Immunology BE433 Lecture 8: T Cell-Mediated Immunity PDF

Immunology BE433 Dr Christine Loscher Lecture 8 T cell-mediated Immunity Dendritic Cells Bacteria Helminths DC Viruses Yeast T helper cells IL-4 IL-10 Th1 IL-12 Th2 Tr1 IFN-g IL-23 Th17 IL-10, TGF-b IL-17 IL-4 PATHOGEN (in cytosol) DENDRITIC CELL B7 T CELL B7 CD40 CD40 ligand TC...

Immunology BE433 Dr Christine Loscher Lecture 8 T cell-mediated Immunity Dendritic Cells Bacteria Helminths DC Viruses Yeast T helper cells IL-4 IL-10 Th1 IL-12 Th2 Tr1 IFN-g IL-23 Th17 IL-10, TGF-b IL-17 IL-4 PATHOGEN (in cytosol) DENDRITIC CELL B7 T CELL B7 CD40 CD40 ligand TCR MHC1 CD8 Peptides B7 B7 CD28 CTLA-4 CD8 Bacteria, viruses IL-12, IL-27, TNFa, TLR4, TLR5, TLR9, CD80, CCR5 Parasites, yeast IL-4, TLR2, CD86, CCR2 Th1 Th2 IFNg, TNFa IL-4, IL-5, IL-10 Armed effector T cells • Activation requirements for these cells different from naïve T cells • Does not need co-stimulation • When an effector T cell encounters its target cell it results in a response – no co-stim • Particularly important for CD8 cytotoxic T cells • Also important for CD4 as they need to be able to act on macrophages and B cells that have taken up antigen but may not be expressing co-stim molecules • Also change the adhesion molecules they express – increase in LFA-1 and lose their L-selectin • Bind tightly to target cell for long time and release their effector molecules directly to target cell Function of effector T cells • To go to site of infection and locate target cell • To bind target cell and release effector molecules – binding of the TCR focuses the release of effector molecules at site of contact with target cell Cytotoxic CD8 T cells • Induce target cell to undergo programmed cell death – apoptosis – cells are highly selective • Cytotoxic effector proteins contained in the granules of CD8 cells • May also induce apoptosis by Fas ligation • Can also release IFNg which inhibits viral replication and increases MHC1 CD4 Th1 Cells • They target cells infected intracellularly (in vesicles) and so are hidden from effects of antibodies and cytotoxic CD8 T cells • Activate macrophage to become microbicidal • Macrophage require 2 signals which can both be delivered by Th1 cells – IFNg and a sensitising signal eg. CD40 ligand • As CD4 Th1 cells need to synthesise molecules they must adhere to their target cell longer than CD8 cell Activated macrophage • Fuse their lysosomes and phagosomes more efficiently killing ingested pathogens • Make oxygen radicals and nitric oxide which have potent anti-microbial activity • Synthesis antimicrobial peptides and proteases for extracellular pathogen killing • Additional changes help to amplify the immune response – increase in B7, MHC2 and CD40 on their surface make the cell more effective at presenting antigen to fresh T cells • Produce IL-12 (for Th1 cells) • Need tight control on activation as they cause tissue damage