Immunity is a matter of profit

What does immunity depend on?

Kirill Stasevich, "Science and Life"

Although genes determine our appearance to a very, very large extent, we should not think that all human characteristics, from molecular to psychological, can be reduced to the genome. A person, like any living organism in general, interacts with the environment all his life, and such interaction does not pass without a trace. And here one of the most difficult questions in biology arises: to what extent is a trait determined by heredity, and to what extent by upbringing, life experience, etc.?

The most heated debates on this topic can be found where it comes to the brain and psychology. But, for example, with immunity, it is also not entirely clear where the genes end and where the "life experience" begins. On the one hand, in the production of antibodies, immune cells use an amazing molecular mechanism of the so-called V(D)J-recombination. Antibodies recognize foreign molecules, but there are a great many such molecules, and it is impossible to predict which infections the body will face. So, by creating antibodies, the B cell shuffles the DNA fragments encoding the part of the immunoglobulin that is responsible for antigen recognition. The result is a lot of antibodies, among which you can already choose the right one. The same gene shuffling is performed by T cells when creating a receptor designed to recognize antigens.

The structure of immunoglobulin and T-cell receptor (scheme with Wikimedia Commons - VM).

That is, the genes determine the construction of antibodies only to some extent. In addition, let's not forget about the acquired immunity, which provides protection from diseases that we have had – it is us, not our parents.

However, the synthesis of immunoglobulins is only part of the immune system. One can imagine, for example, that with a properly designed antibody, too little of it is produced, that immune cells are not very active, they react poorly to the presence of infection. In general, people can find a huge set of differences in immunity (considering how many different cells and molecules make up the immune system), and until recently it was believed that such differences are mainly due to genetic reasons. But researchers from Stanford (USA) tried to separate the inherited part of immunity from the acquired one, and eventually came to the conclusion that the work of immunity is mostly determined by the external environment, the notorious life experience, rather than heredity (Stanford Medicine: Environment, not genes, plays starring role in human immune variation, study finds).

Mark Davis and his colleagues used the usual method to separate the inherited share of the trait from the acquired one – they compared the state of immunity in identical twins. As is known, in this case, both individuals have identical genomes. Although during the development of the organism, errors appear in the DNA associated with the work of the molecular "copying apparatus", it is still believed that the similarity in genes between identical twins is almost 100 percent. That is, all the differences that can be found between them on one or another basis will be due to the influence of the environment. In addition, the study also used data on fraternal twins, which were obtained by simultaneous fertilization of two different eggs. Genetically, fraternal twins are no more similar to each other than ordinary brothers and sisters. However, due to the fact that they were in the mother's womb at the same time, grew up together and were brought up together, they are of some interest to geneticists.

For the study, 78 pairs of identical and 27 pairs of fraternal twins were selected, from whom blood was taken for analysis three times, their immunity was assessed by more than two hundred parameters (among them were the number of different cells, and the activity of immune proteins cytokines, and many others). In an article in Cell (Brodin et al., Variation in the Human Immune System Is Largely Driven by Non-Heritable Influences), the authors write that in 3/4 of cases, the non-hereditary effect on immunity overlapped the hereditary one. That is, vaccinations made in the past, microbes and toxins that once had to be fought, the diet, and even how much a person watched his teeth - all this determined the state of the immune system to a much greater extent than genes. Moreover, the determining influence of the environment was especially noticeable in people over 60 years old, the greatest similarity was in those twins who were less than 20 years old. What is clear: with age, immunity accumulates its own unique experience.

Diagram from the article in Cell – VM

For example, the differences were manifested in the reaction to the flu vaccine: the number of antibodies in response to it in identical twins could be very different, although genetically, we recall, they were identical. Previously, it was believed that the response to vaccination depends almost exclusively on genes, but observations here were conducted mainly for young children, in whom the influence of the external environment in immunity has not yet had time to manifest itself. Moreover, sometimes quite large complex differences in immunity could develop due to a single parameter: for example, due to the presence of cytomegalovirus in one of the twins.

Of course, this virus causes serious disorders in the body, including immunity, but, on the other hand, there are many symbiotic bacteria living in us, which have to negotiate with the immune system about cooperation. Since bacteria may differ from one person to another, the immune settings for the microflora will be different. There is nothing surprising here, but no one expected that external (non-hereditary) factors could have such a strong influence on the state of immunity. And, of course, both groups of factors are interrelated, which further complicates the individual immune portrait.

Of course, it remains to be found out what kind of molecular, cellular, physiological mechanisms mediate external influence on the immune system. It is quite possible that even here there are epigenetic tricks that allow quite a lot of adjustments to the hereditary program recorded in the genes. But, anyway, if you want to find out what diseases you should be afraid of and what you should expect from your own immunity, you should hardly rely on genetic analysis alone – you need to add a complete medical history to it.

Portal "Eternal youth" http://vechnayamolodost.ru22.01.2015