Introduction 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. R egulated 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. Definition The process whereby lymphocytes adhere to and migrate across vascular endothelium into an organ or site of inflammation
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.
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
Pattern of Lymphocyte traffic T cell B cell
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.
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 .
Lymphocyte extravasation Extravasation can be divided into four steps : Rolling Activation Adhesion Transeendothelial Migration Mediated by selectins By chemoatractant stimulus Mediated by integrins
Tethering and rolling 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
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
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. Lymphocyte Function-Associated Antigen 1 ( LFA-1 ) CD11aCD18 Very Late Antigen-4 LFA-1 binds to ICAM-1 ( CD54) VLA-4 binds to VCAM-1 (vascular cell adhesion molecule 1) CD-106
Transmigration 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.
T cell migration
Migration of B lymphocyte
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