Leukocyte-Endothelial Interactions and Recruitment into Tissues Diagram

Leukocytes – Endothelial Interactions and Leukocytes Recruitment into Tissues Part II Leukocyte-Endothelial Interaction and Leukocyte Recruitment into Tissue Leukocyte recruitment from the blood into tissues requires adhesion of leukocytes to the endothelial lining of postcapillary venules and then movement through the endothelium and vessel wall into the extravascular tissue. This is a multi-step process in which different types of adhesion molecules and chemokines orchestrate each step. Studies in vitro and in vivo have established a sequence of events common to the migration of most leukocytes into most tissues. Selectin-mediated Rolling of Leukocytes on Endothelium Macrophages and dendritic cells (DCs) encountering microbes secrete cytokines like TNF and IL-1, which stimulate endothelial cells to express E-selectin. Microbe-activated mast cells and thrombin trigger P-selectin expression on endothelial cells. Inflammatory sites cause blood vessel dilation and slower blood flow, leading leukocytes to marginate towards the vessel lining. Leukocyte rolling is mediated by transient, low-affinity binding of selectins on endothelial cells and their ligands on leukocytes. Chemokine-Mediated Increase in Affinity to Integrins Chemokines displayed on endothelial cells bind to leukocyte receptors, enhancing integrin affinity for their ligands. Stable Integrin-Mediated Arrest of Leukocytes on Endothelium Integrin ligands (VCAM-1, ICAM-1) on endothelial cells are upregulated by inflammatory cytokines. Leukocytes firmly adhere and flatten on the endothelial surface. Transmigration of Leukocytes through the Endothelium Leukocytes typically transmigrate between endothelial cell borders (paracellular migration) via interactions between integrins and CD31. VE-cadherin junctions are transiently disrupted by phosphorylation. Less commonly, leukocytes migrate directly through endothelial cells (transcellular migration). Genetic deficiencies in CD18, selectins, or chemokine receptors can cause Leukocyte Adhesion Deficiencies (LAD-1, LAD-2, LAD-3), leading to recurrent infections. Leukocyte Types and Migration Neutrophils and Monocytes: Neutrophils are recruited early, followed by monocytes. Neutrophils express CXCR1 and CXCR2, binding to CXCL8. Monocytes express CCR2, binding to CCL2. T Lymphocytes Migration: Naive T cells circulate through blood, lymphatic vessels, and lymphoid tissues. Naive T cells enter lymph nodes via High Endothelial Venules (HEVs) and migrate based on chemokine gradients (CCL19, CCL21 binding to CCR7). Effector and memory T cells migrate to infection sites via integrins and chemokine receptors. T Cell Recirculation Naive T cells enter lymph nodes through HEVs using L-selectin, CCR7, and integrins. Chemokines (CCL19, CCL21) guide T cells within lymphoid tissues. Activated T cells suppress S1PR1 temporarily to remain in lymph nodes for differentiation. Effector T Cell Migration to Infection Sites Effector T cells express ligands for E- and P-selectins and chemokine receptors, allowing migration to infection sites. Retention at infection sites depends on integrin and chemokine signaling. Memory T Cell Migration Memory T cells are divided into central memory T cells (CCR7+, L-selectin+) and effector memory T cells (CCR7-, L-selectin-). Tissue-resident memory T cells (TRM) remain in specific tissues long-term. B Lymphocyte Migration Naive B cells enter lymphoid tissues via HEVs using chemokine receptors (CCR7, CXCR5). CXCL13 guides B cells into follicles. Antibody-secreting plasma cells migrate to bone marrow or mucosal tissues depending on specific chemokine receptor expression. Summary Leukocyte migration involves selectins, integrins, and chemokines. Selectins mediate initial rolling; integrins mediate stable arrest; chemokines guide migration. Naive lymphocytes circulate between blood and lymphoid tissues, while effector and memory cells migrate to infection sites. Migration patterns are regulated by adhesion molecules, chemokine receptors, and tissue-specific signals. Thank You, Illustration depicting leukocyte-endothelial interactions. It shows leukocyte rolling, stable arrest, and transmigration into tissues. The diagram includes representations of selectin and integrin interactions. The context involves immune response and inflammation mechanisms