206+ CD14– CXCR4+ CXCR4+ FXIIIa– MHC II+ DC-SIGN/CD209+ DC-SIGN/CD209–
DNAM-1
Integrin aVb5 – CD16 +
TLR1 +
TLR1 +
Langerin/CD207 +
MMR/CD206 +
Langerin/CD207 –
FXIIIa +
CD155/PVR VE-Cadherin
MMR/CD206 – PSGL-1+ TLR2+ TLR2+ MMR/CD206– TLR1+ MHC II+ Langerin/CD207– VE-Cadherin
PSGL-1
CD99
TLR2 +
MMR/CD206 +
MHC II + CD99 (FucTVII+)
ICAM-2 LFA-1 CCR5
TLR2+ MMR/CD206–
JAM-A Th1
TLR4+ TLR2– Presumed Th17 migration, PECAM-1 CXCR3 CD27-
mechanism unknown.
PECAM-1 CCR10
NOTES: CCR6
1
Most common circulating DC phenotype; function unknown. RBC/CD47:SIRPa interaction keeps circulating DCs in an immmature state. E-Cadherin
2
90% of circulating monocytes. Th17
3
10% of blood monocytes. Langerhans Cell CCL20/
CD44 PSGL-1 MIP-3α
β-Defensin 2 CCR6 VLA-4 (FucTVII+)
CCL27/CTACK
β-Defensin 3 OSM RΙΙ CCL20/MIP-3α to vasculature
MIP-3α retains Langerhans CCR5 CCL27/
TLR2 cell in place CTACK
VLA-4 P-Selectin
TLR1 CXCL16
GM-CSF R
CD44 CXCR3 HSPG
E-Cadherin VCAM-1
Endothelial Cell
Stratum Spinosum Langerhans Cell Th1
TNF RΙΙ
Integrin α4β6

LL37 Stratum Basale TGF-β (constitutive TGF-β

E-Cadherin expression retains E-Cadherin
homotypic interactions)
IGF-I R IGF-I
Langerhans Cell MHC II Collagen IV
β-Defensin 3 Integrin α4β6 Basement Basement Membrane
CD44 γδ T Cell membrane
γδ T cells may also
CD1 TNF-α be abundant vWF
& GM-CSF TLR2 (binds to
producers of IL-17. GPIa-IIa
(Plt-to-Collagen) basement
lysis CCR6 TLR1 Immature DDC membrane)
CD207
GM-CSF R IMMUNE RESPONSE Platelet
(Plt)
CLOTTING
TRIGGERED CCL17/TARC GPIb-V-IX
(Plt-to-vWF)
PROCESS
Chemoattracts HSPG
1 TLR2 Macrophage
LANGERHANS CELL Staphylococcus aureus (S. aureus) MMR
CCR4+ TEM Fibrinogen
Afferent
PAF R ACTIVATION TLR1
CRIg
Lymphatic CCL21/SLC
GPIa-IIb MBL/Ficolin-1,-2
(Plt-to-Fibrinogen) MASP-2
TNF-α TNF RII TLR2 Chemoattracts CCR7+ cells CCL5/RANTES
CCL22/MDC MASP-1 C4 (a)
PAF R binds S. aureus Immature DDC Chemoattracts Used for
CD44 MMR monocyte (b)
and induces E-Cadherin TLR2 CCR4+ TEM recruitment
disengages C5a C5b
IL-1α C4a
IL-6 Pro-inflammatory CCR6 Langerhans Cell TLR1 Protein A
IL-10 & Immunomodulatory CCR10
Integrin α4β6 IL-12 R
TNF-α Responses S. aureus C4b
GM-CSF R Th1 (a)
PAF IL-18 IL-12 (b) C2
CD1z IL-18 R C4b C4b
IFN R2 TLR2 C5 (b) (a)
C2a C2a
CCR7 Classic C3b C2b
TCR IFN-γ Monocyte TLR2 Macrophage
MHC II IFN R2 SIRPα TLR1
Th1 CRIg CRIg C4b C2a
Superantigen Mono-DC
IL-31 E-Selectin
Slan DC CD47
MIP-3α
OPSONIZATION
2
CXCL8/ IL-8 Phagosomes C3a
IL-31 R CCL1/I-309
CCL17/TARC C3
Classic HSPG C2b
Monocyte CCL22/MDC C5a (a)(b)
VCAM-1 IL-17 RA:RC IL-23 C3a
Fibroblast
Integrin α4β6 P-Selectin
TNF-α IL-17
Langerhans Cell IL-6 (A,F) IL-23 R CD1a+
CXCL1/GROα Th17 CD83+
CD44 CCR7 MMP-9
G-CSF CCR4 Macrophage-derived DC
lysis (does not produce IL-12)
CCR6
CCL21/SLC 3 Langerhans Cell IL-23
IL-6
CD1 MHC II IL-22

CCR7 Mono-DC
IL-12 TLR2

CCL21/SLC DC SIGN/CD209 Mono-DC

IL-23 to γδ T Cell
CCL21/SLC 4 S. aureus
CCR5
IFN-γ IFN R2
CCR7 CCL3/MIP-1α (from Th1) Type I Macrophage
lysis
Lymphatic Non-sialylated Lex Differentiation
Channel on Mac-1 promotes
APC maturation PMN-derived
MHC II Macrophage CXCL10/IP-10
TNF-α
IL-23
(from Mono-DC) Mac-1 Fibronectin GM-CSF R IFN-β TLR2
Mono-DC S. aureus
IL-23 R TLR1
TLR9
PECAM-1 IL-17 RA:RC γδ T Cell IL-17 (A,F) M-CSF M-CSF R GM-CSF
Mac-1 (from Keratinocytes)
HSPG GM-CSF R
MHC II B7-2/CD86 PSGL-1 IL-17 RA:RC
P-Selectin IL-6 Classic Monocyte
CD28 CCL20/MIP-3α sIL-6 R: IL-6
S. aureus (processed) CXCR2 1 HSPG Fibroblast
PSGL-1 2
HSPG IL-6 R
CD3/TCR Neutrophil CXCL8/IL-8 ICAM-1 TLR2
Activated Th1
CXCR2 Mac-1 CD31
ICAM-2
ICAM-1
CD31 MONOCYTE
LFA-1 S100A9
OSM
Mac-1 TRANSMIGRATION
OSM RΙΙ ICAM-1
Promotes gp130 IL-1β IL-1β
& DIFFERENTIATION
β-Defensin 3 CXCL8/IL-8 permeability
S100A7
S100A8
S100A9 HSPG CCL2/MCP-1 E-Selectin
MMP-1 CD47 LEUKOCYTE ROLLING HSPG
CCL1/I-309
MMP-3 Th17 & ATTACHMENT PSGL-1 ICAM-1
CCL2/MCP-1
IL-17 (A,F) VCAM-1
IL-23 R CTLA-4 CCR2 VLA-4
IL-17 RA:RC Endothelial Cell
Treg Cell Classic
IL-23 CD4 Monocyte
IL-22 TLR1 LAG-3+ VLA-4
TLR2 CCR4 FoxP3+ E-Selectin
IL-22 R HSPG
Mono-DC CD47
IL-1α ↓ Tryptophan blocks CCR8
Promotes inflammatory ↑IDO TEM/Th1 proliferation, CD25
IL-6 cell infiltration at the PSGL-1
promoting suppression CCL5/
IL-8 vascular level Integrin α6β1 RANTES
B7-2/CD86 CLA(FucTVII+) TCR CD47 CCR5

MHC II CTLA-4 CCR5 DNAM-1

ICOS CD99
CD3/TCR CCR10 Th1 Laminin
LFA-1 CD155/PVR
Differentiates into CD2 CCR5
Granzyme A CCR6
Mature Dermal DC CD99
Inflammatory Monocyte
ICAM-2
Apoptosis CD31
MHC II CXCR3 CCR6 JAM-A
Th1
Mac-1 CD31
E-Selectin
Immature CCR6
Dermal DC TLR2 Activated Th1 ICAM-1
S. aureus FnBP-A Integrin α5β1 ICAM-1
IFN-γ 1 MHC II with
IL-18 S. aureus peptide CCR7
Fibronectin
IL-18 R 2
3 VLA-4
Th1 Th1
TLR2 IL-1β CCR5
B7-H2
LFA-3 CCR7
TLR1/2 CLA
CXCR3
HSPG I-TAC
Mono-DC Mast Cell (MCTC)
TNF-α E-Selectin
CCL3/MIP-1α IP-10
IFN R2 TLR2 HSPG
TNF RI HSPG
IFN-γ Neutrophil CXCL11/I-TAC
TLR1
VLA-4
B7-2/CD86 IFN R2
VCAM-1
MHC II
CD28
CXCL11/I-TAC
S. aureus
(processed)
T CELL ACTIVATION & RESPONSE CXCL10/IP-10
IFN-γ ↑NO
CD3/TCR Opsonized S. aureus ↑H2O2

Activated Th1
CR3
(Integrin αMβ2) Hypodermis

Activated Th1
Movement of cell
IFN-γ
Secretory processes TNF-α CD1c+ CD80-
IL-6
IFN R2 Adipose Tissue Macrophage CD11c- CD163+
IL-1β
Receptor-mediated induction CCL2/MCP-1 CD14+ Integrin αVβ5+
CCL3/MIP-1α DC-SIGN/CD209 CD16+
MMR/CD206+

R&D Systems, Inc., 614 McKinley Place NE, Minneapolis, MN 55413 USA
1-800-343-7475, Fax 612-379-6580, www.RnDSystems.com Note: The information in this poster should neither be considered comprehensive nor definitive. The particulars involved are understood to be subject to interpretation. © 2009 R&D Systems, Inc.