Natural killer cells - Block C lecture one Flashcards
(41 cards)
where do NK cells develop ?
They do not develop in the thymus - development starts in Bone marrow and then continues in secondary lymphoid organs e.g. Lymph nodes and tonsils
What cytokines and markers are required for NK development ?
IL-15 from Antigen Presenting Cells such as dendritic cells and CD56 marker are required for development
what are the ligands for NK cells ?
MHC class I/MHC class I-like molecules restricted
is recognition reliant on specific antigen receptor and do they require RAG1 and RAG 2 ?
Recognition is not reliant on specific antigen receptor. They do not have rearrangement of their receptor genes; this is proved because if RAG1 and RAG2 are knocked out in mice there is still NK cells produced
CD3 expressed on NK cells?
no
CD56 ?
yes , CD56+ is expressed isoform neural adhesion factor)
NKp46+
natural cytotoxicity factor, not specific to NK cells) - but no simple marker
are the markers on the NK cell specific to it ?
The markers on the NK cell are not specific to just it , they are also found on other immune cells.
role of IL-21 in development of NK cells ?
IL-21 cytokine induces maturation of human CD34+ cells (stem cells) into NK cells and they become different populations.
CD56 dimCD16+ cell subset ?
CD56dimCD16+ cell subset that represents the majority of NK cells - 90% of blood is NK cells
where are CD56 bright cells found ?
in the secondary lymphoid tissue/tissue cells
if the NK has a high level of granzymes what would this indicate ?
If the granzymes are high then this could be an effector cell.
what are the INK ?
the receptors on the surface of the NK cells
what are the 2 main roles of NK cell ?
secrete cytokines/chemokines and influence immune response main cytokines produced are tumour necrosis factor-α (TNF-α) and interferon γ (IFN-γ)
Kill infected/transformed cells activity very like Tc BUT:
•cytoplasm has granules in it – constitutively expressed whereas Tc cells ( cytotoxic T cells) need to be stimulated before they produce granules. The NK cells are always ready for attack.
how do the NK cells detect the infected cells ?
Interact with infected (virus)/malignant (cancer) cells which have reduced expression of MHC class I molecules which markers it for killing. However, human NK cells can also kill dendritic cells (DC) by apoptosis which express normal amounts of HLA molecules.
can NK cells bind to a pathogen and kill it directly ?
Can only kill your own cells NOT a pathogen by direct contact. They cannot bind to the pathogen like a bacteria cell , they bind to your own cells that are infected with the pathogen.
how do NK cells become activated ?
‘opposing signal’ is the method of activation
positive and negative regulators and the balance of stimulation of activation receptors and inhibitory receptors determines whether they are activated
So you have some ligands/receptors/ things on the surface that can attach to something that will activate it, and some things where a ligand engages with it inhibits it and switches off.
There’s inhibitory and activating receptors , which are signalling inside the cell and this balances decides whether a cell is activated , and can induce apoptosis in infected cells and produce cytokines and chemokines.
think of a tug of war contest
if there are 2 inhibitory interactions and only one activating what occurs ?
there is no activation.
if the cell interaction has no MHC and a primary activating interaction what occurs ?
loss of MHC molecules in the tumour cell which promotes cell killing and a primary activating interaction so that killing occurs.
what does the activation signalling receptors require ?
activation requires receptors such as Natural cytotoxicity receptors, killer cell immunoglobulin-like receptors (KIR).
inhibitory signalling ?
inhibitory immunoglobulin killer receptors (KIR) important as they recognise class Ia (HLA-A, B, C) ligands and or non-classical class Ib ligands (HLA-E)
cytokines involved in activation ?
cytokines involved are IL-2, IL-12, IL- 15, IL-18, IL-21, IFN a/b - can induce cell proliferation, or NK induced cytotoxicity and/or production of IFN-g.
when are NK cells recruited as part of the response ?
NK cells recruited to tissues during an inflammatory response. The NK cells move up the concentration gradient to the infection site where they are required
what are the 2 types of receptor: inhibitory and activating binding to ?
The 2 types of receptors ( activating and inhibitory) are binding to the ligands on the surface of the target cell. it is the overall balance of the receptors between activating and inhibition which lead to the response. If activating, then in the diagram the granzymes are released which target the cell and apoptosis occurs.
