Cytotoxic T cells Flashcards
(35 cards)
What is the markers on cytotoxic T cell ?
Mostly involves CD8+ cells but some CD4+ T cells – most information on CD8+ T cells (Tc)
how are CD4+ T cells activated ?
CD4+ T cells activated in peripheral lymphoid organs by antigen presenting cell - usually a dendritic cell – that is expressing the specific antigen for the T cell receptor . This leads to clonal expansion of the specific T cell and production of memory cells .
what are MHC class II and MHC class I molecules restricted by ?
MHC class II molecules are restricted with CD4+ T cells while MHC class I molecules are restricted with CD8+ T cells.
can cytotoxic T cells directly kill a pthogen and why >
Tc kill other cells and once it killed a cell it can go on to another target cell – cannot directly kill pathogens. This is due to MHC restriction
do they tend to hit the same trget twice ?
nope
what’s the difference in timespan of killing for in vivo and in vitro ?
In vitro study showed it took 45 mins for a target cell to completely disintegrate by apoptosis - in vivo studies suggest its much quicker
activation stages for cytotoxic T cell ?
Recognition of specific Ag using T cell receptor by APC
- Environmental cues important
- cytokines upregulate activity e.g. IL-2, IL-12, IL-15,
- Cytotoxic CD8+ T cells have their activity upregulated by a range of cytokines e.g. IL-2, IL-12, IL-15, IL-18, IL-23, IL-27 – leading to more cells producing their effectors molecules/increase in amount or effector molecule produced/cell
- So innate responses can provide the environment for developing specific immune response
- In comparison to NK cells , Tc killing involves granules which are induced AFTER stimulation or direct death signal
on a stidy comparing the activity of cytotoxic T cell against influenza A , what did the activity depend on ?
Studies comparing the activity of cytotoxic T cells against influenza A virus showed that activity
i) depends on the epitope recognised by T cell (i.e. specificity)
ii) reaction depends on the person used to isolate the cells CD8+ T cells , this involves MHC molecules
what did the low affinty Fc receptors on self specific CD8+ T cells find?
low affinity Fc receptor on self-specific CD8+ T cell found they acted as a receptor for antibody-mediated cytotoxicity. Antibody acts as an opsonin.
they also found that receptor such as NKG2 , CD244 and CD94 where upregulated what did this reveal ?
Upregulated receptors for other molecules – NKG2D, CD244, CD94 these could have a role in stimulation and killing by Tc.
what did upregulatiion of receptors IL-12 and IL-18 reveal ?
receptors for IL-12 and IL-18 up regulated on effector and memory cells. Therefore, products of innate immune cells influence specific response
soluble effectors released from CD8+?
cytotoxins such as perforin and granzymes , mediators were IFN gamma and TNF alpha
membrane bound effectors for CD8+ T cells ?
Fas ligand
Th1 soluble effectors ?
IL-2 , IL-3 , TNF alpha , IFN gamma and GM-CSF
membrane bound effectors for Th1 >
FasL on activation , antigen specific and TNF beta
TH2 Soluble effectors /
IL-3 , 4 , 5,6, 10 , 13 GM-CSF
membrane bound effectors Th2 ?
FasL low
how come cytoxic T cells are serial killers ?
need conjugation ( close contact) between cytotoxic T lymphoctye (CTL) and target cell – called an immunological synapse.
Can kill infected cell but not a pathogen directly since it will NOT express MHC molecules)
kill the cell target directly by granules/perforin induce apoptosis in target cell
Kill a cell indirectly by cytokines they produce which are directly toxic (TNF-a) – or induce toxic reactions (IFN-gamma) which induces phagocytosis.
what does the production of TNF and IFN beta have on the target cell >
Produced TNF and IFN gamma which can act on TNF receptor and IFN receptor on target cell.
what occurs at the immunological synapse ?
If there’s an interaction between CTL and target through the receptors then at the immunological synapse granzymes are released which enter the target cell and induce apoptosis
death signal ?
Another way that apoptosis is initiated in the target cell is through the death signal that is induced via the Fas-L ligand of the Tc and the CD95 of the target cell and caspases are activated and apoptosis is initiated.
differences between cytotoxic T cells and Nk cells ?
Know that NK are innate – they have no immunological memory
Know that activation is different for the two cell types – NK cells - balance between activation/inhibition important – Tc cells recognition via T cell receptor
Know that Tc produce granules on stimulation whereas NK constitutively have granules present
Perforin role ?
Form pores for granules to enter target cell
- Granules taken up in endosomes and perforin allows release into cytosol to induce apoptosis?
- Perforin essential for granule mediate cytotoxicity (KO knock out gene sequence for perforin studies) and ability to control tumours and infections lost in KO studies.
- lots of different granzymes e.g. humans have four – B, A, K and M and mice have 10
- B and A most abundant in humans and B major constituent
overview of granzymes B ?
Overview of Granzyme B suggests that perforin forms a pore which allows granzyme to enter the target cell. The granzyme then has various effects on the signalling pathways within the target cell , it activates caspase 3 and 7 which activates a caspase cascade and results in substrate proteolysis and cell death.
The granzyme can have more than one effect within a cell , it can also act on BID in a golgi and this activates cells which are pro apoptotic and cause an apoptosome to form which results in apoptosis.
Multiple pathways are available for apoptosis , so that if a pathogen develops the ability to block a pathway there are other ways to induce apoptosis.
