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