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Natural killer cell
Natural killer cells (or NK cells) are a type of cytotoxic lymphocyte that constitute a major
component of the innate immune system. NK cells play a major role in the rejection of tumors
and cells infected by viruses. They kill cells by releasing small cytoplasmic granules of proteins
called perforin and granzyme that cause the target cell to die by apoptosis (programmed cell
death).
NK cells are defined as large granular lymphocytes (LGL) and constitute the third kind of cells
differentiated from the common lymphoid progenitor generating B and T lymphocytes.
They were named "natural killers" because of the initial notion that they do not require
activation in order to kill cells that are missing "self" markers of major histocompatibility
complex (MHC) class I. They are distinct from Natural Killer T cells.
[Note: Natural killer T (NKT) cells are a heterogeneous group of T cells that share properties of
both T cells and natural killer (NK) cells]
Mechanism
NK cells are cytotoxic; small granules in their cytoplasm contain proteins such as perforin and
proteases known as granzymes. Upon release in close proximity to a cell slated for killing,
perforin forms pores in the cell membrane of the target cell, creating an aqueous channel
through which the granzymes and associated molecules can enter, inducing either apoptosis or
osmotic cell lysis. The distinction between apoptosis and cell lysis is important in immunology:
lysing a virus-infected cell would only release the virions, whereas apoptosis leads to
destruction of the virus inside.
NK cells are activated in response to interferons or macrophage-derived cytokines. They serve
to contain viral infections while the adaptive immune response is generating antigen-specific
cytotoxic T cells that can clear the infection. Patients deficient in NK cells prove to be highly
susceptible to early phases of herpes virus infection.
In order for NK cells to defend the body against viruses and other pathogens, they require
mechanisms that enable the determination of whether a cell is infected or not. The exact
mechanisms remain the subject of current investigation, but recognition of an "altered self"
state is thought to be involved. To control their cytotoxic activity, NK cells possess two types of
surface receptors: activating receptors and inhibitory receptors. Most of these receptors are not
unique to NK cells and can be present in some T cell subsets as well.
These inhibitory receptors recognize MHC class I alleles, which could explain why NK cells kill
cells possessing low levels of MHC class I molecules. This inhibition is crucial to the role played
by NK cells. MHC class I molecules consist of the main mechanism by which cells display viral or
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tumor antigens to cytotoxic T-cells. A common evolutionary adaption to this seen in both
intracellular microbes and tumours is a chronic down-regulation of these MHC I molecules,
rendering the cell impervious to T-cell mediated immunity. It is believed that NK cells, in turn,
evolved as an evolutionary response to this adaption, as the loss of the MHC would deprive
these cells of the inhibitory effect of MHC and render these cells vulnerable to NK cell mediated
apoptosis.
T cell
T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central
role in cell-mediated immunity. They can be distinguished from other lymphocyte types, such as B cells
and natural killer cells (NK cells) by the presence of a special receptor on their cell surface called T cell
receptors (TCR). The abbreviation T, in T cell, stands for thymus, since this is the principal organ
responsible for the T cell's maturation. Several different subsets of T cells have been discovered, each
with a distinct function.
Types
Helper
T helper cell (TH cells) assist other white blood cells in immunologic processes, including
maturation of B cells into plasma cells and memory B cells, and activation of cytotoxic T cells
and macrophages, among other functions. These cells are also known as CD4 + T cells because
they express the CD4 protein on their surface. Helper T cells become activated when they are
presented with peptide antigens by MHC class II molecules that are expressed on the surface of
Antigen Presenting Cells (APCs). Once activated, they divide rapidly and secrete small proteins
called cytokines that regulate or assist in the active immune response.
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Cytotoxic
Cytotoxic T cells (TC cells, or CTLs) destroy virally infected cells and tumor cells, and are also
implicated in transplant rejection. These cells are also known as CD8+ T cells since they express
the CD8 glycoprotein at their surface. These cells recognize their targets by binding to antigen
associated with MHC class I, which is present on the surface of nearly every cell of the body.
Memory
Memory T cells are a subset of antigen-specific T cells that persist long-term after an infection
has resolved. Memory T cells comprise two subtypes: central memory T cells (T CM cells) and
effector memory T cells (TEM cells). Memory cells may be either CD4+ or CD8+.
Regulatory
Regulatory T cells (Treg cells), formerly known as suppressor T cells, are crucial for the
maintenance of immunological tolerance. Their major role is to shut down T cell-mediated
immunity toward the end of an immune reaction and to suppress auto-reactive T cells that
escaped the process of negative selection in the thymus.
Natural killer
(see before)
γδ
A majority of T cells have a TCR composed of two glycoprotein chains called α- and β- TCR
chains. However, in γδ T cells, the TCR is made up of one γ-chain and one δ-chain.
B cell
B cells are lymphocytes that play a large role in the humoral immune response (as opposed to
the cell-mediated immune response, which is governed by T cells). The principal functions of B
cells are to make antibodies against antigens, perform the role of antigen-presenting cells
(APCs) and eventually develop into memory B cells after activation by antigen interaction. B
cells are an essential component of the adaptive immune system.
The abbreviation "B", in B cell, comes from the bursa of Fabricius in birds, where they mature.
In mammals, immature B cells are formed in the bone marrow, which is used as a backronym
for the cells' name.
Immune Tolerance
Like their fellow lymphocytes, the T cells, immature B cells are tested for auto-reactivity by the
immune system before leaving the bone marrow. In the bone marrow (the central lymphoid
organ), central tolerance is produced. The immature B cells whose B cell Receptors (BCRs) bind
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too strongly to self antigens will not be allowed to mature. If B cells are found to be highly
reactive to self, three mechanisms can occur.

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Clonal deletion: the removal, usually by apoptosis, of B cells of a particular self antigen
specificity.
Receptor editing: the BCRs of self reactive B cells are given an opportunity to rearrange
their conformation. This process occurs via the continued expression of the
Recombination activating gene (RAG). Through the help of RAG, receptor editing
involves light chain gene rearrangement of the B cell receptor. If receptor editing fails to
produce a BCR that is less autoreactive, apoptosis will occur. Note that defects in the
RAG-1 and RAG-2 genes are implicated in Severe Combined Immunodeficiency (SCID).
The inability to recombine and generate new receptors lead to failure of maturity for
both B cells and T cells.
Anergy: B cells enter a state of permanent unresponsiveness when they bind with
weakly cross-linking self antigens that are small and soluble.
T-cell activation:
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Mechanism of action of B cell
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