Autoimmune disease apoptosis-associated

Diseases associated with inhibition of apoptosis include autoimmune diseases, cancer, viral infection, and allergic inflammation. 

Apoptosis is attributed a central importance in homeostasis of tissues in an organ or a tissue, the cell number must be kept constant within narrow limits. An increase in cells due to cell division is compensated by processes to eliminate cells that are no longer functional or are old. Apoptosis is a process that helps to keep the cell number in a tissue within limits that are suitable for the development and function of the organism. If defects occur in the apoptotic program, the consequence may be a pathologic increase or decrease in cells (Fig. 15.2). Examples of diseases associated with an increased rate of cell survival are cancer and autoimmune diseases. Diseases associated with increased apoptosis include AIDS and neurodegenerative diseases (Thompson, 1995). 

TNF is a cytokine produced mainly by activated macrophages, and is the major extrinsic mediator of apoptosis. Most cells in the human body have two receptors for TNF TNF-Rl and TNF-R2. The binding of TNF to TNF-Rl has been shown to initiate the pathway that leads to caspase activation via the intermediate membrane proteins TNF receptor-associated death domain (TRADD) and Fas-associated death domain (FADD). The link between TNF and apoptosis shows why an abnormal production of TNF plays a fundamental role in several human diseases, especially autoimmune diseases (see Chapter 15). 

P2. Peters, A. M., Kohfink, B., Martin, H., Griesinger, F., Wormann, B., Gahr, M., and Roesler, J., Defective apoptosis due to a point mutation in the death domain of CD95 associated with autoimmune lymphoprohferative syndrome, T-cell lymphoma, and Hodgkin s disease. Exp. Hematol. 

Increased apoptosis. Evidence of increased apoptosis in SLE is demonstrated by the fact that lymphocytes of both SLE patients and lupus mice show an increased rate of apoptosis ex vivo (E6, V4, L22). In addition, elevated levels of circulating oligonucleosomes are noted in SLE (R21, A19). The reason for increased apoptosis in SLE patients was revealed by studies of two environmental factors linked with SLE UV radiation and viral infection. UV radiation (UVB) was shown to cause apoptosis of keratinocytes and formation of surface blebs. The Ro antigen is then expressed in the surface of the blebs and may contribute to the induction of autoimmunity to Ro (C4). Viral infection, on the other hand, is well associated with disease relapse. 

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