Page 1301 - Clinical Immunology_ Principles and Practice ( PDFDrive )

CHaPter 93 Assessment of Functional Immune Responses in Lymphocytes 1263

CD56 dim/- CD16 bright

CD56 bright

IL-2NRα
IL-2/-15Rβ IL-2/-15Rβ
CD94- γc γc
NKG2A CD56 bright CD56 dim
c-kit PEN5-PSGL-1
L-selectin high

CCR7 CXCR1
TNF-α GM-CSF
CX CR1
3
TNF-β
High cytokine production Low cytokine production
INF-γ
IL-10

NKRs: Effector functions: NKRs: Effector functions:
+KIR +ADCC +++KIR +++ADCC
+++CD94-NKG2A +++LAK +++CD94-NKG2A +++LAK
+Natural cytotoxicity +++Natural cytotoxicity

FIG 93.8 NK Cell Subsets in Blood. Natural killer (NK) cells are present as two major subsets
+/-
++
in blood: cytotoxic NK cells (CD16 CD56 ) and cytokine-producing NK cells (CD56 ). The former
++
accounts for 90% of NK cells in circulation and the latter, 10%. The cytotoxic NK cells are very
efficient in mediating target cell killing via spontaneous (natural), lymphokine-activated (LAK), or
antibody-dependent cytotoxicity mechanisms. (Adapted from figure in Cooper MA, et al. Trends
Immunol 2001;22:633–40.)

Activation receptor
+
NK Target

−
FIG 93.9 NK Cell Recognition of Target for Cytotoxic Function.
Inhibitory receptor Natural killer (NK) cells have inhibitory receptors for self-major his-
tocompatibility complex (MHC) class I. Therefore NK cells do not kill
target cells expressing MHC class I (upper panel). However, when
MHC class I expression is downregulated (viral infections, tumors),
the target cell is primed for NK cell cytotoxicity, which is mediated
Activation receptor by granule exocytosis and release of cytotoxic proteins, including
ligand perforin and granzymes (lower panel). (Adapted from figure in French
NK +
Target AR and Yokoyama WM. Arthritis Res Ther 2004;6:8–14.)

Cytokine production Granule release (Cytotoxicity)