What are the 4 steps of leukocyte trafficking (in order)?
Rolling → Activation → Firm adhesion → Diapedesis
Where does leukocyte egress occur?
Post-capillary venules
Why are post-capillary venules ideal for leukocyte egress?
Slow blood flow, thin walls, high adhesion molecules, easier cell passage
What are High Endothelial Venules (HEVs)?
Specialized lymph node vessels that allow lymphocyte entry from blood
What molecules are involved in rolling?
Selectins (L, E, P) and Sialyl Lewis X
What molecules are involved in activation?
Chemokines and chemokine receptors
What molecules are involved in firm adhesion?
Integrins and ICAMs
What molecules are involved in diapedesis?
Integrins, ICAMs, and junction adhesion molecules
What are selectins?
Adhesion molecules that mediate leukocyte rolling
What do selectins bind to?
Carbohydrate-containing mucin-like molecules
What are lectin domains?
Carbohydrate-binding regions of proteins
What is Sialyl Lewis X (SLeX)?
Carbohydrate ligand that binds selectins
What are chemokines?
Small signaling proteins that guide leukocyte movement
What are key characteristics of chemokines?
Small, form gradients, bind GPCRs
What are chemokine receptors?
7-transmembrane GPCRs on leukocytes
What are integrins?
Adhesion receptors for firm binding
What is the structure of integrins?
Alpha and beta subunits
What do integrins bind to?
ICAMs and extracellular matrix proteins
What is inside-out signaling?
Chemokines activate integrins to increase binding affinity
What are ICAMs?
Immunoglobulin superfamily adhesion molecules
What do ICAMs bind to?
Integrins
What is the role of ICAM-1?
Adhesion during inflammation
What is the role of ICAM-2?
Leukocyte trafficking
What is the role of ICAM-3?
T cell interactions
What is the function of L-selectin?
Helps lymphocytes enter lymph nodes
What is the function of P-selectin?
Initiates leukocyte rolling
What is the function of E-selectin?
Helps leukocytes roll at inflamed tissue
What is αMβ2 (Mac-1)?
Integrin for firm adhesion and migration
What are sentinel cells?
Tissue-resident cells that detect infection
What are examples of sentinel cells?
Macrophages, dendritic cells, mast cells
What do sentinel cells release?
Cytokines and chemokines
What are the consequences of sentinel cell activation?
Recruit leukocytes, increase adhesion molecules, initiate inflammation
What is the purpose of myeloid cell migration?
Move to sites of infection
What is the purpose of lymphocyte migration?
Immune surveillance
How does antigen arrive at lymph nodes?
Free antigen via lymph, dendritic cells, subcapsular macrophages
How do lymphocytes circulate?
Blood → lymph node → lymph → blood
What is in the cortex of a lymph node?
B cells
What is in the paracortex?
T cells
What is in the medulla?
Plasma cells and macrophages
What is the role of chemokines in lymph nodes?
Guide cells to correct zones
How do T cells meet antigen-presenting cells?
Both follow CCL19/CCL21 via CCR7 to the paracortex
What is the fibroblastic reticular cell (FRC) network?
Scaffold guiding T cell movement
What do FRCs secrete?
CCL19 and CCL21
What is S1P?
Lipid signaling molecule high in blood and lymph
What is S1PR1?
Receptor for S1P on lymphocytes
What is the function of S1P
S1PR1? / Controls lymphocyte exit from lymph nodes
How does S1P signaling work?
Cells follow gradient from low (node) to high (blood) to exit