With regard to chronic intestinal inflammation, recent data indicate that increased production of cytokines (IL-12) prevent Fas-mediated T-cell apoptosis, resulting in T-cell accumulation in the gut. This mechanism of disease perpetuation can be successfully blocked by antibodies to IL-12. In summary, the death-receptor pathway as typified by Fas (CD95/APO-1) includes the following. Oligomerization of Fas […]

Of note, three groups have been identified in Bcl-2 family members. Group A contains antiapoptotic proteins such as Bcl-2 and Bcl-xL that are characterized by four short conserved Bcl-2-homology (BH) domains (BH1-BH4), as well as a car-boxy-terminal hydrophobic transmembrane tail domain, which localizes the proteins to the outer mitochondrial membrane and endoplasmic reticulum (ER). Group […]

Notably, active caspase 8, depending on its amounts, can trigger one of two different signalling pathways. The first pathway of Fas-mediated apoptosis is activated by low amounts of caspase 8 and involves the cleavage of the proapop-totic Bid molecule, followed by the release of Cyt c from mitochondria into the cytoplasm, and subsequent death of […]

Of note, Ced-3 gene encodes a protein related to mammalian, IL-1p-converting enzyme (ICE; caspase 1), which exerts proteolytic activation of the caspase cascade, thereby emerging as the most central step of apoptosis. To date, 14 mammalian caspases have been identified and involved in different aspects of cell death, although the exact function of each individual […]

At the molecular level, disturbances in the regulation of these forms of apoptosis within the mucosal immune system, lead to mucosal inflammation that predispose to cancer development. Death of intestinal TLs mediated by Fas-FasL Activated T-cells are more susceptible to apoptosis than resting T-cells. As most T-cells in the LP normally exhibit a higher state […]

During lymphocyte maturation and activation, fluctuations in the levels of expression of Bcl-2 or Bcl-xL appear to correlate inversely with susceptibility to apoptosis. Overexpression of Bcl-2 or Bcl-xL leads to enhanced survival of immature lymphocytes and prolonged antibody responses. Conversely, knockout of Bcl-2 or Bd-xL results in reduced survival of mature or immature lymphocytes. It […]

If an adequate number of polymerized channels are assembled, the target cell will be unable to exclude ions and water, resulting in osmotic swelling and lysis. A second, equally important, function of perforin is to provide a means for introducing granzymes into the target cell. Granzyme B is a serine protease that preferentially cleaves protein […]

Step 3: Delivery of lethal hit mediated by perforin and granzyme B and/or Fas-FasL complex. During this process, CTLs develop specific membrane-bound cytoplasmic granules that contain numerous macromolecules, including a membrane pore-forming protein called perforin or cytolysin; enzymes frequently called granzymes that contain reactive serines in their active sites; and proteoglycans. In addition, CTLs share […]

Apoptotic procedure is implicated in tumourigenesis. Thus, some cancer-causing viruses use ‘tricks’ to prevent apoptosis of the cells they have transformed. For instance, two human papilloma viruses have been implicated in inducing cervical cancer, and one of them produces a protein (E6) that binds and inactivates the apoptosis promoter p53. Even tumour cells produced without […]

There are two different reasons by which a cell commits suicide. First, programmed cell death is as important as mitosis in the development and maintenance of host homeostasis. For example, during embryogenesis, excess numbers of developing cells die and in hormone-responsive tissues, such as the uterus, cyclical depletion of specific hormones leads to the death […]