CD8+ T cells Flashcards
What is cytotoxicity?
CD8+ CTL recognising and destroying a target
Steps of cytotoxicity
TCR/CD8 interactions with MHC class I/peptide
Target cell is programmed to enter apoptosis
Only kills target cell but can then keep moving on to more
What does it mean for the CD8+ CTL to be antigen specific?
Recognises and kills infected cells but not uninfected neighbours
What is the function of effector molecules in CD8+ granules?
To mediate the killing; the stimulate the target to begin apoptosis
What effector molecules are contained in CD8+ granules?
Granzymes
Granulysin
Perforin
What mediates the detection of the apoptosis trigger?
Bcl-2 family of proteins
What does the induction of apoptosis lead to?
The release of cytochrome c from mitochondria, which is then responsible for activation of other effector proteins -> leads to the release of CAD (caspase-activated DNase)
What causes cytochrome c to be released from mitochondria?
Stimuli (eg CD8+ t cell interaction) detected by sentinel proteins, which either activate executioners or block the protectors that would usually inhibit executioners. Executioners bind to mitochondrial membranes, leading to the release of cytochrome c and subsequent cell death.
Immunological synapse
Formed when CD8+ cell attaches to target cell and there is specific recognition between TCR and MHC complex. Granules contained within the CD8+ t cell are released at the synapse, leading to the killing of the target cell
Perforin
aids in delivering granule contents to target cell cytoplasm
granzymes
serine proteases that activate apoptosis once in the target cell cytoplams
granulysin
has antimicrobial actions and can induce apoptosis
Intrinsic (mitochondrial) apoptosis pathway
1) engagement of CR by MHC/peptide complex causes release of granules
2) granzyme b is deilvered to cytosol of infected cell via pores formed by perforin and targets BID and pro-caspase 3
3) truncated BID disrupts mitochondrial outer membrane and activated caspase-activated DNase
4) Release of cytochrome c into cytosol activates apoptosis, and CAD indices DNA fragmentation
Extrinsic apoptosis pathway
1)Trimeric Fas ligand binds to and trimerises Fas
2) Clustering of the death domains in the Fas cytoplasmic domain allows Fas to recruit FADD via its death domain
3) The clustered death effector domains (DEDs) of FADD recruit pro-caspase 8 via similar DEDs in the pro-caspase
[perforin-independent killing]
T-lymphocytes with different TCRs
alpha beta T cell
gamma delta T cell
Invariant T cell subsets
iNKT - invariant NKT cells
MAIT - mucosal associated invariant T cells
gamma delta T cells
About five percent of t cells express the gamma delta TCR
Not restricted by MHC class I or II
Recognise whole antigen instead of peptides
Mainly present in epithelial tissues
Difference between classical t cell and invariant t cells
Same V(D)J segments but invariants have less diversity in the J region
iNKTs
Type pf innate-like lymphocyte that carry a TCR with limited diversity
Recognise micrpbial glycolipid antigens presented by CD1d, and MHC-like molecule
Produce Th1 and Th2 cytokines
Relatively low in numbers but are all the same
MAIT
Primarily alpha beta t cells with limited diversity
Part of the mucosal system
Respond to bacterially-derived folate derivatives
Abundant in humans
