One of the most important issues in the course of the epidemic of the coronavirus, which has yet to be answered is what kind of immunity people get after an illness. It is important to understand whether re-infection, and of course, extremely important for the development of a vaccine. We are getting more information in this area, and a good example is the new research team of scientists from the Institute of immunology in San Diego, the University of North Carolina, University of California San Diego and the hospital “Mount Sinai” (new York). The report on the results of the work discussed on the T-cells of people who recover from coronavirus infection. Here a little explanation is required to better understand the results of this work, so below I will briefly talk about T-cells and on acquired immunity.
Of course, everyone has heard about the white blood cells leukocytes. One such group is called Taurus lymphocytes (literally, “cells of lymph”, where they can be easily found), which are divided into B-cells, T-cells, NK-cells. Here we see three major branches of the immune system. NK-cell (NK — natural killer, natural killer) is part of a natural, innate immunity non-specific properties, and it relates to cell-mediated cytotoxic lymphocytes. The other side of the immune system is the acquired immune system. I wrote about the b-cells in their posts about the antibodies, as part of an adaptive system, they produce specific antibodies upon contact with the antigen. T cells also belong to the acquired immunity, but they belong to the cell-mediated part of this vast army.
T cells — from the Latin thymus (“thymus”, thymus), as it is called the organ of lymphopoiesis person. You will surely ask the question, what kind of authority, and what he does for us. That’s a good question. All of these cells have a particular surface protein, T-cell receptor. Just as the immune system produces huge amounts of antibodies, shuffling and mixing the protein expression, there is a huge number of T-cell receptors, waiting to recognize common antigens. The progenitors of T-cells emerge from bone marrow and migrate to the thymus, where they begin to branch. The growth continues even when they leave the thymus and begin to circulate in lymph and blood.
The heirs are T-suppressor cells, or cells CD8+ T with some other names. CD8 is another special protein with the cell surface, which distinguishes this type. These cells do not looking for viral particles; they are looking for infected cells and kill them until they opened and didn’t release additional virus particles. Similarly, they destroy bacterial cells. Immunotherapy using T cells with chimeric antigen receptors, is trying to mobilize these cells to recognize cancer cells and also destroyed them. How do they do it? They work very carefully, including several lethal mechanisms. The most common mechanism is the secretion of cytokines, especially TNF-alpha and interferon-gamma, which search for other cellular systems, that they found targets for attack. (A drug based on monoclonal antibodies against arthritis actually clears the way for tumor necrosis factor-alpha (TNF-alpha), because in rheumatoid arthritis T cells are the wrong way to attack the tissues of the joints.) The second function of the CD8+ is the allocation of proteobacteria vacuoles. It is a devastating combat load that locks on the cage-the target, when the T-cell is firmly attached to it (the immune synapse). Such proximity is necessary because proteobacteria vacuoles are bad news. They contain proteins that open a pore in the target cell, and, through them, penetrate inside serinova enzymes proteases, which are beginning to destroy intracellular proteins, causing total chaos (and eventually the death of cells). And the third method of killing — through another surface protein is present in cells CD8+. It’s called the Fas-ligand is a transmembrane protein. It binds to the normal protein Fas on target cells, causing a cascade of signals inside the cell and also leads to her death. (Interestingly, cells CD8+ using the system after the weakening of the infection to kill each other and return the level to normal.)
There is another group of T cells — CD4+, or T-helper cells. They work with another class of immune cells that present antigens. When CD4+ meets one of these cells, it involves a two-step activation process (the second step is a sort of check to make sure that it really is a foreign antigen and not something that is already present in the body). If the process is successful, begins the proliferation of such cells. You’ll hate me for saying this, but I have to say that so far everything was easy, but after that the situation becomes more complicated. But it’s immunology. The T-helper cells there is a long list of immune system function, and they interact with many other cell types. Among other things, they help you get just described the process of proliferation of cells CD8+, they activate b-cells to produce specific antibodies and they are involved in the allocation of additional molecules of the cytokine signals that I can list, although it is not necessary. Those cells which strike HIV, and that the loss of such important players in the immune response makes this disease so devastating.
Here is a brief explanation necessary to understand the essence of the new work. The authors examined in detail the virus-specific cells in CD8+ and CD4+ that occur in response to infection in patients who recover. As you already know, both of these subtype adaptive; they recognize specific antigens and respond to them. So how strong is this reaction, and what coronavirus antigens boost? You know how important these items. Depending on what happens, you can get an infection that will not cause a strong enough reaction to leave In-cell and T-cell memory foam what is happening and makes people vulnerable to re-infection. Or the reaction will be too strong — we’ve all heard about the “cytokine storm”. CD4+ cells are in the center of it all. Next, I mentioned the problems TNF-alpha, which is a sign of mismatched reactions CD8+. The new coronavirus unfortunately well evades the innate immune system, and therefore should be more active acquired immunity. One of the reasons (among many) a more severe illness in elderly patients is that the number of cells representing the antigen, decreases with age, and the first steps of the immune response, a key, are weak and muted. And when the infection starts to act seriously, it could lead to late and too violent reaction of T cells, i.e. cytokine storm. Somewhere in the middle is what we need: active and strong reaction, which kills the virus, remembers the incident for the future, and in the process does not attack the body tissue of the patient.
Comparing infected patients with those not infected with coronavirus, the research team went through the list of 25 produced by the coronavirus viral proteins. In the cells of CD4+ stood spiky protein, M-protein and N-protein: 100% of the infected patients had CD4+ cells that responded to all three proteins. CD4+ are also actively respond to other viral proteins: nsp3, nsp4, ORF3s, ORF7a, nsp12 and ORF8. The conclusion is that the vaccine that uses epitopes thorn of protein should be enough for a good immune response. But there are other possibilities. For example, if you add epitopes of M-protein and N-protein, the vaccine will be even more like real-coronavirus infection, and will better prepare the immune system.
As for cells CD8+, the situation is slightly different. M-protein and the protein was barely strong enough, and N-protein and two other proteins (ORF3a and nsp6) behind them. But the last three proteins gave about 50% of the immune response, acting together, and therefore to identify a single dominant protein in the immune response impossible. Therefore, to ensure a good response CD8+ makes sense to add epitopes from one or two of these proteins to the protein epitopes of the thorn, otherwise the reaction may be somewhat limited.
Here’s something to think about. 40-60% of uninfected patients were CD4+ cells that have already reacted to the new coronavirus. This does not mean that they were exposed to coronavirus as such: here we are talking about immune cross-reactivity. It seems that many people have appeared the immune response to other antigens, which partially protects against the new virus. There are important questions to find the answers will have to put a lot of effort. What kind of antigens as well protects immune response, does it help to reduce the severity of the disease in different patients (and groups of people)? As noted in the study, this cross-reactivity has apparently become an important factor that helped to make the epidemic H1N1 swine flu less severe than feared experts, because the population was already immune reserve, have proved more durable than expected.
Thus, the prospects of a vaccine very good, judging by the findings of the study. Acquired immunity really highly effective reacts to certain proteins of the coronavirus. And the developers of the vaccine will have to think about adding some of the other antigens mentioned in this work, in addition to protein antigens thorn, which until now were the center of attention. But it should be noted that the first series of vaccines will be primarily focused on thorn protein and other antigens to be included in their composition later. But it seems that thorn and focused on protein vaccines are highly effective, and it is good. The other good news is that the researchers were looking for signs of a reaction-dependent antibody amplification, and found them at convalescent patients (I’m in the money, but decided to mention this conclusion that gives a lot of hope). In addition, after infection (or after immunization) will certainly occur for a long period of immunity, that’s fine too. I understand that it is this immune response in this case and need. All will be solved by clinical data, but there is reason to believe that a person will have such immunity, if all requirements are met.
So let’s wait for new research on this and other topics; but the work performed is good and solid look at the immunology of this outbreak. Well, so far so good.
