what are the 3 states that regulate NK cell targeting
- protection- healthy cells express both stimulatory and inhibitory signals
- Missing-self- reduced MHC I expression
- Induced-self- unhealthy cells increase stress ligand expression
T/F Not all NK cells detect all MHC I receptors or stress ligands
true
what must NK cells be in order to detect lack of receptor expression
the must be educated
what role do cytokines play dealing with NK cells
stimulating signal
receptor expression
IFNs, IL-12
what are the two activating receptors on NK cells
NKG2D
CD16 (Fc receptor)
what are the two inhibitory receptors on NK cells?
NKG2A
KIR family
can NK cells form memory cells?
yes
T/F stimulating signals must overcome inhibitory signals?
true
what does the NKG2D bind?
binds MIC proteins (stress ligands)
what does NKG2A bind?
binds MHC I
what does Killer-cell Immunoglobulin-like Receptor (KIR) family bind?
binds MHC I
inhibit activation
generally inhibitory receptors bind what?
MHC I
does cells express NKG2A and KIR at the same time?
no, there express one or the other
infected cells do what with there surface ligands
MHC I down regulation
increase stress ligand signaling
if a NK detects MHC I on a cell surface what happens?
nothing, the cell stays alive
if a NK doesn’t detect a MHC I on the surface what happens?
kills the cell
what is NK cell education
MHC I exposure during development
what are the three absolute things that happen after education
NK cells detect that specific MHC I isotype
NK cells must detect that MHC I isotype
NK cells only detect that MHC I isotype
NK cell activation and effector response
target cell response
target cell interaction:
- downregulation MHC I
- stress ligands
- CD 16
NK cell activation and effector response
leukocyte interaction
APCs
Th cells
NKT cells
NK cell activation and effector response
cytokines
IFNs, IL-12
proliferation, receptor expression, cytokine and granule production
effector functions
cytokine release
cytotoxicity
for NK cells to be activated you need what?
at least 2 stress signals and a downregulation of MHC I
Innate mechanism to activate NK cells
2 signals
stress ligands
adaptive mechanism the activate NK cells
single signal Ig targeting (CD16 receptor on NK cell)
how to NK cells kill?
- Degranulation
- perforin
- granzyme - Death receptors(triggers apoptosis)
- FasL
- TRAIL - Interferons(gamma) and nitric oxide
what is the major role and gamma/delta T cells?
removed diseased and malignant cells
where can you find gamma/delta T cells?
tissues and mucosal surfaces
- sit in epithelial layers
- intraepithelial lymphocytes (IEL)
what antigens do gamma/delta T cells bind?
phospho-antigens
phospholipids
lipids
functions of gamma/delta T cells?
both like CD8 and CD4 like activity
- direct killing
- cytokine and chemokine release
- NK, Macs and DC activations
can gamma/delta T cells be antigen presenting cells?
yes
do gamma/delta T cells have stress ligand receptors?
yes they are similar to NK cells
-detect presence and absence of MHC I
what cells promote tissue repair and homeostasis?
gamma/delta T cells
what receptors do epithelial cells have that present the lipid antigens(both self and non self) to gamma/delta T cells
CD1
when a gamma/delta T cells interacts with a CD1 what does this allow
discriminate self from non self
activate, and targeted killing
-**Co-signal dependent
very specific detection
gamma/delta T cell receptors bind?
phospholipid receptors
MHC-I related receptors
stress ligands
*they monitor the health of mucosal tissues
what is the gamma/detla response
relatively rapid response the local pathogens and disease
- PAMPs
- Stress ligands
gamma/delta T cell effector functions
- promote inflammation
- Th17, Th1 activation
- NK activation - Drive adaptive initiation
- DC and Mac stimulation
- Direct presentation - Directly cytotoxic
- Perforin and granzyme
- CD16 (Fc receptor)
Will MHC I always inhibit NK cells?
no, you can abundant stress signals
