Immunity should be in moderation
Excess immunity
5 facts about infection,
strengthening immunity
and gamma interferonPost -science
Everyone knows that a quantitative lack of an immune response is bad. Such a lack of immunity can be expressed in an increased incidence of both young children and the elderly.
1. Fighting infectionClassic examples of what happens to people who suffer from immunodeficiency are diseases that affect people with severe HIV infection and congenital defects of the immune system.
But because of these extreme examples, many have a strange feeling that the higher the immunity, the better it will be for someone who needs to deal with adverse effects, in particular infection. Infection is in the first place, because, most likely, evolutionarily immunity arose precisely as a fight against infections, and not with anything else. Tumors may also have something to do with this, but still, most likely, this is secondary.
2. Malfunctions of the immune systemMeanwhile, boosting immunity can be extremely dangerous.
There is such a thing as autoimmunity – a situation when the immune system begins to recognize and respond to its own, which it is normally not supposed to do. Unfortunately, there are many different genetic reasons why the immune system can't cope with not responding to its own.
Normally, the functioning of the immune system is accompanied by constant support of molecular mechanisms that remove clones of cells from the body that are able to respond to their own antigens. But, as in any complex system, there are many failures, and then cells that are able to recognize their own break out into the circulation, into the periphery, into the bloodstream and into the lymphstream, and then problems begin: systemic lupus erythematosus, rheumatoid arthritis, autoimmune diabetes and others.
3. The danger of increasing immunity When an immunologist who works not with autoimmunity, but with immunodeficiency, wants to make the patient better, he often says that he needs to increase the level of the immune response.
As a rule, the doctor suggests increasing immunity in general. What this can lead to, I can tell you with some infectious examples.
The most important factor of the immune response against intracellular parasites is gamma interferon. This is interferon, which is produced by different cells, but primarily by T-lymphocytes. Its main effector, that is, its final function, is the activation of macrophages, that is, phagocyte cells that absorb microbes, but do not always know how to kill them by themselves. They are helped in this by cells that produce gamma interferon. Macrophages undergo activation, they acquire some new properties and then become capable of killing the parasite. But the action of gamma interferon is realized at a very short distance, at the contact points of the macrophage and the activating cell. At the same time, no one knows how much it needs to be injected from the outside so that it can work, and gamma interferon is very toxic. That is why attempts to treat tumors with gamma interferon failed, which were actively undertaken in the 90s of the twentieth century and practically stopped, because it must be administered in such doses that it was not a benefit for the host, but a danger. Can we internally increase the level of the same gamma interferon without introducing it, but simply by stimulating the immune system to dangerous values? There is no answer to this question, so we need to be extremely careful about saying that we need to increase immunity.
4. Facing serious illnesses Another example: other phagocytes, neutrophils, are the first to enter the pathogenic bacterium into the host body.
This is a splinter and purulent inflammation around it, this is purulent inflammation in the glands when streptococci cause tonsillitis or sore throat. This is a very fast reaction, and the incoming cells first of all phagocytize bacteria, cope with the parasite, and this process is necessary.
But bacteria – and not only bacteria, but also protozoa and fungi that enter the host body are not limited to streptococci, staphylococci, E. coli or salmonella. Complex pathogens such as the causative agent, for example, leishmaniasis or tuberculosis, can enter the host's body. And then a strange and paradoxical situation arises: neutrophils also come to the place of such an invasion, they also begin to absorb, phagocytize pathogens. And it turns out that they are not able to cope with them. And the pathogen, getting inside such cells, becomes shielded from all other factors of the immune response. Let it be temporary – neutrophils die quite quickly – but for some hours or days the pathogen turns out to be fenced off from other immune factors, thereby invulnerable. And when he goes outside again, it may be too late.
5. Excess immune responseIn the last seven years, a direction has been developing very rapidly, figuring out how to allow the protective factors of immunity to fight isolated pathogens.
Paradoxically, it turns out that if neutrophils are systematically removed from the host body, then diseases such as leishmaniasis and tuberculosis proceed more easily than when neutrophils are present in full. Such experiments are not yet done in the clinic, but are carried out only in experiments, mainly on mice, but quite successfully. It follows that it is not always safe to artificially eliminate neutrophil deficiency (which happens in some pathologies) by simply adding neutrophils from the outside.
Or if the lung is affected by tuberculosis or the spleen is affected by brucellosis, the formation of rather complex formations consisting of cells of the immune system, which are called granulomas, immediately begins – this is such a response factor when many different types of cells come: macrophages and neutrophils (phagocytes – factors of innate immunity), T- and B-cells (lymphocytes – factors acquired immunity). They form rounded formations, inside of which the parasite is enclosed. First of all, they prevent the dissemination of the parasite, that is, its spread further through organs and tissues or inside one organ.
But this reaction must be very tightly controlled. If it goes a little further than we would like, that is, if the size of the granuloma is too large or there are too many of them and they begin to merge, then this will lead to necrosis starting inside these barrier formations, because there will not be enough access of oxygen and nutritional factors. Necrotic inflammation will lead to the fact that in this necrotic focus the parasite will feel fine and completely invulnerable, and this inflammatory immune response, which will capture most of the organ, will lead to the fact that it will be just a huge cavity, which will turn off a whole piece of the lung from the respiratory function. This means that an excessive immune response will lead to the fact that part of the organ, and sometimes the entire organ, will lose its main function. Then the excess immune response will directly kill the host.
The paradox is that a lack of an immune response is very bad, and an example of this is immunodeficiency, but excess is not a protection factor, but a pathogenesis factor. That is, due to the fact that the host's body has overdone the immune response, some of the very important vital functions begin to be lost.
About the author:
Alexander Apt – Doctor of Biological Sciences, Professor of the Department of Immunology of the Faculty of Biology of Moscow State University, Head of the Laboratory of Immunogenetics of TSNIIT RAMS.
Portal "Eternal youth" http://vechnayamolodost.ru03.06.2014