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PROFESSIONAL ANTIGEN PRESENTING CELLS Express MHC class I and class II molecules Express co-stimulatory molecules (CD40, B7) Take up extracellular antigens B cells – soluble proteins, toxins ADAPTIVE – Ag specific Macrophages – extracellular pathogens (bacteria, yeast) Dendritic cells – viruses, apoptotic cells INNATE THE ROLE OF PROFESSIONAL ANTIGEN PRESENTING CELLS IN THE IMMUNE RESPONSE Gatekeeper function Sensing pathogens Priming adaptive immune responses Maintenance of self tolerance to self structures Infectious diseases Tissue transplantation Elimination of tumors Autoimmune diseases Dendritic cells are sensors, gatekeepers and messengers Activation induces a phenotype essential for the initiation of the adaptive immune response CONTACT OF DENDRITIC CELLS AND T - LYMPHOCYTES IN LYMPHOID ORGANS Activated dendritic cells act as professional antigen presenting cells MHC-peptide complexes Co-stimulatory molecule Cytokines 1. signal STRANGER 2. signal AMPLIFICATION 3. signal DANGER They are in close contact with specific T lymphocytes INTERDIGITATING RETICULAR (MATURE DENDRITIC) CELL IN T CELL AREAS OF LYMPH NODES NUCLEUS T CELL T CELL CYTOPLASM Cell-surface molecules of the immunoglobulin superfamily initiate lymphocyte adhesion to professional antigen-presenting cells B. A. A Initial contact Transient interactions are stabilized by Ag-binding CHANGES OF TISSUE ENVIRONMENT INDUCES THE ACTIVATION OF MACROPHAGES AND DENDRITIC CELLS Phagocytosis and degradation of backteria (LPS, TLR) DANGER SIGNAL Macrophage Monocyte Dendritic cell Activated macrophage Activated dendritic cell Virus, extracellular pathogens, inflammatory cytokines (LPS, TLR) DANGER SIGNAL BLOOD TISSUE LYMPHOID TISSUE ACTIVATION AND MIGRATION OF DENDRITIC CELLS TISSUE LYMPH NODE Lymphatics Activated DC TISSUE Effector and memory T cells Inflammation Pathogen Naive T cells ANTIGEN Tissue DC DC AND T CELLS ENCOUNTER T CELL ACTIVATION CIRCULATION Rapid DC Migration in the Subcapsular Space Bone-marrow derived DCs (either 5 µM CFSE, green) or (50 µM Cell Tracker Blue, blue) were injected into the footpad of a C57BL/6 mouse, followed 18 hours later by intravenous injection of freshly isolated polyclonal CD4+ T cells (5 µM SNARF, red) and CD8+ T cells (5 µM CFSE and 5 µM SNARF, yellow). The draining LN was removed 6 hours after injection Capture of an Ag-Specific T Cell by an Ag-Bearing DC Bone-marrow derived DCs (yellow) were pulsed with 1 µM Ova 4 peptide and 10 µM Ova for 1 hour at 37oC, then injected into the footpad of a C57BL/6 recipient. This was followed 6 hours later by i.v. coinjection of OT-I CD8+ T cells (5 µM CFSE, green) and OT-II CD4+ T cells (5 µM SNARF, red). Huang et al Immunity 2004 Morphology of plasmacytoid dendritic cells IPC/DC2 pDC Scanning EM monocyte Transmission EM Plasmacytoid DCs control the function of many immunocytes HIV infects PDC IFNα is impotant in SLE pathology Role in immune response and in the pathogenesis of autoimmune diseases and cancer PLASMACYTOID DENDRITIC CELLS AS PROFESSIONAL TYPE I INTERFERON SECRETING CELLS TLR4 TRAM TRIF Vírus infection Enhanced NK cell cytotoxic activity TLR7 TLR8 TLR9 TLR3 TRIF MyD88 IRAK-1 TRAF-6 TANK Activation of and γδ T cells RIG-1 IKKε TBK1 IRF-3 IRF-5 IRF-7 IFN-β IFN-α1 Cross-presentation by conventional dendritic cells is enhanced IRF-7 Type I interferon receptor Ig production by B cells is induced Migration Pathways of PDC/IPC versus mDC into a lymph node mDC: afferent lymphatics IPC: HEV Both migrate into the T-cell rich areas
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