Cellular Movement Flashcards

The lecture focuses on how immune cells circulate through the lymphatic system to reach sites of infection or inflammation.
Key topics include leukocyte migration, adhesion molecules, high endothelial venules (HEVs), and lymphocyte recirculation.

Delivers immune cells to tissues or sites of infection (e.g., neutrophils for extracellular bacteria).
Moves myeloid cells from the blood to tissues.
Transports lymphocytes (T cells to the thymus, B cells to secondary lymphoid tissues).
Enables the adaptive immune system to move from lymph nodes to tissues.
Cells from the bone marrow must reach infected tissues (e.g., fingertip). This is mediated by adhesion molecules and chemokines.

Homing: Movement from blood to a specific site (e.g., site of inflammation).
Migration/Recruitment: General leukocyte movement from blood into tissues.
Recirculation: Movement from blood to secondary lymphoid organs and back into the blood.

Function as "speed bumps" for cells in venules, where blood flow is rapid.
Adhere leukocytes to endothelial cells.
Two main classes:
- Selectins and selectin ligands.
- Integrins and integrin ligands.
Selectins slow down and stop cells; integrins send signals to the cytoskeleton, changing cell morphology for extravasation.
Expression of adhesion molecules varies among different leukocytes.

P selectin
- On endothelium, activated by histamines (released by mast cells).
- Interacts with ligands on neutrophils, monocytes, and T cells (effector or memory cells).
E selectin
- On endothelial cells, upregulated by TNF and interleukin-1 (IL-1).
- Interacts with neutrophils, monocytes, T cells, and B cells.
L selectin
- On leukocytes (neutrophils, monocytes, T cells).
- Binds to ligands on high endothelial venules (HEVs), particularly for T cell binding.

Upregulated after selectin binding.
Transition from low to high affinity state upon chemokine receptor interaction with chemokines.
Change structure upon chemokine binding, exposing a larger binding area.
Integrins facilitate the movement of large cells through tight junctions between endothelial cells.
There are >30 different types of integrins with varying functions.

Expressed on neutrophils, monocytes, and T cells.
Interacts with ICAM-1, its ligand, on endothelial cells.
Integrates extracellular signals to the intracellular part of the cell, regulated by chemokines.

Chemotactic cytokines that recruit cells to an area by guiding cells from low to high concentration gradients.
Different cells express different chemokine receptors.
Guide B cells moving from B cell zones to T cell zones and vice versa.

Leukocytes slow down, roll along vessel walls, and then extravasate into tissues.
Requires a transition from low to high affinity binding to withstand shear forces from blood flow.
Tissue-resident cells (macrophages, dendritic cells, mast cells) produce chemokines and cytokines based on pathogen recognition.
The major cytokines are TNF and IL-1. These stimulate the upregulation of selectins on the endothelial surface.

Tissue-resident cells promote inflammation, leading to the production of TNF and IL-1.
Selectins (E and P selectin) are upregulated on endothelial cells.
Initial weak binding and rolling occur as selectins interact with ligands on leukocytes.
Integrins are upregulated and transition to a high-affinity state.
Firm binding and arrest occur via integrin binding.
Cells change shape (from ovoid to flattened/fried egg shape) to facilitate extravasation.
Cells interact with fibrin and fibronectin in the extracellular matrix to crawl into the tissue towards the chemokine gradient.

Mainly for naive T cells.
T cells move from the bone marrow to the thymus for education.
Naive T cells circulate in lymphoid tissues via high endothelial venules (HEVs).

Found within lymph nodes; facilitate the interaction between T cells and antigen-presenting cells.
Distinct cuboidal morphology compared to normal vessel endothelial cells.
Express specific homing receptors that allow lymphocytes to recirculate.

Naive T cells enter HEVs.
L selectin (on T cells) binds to ligands on HEVs, arresting T cells.
CCR7 (on naive T cells) recognizes CCL19 and CCL21 chemokines, which are guiding interactions and movements.
LFA-1 (on T cells) binds to ICAM-1 (expressed by HEVs), further stopping T cells.
T cells are held in place to allow interaction for antigen recognition.
If no antigen is recognized, T cells re-express receptors and follow chemokine gradients to move out and recirculate.

Ensures T cells encounter their specific antigen.
Allows T cells from different locations to find antigens in different lymph nodes.

Another receptor found on T cells which recognizes sphingosine phosphate (S1P).
S1P is in high concentrations in lymph and blood.
Binding leads to receptor internalization and temporary arrest in HEVs.
S1P lyase in tissues breaks down S1P, preventing naive T cells from being drawn into tissues.
If a T cell doesn't engage with an antigen, it upregulates S1PR1 and egresses.
S1P is maintained in high concentrations in lymphoid tissue and blood, facilitating movement around the system.