Week 3 Study Questions Flashcards
Name the main primary lymphoid tissues and describe their roles in relation to lymphocyte development and migration.
- Bone marrow
- Foetal liver
- Thymus
- These site produce naive lymphoctes
Name the secondary lymphoid tissues and describe their roles in relation to lymphocyte development and migration
- These sites drain defined tissues and compartments that collect antigens, and are the main sites of lymphocyte differentiation
- These are also where the antigen is presented to the naive lymphocytes, and the lymphocytes mature
- Lymph nodes
- Spleen
- GALT (gut-associated lymphoid tissue)
- MALT/BALT (mucosal-associated lymphoid tissue, bronchial-associated lymphoid tissue)
What is the pathway of T lymphocyte migration and homing?
- Naïve T cells preferentially leave the blood and enter lymph nodes across HEVs (high endothelial venules)
- DCs carrying antigens enter the lymph nodes via lymphatic vessels
- If the T cells recognise the antigen they are activated, & they return to the circulation via the efferent lymphatics.
- Effector & memory T cells preferentially leave the blood and enter peripheral tissues through venules at sites of inflammation
What are the different families of adhesion molecules?
- Selectins
- mucins
- Ig-super family
- Integrins
Describe the steps of leukocyte migration across the endothelial layer, mentioning the different adhesion molecules that are involved in each step.
- P-selectin is most important selectin for rolling. It is rapidly expressed on
endothelial cell surfaces – upon = stimulation by trauma or inflammatory cytokines (e.g. TNF-α). Its ligand, PSGL-1 is on all lymphocytes, monocytes, neutrophils and eosinophils. Mice lacking P-selection → no rolling. - L-selectin captures leukocytes and initiates rolling, but is less effective at rolling than P-selectin.
- E-selectin is involved in slow rolling and appears on the endothelial surface a few
hours after P-selectin, and acts towards initiating the firm adhesion step
The adhesion capability of CD18 integrins is dependent upon their activation status. What does this mean and how is it associated with the regulation of leukocyte migration?
- CD18 is involved in slow rolling
- When CD18 is activated: higher affinity and avidity
- Lymphocytes rolling on endothelium do not stop unless their CD18 integrins are triggered into their high affinity conformation
- Chemokines help to activate integrins, and chemokine up-regulated integrins induce arrest and firm adhesion of rolling cells
- The importance of rolling time is related to activation of the leukocyte and of leukocyte CD18 integrins by chemokines (e.g. IL-8) that are presented on the endothelial cell surface
How do chemokines contribute to leukocyte homing to lymph nodes?
- Homing of naїve lymphocytes to secondary lymphoid tissue – B cells localise to B cell areas (follicles) and the T cells to T cell areas (paracortical area).
- This movement is controlled by chemokines and their receptors
- B cells express CXCR5, the lymph node follicles express a ligand for CXCR5,
CXCL13. CXCL13-CXCR5 ligand-receptor pair mediates compartmental homing of B cells in lymph nodes. - Chemokines guide movements in the T cell areas by binding CCR7 on T cells. The CCR7 ligand, CCL21 is expressed by stromal cells within T cell areas of lymph nodes, spleen and Peyers patches. A
second CCR7 ligand, CCL19 is also expressed in the same areas - Both act to mediate homing of T cells in secondary lymphoid tissue.
Different combinations of adhesion molecules and chemokines act together to regulate leukocyte migration into different tissues, explain what this means using naïve and effector T cell migration patterns to illustrate your answer
- Cooperative interactions between adhesion molecules regulate migration. Naїve and effector & /or memory T cells share some adhesion molecules, but each subset has adhesion molecule combinations that are peculiar to that cell type → specificity of migration pathways
- Migration of naïve T cells into lymph nodes, and the migration of effector T cells into infected (or inflamed) tissue sites involves a different set of chemokines and chemokine receptors
- Finely tuned specificity → different cell types directed to particular sites
What are the different stages of leukocyte extravasation and what adhesion molecules are involved in each stage?
- Capture
- Rolling
- Slow rolling
- Adhesion
- Transmigration
How does the migration pattern of naive T cells differ to that of effector/memory T cells?
- Naïve T lymphocytes migrate to secondary lymphoid tissues
- Effector/memory cells migrate to extra-lymphoid tissues to fight infection.
- Process is not random: it is regulated by cell adhesion molecules belonging to the families: Selectin, Mucin, Integrin and Ig superfamily
Role of lymph node as a secondary lymphoid tissue
located at points of convergence of vessels of lymphatic system, collect antigens from lymph (extracellular tissue fluid)
Role of spleen as a secondary lymphoid tissue
collects blood antigens
Role of GALT as a secondary lymphoid tissue
collect blood antigens, and include tonsils, adenoids, appendix and Peyer’s patches
Role of MALT/BALT as a secondary lymphoid tissue
- This is more diffuse lymphoid tissue, collect antigens via APC
Role of E selectins
- E-selectin is found exclusively on endothelia
- Selectin ligands are cell surface, transmembrane mucins which present glycosylation structures to the selectins, strong binding ability
- Ligands for E-selectin include PSGL-1 and ESL-1 (E-selectin ligand-1)
