==NK cells Characteristics==
made in bone marrow from common lymphoid progenitor
circulate blood and move into tissue during inflammation
larger than other lymphocytes (B and T cells)
contains granules like T cells
mechanism of killing is like CTL → release proteins from granules which enter target cell and signal it for apoptosis
known to kill certain tumor cells and are important in immunity to intracellular pathogens including viruses
==NK cells Activation==
Interferon:
@@type I interferon@@ = IFNα and IFNβ = produced by cells in response to viral infection
@@type II interferon@@ = IFNγ → doesn’t activate NK cells
dsRNA binds to TLR-3 = makes IFNα and IFNβ
all secreted by infected cell
Functions of interferons:
type I interferons binds to interferon receptor on infected cell & neighboring cell = anti-viral state
(look at slide 4)
Activation of NK cells:
binding of type I interferons to interferon receptors on NK cells stimulates increased expression of IL-12 receptors
^^IL-12^^
produced by macrophage during infection
activates NK cells, stimulating production of IFNγ
effects of IL-12 are increased when NK cells are exposed to TNFα, or IL-18, or IL-1β at the same time as IL-12
these cytokines are activated by macrophages
^^IL-15^^
NK cell growth factor
produced by macrophages during infection
knockout mice that cannot make IL-15 or its receptor produce very few NK cells
^^IL-2^^
high concentrations of IL-2 increase the killing ability of NK cells
produced by T helper cells
==Functions of NK cells==
@@1.) Production of cytokines@@
activated NK cells and secrete large amounts of IFNγ
IFNγ activates macrophage
macrophage must be activated by respiratory burst and make nitric oxide → activated macrophage are good at killing organisms brought in by phagocytosis or intracellular pathogens
activated macrophages produce and secrete more IL-12 than before activated
activated NK cells produce $$TNFα$$ (promotes inflammation and activates macrophages, $$GM-CSF$$ (produces granulocytes and macrophages), and $$chemokines MIP1α & MIP1β$$ (recruit and activate macrophages)
@@2.) Antibody Dependent Cell Cytotoxicity (ADCC)@@
cells infected with viruses or intracellular bacteria expresses viral or bacterial proteins on surface
antibodies against these proteins can bind to cells
NK cells express $$FcγRIII$$ (CD16) → receptor for Fc region of IgG
more than one IgG bound to surface binds to FcγRIII on NK cells = triggers NK cell to kill cell
@@3.) Cytotoxicity (cell killing)@@
$$A.) release enzymes from granules by CTLs$$
degranulation = granules move to surface of cell where granule membrane fuses with cell membrane releasing granule contents
perforin = protein released during degranulation
binds to target cells and transports granzyme into cell
presence of granzyme inside cell is a signal to the cell that it should undergo apoptosis
$$B.) activation of apoptosis without degranulation$$
NK cells produces TRAIL (protein)
TRAIL binds to DR4 & DR5 = DR4 & CR5 cluster
inside cell to be killed, FADD binds to clustered DR4 & DR5 = active
active FADD cleaves pro-caspase 8 into active caspase 8 = starts apoptosis
==Control of NK Cell Killing==
@@1.) cytotoxicity activating receptors bind to ligands@@
send signal inside NK cell that starts killing process
@@2.) cytotoxicity inhibitory receptors bind to ligand@@
inhibitory receptors bind to class I MHC
no killing
@@3.) infected cell and tumor cell have altered expression of class I MHC@@
class I MHC = signals to not kill cell
@@4.) NK cells kill cells that have changed due to stress@@
NKG2D = activating receptor
binds to MIC-A, MIC-B, or RAET1
stress = infection with intracellular bacteria, infection with virus, DNA damage, or transformation to malignant tumor cells
NKG2D binds to ligand = activates killing
@@5.) Innate Lymphoid Cells (ILCs)@@
NK cells are a type of ILC
non NK cell ILC does not kill other cells like NK cells
ILC produced through hematopoiesis from common lymphoid progenitor
bone marrow → bloodstream → lymphoid tissue → dermis, liver, small intestine and lungs
ILC1 = fighting viral & intracellular infections
ILC2 = fighting parasites
ILC3 = fighting extracellular bacteria & fungi
Immunology Chapter 6
==NK cells Characteristics==
==NK cells Activation==
^^IL-12^^
^^IL-15^^
^^IL-2^^
==Functions of NK cells==
@@1.) Production of cytokines@@
@@2.) Antibody Dependent Cell Cytotoxicity (ADCC)@@
@@3.) Cytotoxicity (cell killing)@@
A.)releaseenzymesfromgranulesbyCTLs
B.)activationofapoptosiswithoutdegranulation
==Control of NK Cell Killing==
@@1.) cytotoxicity activating receptors bind to ligands@@
@@2.) cytotoxicity inhibitory receptors bind to ligand@@
@@3.) infected cell and tumor cell have altered expression of class I MHC@@
@@4.) NK cells kill cells that have changed due to stress@@
@@5.) Innate Lymphoid Cells (ILCs)@@