Medical Application of Apoptosis

immunology

1) Apoptosis during thymocyte maturation: thymocytes become various types of immunocompetent cells through a series of development processes. In this development process, a series of positive cell selection and negative cell selection processes are involved. To form CD4+T lymphocyte subtypes and CD8+T lymphocyte subtypes; At the same time, it selectively eliminates the T cell clones that recognize autoantigens, and the mechanism of cell clone death is mainly through programmed cell death. Therefore, the normal development of the immune system results in the formation of both immunocompetent lymphocytes and immune tolerance to autoantigens. The formation of tolerance mechanism mainly depends on the activation of programmed cell death mechanism of T lymphocyte clone that recognizes autoantigen.

2) Activation induced cell death (AICD) is another major type of programmed death of T lymphocytes. When normal T lymphocytes are stimulated by invading antigens, T lymphocytes are activated and a series of immune responses are induced. In order to prevent the excessive immune response or the unlimited development of this immune response, the body has AICD to control the life span of activated T cells. In fact, T lymphocyte proliferation and T lymphocyte AICD share the same signal pathway. T lymphocytes start to activate after being stimulated. If there is growth factor in activated T lymphocytes, reproductive reaction will occur. If there is no or less growth factor, AICD will occur. 3) Lymphocyte attack on target cells: immunocompetent cells, especially lymphokine activated killer cells (LAK), are an important form of adoptive immunotherapy. It plays an important role in anti-tumor, anti-virus and immune regulation. These immunocompetent cells can induce programmed cell death when attacking tumor cells and virus infected cells.

clinical medicine

The reason why apoptosis has become a hot research topic, to a large extent, depends on the close relationship between apoptosis and clinical viruses. This relationship is not only manifested in the study of apoptosis and its mechanism, which clarifies the pathogenesis of a large class of immune diseases, but also can lead to the emergence of new therapies for diseases. Especially, the close relationship between apoptosis and cancer and AIDS has attracted much attention.

1) The decrease of CD4+cells caused by HIV infection is through the mechanism of apoptosis

HIV infection causes AIDS, and its main pathogenesis is that HIV infection specifically destroys CD4+cells, making CD4+and its related immune function defects prone to opportunistic infections and tumors. But how can HIV infection specifically destroy CD4+cells? It is generally believed that the significant decrease in the absolute number of CD4+T lymphocytes is mainly due to the mechanism of apoptosis. This not only clarifies the main reason for the decrease of CD4+T cells in AIDS, but also points out an important exploration direction for AIDS treatment research.

2) From the perspective of apoptosis, the occurrence of tumor is due to the inhibition of apoptosis

It is generally believed that malignant transformation of tumor cells is due to uncontrolled growth and excessive proliferation. From the perspective of apoptosis, it is believed that it is the result of inhibition of tumor apoptosis mechanism and failure of normal cell death clearance. A series of oncogenes and proto oncogenes are activated and overexpressed in tumor cells. The activation of these genes is closely related to the occurrence and development of tumors. A large class of oncogenes belong to the growth factor family and a large class of oncogenes belong to the growth factor receptor family. The activation and expression of these genes directly stimulate the growth of tumor cells. These oncogenes and their expression products are also important regulators of cell apoptosis. After the expression of many kinds of oncogenes, they block the apoptosis process of tumor cells and increase the number of tumor cells. Therefore, Understanding the mechanism of tumor from the perspective of cell apoptosis is due to the inhibition of tumor cell reduction due to the mechanism of tumor cell apoptosis. Therefore, to design a treatment method for tumors through the perspective and mechanism of apoptosis is to reconstruct the apoptosis signal transduction system of tumor cells, that is, to inhibit the expression of survival genes and activate the expression of death genes of tumor cells.

3) The study of apoptosis will bring a real breakthrough to autoimmune diseases

Autoimmune diseases include a large class of diseases caused by refractory immune disorders. Autoreactive T lymphocytes and antibody producing B lymphocytes are the main immune pathological mechanisms that cause autoimmune diseases. Under normal circumstances, the activation of immune cells is an extremely complex process. Under the stimulation of autoantigens, the immune cells that recognize autoantigens are activated and cleared through the mechanism of cell apoptosis. However, if this mechanism is blocked, the clearance of immunocompetent cells that recognize autoantigens will be blocked. It was observed that Fas encoded gene abnormality was observed in lymphoproliferative mutant mice, and normal Fas transmembrane protein molecules could not be translated. For example, Fas abnormality also blocked the apoptosis mechanism mediated by Fas, which caused lymphocyte proliferative autoimmune disease.

4) Degenerative diseases of the nervous system: Alzheimer's disease is caused by the accelerated apoptosis of nerve cells. Alzheimer's disease (AD) is an irreversible degenerative neurological disease. Mutations of amyloid precursor protein (APP) presenilin-1 (PS1) and presenilin-2 (PS2) lead to familial Alzheimer's disease (FAD). It has been proved that PS is involved in the regulation of neuronal apoptosis. The overexpression of PS1 and PS2 can enhance the sensitivity of cells to apoptosis signals. Two members of Bcl-2 gene family, Bcl xl and Bcl-2, participate in the regulation of apoptosis.