Autoimmune diseases apoptosis

Double negative (CD4-CD8-) TCR-ap-f Treg cells that mediate tolerance in several experimental autoimmune diseases have been described [ 111 ]. These double negative T cells are specific for MHC class I molecules and the suppressive effect of these cells on the proliferation and cytotoxic activity of CD8-I- T cells with the same antigen specificity was not mediated by cytokines, but instead was attributed to Fas-mediated apoptosis of alloreactive T cells [112]. 

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). 

Melatonin has been shown to boost certain parts of the immune system. It boosts the activity of natural killer cells, a type of immune cell. It also prevents apoptosis, a type of destruction of T-lymphocytes, which are other important immune cells found in the bloodstream. Melatonin also limits the effect of corticosteroids on the immune system Corticosteroids are very potent drugs that are sometimes used to inhibit the immune system. Some people have autoimmune diseases in which their immune system attacks the cells of their own bodies. Physicians frequently prescribe corticosteroids for these individuals. 

L22. Lorenz, H.-M., Griinke, M., Hieronymus, T., Herrmann, M., Kiihnel, A., etal., In vitro apoptosis and expression of apoptosis-related molecules in lymphocytes from patients with systemic lupus erythematosus and other autoimmune diseases. Arthritis Rheum. 40, 306-317 (1997). 

In addition to cancer, too little apoptosis can also result in diseases such as autoimmune lymphoproliferative syndrome (ALPS). This occurs when there is insufficient apoptosis of auto-aggressive T cells, resulting in multiple autoimmune diseases. An overproliferation of B cells occurs as well, resulting in excess immunoglobulin production, leading to autoimmunity. Some of the common diseases of ALPS include hemolytic anemia, immune-mediated thrombocytopenia, and autoimmune neutropenia. The different types of this condition are caused by different mutations. Type 1A results from a mutation in the death domain of the Fas receptor, Type IB results from a mutation in Fas ligand, and Type 2 results from a mutation in caspase 10, reducing its activity. 

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). 

Gold R, Hartung HP, Lassmann H (1997) T-cell apoptosis in autoimmune diseases Termination of inflammation in the nervous system and other sites with specialized immune-defense mechanisms. Trends Neurosci 20 399 04. 

Inappropriate Regulation of Apoptosis May Head to Cancer and Autoimmune Diseases... 

Aberrant regulation of apoptosis contributes to well-known pathologies such as autoimmune diseases, cancer, and viral infections. As discussed above, p53 serves as a checkpoint for cell cycle and apoptotic cell death. While massive apoptotic death may signal cell... 

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