Views:2 Author:Site Editor Publish Time: 2020-03-20 Origin:Site
What is the response of the body to viral infection?
Human history is a history of combating diseases, including viruses. Far away, such as smallpox virus, and more recently, polio virus, we humans have finally defeated these extremely terrible viruses. In the process, the human immune system is constantly evolving and becoming more and more powerful.
In the fight against the new crown virus, in addition to scientific symptomatic treatment, what role does the human immune system play?
1.Identical virus and multiple antibody production
As far as this new type of coronavirus is concerned, most individuals have no symptoms or only mild symptoms after exposure to the virus, and some have symptoms such as fever and chest tightness, which improves on their own after a period of time; but for those with weak or low immune function However, virus infection is a severe test.
Up to now, many people have developed infectious pneumonia due to new coronavirus infections. Whether it is government departments, scientific research teams, or the general public, everyone is looking forward to the emergence of antibody drugs, and the practice of directly collecting sera from cured patients during SARS to treat critically ill patients directly reflects the importance of antibodies for the treatment of such infectious diseases. .
It is true that antibodies are one of the most important weapons for the body to fight viral infections. Once the neutralizing antibody (English name neutralizing antibody) is produced, it is not only large in quantity but also durable, thus blocking the virus from entering the cells highly effectively. Can not enter the cell, can not reproduce, expand, the virus outside the cell will gradually self-decompose, this is the magic of antibodies.
If inactivated virus particles are directly injected into the body, the body will produce antibodies against the virus, which is a traditional vaccine that produces the effect of vaccination. The current development of vaccines for new crown virus also follows this basic principle.
However, as long as the body produces antibodies, it can control the virus. This idea may be only an illusion. The actual situation is far from this. Some antibodies can even promote the development of new coronary pneumonia. So, is this alarmist, or is it scientific? One fact is that many antibodies have been produced in many patients with severe neonatal pneumonia. Why can't these antibodies control the virus? This is due to the complexity of the antibody.
There are 20 kinds of amino acids in the body. Chemical covalent bonds link the amino acids one by one to form a long chain. This is commonly known as a protein. An antibody is a protein molecule that presents a branch-like Y-shaped structure, and the branch part recognizes and binds to the antigen (usually a foreign protein). There are various heterologous proteins in nature. To recognize them, the branches of the branches are also various (biologically called the variable regions of antibodies), and even various Antibodies, but the trunk part of these different antibodies is basically the same (the constant region of the antibody is called biologically).
The nucleic acid substance RNA of the new coronavirus is located at the core and is enveloped by a nucleocapsid protein. The envelope is covered with spike protein (like a nail after amplification), envelope protein, envelope protein, and membrane protein. protein. In addition to these proteins that maintain the structure of the virus, the genetic material of the nucleic acid of the virus can also direct the production of other viral proteins that are not involved in the structure of the virus (these viral proteins are present in the infected cells and not in the virus particles). All these viral proteins are foreign proteins. For any foreign protein, the body may produce antibodies specific to it. As a result, individuals infected with the new coronavirus can produce a variety of different antibodies against the virus.
2. Some antibodies lack antiviral effect
Now that the body has produced a variety of antibodies against the virus, does each antibody play an antiviral protective role? the answer is negative.
Antibodies need to play an antiviral role, provided that the antibodies recognize and bind to viral particles. However, non-structural viral proteins do not exist in the virus particles (in the infected cells), so antibodies against this large class of viral proteins have no antiviral effect.
So, if the antibody targets the protein that is present in the virus particles (the so-called targeting, in general, it is a radish and a pit, this antibody specifically binds this protein), does it have an antiviral effect? The answer is that only antibodies against viral surface proteins can produce antiviral effects.
The surface of the new coronavirus is an envelope. The antibodies to the viral protein inside the envelope cannot be contacted. Therefore, this part of the antibody does not have antiviral effects.
In short, after the virus particles infect the body, a variety of different antibodies against viral proteins can be produced in the body, but most antibodies do not have an antiviral effect. Only antibodies that recognize the protein on the surface of the virus particle can have an antiviral effect.
3. Mode of action of effective antibodies against viruses
Antibodies that recognize proteins on the surface of virus particles can produce antiviral effects, so how do these antibodies work?
Coronavirus is caused by the spike protein (nail protein) on the surface of virus particles and a protein called angiotensin-converting enzyme 2 (ACE2) on the surface of lung epithelial cells, and ACE2 subsequently takes shape The structural change causes the virus to enter the cell, and uses the cell's own amino acid molecules, nucleotide molecules and lipid molecules to synthesize new virus particles through chemical reactions. These new virus particles are released outside the cell in the same way. , Infect the surrounding normal cells. Antibodies to spike proteins, which bind to spike proteins on the surface of virus particles, block the binding of spike proteins to ACE2, which also blocks the virus from entering cells. The antibodies against spike proteins are so-called neutralizing antibodies. Neutralizing antibodies play a protective role by preventing viruses from invading cells, which is the main force for antibodies to exert antiviral effects. There are envelope proteins and membrane proteins on the surface of the coronavirus, but these two proteins may not mediate the virus's entry into the cell. Therefore, the binding of the antibody to the envelope protein or the membrane protein may not affect the virus's entry into the cell, but if this binding Affecting the conformation (three-dimensional space structure) of spike protein, so that spike protein does not bind well to ACE2, can prevent the virus from entering the cell (the probability of this situation is low). Antibodies to envelope proteins or membrane proteins, after binding to the corresponding proteins on the surface of the virus, even though spike protein does not affect the virus to enter the lung epithelial cells, it can mediate the phagocytosis of virus particles by the immune cells of the body. This is due to the presence of specific proteins on the surface of phagocytic cells (called Fc receptors) that are able to recognize the trunk part of the antibody, the constant region. In this way, the antibody binds to the virus through its variable region and binds to phagocytes through its constant region, which greatly promotes the phagocytosis of virus particles by the phagocytic cells, and the phagocytosed virus is decomposed and eliminated in the phagocytic cells.
In summary, the ways in which antibodies work are divided into two categories: neutral surface antibodies bind to the virus to prevent the virus from entering the cell (protecting the enemy from outside the country); non-neutral surface antibodies bind to the virus, and mediate the phagocytosis and elimination of immune cells Viruses (kill the enemy within the country).
4. The disadvantages of antibody anti-virus
Non-neutralizing surface antibodies bind to viruses and mediate the phagocytosis of immune cells, which are mainly macrophages (full-time phagocytic cells in the human body). After the macrophages swallow the virus, the virus particles are wrapped in a vesicle called an endosome, and the endosome then moves away from the cell surface and moves towards the center of the cell. In the process, it interacts with a type called a lysosome. The vesicles are fused, and the lysosome contains a variety of hydrolytic enzymes that can hydrolyze the virus, thereby eliminating the virus.
But while the immune system has evolved such an anti-virus mechanism, the virus is also evolving, using all means to escape the swallowing and killing. One of these mechanisms is that the virus escapes from the endosome before the endosome is fused with the lysosome. How to escape? After the endosomes envelop the virus, the fluid in the endocytic body's cyst cavity is gradually acidified (the pH value decreases). The virus can remove the outer envelope by acidification to expose the viral nucleic acid and take the viral nucleic acid from the endocytic body. In the cytoplasm, viral nucleic acids can be replicated to form new viral particles and released outside the cell. In this way, the virus uses surface antibodies to transform immune cells into virus intermediates to escape immune killing.
The virus's intracellular expansion in macrophages may not be the worst thing. Worse still, the virus may promote the inflammatory storm through macrophages.
Damage to lung cells by new coronaviruses generally does not directly lead to death of patients. The main cause of patient death is the excessive activation of non-specific immune cells, which release a large number of pro-inflammatory factors, such as interleukin-1 and leukocytes. Interleukin-6, tumor necrosis factor, etc. form a so-called cytokine storm, scientific name is cytokine release syndrome (cytokine release syndrome, CRS). The pathological damage of CRS is mainly manifested in capillaries. The capillary tube wall is arranged by a single layer of vascular endothelial cells. The gap between the endothelial cells is small only 1-2 nanometers, and the big one is only 5-8 nanometers. This is because the endothelial cells border the endothelial cells. There are numerous connexins on the surface, which are closely connected to each other, resulting in such a small gap. However, the above-mentioned pro-inflammatory factors act on capillary endothelial cells in lung tissue, so that the surface of endothelial cells is no longer expressed or the amount of connexin is greatly reduced. In this way, the gap between endothelial cells suddenly becomes very large, and the blood in the capillaries It flows out from the enlarged gap and fills the alveoli. This is the inflammation storm.
So, what kind of immune cells are the cytokines that trigger the inflammatory storm? Macrophages are the culprit. Macrophages are important first-line defense cells in the body, with a large number. Virus infection of macrophages can quickly activate macrophages and induce macrophages to release pro-inflammatory factors, but when the virus multiplies in macrophages, the activation of macrophages is particularly strong and can release excess pro-inflammatory Factor, triggering a cytokine storm.
5. The effect of non-neutralizing surface antibodies depends on the phase
Since the virus multiplies in macrophages, and there is a risk of causing great harm to the body, isn't the non-neutralizing surface antibody completely bad? The answer is not yes, it depends on the time.
In the early stages of viral infection, macrophages are functional in all aspects, phagocytosing antibody-mediated viruses, and more often hydrolyzing them in lysosomes. Even if some viruses escape to the cytoplasm, macrophages interfere with startup The protein signaling pathway can also effectively inhibit virus replication and amplification. In the middle and late stages of viral infection, macrophages not only sense the signals of the virus, but also the signals of various cytokines. The function of the macrophages changes, and the virus takes advantage of this opportunity to escape to the cytoplasm on the one hand; In terms of a large number of amplifications, the large number of amplified viruses, in turn, forced macrophages to be strongly activated, and then released excessive amounts of pro-inflammatory factors, causing damage to lung tissue.
Therefore, against virus surface proteins, neutralizing antibodies always play a protective role by preventing the virus from entering the lung epithelial cells, but non-neutralizing antibodies mainly mediate the virus into macrophages and play an antiviral role in the early stages, but in In the middle and late stages, it may be mainly caused by lung immune damage.
6. The body's elimination of viruses ultimately depends on T cells
Neutralizing antibodies are outside the cell, but they are powerless for viruses that have entered the cell. At the same time, neutralizing antibodies can only prevent most of the virus from invading the cell, and a small part or part of the virus will still enter the cell. . For viruses that hide inside cells, the ultimate killing depends on T cells in the human body. The virus in the lung epithelial cells will express the information of the viral protein on the surface of the infected cell, and the T cell can recognize the information of the viral protein on the surface of the infected cell, thereby launching an attack on the infected cell and killing it The end result is that the infected cells die, and the virus hiding inside also suffers the fate of being degraded. Therefore, even if it is a neutralizing antibody, it is not a panacea, but it can remove obstacles well and allow T cells to play their final role.
In short, for new coronary pneumonia, too many hopes are pinned on antibodies, but antibodies are not generally understood as simple, that is, as long as the body has antibodies, it can clear the virus. We need to know enough about the complexity of antibodies and even the worsening side of the disease. At the same time, this also has important guiding significance for vaccine development, because the purpose of vaccination is to let the body produce antibodies, in fact, to produce neutralizing antibodies against the surface proteins of virus particles. It is easy to vaccinate the body to produce antibodies, but it is not easy to produce such protective neutralizing antibodies, which poses a huge challenge to vaccine development. We should take a cautious attitude and carry out in-depth and detailed work. If everyone understands the protective mechanism of the body's immune system to the human body and understands that we can improve immunity through lifestyle and diet, we can reduce the fear and powerlessness brought about by the new virus. We firmly believe that the human immune system will once again prove that it is the elimination of evil viruses