NK cells Flashcards
Describe NK cells.
Small cell- looks a bit like a lymphocyte.
Contains granules which contain killing machinery of cell. When these become activated by IL-2, they become large granular lymphocytes.
NK cells are very abundant cells in the blood, making up around 15% of leukocytes
They express specific markers such as CD56 and NKRP46 that distinguish them from other leukocytes
Use patients own NK cells to cure cancer tumour- could have toxic side effects.
Abundant in blood.
CD56 unique to NK cells.
NKR- activating receptor, unique.
Where are NK cell derived from?
What are some similarities and differences to T cells?
NK cells are lymphoid cells derived from bone marrow progenitors. In adult, all lymphoid cells are derived from bone marrow.
Similar to CD8+ T lymphocytes, NK cells can be activated with IL-2 to develop into potent killer cells. NK T cells have T cell receptor, NK cells don’t. Otherwise, have many features in common.
What are some key features of NK cell recognition?
Natural killer (NK) cells are part of the innate immune system. They make up 5–15 % of peripheral blood leukocytes and a greater percent of resident leukocytes in certain tissues such as the liver.
Unlike B and T lymphocytes, NK cells do not express somatically rearranged receptors, but rather possess a variety of germline-encoded receptors.
NK cells are capable of recognising cells that are transformed or infected with pathogens and kill these cells via the release of cytotoxic granules or through death receptors.
Consequently, NK cells have been studied as potential tools for immunotherapy, especially in the treatment of leukemia.
Make a rapid response to pathogens/infection/damage.
Rearranged receptors- undergo gene rearrangement for maturation (immunoglobulins in B cells, T cell receptors in T cells).
Transformed cell- cancer.
What do NK cells do and how are they controlled?
NK cells secrete cytokines such as IFN-gamma, which is pivotal in fighting infection and in shaping the developing immune response .
NK cell activity is controlled by signals derived from activating and inhibitory receptors.
In general, activating receptors recruit kinases through associated immunoreceptor tyrosine-based activating motif (ITAM)-containing proteins whereas the inhibitory receptors recruit phosphatases through the immunoreceptor tyrosine-based inhibitory motifs (ITIMs) located in their long cytoplasmic tails.
Gamma- important for activating macrophages.
Signals- get both, but the more dominant one wins. Inhibitory is usually the more dominant one.
ITAM- Recruit kinases that can activate T and B cells through phosphorylation.
ITIMS- recruit phosphatatses, allows for inhibition and control through dephosphorylation.
What is the “missing-self hypothesis”?
Integration of all the inhibitory and activating signals determines whether the NK cells will kill or spare the target cells.
The inhibitory receptors mostly interact with major histocompatibility complex (MHC) class I ligands that normally present peptide antigens to CD8+ cytotoxic T cells
Thus, cells evading recognition by CD8+ T cells through down-regulation of MHC class I proteins might become susceptible to NK cell-induced cytolysis.
(MHC 1 expressed on every cell except RBCs- present peptides derived from antigens to cytotoxic T cells.
Switch off MHC 1, lose T cell detection, NK cells are secondary defence that can be activated.)
What does “ missing self” do?
Loss of MHC I removes the inhibitory signals provided by inhibitory receptors known as KIRs (killer inhibitory receptors) on NK cells, this allows NK cells to detect and eliminate infected or transformed cells that express one or ore ligands for activating NK cell receptors. NK cells can kill target cells.
Pathogen can learn to downregulate MHC1- MHC normally inhibits NK cells, without MHC, NK cells are not inhibited.
