Cytotoxic T Cell Mediated Type Iv Dth Gpp 32

Front 1

distinguish classical DTH from cytotoxic T cell mediated DTH

Back 1

classical CD4+ Th1 cells; macropahges recruited to destroty antigen
cytotoxic T cell mediated: CD8+ cytotoxic T lymphocytes kill antigen directly

Front 2

5 major steps of cytotoxic T cell lymphocyte killing

Back 2

antigen recognition
increased adhesion between CTL & target cell
lethal hit to target cell
recycling of CTL
death of target cell

Front 3

recognition of target cell

Back 3

T cell receptor in context with MHC-I moleule recognizes antigen on cell surface

Front 4

adhesion between CTL and target cell

Back 4

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

Front 5

ICAM-1

Back 5

on target cell
binds LFA-1 on CTL in adhesion

Front 6

LFA-1

Back 6

on CTL
binds ICAM-1 on target cell in adhesion

Front 7

CD-2

Back 7

on CTL
binds LFA-3 on target cell in adhesion

Front 8

LFA-3

Back 8

on target cell
binds CD-2 in adhesion

Front 9

2 possibilities for the lethal hit

Back 9

Fas-Fas ligand
CTL excretes proteins via exocytosis

Front 10

4 proteins excreted by CTL in lethal exocytosis

Back 10

perforin; granzyme A & B; granulysin

Front 11

what triggers the Fas-associated death domain?

Back 11

accumulation of Fas molecules on target cell surface; Fas binds to Fas ligand on CTL
[lethal hit]

Front 12

what is the immediate result of the Fas-associated death domain?

Back 12

activation of caspase-8
[lethal hit]

Front 13

caspase-8

Back 13

activation of caspase-8 by the Fas-associated death domain leads to apoptosis
[lethal hit]

Front 14

what is an important component of apoptosis in the lethal hit?

Back 14

fragmentation of DNA, both of the host/target cell and of the virus

Front 15

IFN-gamma and -alpha

Back 15

produced by the CTL in lethal hit phase; also interferes with virus

Front 16

exocytosis of proteins from CTL: main points

Back 16

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

Front 17

perforin

Back 17

creates pore in target cell during exocytosis of proteins from CTL / lethal hit phase

Front 18

granzyme B

Back 18

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

Front 19

cytochrome C

Back 19

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

Front 20

granzyme A

Back 20

localizes to SET complex in ER during protein exocytosis phase of lethal hit
SET complex contains molecules that cause DNA breaks

Front 21

SET complex

Back 21

acted on by granzyme A during protein exocytosis phase of lethal hit
contains molecules that cause DNA breaks

Front 22

NM23H1

Back 22

SET complex endonuclease that causes single-stranded DNA breaks

Front 23

ss DNA breaks

Back 23

NM23H1

Front 24

ds DNA breaks

Back 24

TREK-1

Front 25

TREK-1

Back 25

SET complex exonuclease that converts ss DNA breaks to ds breaks, causing DNA fragmentation of both host cell and virus

Front 26

granulysin

Back 26

protein exocytosed from CTL during lethal hit phase
2 forms - the smaller one punches holes in mammalian, fungal, and bacterial cells, releasing AIF

Front 27

AIF

Back 27

apoptosis-inducing factor released by granulysin during lethal hit phase
moves from mitochondria into nucleus to cause nuclear condensation and fragmentation

Front 28

nuclear condensation and fragmentation

Back 28

caused by AIF, which is released by granulysin

Front 29

CTL recycling

Back 29

after killing 1 target cell, CTL detaches and moves on to other target cells, w/o decrease in killing efficiency

Front 30

exquisite specificity

Back 30

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