[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Immunology](https://durgical.com/en/immunology/) › [Immune cells](https://durgical.com/en/immunology/#a-cells) › Lymphocyte recirculation and homing

[Immunology](https://durgical.com/en/immunology/) · [Immune cells](https://durgical.com/en/immunology/#a-cells)

# Lymphocyte recirculation and homing

- Process

Lymphocytes travel all the time between blood, lymph nodes and tissues, following address labels. Some multiple sclerosis drugs work by blocking these labels.

Updated 2026-11-01

**See it in 3D:** [Neck lymph nodes](https://durgical.com/en/anatomy/lymph-nodes-of-neck/)

## Key points

- Entry into nodes: L-selectin → CCR7 (CCL19/CCL21) → LFA-1/ICAM-1 through HEVs.
- Exit from nodes: S1P gradient through S1PR1; fingolimod blocks it and causes lymphopenia.
- Natalizumab blocks α4 integrin (VLA-4/VCAM-1 in the brain, α4β7 in the gut): multiple sclerosis and Crohn disease; risk of PML.
- Memory and effector cells home to tissues; naive cells home to lymph nodes.
- LAD-1 (CD18) = late cord separation and infections without pus.

## What it is

Naive lymphocytes patrol the body by moving from blood into lymph nodes through high endothelial venules (HEVs), scanning for their antigen, and leaving through the lymph back to the blood. Entry depends on a sequence of adhesion molecules and chemokines; exit depends on a lipid gradient (sphingosine-1-phosphate, S1P). Effector and memory cells switch to new receptors that send them to inflamed tissues, skin or gut. Blocking these steps is the basis of drugs such as natalizumab and fingolimod.

## Key facts

- HEVs are post-capillary venules lined by tall, plump endothelial cells, found in lymph nodes and MALT but not in the spleen.
- A naive lymphocyte may pass through many lymph nodes a day, which raises the chance of meeting its rare antigen.
- Integrin binding pairs: LFA-1 with ICAM-1; VLA-4 (α4β1) with VCAM-1; α4β7 with MAdCAM-1 in gut venules.
- The same rolling, activation, firm adhesion and transmigration sequence is used by neutrophils at sites of inflammation.

## Step by step

- Naive T cells carry L-selectin (CD62L) and the chemokine receptor CCR7.
- In the lymph node, L-selectin binds addressins on high endothelial venules, so the cell rolls along the vessel wall.
- Chemokines CCL19 and CCL21 on the HEV signal through CCR7 and switch integrin LFA-1 to its high-affinity form.
- LFA-1 binds ICAM-1, the cell stops firmly and crawls through the HEV wall into the T-cell zone.
- If it does not find its antigen, the cell follows the S1P gradient (high in lymph and blood) through S1PR1 and leaves by the efferent lymph.
- If it finds its antigen, CD69 holds S1PR1 down, the cell stays to proliferate, then leaves as an effector cell.
- Effector and memory cells lose CCR7 and L-selectin and gain tissue receptors: VLA-4 for inflamed tissue and brain, α4β7/CCR9 for gut, CLA for skin.

## Markers

- CD62L (L-selectin)
- CCR7
- LFA-1
- ICAM-1
- VLA-4 (α4β1)
- α4β7
- S1PR1
- CD69

## Clinical notes

- Natalizumab, an antibody against α4 integrin, blocks entry of lymphocytes into the brain and gut; it is used in relapsing multiple sclerosis and Crohn disease.
- Natalizumab carries a risk of progressive multifocal leukoencephalopathy (PML) from JC virus, higher with positive JC virus antibodies and longer treatment.
- Fingolimod, an S1P receptor modulator, causes the receptor to be internalised, so lymphocytes stay trapped in lymph nodes and blood lymphocytes fall; it is used in multiple sclerosis.
- Fingolimod can slow the heart rate after the first dose and raises the risk of infections such as herpes zoster.
- Leukocyte adhesion deficiency type 1 (CD18 integrin defect): delayed separation of the umbilical cord, high neutrophil counts in blood and infections without pus.

## Memory aid

Getting in needs a ticket (L-selectin), a password (CCR7) and a handshake (LFA-1); getting out needs the S1P exit sign, which fingolimod switches off.

## Test yourself

Think of the answer, then tap the question to see it.

## Which chemokine receptor brings naive T cells into lymph nodes?

CCR7, responding to CCL19 and CCL21 on high endothelial venules.

## How does fingolimod lower blood lymphocyte counts?

It modulates S1P receptors, causing their internalisation, so lymphocytes cannot follow the S1P gradient out of lymph nodes.

## Which molecule does natalizumab block and which serious infection is associated with it?

α4 integrin (VLA-4 and α4β7); progressive multifocal leukoencephalopathy caused by JC virus.

## Which integrin-ligand pair mediates firm adhesion of lymphocytes to HEVs?

LFA-1 on the lymphocyte binding ICAM-1 on the endothelium.

[Add to my cards (4)](https://durgical.app/estudiar/?add=/en/immunology/lymphocyte-recirculation-and-homing/)

## See it in 3D

The structures of Durgical's 3D anatomy where it is found.

- [Neck lymph nodes](https://durgical.com/en/anatomy/lymph-nodes-of-neck/)

## Related

- [Adhesion molecules: selectins and integrins](https://durgical.com/en/immunology/adhesion-molecules-selectins-and-integrins/)
- [IL-8 and the chemokines](https://durgical.com/en/immunology/il-8-and-the-chemokines/)
- [Lymph node: cortex, paracortex, medulla](https://durgical.com/en/immunology/lymph-node-cortex-paracortex-medulla/)
- [Mucosa-associated lymphoid tissue (tonsils, Peyer patches)](https://durgical.com/en/immunology/mucosa-associated-lymphoid-tissue/)
- [T-cell activation: two signals and superantigens](https://durgical.com/en/immunology/t-cell-activation-two-signals-and-superantigens/)
- [Phagocyte defects: CGD, LAD, Chédiak–Higashi](https://durgical.com/en/immunology/phagocyte-defects-cgd-lad-chediak-higashi/)
- [Monoclonal antibodies and biologics: naming and targets](https://durgical.com/en/immunology/monoclonal-antibodies-and-biologics-naming-and-targets/)

## Related conditions

- [Multiple sclerosis](https://durgical.com/en/conditions/multiple-sclerosis/)
- [Crohn disease](https://durgical.com/en/conditions/crohn-disease/)

[← All of immunology](https://durgical.com/en/immunology/)

Educational content on the immune system; not a treatment or individual vaccination guide and no substitute for a health professional's advice. No doses are given.

Sources: [21.1 Anatomy of the Lymphatic and Immune Systems](https://openstax.org/books/anatomy-and-physiology-2e/pages/21-1-anatomy-of-the-lymphatic-and-immune-systems) (OpenStax (Anatomy and Physiology 2e), 2022); [Natalizumab Injection: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a605006.html) (U.S. National Library of Medicine (MedlinePlus), 2026); [Fingolimod: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a611006.html) (U.S. National Library of Medicine (MedlinePlus), 2026).

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Representative model, for educational purposes only.

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Source: https://durgical.com/en/immunology/lymphocyte-recirculation-and-homing/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/immunology/lymphocyte-recirculation-and-homing/