Natural Born Killers: NK Cells And CD8+ T Lymphocytes Flashcards
What are cytotoxic T cells controlled by?
T cell receptor recognition with CD8 acting as a coreceptor
Which immune response are cytotoxic T cells involved in?
Adaptive immune response
Which immune response are natural killer cells involved in?
Innate immune response
What are NK cells controlled by?
A balance of signals between different activating and inhibitory receptors on their surface
Which of NK cells and cytotoxic T cells are more specific?
Cytotoxic T cells
Why do we need more that one type of cytotoxic lymphocyte?
Combat infection in the time before a T cell response develops
Provide an alternative system when a tumour or infected cell evades cytotoxic T cell responses
To provide an additional mechanism for killing infected targets via antibody recognition
What is low NK cell activity correlated with?
Severe disseminating herpesvirus infections
Where are MHC class 1s found?
All uncleared cells
What are MHC class 1s made up of?
Two polypeptides that are non-covalently bound
What are the three gene loci for HLAs?
A, B and C
Where are MHC polymorphisms found?
In the upper peptide-binding part of the MHC protein
What do TCRs recognise?
MHC protein itself
Antigenic peptide presented by MHC protein
What allows CD8 and TCR to bind to MHC-1 at the same time?
Distant binding sites
What does CD8 act as for MHC-1?
Coreceptor
What does TCR bind to (specifically)?
Alpha1alpha2 domains
What does CD8 bind to?
Support domains- alpha3 and beta2
Where does inhibitory KIR bind?
Same face of MHC-1 as the T cell receptor
What does KIR do?
Recognise subsets of the MHC-1 alleles
What do different MHC-1/KIR combinations show?
Disease associations (eg in HIV)
What does KIR stand for?
Killer Ig-like receptors
What happens when KIR recognise MHC-1s?
Inhibit NK cells from releasing lytic granules
What happens if a target cell does not express MHC-1?
No KIR inhibition
Lytic granules will be released to lyse the target
What do natural cytotoxicity receptors do?
Provide activating signals to NK cells
What does target cell death/survival depend on?
Balance of activating and inhibitory signals
How does antibody dependant cell mediated cytotoxicity work?
NK cells express a receptor that recognises the Fc portion of antibodies
Strong activating signal when it recognises antibodies bound to a cell surface
Target cell lysis
What are the two mechanisms of lysis?
Cytotoxic granules
Fas/FasL interaction
What does perforin do?
Aids in delivering contents of granules into the target cell cytoplasm
What are some examples of cytotoxic granules?
Perforin
Granzyme
Granulysin
What does granzyme do?
Serine proteases which activate apoptosis once in the cytoplasm of the target cell
What does Granulysin do?
Antimicrobial actions and can induce apoptosis
How does Fas/FasL work?
FasL triggers apoptotic pathways in target cells
Where is FasL found?
T cells
What does loss of Fas result in?
Autoimmune lymphoproliferative syndrome
What is Fas/FasL triggered apoptosis used to do?
Dispose of unwanted lymphocytes
Where do T cell receptors and co-receptors cluster?
At the site of cell-cell contact
What does the immunological synapse do?
Polarises the T cell to release effector molecules at the point of contact
