Within the scientific discipline of

toxicology Toxicology is a scientific discipline, overlapping with biology, chemistry, pharmacology, and medicine, that involves the study of the adverse effects of chemical substances on living organisms and the practice of diagnosing and treating expos ...

, Cytotoxic T lymphocytes (CTLs) are generated by immune activation of

cytotoxic T cells A cytotoxic T cell (also known as TC, cytotoxic T lymphocyte, CTL, T-killer cell, cytolytic T cell, CD8+ T-cell or killer T cell) is a T lymphocyte (a type of white blood cell) that kills cancer cells, cells that are infected by intracellular pa ...

(T_c cells). They are generally CD8⁺, which makes them

MHC class I MHC class I molecules are one of two primary classes of major histocompatibility complex (MHC) molecules (the other being MHC class II) and are found on the cell surface of all nucleated cells in the bodies of vertebrates. They also occur on ...

restricted. CTLs are able to eliminate most cells in the body since most nucleated cells express class I MHC molecules. The CTL-mediated immune system can be divided into two phases. In the first phase, functional effector CTLs are generated from naive T_c cells through activation and differentiation. In the second phase, affector CTLs destroy target cells by recognizing the antigen-MHC class I complex.

Phase 1

In phase one, effector CTLs are generated from CTL precursors. The CTL precursors include naive T_c cells since they are incapable of killing target cells. After a precursor cell has been activated, it can then differentiate into a functional CTL with cytotoxic activity. There are three sequential signals that are required to complete this process. First, there is

TCR TCR may stand for: Arts and entertainment * ''TCR'', the musical project of Robin Moulder and TC Smith * "TCR", a single by Prolapse * The Comic Reader, a comics news-fanzine 1961–1984 Businesses and organizations * TCR (record label), or Thur ...

recognition of the peptide-MHC class I complex. This step allows the cell to become licensed to an

antigen-presenting cell An antigen-presenting cell (APC) or accessory cell is a cell that displays antigen bound by major histocompatibility complex (MHC) proteins on its surface; this process is known as antigen presentation. T cells may recognize these complexes using ...

. Second, a costimulatory signal is transmitted by the interaction between

CD28 CD28 (Cluster of Differentiation 28) is one of the proteins expressed on T cells that provide co-stimulatory signals required for T cell activation and survival. T cell stimulation through CD28 in addition to the T-cell receptor ( TCR) can prov ...

and B7 of the precursor cell and the licensed antigen-presenting cell. Last, a signal is induced by the interaction between

IL-2 The Ilyushin Il-2 (Russian: Илью́шин Ил-2) is a ground-attack plane that was produced by the Soviet Union in large numbers during the Second World War. The word ''shturmovík'' (Cyrillic: штурмовик), the generic Russian term ...

and the high-affinity

IL-2 receptor The interleukin-2 receptor (IL-2R) is a heterotrimeric protein expressed on the surface of certain immune cells, such as lymphocytes, that binds and responds to a cytokine called IL-2. Composition IL-2 binds to the IL-2 receptor, which ...

. This results in proliferation and differentiation of the antigen-activated precursor cell into a functional effector CTL.

Phase 2

In phase two, the now functional effector CTLs destroy the target cells. This can be done in two ways. These pathways are the cytotoxic protein pathway and the Fas ligand pathway. Apoptosis is the primary mechanism for both of these pathways.

Cytotoxic protein pathway

One pathway is the cytotoxic protein pathway. In this pathway perforins and

granzymes Granzymes are serine proteases released by cytoplasmic granules within cytotoxic T cells and natural killer (NK) cells. They induce programmed cell death (apoptosis) in the target cell, thus eliminating cells that have become cancerous or are infe ...

are taken up by the target cell. In this pathway, the perforins facilitate the entry of granule contents into the cell. The granzymes then activate the endogenous apoptosis pathway, which induces cell death without necrosis. This leaves packages of fragmented DNA material from the target cell for the

macrophages Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer ce ...

to dispose of.

Fas ligand pathway

The other pathway is the Fas ligand pathway. In this pathway, a Fas ligand (FasL) on the CTL binds to

Fas receptor The Fas receptor, also known as Fas, FasR, apoptosis antigen 1 (APO-1 or APT), cluster of differentiation 95 (CD95) or tumor necrosis factor receptor superfamily member 6 (TNFRSF6), is a protein that in humans is encoded by the ''FAS'' gene. Fas ...

(FasR) on the target cell. This pathway is independent of granzymes. Instead it involves Interleukin-1β converting enzyme (

ICE Ice is water frozen into a solid state, typically forming at or below temperatures of 0 degrees Celsius or Depending on the presence of impurities such as particles of soil or bubbles of air, it can appear transparent or a more or less opaq ...

; also known as

Caspase 1 Caspase-1/Interleukin-1 converting enzyme (ICE) is an evolutionarily conserved enzyme that proteolytically cleaves other proteins, such as the precursors of the inflammatory cytokines interleukin 1β and interleukin 18 as well as the pyroptos ...

) activation, which is similar to

granzyme B Granzyme B (GrB) is one of the serine protease granzymes most commonly found in the granules of natural killer cells (NK cells) and cytotoxic T cells. It is secreted by these cells along with the pore forming protein perforin to mediate apoptosi ...

. This ultimately leads to DNA fragmentation.

References

*Kindt, Thomas, Richard Goldsby, Barbara Osborne, and Janis Kuby. ''Kuby Immunology''. W. H. Freeman, 2007. 353–360. Toxicology