Summarised Mechanism of action of NK cells and CD8+ cells

1. COMPARISON BETWEEN
MECHANISM OF ACTION OF
NK CELLS AND CD8+ CELLS
DR. ISSAH SATIA
M.B.CH.B KENYATTA UNIVERSITY

2. INTRODUCTION
• Natural killer cells [NK Cells] are a type of lymphocyte and a
component of the innate immune system.
• These immune cells can recognize and kill the cells that have been
infected virus. Natural killer cells can also recognize and destroy
tumor cells.
• Cytotoxic T cells [CTL] is a T lymphocyte and a component of the
adaptive immune system
• These immune cells kill cancer cells, cells that are infected
[particularly with viruses]or cells that are damaged in other ways.

3. MECHANISM OF ACTION OF CYTOTOXIC T
CELLS
• Class I MHC is expressed by all nucleated host cells. When these
cells are infected with a virus the cells degrade foreign proteins
via antigen processing. These result in peptide fragments, some of
which are presented by MHC Class I to the CD8+ T cells. The
activation of T cells occurs as follows:
• Interaction between a T cell receptor and an MHC I bound peptide.
There is a second interaction between the CD28 co-receptor and
the class I MHC molecule to stabilize the signal. Once activated the
cytotoxic T cell undergoes clonal expansion with the help of
interleukin II. The mechanisms of killing are as follows;
• When exposed to infected cells, TC cells release the
cytotoxins perforin, granzymes, and granulysin. Through the
action of perforin, granzymes enter the cytoplasm of the target cell

4. • A second way to induce apoptosis is via cell-surface interaction
between the TC and the infected cell. When a TC is activated it
starts to express the surface protein FAS ligand which can bind
to Fas molecules expressed on the target cell. Engagement of
Fas with Fas-L allows for recruitment of the death-induced
signaling complex. This allows recruitment of
procaspases. These caspases then activate the effector
caspases, leading to cleavage of death substrates. The final
result is apoptosis of the cell that expressed Fas.

5. MECHANISM OF ACTION OF NK CELLS
• Upon viral infection, cells release cytokines which serve to signal the
NK cell the presence of viral pathogens in the affected area. The
cytokines include IL-12, IL-15, IL-18 and IL-2. NK cells are activated
in response to interferons or macrophage-derived cytokines. Cells
that express an activating ligand but lack the MHC I (Inhibitory ligand)
e.g Viral infected cells and tumor cells will be killed by the NK cells.
NK cells work to control viral infections by secreting IFNγ and TNFα.
IFNγ activates macrophages for phagocytosis and lysis, and TNFα acts
to promote direct NK tumor cell killing.
• NK cells have small granules in their cytoplasm that contain proteins
such as perforin and proteases known as granzymes. Upon release in
close proximity to a target cell, perforin forms pores in the cell
membrane of the target cell, creating an aqueous channel through

6. • Lysing a virus-infected cell could potentially only release the virions,
whereas apoptosis leads to destruction of the virus inside. α-
defensins and other antimicrobial molecules are also secreted by NK
cells, and directly kill bacteria by disrupting their cell walls.
• Also,infected cells are routinely opsonized with antibodies for
detection by immune cells. Antibodies that bind to antigens can be
recognised by FcϒRIII (CD16) receptors expressed on NK cells,
resulting in NK activation, release of cytolytic granules and consequent
cell apoptosis. This the cell mediated cellular cytotoxicity(ADCC).

7. SIMILARITIES IN MECHANISM OF ACTION
BETWEEN NK CELLS AND CYTOTOXIC T CELLS
• Both are cytotoxic in nature [cytotoxicity is the quality of being
toxic to cells].
• Both destroy cancer cells, tumor cells and cells that have been
infected virus or are damaged.
• Both are from the lymphoid lineage of development of immune
cells.
• Both release granzymes and perforins during immune
responses.
• Both induce cell apoptosis.

8. DIFFERENCES IN MECHANISM OF ACTION
BETWEEN NK CELLS AND CYTOTOXIC T CELLS
• Cytotoxic T cells are under the adaptive immune response and
therefore have memory while natural killer cells are under the innate
immune system and therefore have no memory.
• NK cells kill target cells in an antigen-nonspecific manner regulated
by a wide range of inhibitory and activating surface receptors. In
contrast, CD8 + T cells destroy target cells by recognition of HLA
class I restricted peptide antigen. Fas molecule is expressed on target
cells, whereas FasL molecule is expressed on cytotoxic T cells.
• MHC RESTRICTION-Cytotoxic T cells are MHC restricted while natural
killer cells are MHC non-restricted.

9. • RECEPTOR TYPE-Cytotoxic T cells possess a T cell
receptor while natural killer cells possess Fc receptors
and inhibitory receptors.
• ABSENCE OF CLASS I MHC -Cytotoxic T cells has lack of
recognition while a natural killer cells undergoes
immediate cytotoxicity.
• PRESENCE OF MHC I-Cytotoxic T cell has a T cell
receptor engagement while natural killer cell has an
inhibitory signal.
• PRESENCE OF GRANULES-Cytotoxic T cells do not
contain granules and therefore priming is required while
natural killer cells have cytoplasmic granules and
therefore priming is not required.

10. • NK cell cytolytic activity is also induced through the expression
of cell stress-induced MHC class I-related chain A (MICA) and B
(MICB) proteins (10). In contrast, CD8+ T cells kill target cells by
recognition of MHC-I restricted peptide antigens or CD1-
restricted nonpeptide antigens.