A cytotoxic T cell (also known as TC, CTL, T-Killer cell, CD8+ T-cells or killer T cell) belongs to a sub-group of T lymphocytes (a type of white blood cell) which are capable of inducing the death of infected somatic or tumor cells; they kill cells that are infected with viruses (or other pathogens), or are otherwise damaged or dysfunctional. T cells belong to a group of White blood cells known as Lymphocytes, and play a central role in Cell-mediated immunity. An infection is the detrimental Colonization of a host Organism by a foreign Species. "Somatic" redirects here for the musician known as Somatic see Hahn Rowe. See also Cancer A tumor or tumour is the name for a swelling or lesion formed by an abnormal growth of cells (termed neoplastic A virus (from the Latin virus meaning Toxin or Poison) is a sub-microscopic infectious agent that is unable A pathogen (from Greek πάθος pathos "suffering passion" and γἰγνομαι (γεν- gignomai (gen- "I give birth to" infectious Most cytotoxic T cells express T-cell receptors (TcRs) that can recognize a specific antigenic peptide bound to Class I MHC molecules, present on all nucleated cells, and a glycoprotein called CD8, which is attracted to non-variable portions of the Class I MHC molecule. The T cell receptor or TCR is a molecule found on the surface of T lymphocytes (or T cells that is in general responsible for recognizing Antigens bound An antigen (from antibody-generating) or immunogen is a substance that prompts the generation of Antibodies and can cause an immune response Peptides (from the Greek πεπτίδια, "small digestibles" are short Polymers formed from the linking in a defined order of α- Amino The major histocompatibility complex ( MHC) is a large genomic region or Gene family found in most Vertebrates It is the most gene-dense region Not to be confused with Peptidoglycan. Glycoproteins are proteins that contain Oligosaccharide chains ( Glycans) covalently attached CD8 ( Cluster of differentiation 8 is a transmembrane Glycoprotein that serves as a Co-receptor for the T cell receptor (TCR The affinity between CD8 and the MHC molecule keeps the TC cell and the target cell bound closely together during antigen-specific activation. CD8+ T cells are recognized as TC cells once they become activated and are generally classified as having a pre-defined cytotoxic role within the immune system.
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Cytotoxic T cell development
Hematopoetic stem cells in the bone marrow migrate into the thymus, where they undergo VDJ recombination of their beta-chain TcR DNA to form a developmental form of the TcR protein, known as pre-TcR. Hematopoietic stem cells (HSCs are Stem cells that give rise to all the blood cell types including Myeloid ( Monocytes and Macrophages, Neutrophils Bone marrow is the flexible tissue found in the hollow interior of Bones In adults marrow in large bones produces new Blood cells It constitutes 4% of In Human anatomy, the thymus is an organ located in the upper Anterior portion of the chest cavity just behind the Sternum. V(DJ recombination is a mechanism of Genetic recombination that occurs in Vertebrates which randomly selects and assembles segments of Genes encoding The T cell receptor or TCR is a molecule found on the surface of T lymphocytes (or T cells that is in general responsible for recognizing Antigens bound If that rearrangement is successful, the cells then rearrange their alpha-chain TcR DNA to create a functional alpha-beta TcR complex. This highly-variable genetic rearrangement product in the TcR genes helps create millions of different T cells with different TcRs, helping the body's immune system respond to virtually any protein of an invader. Proteins are large Organic compounds made of Amino acids arranged in a linear chain and joined together by Peptide bonds between the Carboxyl The vast majority of T cells express alpha-beta TcRs (αβ T cells), but some T cells in epithelial tissues (like the gut) express gamma-delta TcRs (γδ T cells), which recognize non-protein antigens. T cells belong to a group of White blood cells known as Lymphocytes, and play a central role in Cell-mediated immunity.
T cells with functionally stable TcRs express both the CD4 and CD8 co-receptors and are therefore termed "double-positive" (DP) T cells (CD4+CD8+). CD4 ( Cluster of differentiation 4 is a Glycoprotein expressed on the surface of T helper cells, Regulatory T cells, Monocytes, CD8 ( Cluster of differentiation 8 is a transmembrane Glycoprotein that serves as a Co-receptor for the T cell receptor (TCR A co-receptor is a cell surface receptor that binds a signalling molecule in addition to a primary receptor in order to facilitate Ligand recognition and initiate The double-positive T cells are exposed to a wide variety of self-antigens in the thymus and undergo two selection criteria :
- (1) positive selection, in which those double-positive T cells that bind too weakly to MHC-presented self antigens undergo apoptosis because of their inability to recognize MHC-protein complexes.
- (2) negative selection, in which those double-positive T cells that bind too strongly to MHC-presented self antigens undergo apoptosis because their propensity to become autoreactive could lead to autoimmunity. The major histocompatibility complex ( MHC) is a large genomic region or Gene family found in most Vertebrates It is the most gene-dense region An antigen (from antibody-generating) or immunogen is a substance that prompts the generation of Antibodies and can cause an immune response Autoimmunity is the failure of an organism to recognize its own constituent parts as self, which results in an immune response against its own cells and tissues
Only those T cells that bind to the MHC-self-antigen complexes weakly are positively selected. Those cells that survive positive and negative selection differentiate into single-positive T cells (either CD4+ or CD8+) dependent on whether their TcR recognizes an MHC class I presented antigen (CD8) or an MHC class II presented antigen (CD4). It is the CD8+ T-cells that will mature and go on to become cytotoxic T cells following their activation with a class I restricted antigen.
Cytotoxic T cell activation
With an exception of some cell types such as non-nucleated cells (including erythrocytes), Class I MHC is expressed by all host cells. In Cell biology, the nucleus (pl nuclei; from Latin la ''nucleus'' or la ''nuculeus'' "little nut" or kernel is a membrane-enclosed Red blood cells are the most common type of Blood cell and the Vertebrate body's principal means of delivering Oxygen to the body tissues via the Blood In Biology, a host is an organism that harbors a Virus or Parasite, or a mutual or Commensal Symbiont, typically providing nourishment When these cells are infected with a virus (or another intracellular pathogen), the cells degrade foreign proteins via antigen processing. A virus (from the Latin virus meaning Toxin or Poison) is a sub-microscopic infectious agent that is unable Not to be confused with Intercellular, meaning "between cells" A pathogen (from Greek πάθος pathos "suffering passion" and γἰγνομαι (γεν- gignomai (gen- "I give birth to" infectious Antigen processing is a Biological process that prepares Antigens for presentation to special cells of the Immune system called T lymphocytes These result in peptide fragments, some of which are presented by MHC Class I to the T cell antigen receptor (TcR) on CD8+ T cells. The T cell receptor or TCR is a molecule found on the surface of T lymphocytes (or T cells that is in general responsible for recognizing Antigens bound
The activation of cytotoxic T cells is dependent on several simultaneous interactions between molecules expressed on the surface of the T cell and molecules on the surface of the antigen presenting cell (APC). See also Antigen presentation An antigen-presenting cell ( APC) or accessory cell is a cell that displays foreign Antigen complexed For instance, consider the two signal model for TC cell activation.
| Signal | T cell | APC | Description |
| first signal | TcR | peptide-bound MHC class I molecule | There is a second interaction between the CD8 coreceptor and the class I MHC molecule to stablize this signal. The T cell receptor or TCR is a molecule found on the surface of T lymphocytes (or T cells that is in general responsible for recognizing Antigens bound There are two primary classes of Major histocompatibility complex (MHC molecules class I and MHC class II. CD8 ( Cluster of differentiation 8 is a transmembrane Glycoprotein that serves as a Co-receptor for the T cell receptor (TCR |
| second signal | CD28 molecule on the T cell | either CD80 or CD86 (also called B7-1 and B7-2) | CD80 and CD86 are known as costimulators for T cell activation. CD28 is one of the Molecules expressed on T cells that provide co-stimulatory signals which are required for T cell activation The protein CD80 ( C luster of D ifferentiation The protein CD86 ( C luster of D ifferentiation 86) is a molecule expressed on antigen-presenting cells that provide costimulatory signals necessary for During the activation of T cells co-stimulation is often crucial to the development of an effective immune response. This second signal can be assisted (or replaced) by stimulating the TC cell with cytokines released from helper T cells. T helper cells (also known as effector T cells or Th cells) are a sub-group of Lymphocytes (a type of White blood cell or |
Once activated, the TC cell undergoes clonal expansion with the help of a cytokine called Interleukin-2 (IL-2) that is a growth and differentiation factor for T cells. Interleukin-2 ( IL-2) is an Interleukin, a type of Cytokine Immune system signaling molecule that is instrumental in the body's natural response This increases the number of cells specific for the target antigen that can then travel throughout the body in search of antigen-positive somatic cells. Somatic cells are any cells forming the body of an organism as opposed to Germline cells
Cytotoxic T cell effector functions
When exposed to infected/dysfunctional somatic cells, TC cells release the cytotoxins perforin and granulysin. Perforin 1 (pore forming protein, also known as PRF1, is a human Gene. Granulysin is a substance released by Cytotoxic T cells ( CD8) when they are attached to infected body cells These form pores in the target cell's plasma membrane causing ions and water to flow into the target cell that make the cell expand and eventually undergo lysis. The cell membrane (also called the plasma membrane, plasmalemma, or "phospholipid bilayer" is a Selectively permeable Lipid bilayer Lysis ( Greek, lysis from lyein = to separate refers to the death of a cell by breaking of the cellular membrane often by viral or osmotic TC also release granzyme, a serine protease, that can enter target cells via the perforin-formed pore and induce apoptosis (cell death) by activation of cellular enzymes called caspases. Granzymes are Serine proteases that are released by cytoplasmic granules within Cytotoxic T cells and Natural killer cells Their purpose is to induce Serine proteases or serine endopeptidases (newer name are Proteases ( Enzymes that cut Peptide bonds in Proteins in which one of Caspases, or c ysteine- asp artic acid prote ases, are a family of Cysteine proteases which play essential roles in Apoptosis (programmed A second way to induce apoptosis is via cell-surface interactions between the TC and the infected cell. When a TC is activated it starts to express the surface protein FAS ligand (FasL), which can bind to Fas molecules expressed on the target cell. Fas ligand ( FasL) is a type II transmembrane protein that belongs to the tumor necrosis factor (TNF family However, this Fas-Fas ligand interaction is thought to be more important to the disposal of unwanted T lymphocytes during their development or to the lytic activity of certain TH cells than it is to the cytolytic activity of TC effector cells. T cells belong to a group of White blood cells known as Lymphocytes, and play a central role in Cell-mediated immunity.
Cytotoxic T cell role in disease pathogenesis
- Hepatitis B virus (HBV) infection
During HBV infection cytotoxic T cells play an important pathogenetic role. They contribute to nearly all of the liver injury associated with HBV infection and, by killing infected cells and by producing antiviral cytokines capable of purging HBV from viable hepatocytes, cytotoxic T cells also eliminate the virus. [1] Recently platelets have been shown to facilitate the accumulation of virus-specific cytotoxic T cells into the infected liver. Platelets, or Thrombocytes, are small cytoplasmic bodies derived from cells They circulate in the Blood of Mammals and are involved [2]
References
- ^ Iannacone M. et al (2006). "Pathogenetic and antiviral immune responses against hepatitis B virus". Future Virology 1 (2): 189-196.
- ^ Iannacone M. et al (2005). "Platelets mediate cytotoxic T lymphocyte-induced liver damage". Nat Med 11: 1167-1169.
Dictionary
cytotoxic T cell
-noun
- (immunology) A subgroup of T cell that are capable of inducing death to infected somatic or tumor cells.
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