MICROBIOLOGY

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NATURAL
KILLERS
O Natural Killer (NK) Cells are lymphocytes in the same
family as T and B cells, coming from a common progenitor.
O NK cells are large granular lymphocytes derived from the
common lymphoid progenitor cells(lymphoblasts).
O NK cells constitute5%-10% of lymphocytes in human
peripheral blood.
O NK cells are cytotoxic; small granules in their cytoplasm
contain proteins such as perforin and proteases known as
granzymes, that will trigger either apoptosis or cell lysis in
an abnormal cell.
O Defensins, an antimicrobial secreted by NK cells, directly
kills bacteria by disrupting their cell walls.
O NK cells differentiate and mature in thymus, spleen, bone
marrow, lymph nodes and tonsils.
O However, as cells of the innate immune system,
NK cells are classified as group I Innate
Lymphocytes (ILCs) and respond quickly to a
wide variety of pathological challenges.
O NK cells are best known for killing virally infected
cells, and detecting and controlling early signs of
cancer. As well as protecting against disease,
specialized NK cells are also found in the placenta
and may play an important role in pregnancy.
• NK cells were first noticed
for their ability to kill tumour
cells without any priming or
prior activation (in contrast
to cytotoxic T cells, which
need priming by antigen
presenting cells).
• They are named for this
‘natural’ killing.
• Additionally, NK cells
secrete cytokines such as
IFNγ and TNFα, which act
on other immune cells like
Macrophage and Dendritic
cells to enhance the immune
response.
O While on patrol NK cells constantly contact other cells.
Whether or not the NK cell kills these cells depends on a
balance of signals from activating receptors and inhibitory
receptors on the NK cell surface.
O Activating receptors recognise molecules that are expressed on
the surface of cancer cells and infected
cells, and ‘switch on’ the NK cell.
O Inhibitory receptors act as a check on NK cell killing. Most
normal healthy cells express MHC I receptors which mark
these cells as ‘self’.
O Inhibitory receptors on the surface of the NK cell recognise
cognate MHC I, and this ‘switches off’ the NK cell, preventing
it from killing.
O Cancer cells and infected cells often lose their MHC I, leaving
them vulnerable to NK cell killing. Once the decision is made
to kill, the NK cell releases cytotoxic granules containing
perforin and granzymes, which leads to lysis of the target cell.
• The genes for both MHC I and
the NK cell inhibitory
receptors which recognise them
vary a lot between individuals.
• The versions (or alleles) of these
genes a person carries have
been linked to their ability to
fight HIV infection and their risk
of some autoimmune diseases.
• NK cell varieties also change
with age and are affected by
chronic viral infections such as
cytomegalovirus (CMV).
• Because of their ability to kill
tumour cells, NK cells are an
attractive target for cancer
immunotherapies. Some
therapeutic monoclonal
antibodies rely on NK cell killng.
TYPES OF NK CELLS
O On the basis of the abundance of the CD56
glycoprotein on the cell surface and their cytotoxic
potential NK cells are divided into two
subpopulations:
1) CD56dim NK cells:
O It comprises upto 90%, of NK cells and is considered
the most cytotoxic subset.
O It binds to the FC portion of IgG antibodies and
mediate antibody dependant cell-mediated
cytotoxicity (ADCC) of antibody-bound target cells.
O Expression of granzyme B and perforin is also high
in this subset compared with CD56bright NK cells.
2) CD56bright NK cells:
O This subtype comprises up to 10% of NK cells.
O This subset is known as the cytokine producing subset
of NK cells, and rapidly produces cytokines and
chemokines including IFNγ, TNFα, GM-CSF after
activation.
O A specialized population of NK cells are found in
woman’s uterus, called uterine NK cells (uNK).
O They are essential for forming the placenta.
O The role of the uterine NK cells is not to kill cells and
develop inflammation but to cooperate with fetal
trophoblast cells in enlarging maternal blood vessels so
that they have the capacity to supply the placenta, and
thus the growing fetus, with sufficient oxygen and
nourishment throughout pregnancy.
FUNCTIONS
O NK cells kill cells infected
with virus by blocking
replication of virus.
O It maintains and even
increase the inflammation
in the infected tissue by
secreting inflammatory
cytokines such as
interleukin (IL)-2, IL-12, IL-
15 and interferon gamma.
O NK cells also kills tumor
cells, they recognizes cells
that lack expression of
major histocompatibility
complex (MHC) class I
antigens.
 Diseases caused by lack of NK cells
O Herpes simplex viruses (HSVs) inhibit the lytic
activity of natural killer cells and interleukin 2-
activated killer cells.
O Chediak-Higashi syndrome is an autosomal
recessive disorder in which mutations in CHS1,
gene,which leads to the downregulation of immune
response that includes neutrophils, macrophages,
and NK cells.
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