Autoimmune Diseases: When Your Enemy Is You

Distinguishing one’s own from a foreign one is not as easy as it might seem at first glance. At least for our immune system, which is responsible for our defense, which must decide when to attack and when not to.

The decision is made thanks to the very specific receptors possessed by lymphocytes. There are millions of them, randomly generated during cell development, and each receptor recognizes one substance (antigen). Sometimes strange, both with an infection, and strangers.

And that’s the crux of the matter. Because if lymphocyte receptors are randomly generated and always recognize some antigen (self or foreign), how can you be sure that they do not react aggressively to their own structures?

Importance of education of tolerance

Theoretically, this is as simple as making the previous selection. During the development of lymphocytes, the body allows only those of them that do not respond to their own structures to mature and enter the peripheral circulation. This is known as central tolerance.

But also, as a second checkpoint, we have peripheral mechanisms that block any autoreactive lymphocytes that might have escaped the first filter.

The combination of central and peripheral tolerance mechanisms ensures that there are no circulating cells that could potentially destroy their own structures. If this works, we’ll only have cells capable of recognizing the strange. But if any of these tolerance mechanisms fail, we harm ourselves and suffer from an autoimmune disease.

The more hygiene, the more autoimmunity?

In developed countries, while infectious diseases are falling sharply, the incidence of autoimmune diseases and allergies continues to rise. For more than 20 years, the option has been considered that this is not a coincidence, but exposure to certain pathogens (even potentially dangerous ones) has a protective effect against the development of autoimmunity.

For example, some strains of mice raised under strictly sterile conditions develop diabetes easily, while the incidence is markedly reduced if the animals are raised under standard conditions, which are already quite hygienic.

In humans, the case of the region of Karelia, on the border of Finland and Russia, is striking: given the same ecological and genetic conditions of the population, but great economic and social differences, autoimmune and allergic diseases are much more common among Finns. region .

On the other hand, recently the composition of the microbiota (that is, the beneficial bacteria that we have in the intestines) has been associated with some diseases, including autoimmune ones. In fact, the introduction of probiotics of some commensal bacteria to achieve a protective microbiota is a new area for the treatment of these pathologies.

Without going into too much detail, when mice that have developed diabetes under sterile conditions are given certain bacteria from Russians from Karelia (which have little to no autoimmunity), the problem goes away. On the contrary, the introduction of commensal bacteria from the Finnish region predisposes these animals to autoimmunity.

Can we conclude that microbes are always protective? Absolutely. Suspicions that have accumulated over the years that some autoimmune diseases occur after certain infections are becoming more and more solid. A recent study, for example, shows a very strong association between multiple sclerosis and prior infection with the Epstein-Barr virus, which causes infectious mononucleosis. The relationship is so close that we can almost say that without this previous infection there would not have been multiple sclerosis.

Therefore, there are microorganisms with a protective effect and microorganisms that predispose to the development of autoimmune pathologies.

Complicated Causes of Autoimmunity

Only in rare cases, autoimmunity occurs due to a mutation in one of the genes that control tolerance or immune response. But in the vast majority of cases, a combination of genetic predisposition with environmental factors and provoking elements is necessary.

A striking example of a genetic predisposition can be found in ankylopoietic spondylitis: 95% of patients with this disease have the HLA B27 molecule, which is also present in a percentage of the healthy population. Similarly, in the case of type I diabetes, most patients have certain HLA molecules that we can also find in the healthy population.

Therefore, genetics predisposes (sometimes strongly), but almost never enough for the development of autoimmunity.

More autoimmunity in women

The frequency of autoimmune diseases is significantly higher in women. For example, more than 90% of people with Sjögren’s syndrome or systemic lupus erythematosus are women, although it is true that there are more men with type 1 diabetes.

The reasons for these differences are not entirely clear, but it should be remembered that hormones play an important modulating role in several regulatory pathways of the immune response associated with autoimmunity. In addition, hormones also modulate the microbiota, causing males and females to have different compositions.

Another reminder that in any biomedical research, sex is a fundamental factor to keep in mind.

Ignacio J. Molina Pineda de las Infantas, Professor of Immunology, Center for Biomedical Research, University of Granada

This article was originally published on The Conversation. Read the original.

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