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Unformatted text preview: Immunology 16 Immature DCs • Not ready to present Ag yet; tissue resident; specialized to take up Ag • Routes of Ag processing and presentation by DCs: • 1. Receptor mediated phagocytosis; presents extracellular pathogens and loaded onto MHC II • 2. Macropinocytosis; presents extracellular bacteria, soluble Ags, virus particles and loaded onto MHC II (non specific) • 3. Viral infection; virus particles loaded onto MHC I • 4. Cross presentation after phagocytic or macropinocytosis uptake; presents viruses to MHC I; takes in external pathogen and displays it on MHC I; many pathways • Maturation induced through innate recognition of pathogens via PRRs (especially TLRs); TLR recognizes PAMP and DC shuts off mechanism of recognizing pathogens; changes migratory pathways; signalling induces CCR7 and enhances processing of pathogen derived antigens • Ag uptake by Langerhans cells in skin; langerhans cells leave the skin and enter the lymphatic system; mature DCs enter the lymph nodes from infected tissues and can transfer some Ag to resident DCs Lymph Node • T-cell zone in middle; T cells express CCR7 which is attracted to CCL19/21 in T-cell zone • Lymphocytes recruited via HEV • DC ends up in T-cell zone due to expression of CCR7; DCs come through afferent lymphatics • B cells remain in periphery in follicles; express CXCR5 which is attracted to CXCL13 in the follicular zone • In the T cell zone of the secondary lymphoid tissue the naive CD4 T cell can be activated through interactions with mature DC; mature DC relocates to T cell zone and is specialized for Ag presentation to T cells and not Ag uptake • Mature DC’s surface markers change: increase in MHC1/II and B7; CCR7 directs migration into lymphoid tissues and augments expression of costimulatory molecules and MHC molecules APCs • DCs, macrophages and B cells; express MHC I/II and B7; can all activate CD4 T cell • Very specific localization within the lymph node architecture • DCs in T cell zone; macrophages in medullary cords; and B cells in B-cell follicles • DCs predominate in associating with naive T cells; DC and T cells interact in T cell zone by forming long interactions Formation of Immune Synapse • Supramolecular activation complex (SMAC); maintains long term contacts between T cells and targets; APCs or targets as effectors; important for signal integration • 1. LFA1 interacts with ICAM I on APC; tells T cell that there is a APC • 2. binding of TCR signals a conformational change in LFA-1 that increases affinity and prolongs cell-cell contact • SMAC reorganizes so that MHC and TCR are in the middle • 3 signal hypothesis: • 1. TCR-Ag specific activation signal • 2. Co stimulatory signal: CD28 on T cell↔B7; IL-2 induction (inflammatory signal); modifiable by other B7 family members: ICOS↔ICOSL (not B7 family); B7↔CTLA-4; CD40L↔CD40; gives inflammatory signal and gets survival signal • 3. Cytokine signalling: determines the type of response that develops; different cytokines drive effector T cell 3....
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This note was uploaded on 02/08/2012 for the course PATHOLOGY 3245 taught by Professor X during the Spring '11 term at UWO.
- Spring '11