Natural Born Killers: NK cells and CD8+ T lymphocytes Flashcards
Which part of immune response does NK cells fit under and why?
Innate (non-specific immediate response) and adaptive (cells are lymphocytes - where B and T cells also start off)
What is the origin of NK and T cells?
Common lymphoid progenitor
- lymphocyte lineage
What is the innate lymphoid cell?
NK cells
What is the role of cytotoxic lymphocytes?
Destroy cell infected with bacteria,virus, parasites
Destroy tumour cells
- anything considered non-self
How do cytotoxic lymphocyte know to kill tumour cells?
They become non self and lymphocytes are able to detect self cell.
What is CTL?
Cytotoxic T lymphocyte
List a few cytotoxic T cells
CD* T cells
CTL - cytotoxic T lymphocyte
Which immune response are cytotoxic T cells involved in?
Adaptive immunity
What are the similarities between NK cells and cytotoxic T cells?
Kill virally infected cells and tumour cells
What is the main difference between NK cells and cytotoxic T cells?
No specific, doesnt recongise one specific antigen like T cells
Controlled by a blaance of activating and inhibitory receptor signals on NK surface
What determines whether an Nk cell will kill or not?
Dont kill if inhibitory signal from inhibitory receptors and kill if balance more towards activating receptors
Why do we need NK to be cytotoxic cells when there are cytotoxic T cells already present? - multiple reasons
1) Combat infection until T cell response develops (innate whilst adaptive develops)
2) Some tumour cells/infected cells evade cytotoxic t cells
3) Additional mechanism for killing infected targets by interacting with antibodies (are able to interact with antibodies)
What might happen if there is a deficiency of Nk cells
Infections end up being more severe e.g chickenpox normally not awful, ends up severe without NK cells
What do MHC class 1 proteins present?
Proteins expressed within the cell whether theyre normal, mutated or viral proteins
What is the mechanism for processing and presenting antigens on MHC class 1?
1) Protein (healthy, mutated or viral) enter proteosome forming proteosome complex
2) Proteosome breaks down protein into smaller fragments
3) Peptide fragments enter ER where it binds to MHC class 1.
4) Complex moves towards membrane via secretory pathway and displayed on surface
Where si the humna MHC gene complex located?
Chromosome 6
How are the 2 polypeptides in MHC class 1 bound together?
Non-covalently
Where are MHc class 1 molecules found?
On all nucleated cells
What is the structure of an MHC class 1 proteins?
2 alpha helices where peptide binds beta 2 microglobulin forms lover structure of mHC class 1 protein to act as support for peptide binding groove
How many genes are there for MHC molecules
3 for MHC class 1 and 3 for MHC class 2 on each chromsome for 6 each and each gene is polymorphic (many variants)
Why is MHC variability important against pathogen mutations?
range of MHC can be produced similair
Which part of the MHc is polymorphic?
Amino acids in the Peptide binding groove region
What features of peptide binding groove affects which peptide will fit?
Size, shape and charge of pockets in the groove (larger peptides fit in large pockets etc…)
Which part of the binding groove do peptides bind in on MHc molecules? and why?
in the pockets created by amino acids to anchor in the peptide
What do T cell receptors recongise?
Antigen presented on MHC protein
MHC protein itself - reason transplants reject in people with diff MHC
How do T cell receptor binds to MHC’?
diagonally to recongise both MHC (across both alpha helices) and the peptide
Why is CD8 able to bind to TCR at same time to the MHC-1?
Binding sites are distant - far from eachother)
Why must both CD8 and TCR bind to MHC-1?
co-stimulation signal (using co-receptor) needed for effective response
Where does TCR bind on the MHC?
alpha 1 and alpha 2 domains
Where does the CD8 bind on thr MHc-1?
a3 and b2m (the conserved lower region)
How do different viruses affect MHC-1 presentation
Inhibit MHC-1 transcription - adenovirus Block peptide transport to ER - HSV Keep MHC -1 in ER - adenocirus and HCMV Taret MHC-1 for disposal Donwregulate MHC-1 from cell surface - HIV
How does body combat issue if pathogen prevents presentationn of MHC-1?
NK cells work since cytotoxic T cell response is evaded since lack of / low levels of MHC-1 detected, NK cells kill those cells
How is a lack of MHC-1 detected?
MHC-1 present on all nucleated cells so KIR (killer Ig like receptor) detects lack off
What do KIR do when MHC-1 are present?
Prevent NK cells from releasing lytic granules by releasing inhibitory signal
Why do viruses donwregulate MHC-1?
To evade cytotoxic T cell response
What happens when KIR doesn’t detect MHC-1?
No KIR inhbition (lack of inhibitory signal) so Nk cells release lytic granules lysing target
Where does KIR bind on MHC-1?
Same binding groove as TCR but on the side (TCR binds diagonally across leaving some space for KIR)
How can KIR show which disease you have?
KIR is polymorphic ad different combinations of KIr with MHC-1 shows disease association e.g. HIV. Diff KIR target diff MHC-1 alleles
How do NK cells know there is a KIR attached?
Many diff KIR receptors on NK cells (since KIR is polymorphic) which it attached to
What type of receptor is KIR for NK cells?
Inhibitory receptor
What are the acivating receptors on NK cells?
Natural cytotoxicity receptors
What do activating receptors on NK cells detect?
Certain ligands e.g. viral haemogluttin, stress induced protein etc..
What do activating signals do to NK cells?
Deliver signal to NK cells to kill cell
Is there lysis of cell where KIR attaches to MHC-1?
If there are also activating signal present yes but if there are more KIR caused inhibitory signals to NK cells than activating signals, the cell is not lysed
How do Nk cells kill tumour cells?
Tumour cells downregulate MHC-1 to escape cytotoxic T cell response so more susceptible to Nk cells (lack of inhibitory signal from KIR), no inhibition = NK cells kill target cell
What is ADCC?
antibody dependent cell mediate cytotoxicity
How does ADCC result in lysis of cell?
Nk cells expess receptor that recognises Fc portion of antibodies 9the anitbody interaciton mentioned earlier)
This receptors delivers activating signal if bound to antibodies on cell surface causing lysis of target cell
