Lymphocytes continuously recirculate between the vascular system and tissues, which is essential for immune system homeostasis and function. This migration is regulated by cell adhesion molecules and chemokines. Chemokines play a key role in lymphocyte trafficking by facilitating adhesion to and transmigration through vascular endothelium. The process involves lymphocytes first rolling along endothelial cells, then becoming activated and firmly adhering via integrins when they encounter chemokines, and finally transmigrating between endothelial cells into tissues.
2. Lymphocytes continuously recirculate between the vascular system and tissues
These migratory properties of lymphocytes and dendritic cells, which are
essential for the homeostasis and function of the immune system.
Regulated by various cell-adhesion molecules and by a group of chemokines
collectively called “immune chemokines.
Immune chemokines are thus key elements in the genesis, maintenance, and
function of the immune system.
Definitio
n
The process whereby lymphocytes adhere to and migrate across vascular
endothelium into an organ or site of inflammation
3. WHY LYMPHOCYTES TRAFFICKING IS ESSENTIAL
Its necessary for Lymphocyte developmen and differentiation.
For immune response
Mode of motility
Crawling :
• Require them to athere to
there surrounding.
• Take more time for Crawling
lymphocytes to 1 cm.
4. • Blood circulatory system
• Blood circulates in the closed circuit
• Blood vascular system consists of blood, arteries, veins and
heart.
• Blood vascular system is the main transporting system of the
body
Lymphatic system
• It is the extracellular fluid that circulates through the tissue spaces
into blood vascular system
• Lymphatic system consists of lymph, lymph capillaries lymph nodes
and lymph vessels
• It serves as parallel transporting system
7. ROLE OF HEVS IN CELL
MIGRATION
High endothelial venules (HEVs) are specialized blood vessels which
support the migration of naive lymphocytes from the blood stream into
secondary lymphoid organs.
Lymphocyte extravasation can be regulated by high-endothelial
venules.
HEV cuboidal endothelial cells express the adhesion molecules.
8. HEV cuboidal endothelial cells express the adhesion molecules
GlyCAM-1 (in mucosal HEV this is MAdCAM-1), ICAM-1 and CD34.
They also secrete the chemokine CCL21.
9. LYMPHOCYTE
EXTRAVASATION
Extravasation can be divided into four steps :
Rolling Activation Adhesion Transeendothelial
MigrationMediated by
selectins
By
chemoatractan
t stimulus
Mediated by
integrins
10.
11. Lymphocyte rolling initiates the contact between lymphocyte and the endotheliul
cells help of selection.
Lymphocytes have ligand for bind to P selection and E selectin on endothelial.
P-Selectin bind P-Selectin Glycoprotein Ligand-1 (PSGL-1).
E-Selectin bind E-Selectin Ligand-1.
The bond forms and Break rapidly,allowing lymphocyte to roll along surface of
endothelial cells.
The low affinity bonding nature of selection is allow characteristics rolling action
of lymphocytes
12. • Selectine are plasma membrane carbohydrate
binding protein present on lymphocytes and
endothelial cells.
• Bind with specific carbohydrate group.
• Selectin are:
• P-selectin (CD 62P)
• E-selectin (CD 62E)
• L-selectin (CD 62L)
Selection
13.
14. ACTIVATION AND
ADHESION In rolling process lymphocyte contact with endothelial cells of HEVs.
Integrin are low affinity state .
If lymphocyte comes close to endothelial then chemokines displayed on endothelial surface.
Binding of Chemokine their receptor on lymphocyte results integrins are activated.
Integrin
• Integrins are cell surface protein that mediate adhesion
of cell.
• Heteridimer of alpha and beta subunits.
1. Lymphocyte Function-Associated Antigen 1 (LFA-1)
CD11aCD18
2. Very Late Antigen-4
LFA-1 binds to ICAM-1 ( CD54)
VLA-4 binds to VCAM-1 (vascular cell adhesion molecule 1) CD-
106
15. TRANSMIGRAT
ION
hocyte transmigrate between border of endothelial cells apricess called
paracellular transmigration or diapedesis.
This process is integrin intersection dependent.
Actin arrangement
Pseudopod like structure formation and squeezing through endothelial cell gap.
18. Abbas, Abul K., Andrew HH Lichtman, and Shiv Pillai. Cellular and molecular
immunology E-book. Elsevier Health Sciences, 2014.
Kindt, T. J., Goldsby, R. A., & Osborne, B. A. Kuby immunology. 6th ed2007.
https://www.ncbi.nlm.nih.gov/m/pubmed/17202753/
Reference