More Related Content Similar to Cell Adhesion in Leukocyte Trafficking_MS_012915.ppt Similar to Cell Adhesion in Leukocyte Trafficking_MS_012915.ppt (20) Cell Adhesion in Leukocyte Trafficking_MS_012915.ppt7. When a wound gets infected, the immune system needs to react
13. EM image of a neutrophil probing transendothelial cell contacts
14. Immune cells need to open endothelial cell contacts to transmigrate
90% of transmigration events are paracellular
16. Immune cells need to open endothelial cell contacts to transmigrate
90% of transmigration events are paracellular
23. 1. Tethering and Rolling
3. Firm Adhesion
4. Transmigration
2. Activation
Bloodflow
Leukocyte – Endothelial Cell Contacts:
The “Adhesion Cascade“
24. 1. Tethering and Rolling
3. Firm Adhesion
4. Transmigration
2. Activation
Bloodflow
1. Selectins
Leukocyte – Endothelial Cell Contacts:
The “Adhesion Cascade“
25. 1. Tethering and Rolling
3. Firm Adhesion
4. Transmigration
2. Activation
Bloodflow
1. Selectins
2. Chemokines
Leukocyte – Endothelial Cell Contacts:
The “Adhesion Cascade“
26. 1. Tethering and Rolling
3. Firm Adhesion
4. Transmigration
2. Activation
Bloodflow
1. Selectins
2. Chemokines
3. Integrins
Leukocyte – Endothelial Cell Contacts:
The “Adhesion Cascade“
27. 1. Tethering and Rolling
3. Firm Adhesion
4. Transmigration
2. Activation
Bloodflow
1. Selectins
2. Chemokines
3. Integrins
4. Ig-SF molecules
(Immunoglobulin superfamily)
Leukocyte – Endothelial Cell Contacts:
The “Adhesion Cascade“
28. 1. Tethering and Rolling
3. Firm Adhesion
4. Transmigration
2. Activation
Bloodflow
1. Selectins
2. Chemokines
3. Integrins
4. Ig-SF molecules
(Immunoglobulin superfamily)
Leukocyte – Endothelial Cell Contacts:
The “Adhesion Cascade“
31. Regulation of E- and P-selectin expression
Lipopolysaccharide (LPS)
Cytokines: IL-1, TNF-a, INF-g
activation
Weibel-Palade bodies
surface expression:
within minutes
surface expression:
within hours
E- and P-selectin expression in endothelial cells is induced
If E- and P-selectin were constitutively expressed on endothelial cells,
neutrophils would constantly adhere because L-selectin on leukocytes
is constitutively expressed
34. Function and Importance of E-, L-, and P-selectin
L-selectin E-selectin P-selectin
lymphocyte homing
to lymph nodes
inflammation inflammation inflammation
defective normal defective
E-/P- double KO mouse:
very strong defect
Function
Immune
system in
knock-out
mouse
36. 1. Tethering and Rolling
3. Firm Adhesion
4. Transmigration
2. Activation
Bloodflow
1. Selectins
2. Chemokines
3. Integrins
4. Ig-SF molecules
(Immunoglobulin superfamily)
Leukocyte – Endothelial Cell Contacts:
The “Adhesion Cascade“
37. Chemokines
Chemokine =
chemotactic cytokine
Small secreted
proteins ( 8 – 12 kDa)
Characterised by
certain patterns of
cystein residues
Nomenclature:
CCL1 - CCL28
CXCL1 - CXCL17
CL1 - CL2
CX3CL
Synonyms:
e.g. RANTES, SDF-1, MCP-1
Source:
Many different cell types
e.g. leukocytes and
endothelial cells
43. 1. Tethering and Rolling
3. Firm Adhesion
4. Transmigration
2. Activation
Bloodflow
1. Selectins
2. Chemokines
3. Integrins
4. Ig-SF molecules
(Immunoglobulin superfamily)
Leukocyte – Endothelial Cell Contacts:
The “Adhesion Cascade“
44. a b a b a b
Integrins
Integrins
49. 1. Tethering and Rolling
3. Firm Adhesion
4. Transmigration
2. Activation
Bloodflow
1. Selectins
2. Chemokines
3. Integrins
4. Ig-SF molecules
(Immunoglobulin superfamily)
Leukocyte – Endothelial Cell Contacts:
The “Adhesion Cascade“
flattening of firmly
bound leukocytes
50. 1. Tethering and Rolling
3. Firm Adhesion
4. Transmigration
2. Activation
Bloodflow
1. Selectins
2. Chemokines
3. Integrins
4. Ig-SF molecules
(Immunoglobulin superfamily)
Leukocyte – Endothelial Cell Contacts:
The “Adhesion Cascade“
51. Molecules involved in Transmigration
Junctional Adhesion Molecule
Platelet Endothelial Cell Adhesion Molecule
Molecular class:
Integrin
Ig-SF
Mucin
(highly glycosylated)
59. Migration through the inflamed tissue:
Chemokines cause directional movement
2nd task:
chemotactic
gradient
61. Literature
Textbooks
• Janeway‘s Immunobiology, 8th Edition, 2012, Garland Science
• Lodish et al., Molecular Biology of the Cell, 6th Edition, 2007, Freeman
Reviews
• Ley et al., Nat. Rev. Immunol., 2007
• Voisin & Nourshargh, J. Innate Immun., 2013
• Kolaczkowska & Kubes, Nat. Rev. Immunol., 2013