The fact that apoptosis has been the subject of increasing attention and research efforts was highlighted by the award of the 2002 Nobel Prize in Physiology or Medicine to Sydney Brenner[?] (Great Britain), H. Robert Horvitz[?] (US) and John E. Sulston[?] (GB) "for their discoveries concerning genetic regulation of organ development and programmed cell death" (see  (http://www.nobel.se/medicine/laureates/2002/index) ).
virus. The "decision" for apoptosis can come from the cell itself, or from a call that is part of the immune system. If the apoptosis program of a cell itself is damaged (by mutation), or if the initiation is blocked (by a virus), a damaged cell can start growing without restrictions, developing into cancer. B cells and T cells, can become autoreactive, attacking healthy body cells. These are destroyed via apoptosis. Also, to prevent T cells from attacking healthy body cells right away, they are tested for autoimmune reactions within their origin tissue, the thymus. About 95% of the freshly produced T cells are killed right away via apoptosis due to autoimmune reactions.
vertebrate tissue development, and it does not elicit the inflammatory response which is characteristic of necrosis. In other words, apoptosis does not resemble the sort of reaction that comes as a result of tissue damage due to accident or pathogenic infection. Instead of swelling and bursting --and, hence, spilling their internal contents into extracellular space--, apoptotic cells and their nuclei shrink, and often fragment. In this way, they can be efficiently phagocytosed (and, as a consequence of this, their components reused) by macrophages or by neighboring cells.
organ or tissue has to be constant within a certain range. This is called homeostasis. It is achieved when the rate of mitosis in the tissue equals the rate of cells going into apoptosis. If this equilibrium is disturbed, either of two things happen:
Apoptotic messages from outside the cell (extrinsic factors) will be briefly desribed in the next section of this article. (For a detailed description of an extrinsic apoptotic pathway see "The Fas Signaling Pathway: More Than a Paradigm", by Harald Wajant, in Science, Vol. 296, No. 5573, p. 1635, May 31, 2002).
Apoptotic messages from inside the cell (intrinsic factors) emerge from mitochondria.
caspases[?] (see "Controlling the Caspases", by Stephen W. Fesik and Yigong Shi, in Science, Vol. 294, No. 5546, p. 1477, November 16, 2001), which are normally suppressed by IAP[?] (inhibitor of apoptosis) proteins. When a cell receives an apoptotic stimulus, IAP activity is relieved after SMAC (Second Mitochondria-derived Activator of Caspases, also called DIABLO), a mitochondrial protein, is released into the cytosol.
Tumor necrosis factor (TNF[?]), a 157 amino acid inter-cellular signaling molecule (cytokine), is the major extrinsic mediator of apoptosis. The cell membrane has two specialized receptors for TNF: TNF-R1 and TNF-R2. The binding of TNF to TNF-R1 has been shown to fire-off the pathway that leads to activating the caspases (see "TNF-R1 Signaling: A Beautiful Pathway", by Guoqing Chen and David V. Goeddel, in Science, Vol. 296, No. 5573, p. 1634).
The whole process requires energy and a cell machinery not too damaged. If the cell damage is between certain levels, the cell can start the earliest events of apoptosis and then continue with a necrosis.
The link between TNF and apoptosis shows why an abnormal production of TNF plays a fundamental role in several human diseases, especially (but not only) in autoimmune diseases, such as diabetes and multiple sclerosis.