Assignment 6 Flashcards
what do NK cell arise from
bone marrow precursors (lymphoid progenitor cells)
where are NK cells found
blood, spleen, peritoneal exudate
role of NK during a CD4+ Thp cell activation
NK cell which is activated by IL-12 secretes IFNγ which influences the Th0 differentiation primarily to a Th1 subset
role of NK cells in viral infection and cancer
kill autologous cells that are virally infected or infected with cancer by releasing its granules perforin and granzyme and escaping the region so as not to be affected by the toxic effects of the released granules
what cytokine is released when NK cells are stimulated with IL-12
IFNγ
role of IL-15, and IL-18 when NK cells are stimulated with IL- 12
they enhance IFNγ induced by IL-12
source of IL-12, IL-15, IL-18
dendritic cells and macrophages
role that interferon gamma (IFNγ) plays in the differentiation of Th0 cells to CD4+ T cells
it influences Th0 differentiation primarily to a Th1 subset
how are lymphokine activated killer (LAK) cells generated and what is its unique property
in the presence of high concentration IL-2, NK cells differentiate to LAK cells which are potent killers of tumor cells
NK cells express activating and inhibitory receptors that interact DIRECTLY with ligands on the target cell. What are the three classes of ligands for these receptors?
specific self - Class I MHC
MHC Class-I like molecules
molecules unrelated to MHC
“stress- induced” ligand that allows NK cells to destroy target despite normal expression of Class I MHC
MICA (MHC Class I chain related gene A)
three conditions in which MICA is upregulated
on virally infected cells, cancer cells,
Stress :)
three conditions in which Class I MHC decreases on target cell
stress, some viral infections, some tumors
two cytokines whose interaction with target cells leads to upregulation of Class I MHC
IFNγ (Type 2 interferon) or IFNα/β (Type 1 interferons)
source of IFNγ, IFNα, IFNβ
IFNγ - CD4+ Th1 cells, NK cells
IFNα - virally infected leukocytes
IFNβ - virally infected fibroblasts
how does the balance of activating and inhibitory receptors on the NK cell determines the fate of the target cell
if the inhibitory receptor on NK cells is strong enough, the cell expressing Class I MHC is protected and the cell tolerance is maintained
if the activating receptor on NK cells is stronger, the cell will not be protected and will be destroyed
why does NK cells not destroy host cells in the absence of infection or tumors
infections and tumors decrease the amount of self Class I MHC-self peptide expression which makes it impossible for NK inhibitory receptors to deliver inhibitory signals because of insufficient self Class I MHC-self peptide so activating receptor takes over and cell is destroyed
without infection and tumors, there is a sufficient amount of self Class I MHC-self peptide so inhibitory receptor can deliver its signal hence protecting the cell
two molecules that are released from the granules extruded by NK cells (NK cell armamentarium)
granzymes
perforin
immune processes that led to the binding of Fcγ to the target cell
it recognizes Fc region of antibodies so if there is an antibody present on a target cell then Fcγ will bind to it
how are target cells killed when Fcγ binds to it
there is a release of perforin and granzymes which destroys the target cell
why are NK cell not destroyed itself in the process of killing a target cell
granules polarize to the conjugation region and is released in a way that allows the NK cells to escape the harmful effects of granzymes and perforin
why is the Fcγ-FcγR mode of recognition for target cell destruction referred to as “antibody-dependent cell mediated toxicity” (ADCC)
because different antibodies recognize different viral proteins embedded in the cell membrane of the infected cell and then kill the infected cell
