The immune system is ＂sick＂. What’s wrong with it？

The immune system can also get sick and even be life-threatening.

　　"Wang Lin, a qigong master, died of multiple organ failure due to ANCA-related vasculitis and autoimmune peripheral neuritis." This news brought "immune system diseases" into public view.

　　In the course of millions of years of evolution, human beings have formed a complex defense mechanism against foreign microorganisms and harmful substances. This defense mechanism has a clear division of labor and powerful functions, and can cope with the changes and challenges of the living environment. We call it "immune system".

　　But like other organs of the human body, the immune system will get sick and even be life-threatening. What’s wrong with this?

　　The innate immune system is derived from invertebrates.

　　The normal immune system consists of immune organs, immune cells and immune molecules.

　　Immune organs mainly refer to lymph nodes, spleen and thymus. Among immune cells, there are cells involved in immune response and immune regulation, mainly T lymphocytes and B lymphocytes. Among them, T lymphocytes come from thymus and play an important role in the regulation of immune response, while B lymphocytes are mainly involved in the formation of antibodies, including autoantibodies. Immune molecules are mostly synthesized and secreted by immune cells, which play an important role in the initiation and regulation of immune response and the attack on tissues and organs.

　　Humans have inherited the innate immune system of invertebrates in the process of evolution. This ancient defense system identifies invading external pathogenic microorganisms through germinal cells widely distributed in human immune organs; Through the macrophages of innate immune system, we can identify the virulence factors of main microorganisms, directly kill pathogens and protect human body. This kind of protection is an immune response that is quickly started and mobilized, and it is non-specific. That is to say, innate immunity is reacted and cleared in the same way for any foreign microbial invasion, so it is not the most effective.

　　However, while the innate immune system slows down infection, it will activate the acquired immune system-the acquired immune system. Acquired immunity will react specifically to foreign antigens or pathogens. After the first contact with antigens, the second contact with the same antigen can trigger a faster and stronger immune response, attack foreign antigens and remove them from the body.

　　In short, the normal immune system has three important characteristics: one is a variety of antigen receptor libraries, which can identify almost endless pathogens; The second is immune memory, which can initiate a rapid memory immune response, which is why we can be immune for life after injecting some vaccines; The third is immune tolerance to avoid immune damage to normal self-tissues.

　　Distinguish the Immune Tolerance of "Friend or Foe"

　　The most important function of so-called "immunity" is to identify "self" and "non-self", and it will not produce immune response to its own tissue components, which is called immune tolerance.

　　The human body can achieve immune tolerance through autoantigen isolation, so that its own tissues can not contact with the immune system, and the specific immunity of related T or B cells is "unresponsive". For the "non-ego" of foreign microorganisms or foreign tissues and organs introduced into the body, the immune system will protect the body from the damage of intruders by starting an immune "response" reaction.

　　Therefore, if the function of the immune system is disordered and the normal components of the body are regarded as foreign substances, autoimmune diseases will occur. From the pathogenesis, autoimmune diseases are diseases caused by the breaking of immune tolerance. The immune system cannot correctly identify "self" and "non-self", thus attacking its own tissues and organs.

　　In addition, the dysfunction of T cells with the function of regulating immunity can not stop or inhibit the immune response in time, which will also lead to the occurrence of autoimmune reaction.

　　Autoimmune diseases are related to genes.

　　It is necessary for us to understand the role of genes in autoimmune diseases.

　　In the process of immune response, many auxiliary molecules are needed to produce specific immune response against foreign microbial antigens. Among them, the most important helper molecule is MHC (major histocompatibility complex). T cells can be activated and the subsequent immune response can be initiated only after the foreign microbial antigen and MHC molecules combine to form a complex.

　　MHC is usually called human leukocyte antigen (HLA), and its related gene is located on chromosome 6. HLA antigen complex is regarded as the genetic determinant of immune activation. In other words, HLA mainly determines the characteristics of immune response and the occurrence and development direction of immune response. At present, more and more genetic studies show that HLA determines a person’s susceptibility to many diseases, especially autoimmune diseases. People who carry these susceptibility genes have a much higher risk of autoimmune diseases than the general population.

　　In reality, scientists have found some susceptible genes related to autoimmune diseases. It is certain that human immune response is influenced by genetic factors, and some autoimmune diseases have genetic tendencies.

　　People with genetic susceptibility should beware of "molecular simulation"

　　Generally speaking, autoimmune diseases often occur in genetically susceptible people. Their immune cells have abnormal functions, and they will get sick when they encounter suitable external triggers.

　　These external triggers include microorganisms, such as some bacterial or viral infections, and some harmful substances in the environment, such as smoking. For example, some microbial antigens, such as staphylococcal protein A and staphylococcal enterotoxin, can stimulate T or B cells, making these cells transform into autoreactive T or B cells, leading to autoimmune reactions.

　　In addition, because the components of some microorganisms are similar to the fragments in normal human tissues, the normal immune response to foreign microorganisms will activate autoimmune lymphocytes in the form of "molecular simulation" or cross-reaction, causing autoimmune reactions. The most typical autoimmune disease caused by molecular simulation is rheumatic fever. The anti-Streptococcus M protein antibodies in rheumatic fever cross-react with actin, laminin and antigens of nervous system, and start inflammatory reaction in the heart, causing rheumatic heart disease. If these antibodies enter the brain tissue, they can cause chorea. Studies have shown that in type I diabetes, rheumatoid arthritis and multiple sclerosis, there is a "molecular simulation" effect between this microbial protein and human tissues.

　　In a word, the immune system is a delicate and complex barrier to protect the body from external harm. However, the pathogenesis of autoimmune diseases is very complicated, so far, the exact pathogenesis of a considerable number of diseases has not been fully studied. It should be noted that after the occurrence of autoimmune diseases, patients should seek medical advice in time, diagnose and treat early, so as to avoid irreversible damage to important organs. (Tian Xinping, Peking Union Medical College Hospital)