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Langerhans’ cells can take up antigen in the skin and migrate to lymphoid organs where they present it to T cells Homing to PLN CD62L ChR LFA-1 Naïve Lymphocyte PMN Memory Lymphocyte B cell trafficking B cell B BCR Antibodies L-selectin/CLA/α4β7 SLC/TARK/TECK ICAM-1 CCR4/CCR7/CCR9 LFA-1 (low affinity) LFA-1 (high affinity) HEV Rolling Activation Activationthrough dependent Diapedesis G-proteinarrest linked receptors Site of interaction Cell type Interactions Blood HEV Rolling Activation Movement within Diapedesis the organ Arrest Naïve CD62L- CCR7- LFA-1- CCR-7- CXCR5Peripheral T cells PNAd SLC ICAM-1 MIP-3β? BLC lymph CCR7node MIP-3β Naïve CD62L- BCA-1 LFA-1- CCR7- CXCR5B cells PNAd CXCR5 ICAM-1 MIP-3β? BLC The specialized regions of lymphoid tissue provide and environment where antigen-specific B cells can interact with armed helper T cells specific for the same antigen. The affinity as well as the amount of antibody increases with repeated immunization Architecture of Follicle B220 B cells CD23 FDC Germinal centers Light zone centrocytes FDC Dark zone centroblasts TH cells B cells recognize antigen as immune complexes bound to the surface of follicular dendritic cells. Germinal center CXCR5 CXCL13 CXCR5 B cell ICOSL CD40 TH cell ICOS CD40L CXCR5 is required for T cell follicular homing CXCR5 and CXCL13 function in determining light zone position CXCR4 deficiency results in GC disorganization Multiple modes for the encounter of follicular B cells with antigen Cyster, J. Nat. Immunol. 2010 Multiple cues direct B cell migration through the LN follicle Cyster, J. Nat. Immunol. 2010 Deposition of Ag-Ig (PE-IC) complexes occurs in distinct phases B cells “screen” antigen trapped on cells in SCS of LN Inflammation Expression pattern of naïve and activated lymphocytes CD4 CD62L VLA-4 LFA-1 CD2 + + CD4 TCR CD44 CD45 CD45 RA RO N + - + + + + - A - + ++ ++ + + ++ - + „Inflamed endothelium” E-selectin P-selectin Chemokine ICAM-1 VCAM-1 Endothelium Inflammation Armed effector T cells change their surface molecules so that they can home to sites of infection via the blood. Selectin Ligands Leukocytes Endothelium Phagocytic leukocytes are directed to sites of infection through interactions between adhesion molecules induced by cytokines.