Natural Killer Cells

NK Activate vs Inactivate

Healthy cells express MHC molecules which are recognized by killer inhibitory receptors (KIRS) so they not attacked.

NK cells activated by infected cells that don’t have MHC on the surface, no inhibitory signal so kills the cell

ITIMS

Signaling component of KIRS

KIRs are HLA-specific inhib receptors (MHC class 1)

Major NK Cell Activating Receptor

Major ligand for NKG2D is MICA or MICB

MICA/B upregulated by cellular distress
-mutation
-infection
-transformation (oncogenesis)

NK Video 1

Nk type of lymphocyte, innate immunity

pathogens fail to express self MHC

NK look for proteins on surface of cell and bind to both the activation and inhibitory receptor
-if ONLY activation receptor-kills cell
-if has BOTH, leaves cell alone

When inducing apoptosis
-NK uses porferins, rather than allowing cell to lyse
-activates caspase in the cell, induced apoptosis

NK Video 2

NK comes from HSC

NK cells have NK 1.1 marker on surface, highly loaded with cytotoxic granule porferin

Also express Fc receptors and FASL (Fc region antibody, Fas ligand)→mediated cell death

Activator is NKG2D, interacts with HLA E and binds with MICA/B

Inactivator is KIR, interacts with HLA C, and Ly49

NK Video 2 Continued

T cells have CD8+ recognize MHC class 1 to kill cells

Viruses adapted to downregulate MHC, so that’s where NK comes in, will kill cells that don’t display MHC

NK is always signaled to kill, only doesn’t kill if inhib receptor is there

NK cells also kill tumor cells