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30 Cards in this Set
- Front
- Back
distinguish classical DTH from cytotoxic T cell mediated DTH
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classical CD4+ Th1 cells; macropahges recruited to destroty antigen
cytotoxic T cell mediated: CD8+ cytotoxic T lymphocytes kill antigen directly |
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5 major steps of cytotoxic T cell lymphocyte killing
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antigen recognition
increased adhesion between CTL & target cell lethal hit to target cell recycling of CTL death of target cell |
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recognition of target cell
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T cell receptor in context with MHC-I moleule recognizes antigen on cell surface
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adhesion between CTL and target cell
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CTL has surface molecules LFA-1 and CD-2
target cell has ICAM-1 and LFA-3 LFA-1 binds ICAM-1 CD-2 binds LFA-3 |
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ICAM-1
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on target cell
binds LFA-1 on CTL in adhesion |
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LFA-1
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on CTL
binds ICAM-1 on target cell in adhesion |
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CD-2
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on CTL
binds LFA-3 on target cell in adhesion |
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LFA-3
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on target cell
binds CD-2 in adhesion |
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2 possibilities for the lethal hit
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Fas-Fas ligand
CTL excretes proteins via exocytosis |
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4 proteins excreted by CTL in lethal exocytosis
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perforin; granzyme A & B; granulysin
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what triggers the Fas-associated death domain?
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accumulation of Fas molecules on target cell surface; Fas binds to Fas ligand on CTL
[lethal hit] |
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what is the immediate result of the Fas-associated death domain?
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activation of caspase-8
[lethal hit] |
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caspase-8
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activation of caspase-8 by the Fas-associated death domain leads to apoptosis
[lethal hit] |
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what is an important component of apoptosis in the lethal hit?
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fragmentation of DNA, both of the host/target cell and of the virus
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IFN-gamma and -alpha
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produced by the CTL in lethal hit phase; also interferes with virus
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exocytosis of proteins from CTL: main points
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during lethal hit phase, protein-containing vacules are focused to site on interaction between CTL and target cell
adhesion molecules form a ring so that there is a high concentration of secreted proteins in the area of interaction perforin creates a pore in the target cell so other proteins can enter |
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perforin
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creates pore in target cell during exocytosis of proteins from CTL / lethal hit phase
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granzyme B
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acts on mitochondria by acting on BID in cytoplasm
BID associates with another molecule to create a channel through with cytochrome C can leak out of mitochondria and cause apoptosis |
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cytochrome C
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leaks out of mitochondria, leading to apoptosis
first granzyme B must activate BID in cytoplasm; BID then interacts with another molecule to create a channel for cytochrome C leak |
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granzyme A
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localizes to SET complex in ER during protein exocytosis phase of lethal hit
SET complex contains molecules that cause DNA breaks |
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SET complex
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acted on by granzyme A during protein exocytosis phase of lethal hit
contains molecules that cause DNA breaks |
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NM23H1
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SET complex endonuclease that causes single-stranded DNA breaks
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ss DNA breaks
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NM23H1
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ds DNA breaks
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TREK-1
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TREK-1
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SET complex exonuclease that converts ss DNA breaks to ds breaks, causing DNA fragmentation of both host cell and virus
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granulysin
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protein exocytosed from CTL during lethal hit phase
2 forms - the smaller one punches holes in mammalian, fungal, and bacterial cells, releasing AIF |
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AIF
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apoptosis-inducing factor released by granulysin during lethal hit phase
moves from mitochondria into nucleus to cause nuclear condensation and fragmentation |
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nuclear condensation and fragmentation
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caused by AIF, which is released by granulysin
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CTL recycling
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after killing 1 target cell, CTL detaches and moves on to other target cells, w/o decrease in killing efficiency
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exquisite specificity
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CTL kills only cells that express antigen, in contrast to to poor sensitivity of classical DTH, in which both target cells and surrounding normal tissue are destroyed by macrophages
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