What are NK cell-activating cytokines?
IL-15: maturation of NK cells
Type I IFNs: enhance killing functions of NK cells
IL-12: enhance killing functions of NK cells
What receptors activate NK cells?
NKG2D: recognizes molecules that resemble MHC I proteins
CD16: specific for IgG bound to cells
ITAMs (immunoreceptor tyrosine-based activating motifs): in cytoplasmic tails which phosphorylates on tyrosine residues leading to cytotoxic granule exocytosis and production of IFN-y
What are the inhibitory receptors of NK cells?
Killer cells immunoglobulin-like receptors (KIRs)
CD94 and lectin subunit NKG2
ITIMS- phosphorylated ITIMs bind and promote activation of cytoplasmic protein tyrosine phosphatases, which remove phosphate groups from tyrosine resides; counteracting activating ITAMs
How do CD8+ CTL recognize class MHC 1 molecules?
They recognize the MHC I complexes on the surface of infected cells via the TCR and the CD8 coreceptor
How do CD8+ CTL hold on to infected cells?
LFA-1 integrin binds and holds the cell forming the immunologic synapse
How do CD8+ CTL kill infected cells?
When an antigen in recognized a pathway is activated to release granules into the synapse. Perforin is released to make pores in the infected cell for Granzyme B to enter and cleave/activate caspase to induce apoptosis. Also expresses Fas ligand to bind apoptosis inducing Fas in infected cells
What strategies do viral pathogens use to evade cell-mediated immune defenses?
Mycobacteria- inhibit phagolysosomes fusion
Herpes- inhibits antigen presentation by interfering with TAP transporter
Cytomegalovirus- inhibits antigen presentation and proteosomal activity and remove MHC I molecules from ER
Epstein- Barr virus: inhibits antigen presentation macrophage and dendritic cell activation and proteosomal activity
produces IL-10
Pox Virus- inhibition of effector cell activation and produces soluble cytokine receptors