The ongoing pandemic has made many of us, more than ever, interested in health issues, especially the factors influencing our immunity. What specifically strengthens it, what weakens it and how it works in the face of the new coronavirus – says Prof. Joanna Zajkowska from the Medical University of Białystok.
- The basic task of the immune system is to distinguish self from foreign cells – explains prof. Zajkowska
- As the expert adds, some viruses that have a special “key” thanks to which they can enter our cell and make them make copies of the virus
- The SARS-CoV-2 virus enters our cells using ACE-2 receptors, most of which are found in mucosal cells, including in the upper respiratory tract, but also in other organs, such as the intestines and even the brain
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- You can find more such stories on the TvoiLokony home page
Not everyone watched the TV series “Once Upon a Time” in their childhood, in which it was presented in an accessible way how the human immune system works in practice. Could you explain in a few words what are its most important tasks and mechanisms?
The primary function is to distinguish self from foreign cells. Each of our cells is signed that it belongs to us, using the so-called the histocompatibility system, specifically the MHC I and MHC II molecules. With their help, the histocompatibility system gives each of our cells an identifier (as if a name and surname), which is recognized by our immune system. If a cell does not have such an identifier, then the immune system recognizes it as an “unauthorized intruder” and destroys it.
In this way, cells that can give rise to cancer are destroyed every day (cancer is our own cells that divide according to their own rules). This is also how bacteria and viruses that enter our body from the outside are recognized and destroyed. Therefore, a well-functioning immune system protects us against both cancer and infectious diseases. His efficiency increases if he knows and remembers such intruders in advance. This is why vaccines are such an effective way to prevent many diseases, as they simply take advantage of these natural defenses in the body.
But the same mechanisms probably also cause problems sometimes, for example when transplanting some organs or tissues, right?
Actually. Therefore, before transplantation, we first examine the patient’s histocompatibility system, and then we look for a donor who is as similar as possible in this respect. Despite this, the patient (recipient) must be given drugs that weaken the immune system, so that his body does not reject the transplant.
Let’s go back to infectious diseases. Please explain how the immune system recognizes viruses that are not, after all, cellular organisms.
MHC I and MHC II molecules, in addition to labeling our cells, also take part in showing the immune system foreign proteins. If the MHC I molecule does it, then the body generates the so-called a cellular immune response, and if the MHC II molecule does it, it generates the so-called humoral response.
What does it depend on, and how are the two types of immune response different?
If a foreign protein is created in our cell (e.g. a coronavirus spike protein produced on the basis of a vaccine mRNA recipe), then the MHC I molecule presents it to the immune system, and if the foreign protein is absorbed by the cell from outside (e.g. from a vaccine containing a ready-made protein) coronavirus spike), then the MHC II molecule shows them. Both the cellular and humoral responses are designed to destroy the intruder, but differ in their mechanism of action.
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And which of these two types of immune response is associated with the production of antibodies?
The humoral response when the protein is depicted on the MHC II molecule (that is, when the finished protein is “swallowed”).
So it should be most important to us to create it?
It is quite a complex matter. It is worth knowing that our immune system fights viruses differently than against bacteria and their toxins. We fight viruses primarily using the so-called cytotoxic cells, NK lymphocytes, called natural killer. They are an element of both anti-infective and anti-tumor cellular immunity. Meanwhile, we fight bacteria mainly with the help of antibodies, which are an element of humoral immunity. In practice, however, we need both types of immune response to successfully combat viral infections.
In the context of vaccines, it is worth emphasizing that both mRNA and vector vaccines combine these two mechanisms. Thanks to these vaccines, the synthesis of the viral spike protein takes place in our cells, thanks to which MHC I molecules generate a cellular response, but later, when these cells break down, then the foreign protein is absorbed by other cells from the outside, so that MHC II molecules trigger a humoral response.
Thus, other types of vaccines, e.g. protein, that is, containing not a recipe for the coronavirus spike protein but a ready spike, but rather the surface protein “S” forming it, will generate a different immune response?
Yes, the way we present the foreign antigen to the immune system largely determines the type of response. As already mentioned, mRNA and vector vaccines allow us to produce a foreign protein by ourselves, which allows us to generate a strong cellular response first, and then generate a humoral response.
In contrast, vaccines using viral spike protein (e.g. Novavax) or killed virus (e.g. Chinese vaccines) mainly generate a strong humoral response. In practice, therefore, mRNA and vector vaccines work more comprehensively. In this context, it is worth adding that both types of immune response generate the so-called memory cells, or “the intruder’s memory portrait”, which makes it easier to identify him faster and to defeat him in the future.
- How is vectored vaccine different from mRNA? Which type reached Poland?
And do you already know which type of vaccine is the most effective and provides the longest protection?
For many reasons, it is difficult to make an unambiguous assessment at the moment. We suppose, however, that the way mRNAs are introduced into cells may affect the durability of the vaccination effects. As it is known, the carriers of mRNA in genetic vaccines are nanolipid vesicles, which are quite indifferent to the immune system (they elicit a low response from it, if at all). Meanwhile, in vector vaccines, the carrier that introduces mRNA into cells is a weakened adenovirus that is unable to reproduce. However, this adenovirus is no longer indifferent to the immune system, which recognizes its proteins as foreign and responds (antibodies) against them.
This is why postvaccination adverse events are more common after vectored vaccines, although usually mild and transient after the first dose and even weaker after the second. It is worth adding that scientists are constantly analyzing the factors that affect the durability of vaccination effects. One method that is used to do this in some vaccines is by adding adjuvants to them.
We’ve talked a lot about vaccination, but I understand that both of the aforementioned immune mechanisms also arise when you are naturally infected with the new coronavirus. Please tell me how such an infection proceeds step by step, from the point of view of the immune system.
Let’s start with the fact that we encounter a large number of various pathogens, including viruses, on a daily basis, but not all of them infect us. Only those viruses that have a special “key” that allow them to enter our cell do this in order to re-tune its internal machinery so that it creates copies of the virus. This is, in short, the operating philosophy of viruses.
So the new coronavirus has such a key, and in order to multiply, that is, create copies of itself, it enters our cells. For this purpose, it uses ACE-2 receptors, most of which are found in mucosal cells, including in the upper respiratory tract, but also in other organs, such as the intestines and even the brain. If the virus begins to multiply, then it spreads around our body, attacking other cells it can enter, especially those located in the lungs, because it is closest to them.
How does our body react to this invasion?
Once the virus makes copies of itself, it eventually breaks down the infected cells. This alerts our immune system, which at the same time tries to recognize a foreign viral protein, begins to clean up the products of cell breakdown, and mobilizes various forms of immune forces, i.e. inflammation is created, which is aimed at eliminating the invasion of intruders. This is the cause of the symptoms of infection that we notice, i.e. swelling, exudation, alveolar fluid, shortness of breath, fever, cough.
It is the attempt to eliminate the virus that gives us the clinical symptoms of COVID-19. Metaphorically, it can be compared to the Battle of Grunwald, because many different cells of the immune system are involved in this fight against infection, creating separate formations that have different competences: some recognize, others attack, others clean up the battlefield, there are also those that regulate immune response and those that remember the invader.
If the body takes control of the situation in the first week of infection, then the inflammation gradually diminishes, which leads to recovery.
But what happens next if the situation is not brought under control and is out of control?
Some people have an overreaction of the immune system to the infection. They show dysregulation in the activity of infection-fighting cells, mainly macrophages. Then, instead of silencing the inflammation, there is an uncontrolled increase in it, which creates the risk of the so-called a cytokine storm. It often leads to multi-organ failure and a dramatic course of the disease.
And at what point do antibodies form?
In the first phase of infection, mainly the innate (non-specific) immunity mechanism comes into operation, and the formation of specific antibodies is not observed until the 2-3rd week, i.e. when a large number of cells attacked by the virus begins to break down. The virus protein is then released from them, which is then absorbed by macrophages and cells presenting antigens to the immune system (dendritic cells). The latter, in order to effectively present the antigen (foreign protein), first chop it into pieces. This eventually causes antibodies against the viral proteins, first IGM and IGA, and then IGG. Memory cells are also formed. Thus, at this point, the development of the so-called acquired (specific) immunity.
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People who get infected without symptoms also produce all of these antibodies?
Yes, you just can’t see inflammation in them. Such an asymptomatic or mildly symptomatic course of infection is influenced by e.g. a small dose of the virus taken from the environment, as well as the innate features of the immune system. In such cases, the coronavirus infects us but does not cause disease, i.e. the visible symptoms of infection. Nevertheless, intruders are eliminated with such people in the same way as with others. However, observations indicate that the so-called Asymptomatic people have fewer and shorter duration of antibodies, compared to people who have had COVID-19 more severely or have been vaccinated.
And why are young children generally so rarely affected by COVID-19, while seniors are much more likely and harder?
Our immune system changes throughout life. First it educates itself, then it matures and functions to the maximum, and then it starts to work less and less, incl. because after the age of 65, the thymus, which is an important element of the immune system, undergoes gradual involution (disappearance). The aging of the immune system and its weakening with age is called immunosenessence. It is, among others for this reason, seniors are more likely than adolescents to develop cancer. Of course, the course of this phenomenon varies depending on the condition and predisposition of a given person. In general, however, the extreme age groups, i.e. the youngest and the oldest, are the worst at dealing with viral infections, because first the thymus is not fully mature, and then it undergoes gradual involution. Children around the age of 7 develop their immune system. After birth, each individual’s history of contacts with pathogens (intruders) is recorded, i.e. our own immunobiography is written. It is this part of immunity acquired through active contact with various pathogens, as a result of immunization as well as various infections. They are what make up our individual immunobiography.
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But after all, children are not vaccinated against the new coronavirus, and yet, according to statistics, they rarely get COVID-19. How it’s possible?
Their lower incidence of COVID-19 is explained by the fact that they are in the period of systematic vaccination, thanks to which their immune system is constantly stimulated and thus more reactive. Second, entry of this virus into human cells is via the ACE-2 receptor, which is less expressed in children than in adults. Thus, the gate of infection is less accessible.
What else causes some people to get COVID-19 lightly like a common cold without being vaccinated against it?
Some people may suffer from the fact that they have had infections caused by other coronaviruses before. After all, we have known for a long time several coronaviruses that cause common, seasonal colds. Perhaps, then, such people have a certain potential of anti-coronavirus antibodies, thanks to which they also neutralize this new coronavirus SARS-CoV-2. This also confirms the rule that we record our immune history throughout our lives and rearm ourselves through vaccination or contact with pathogens.
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Apart from aging, what else weakens the immune system, increasing the risk of infection and the severe course of COVID-19?
The immune system works weaker when we are exhausted, e.g. after a long journey, exhausted by some disease, malnourished, sleepy, stressed, etc., so when we are generally in a poor condition, both physical and mental. For example, stress negatively affects the body’s ability to cope with infections because it releases specific adrenal hormones (called stress hormones) that depress the immune system. That is why it is worth consciously taking care of your condition through healthy eating, regular physical activity, getting enough sleep, maintaining a healthy balance between work and private life, as well as learning effective techniques to deal with stress. All this translates indirectly into our immunity.
And what’s fashionable lately? Strengthens immunity?
If it is used with the head, i.e. with the appropriate, prior conditioning and hardening of the body, and at the same time regularly and without any extreme stunts, I think that it can help us to better adapt the body to the temperature difference, as well as mobilize it in general. However, this is an activity only for generally healthy people, without any serious burdens.
How else can you temper your body without jumping into the ice hole, which is pretty extreme in a way?
As you know, we often catch colds when we experience some sharp temperature difference, e.g. eating ice cream in summer or not wearing a hat or scarf when leaving the house in winter. Temperature shocks favor, among others, upper respiratory tract infections. So getting used to temperature differences can help your body adapt better to these situations. On the other hand, it is also worth avoiding excessive overheating and overheating of the rooms in which we are staying, so try to eliminate the temperature differences we experience.
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And more and more popular in Poland swallowing supplements for immunity? Does it help or not?
I would not overestimate their importance. The basis is a healthy, balanced diet, which should provide us with all the necessary nutrients, vitamins and trace elements. In our latitudes, in the autumn and winter period, it is only reasonable to supplement the diet with vitamin D3, but this also cannot be overdosed, because you can overdose. As for other immune supplements, however, I would be careful. A healthy diet with lots of vegetables and fruits is a much better idea.
Including lots of garlic and onion?
Indeed, onions, but also chicory, sauerkraut and even bananas are very valuable for the body, incl. because they promote the development of beneficial intestinal microflora. So they are the so-called prebiotics.
Why is eating them important in terms of immunity?
Some scientists estimate that the level of immunity in up to 40 percent. it depends on what is in our belly. It is, of course, about the appropriate composition of the microbiota, i.e. primarily the so-called good gut bacteria, called probiotics. They are an important element of the immune system because, firstly, they prevent the growth of putrefying bacteria that create various toxins, and secondly, they facilitate the absorption of vitamins and proteins from food and create an appropriate, i.e. acidic, pH in the intestines. The composition of the microbiota is therefore influenced by both probiotics (bacteria) and prebiotics (a breeding ground for bacteria).
What about garlic, ginger, echinacea and other immunity-boosting agents that have been used in natural medicine for many years? Are they working or not?
Their use has a long tradition, so they certainly won’t hurt us, as long as we don’t abuse them, of course. The mentioned Echinacea is classified by medicine to the so-called immunomodulators, i.e. agents that improve immunity. However, many other natural products, such as green tea or the aforementioned garlic, also have a beneficial effect. However, these are good prophylactic measures, because in the treatment of infections, especially the more serious ones, they certainly cannot replace drugs. Although the consumption of raspberry juice or watery herbal infusions, i.e. traditional, folk methods used by our grandmothers for a long time, may also be helpful in infections, I would not overestimate it either.
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What about protective masks for the mouth and nose? There are many skeptical voices that they are not a very effective barrier to the new coronavirus.
In my opinion, it has already been proven sufficiently that the use of the so-called DDM rules significantly limit virus transmission, especially in confined spaces. Although, for example, in Sweden like this, the approach to the issue of the widespread use of masks is still quite liberal, believe me, however, that local doctors apply them quite rigorously, just like doctors in other countries.
The facts are that people who breathe their mouths, speak loudly, cough or sneeze while wearing a mask, actually protect others from the bioaerosol they emit. Someone has calculated that one sneeze can emit as many as 7 billion virus particles, at a speed of 60 km per hour. However, masks retain a significant part of this bioaerosol, or at least its larger particles.
To stop the finer aerosol, professional masks with high protective parameters are needed. Therefore, there is nothing to complain about. The use of masks really makes sense and it works both ways, i.e. it protects others from getting infected from us and protects us from getting infected from others, although the latter to a slightly lesser extent. Of course, as long as we use them skillfully and they are of appropriate quality.
I would also like to ask about the new variants of the coronavirus: do they attack us in the same way as the base variant?
The identified mutations concern, inter alia, the famous coronavirus spike. Thanks to them, unfortunately, it connects with our cell receptors more easily, and thus replicates faster. Hence the greater infectivity of the new variants.
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Do you already know to what extent current vaccines protect people against these new variants?
We can say that vaccines are a kind of memory portrait of a pathogen, which we present to the immune system so that it can be recognized and remembered as soon as possible. So if the virus mutates and changes significantly as a result, this portrait will also be less useful for identifying the changed virus. In any case, the virus becomes more or less difficult for the immune system to recognize, since it only has the initial pattern presented in the vaccine. Therefore, manufacturers are already working on the next versions of vaccines that will take into account the most important mutations of the virus.
It promises to be very interesting, among others a new type of vaccine, the so-called mosaic, on which scientists from the American Institute of Technology in Pasadena are working (the work is in the pre-clinical stage). Mosaic technology is based on the fact that coronavirus spines are placed on one protein carrier, but they come from different variants of it. Due to this diversity, animal studies show that this vaccine generates immunity not only against these specific variants, but more broadly against various coronaviruses, perhaps also those that are still dormant somewhere in the animal world. Remember that this is not the first coronavirus epidemic that came out of the animal world, so there may be more. The mosaic vaccine, which contains many memory portraits of the coronavirus, therefore offers great hopes and opportunities.
The virus, however, has gained an advantage over us and is trying to get out of hand. Will it be possible to overcome it in the end, or will it stay with us forever as a seasonal virus, like the flu?
We must remember that it has its own permanent animal reservoir, from which it has jumped onto humans for the third time. Before that, we already had zoonotic epidemics of SARS and MERS caused by similar coronaviruses, but we managed to suppress them quite quickly. This animal reservoir remains. So it’s hard to predict anything. It is also difficult to predict whether the SARS-CoV-2 virus will stay with us permanently as a seasonal virus. One thing only seems certain that this pandemic will not end soon. In every epidemic there are so-called epidemic waves, the peak of the epidemic, as well as the so-called the tail of the epidemic, i.e. its gradual extinction. I think this tail will drag on for a long time. Much depends here on the speed of vaccination. It must be remembered that, apart from obtaining individual protection against the disease, another important goal of vaccination is also to reduce the transmission of the pathogen in the population by building the so-called herd immunity. This is how we most effectively hinder the pathogen’s development by creating new variants (mutations).
Let’s go back to antibodies for a moment. Do we get exactly the same antibodies by vaccinating as for COVID-19?
Not completely. The SARS-CoV-2 vaccines currently in use contain the viral spike protein, so after vaccination our antibodies are directed against this protein, i.e. the S protein. Meanwhile, the virus also contains another type of protein, namely the internal nucleocapsid protein (the so-called N protein) . Therefore, after contracting COVID-19, we will generate anti-S and anti-N antibodies, while after vaccination only anti-S.
I guess that has important implications for the selection and interpretation of serological test results, right?
Yes, we generally do a serological test when we want to check if we have already passed COVID-19. After vaccination, whether we have been vaccinated with an mRNA vaccine or a vector vaccine, there is no need to do such tests. Nevertheless, it is important to know that there are different types of serological tests: some detect only antibodies against the surface of the virus (i.e. the S protein), and others against its interior (i.e. the N protein). Still others detect both types of antibodies. So, the anti-N test will not show us the vaccine antibodies (in which case it will turn out to be zero). So if someone absolutely wants to do a test after vaccination, he should choose the variant detecting anti-S antibodies. Generally, therefore, it is best, as a rule, to test for the presence of anti-S antibodies, which we acquire both after vaccination and after infection, and if we get high titers, then we can feel safe.
Nevertheless, survivors are also advised to vaccinate.
Yes, because with time the amount of antibodies in the healed decreases, and much faster than in the vaccinated. Therefore, you should not delay vaccination for too long, even after contracting COVID-19. Especially since the amount of antibodies generated can vary greatly from person to person. The level of protection obtained after an outbreak may simply not be sufficient to fight a subsequent infection. That is why, three months after passing COVID-19, it is recommended that convalescents be vaccinated.
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Let us also remind you when it is best to perform antigen and genetic tests, which in turn are used to detect the current infection.
The PCR (genetic) method detects fragments of the genetic material of the virus. Such a test is best done 5-7 days from the moment of potential infection, while the antigen test is performed ad hoc, when any symptom of COVID-19 appears in someone. It is worth knowing that an antigen test in asymptomatic people with a lower viral load may result in a false negative. Therefore, it is most relevant in symptomatic patients. Thus, genetic tests are more sensitive and operate over a wider time frame. It is worth knowing that the remnants of the virus can be excreted for up to 8 weeks from the moment of infection, when we do not contaminate anymore. The genetic test can even then detect this infection that has already been present much earlier. In turn, the antigen test confirms that we are actively infected when there are symptoms of infection.
Finally, in the context of the fight against COVID-19, please tell me about what undesirable post-vaccination reactions you encountered in your clinic or about which NOPs you heard from your colleagues.
In general, the number of NOPs is as expected, and most of them are mild and temporary. It is simply the expected and calculated price we pay for generating immunity. Anyway, these reactions signal that the vaccine is working and that our body is responding to the administered antigen. At the vaccination point where I work, we did not have major NOPs. The potentially most dangerous of these is anaphylactic shock, which, however, is extremely rare, with an average of 1-5 people per million vaccinated.
The risk of such a shock, even despite careful qualification for vaccinations by a doctor, cannot be completely eliminated, right?
Unfortunately yes. Some of these reactions are unpredictable, especially since we don’t know if a person is allergic to a specific component of the vaccine, such as polyethylene glycol. When a doctor asks a patient about it, he will certainly not know. If someone is allergic, as a precautionary measure, the time of observation after vaccination is extended to half an hour or the person is sent to an allergist for consultation before vaccination. However, remember that such a shock may appear even after the first administration of a polopyrin or aspirin tablet.
From time to time, media reports of deaths following COVID-19 vaccination. Have you come across such a case?
Personally, not, but I know that there were, among others cases of death of elderly people after vaccination, but not from NOPs, but rather from other causes. In my experience, older people who get vaccinated are very stressed because in order to get vaccinated, they must first get to the vaccination site, find a suitable room, be there at a specific time, and are afraid of the vaccination itself. All of this often results in an increase in blood pressure, which is known to increase the risk of a heart attack or stroke. Therefore, it is worth creating a good, friendly atmosphere during vaccinations and mentally prepare patients in advance, and thus ensure their comfort as much as possible.
This can also please tell you about the most important contraindications for vaccination against COVID-19. Are they the same as with other vaccinations?
The most important contraindication is the occurrence of anaphylactic shock after the administration of the first dose of the vaccine. This disqualifies the patient from administering the second dose. The rest is relative and depends largely on the individual’s risk calculation. Maybe I would recommend special caution in the case of vaccination of the so-called age-old people. brittleness syndrome. In such a case, it is probably better to vaccinate all people in the close vicinity of such seniors and thus protect them from infection, because for them, vaccination could be too strong a stimulus that could disturb their fragile internal balance.
Interviewed by: Wiktor Szczepaniak, Zdrowie.pap.pl
The interview was carried out as part of the “Science will win” educational project sponsored by Pfizer.
Prof. Joanna Zajkowska, infectious diseases specialist
She graduated from the Faculty of Medicine of the Medical Academy in Łódź. Infectious diseases and epidemiology specialist. Her professional interests mainly concern clinical immunology. He works as a lecturer at the Medical University of Bialystok, and also as a clinician – he is the deputy head of the Department of Infectious Diseases and Neuroinfections at the University Teaching Hospital in Bialystok.
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