Induced Innate Immune Responses: Extravasation of Immune Cells

Introduction

• Focus on extravasation of immune cells: monocytes and neutrophils.
• Understanding chemokines and their role in immune response.
• Overview of inflammation:
  • Recognition of pathogens by host.
  • Directs molecules and cells to infection site.
  • Activates immune cells.
  • Induces localized blood clotting.
  • Aids in tissue repair.

Inflammation and Chemokines

• Inflammation triggered by cytokines, chemokines, and mediators like histamine.
• Chemokines induce directed chemotaxis, moving cells toward the infection site.

Groups of Chemokines:

1. C Chemokines:
   • Contain two cysteines forming a disulfide bridge.
2. CC Chemokines:
   • Two cysteines forming two disulfide bridges next to each other in sequence.
3. CXC Chemokines:
   • Two cysteines with an amino acid in between.
4. CX3C Chemokines:
   • Two cysteines with three amino acids in between.

• Chemokines recruit immune cells to infection site.

Extravasation Process

• Immune cells circulate in blood and need to leave vessels to reach infection sites.
• Chemokines guide immune cells to exit blood vessels (extravasation).

Steps of Extravasation

1. Interaction with Endothelial Cells:

   • Involves protein-protein interactions.
   • Uses adhesion molecules: selectins, integrins, and immunoglobulin superfamily (ICAM).

2. Selectins and Integrins:

   • Selectins (P-selectin, E-selectin) expressed in endothelial cells.
   • Integrins in immune cells (monocytes, neutrophils).
   • ICAM present on endothelial and immune cells.

3. Rolling:

   • E-selectin on endothelial cells triggers rolling of neutrophils and monocytes.
   • Involves weak interaction with sulfated sialyl Lewis X on leukocytes.

4. Tight Binding/Margination:

   • Chemokines bind to proteoglycans on endothelial cells.
   • Neutrophils slow down and interact with chemokine receptors.
   • Induces integrin conformation change, interacts with ICAM.
   • Results in tight binding of immune cells to endothelium.

5. Diapedesis:

   • Crossing of endothelial barrier by squeezing through junctions.
   • Facilitated by integrins and PCAMs (found on immune and endothelial cells).

6. Migration:

   • Chemokine concentration gradient guides immune cells to infection site.
   • Neutrophils migrate first in large numbers, followed by slower monocytes.

Conclusion

• Overview of chemokine groups and their functions.
• Detailed steps in extravasation: rolling, tight binding, diapedesis, migration.
• Neutrophils migrate rapidly in large numbers, monocytes follow slower.
• Essential for effective immune response during infections.