3B Tissues

Neutrophil transmigration

Movement of neutrophils from blood into inflamed tissues

Monocyte transmigration

Movement of monocytes from blood into tissues

Reason for different leukocyte migration

Differences in adhesion molecules and chemokine receptors

Neutrophil chemokine receptors

CXCR1 and CXCR2

Neutrophil chemoattractants

CXCL1 (GROα) and CXCL8 (IL-8)

Primary role of neutrophils

Early innate immune defense

Monocyte chemokine receptors

CCR2 and CCR5

Monocyte chemoattractants

CCL2, CCL3, CCL4, CCL5

Outcome of monocyte tissue entry

Differentiation into macrophages or dendritic cells

Integrins role in leukocyte migration

Stable adhesion and transmigration

Lewis ligands function

Bind selectins during leukocyte rolling

Naïve T lymphocyte recirculation

Continuous migration through secondary lymphoid organs

Purpose of naïve T cell recirculation

Maximize antigen encounter

Memory T cell migration pattern

Lymphoid organs, mucosa, and skin

Effector T cell migration

Migrate to infected or inflamed tissues

Naïve T cell chemokine receptor

CCR7

CCR7 ligands

CCL19 and CCL21

Location of CCL19 and CCL21

Lymph nodes

Entry of naïve T cells into lymph nodes

High endothelial venules (HEVs)

Adhesion molecule for naïve T cell entry

L-selectin

L-selectin ligand

Sulfated sialyl-Lewis X

Function of HEVs

Facilitate lymphocyte entry into lymph nodes

S1P definition

Sphingosine-1-phosphate

S1P concentration gradient

High in blood and lymph, low in tissues

S1PR1 function

Directs lymphocyte egress from lymph nodes

Naïve T cell S1PR1 expression after entry

Low expression

Effect of low S1PR1

Retention in lymph node

Average naïve T cell retention time

Approximately 12 hours

Effect of antigen activation on S1PR1

Downregulation for several days

Purpose of S1PR1 downregulation

Allow T cell activation and proliferation

Central memory T cells

Reside in secondary lymphoid organs

Chemokine receptor on central memory T cells

CCR7

Effector memory T cells

Reside mainly in tissues

CCR7 expression on effector memory T cells

Low

Resident memory T cells

Remain permanently in tissues

Marker of resident memory T cells

CD69

Function of CD69

Inhibits S1PR1

Additional resident memory marker

CD103

CD103 ligand

E-cadherin

Purpose of resident memory T cells

Rapid local immune protection

Naïve B cell entry into lymph nodes

Through HEVs

Chemokine receptor on naïve B cells

CCR7

Chemokines guiding B cell entry

CCL19 and CCL21

B cell migration within lymph node

Toward follicles

Follicular chemokine

CXCL13

B cell chemokine receptor

CXCR5

Outcome of B cell activation

Plasma cells and memory B cells

Plasma cell bone marrow homing

CXCR4 expression

Plasma cell mucosal homing

CCR9 expression

Memory B cell fate

Return to circulation

B cell lymph node egress

S1P–S1PR1 dependent

Shared egress mechanism of T and B cells

S1P gradient