Buenos Aires 04 de Enero del 2021

What Happens When Your Immune System Works Against You?


What Happens When Your Immune System Works Against You?


                                                                        Lindsay Nicholson (University of Bristol, UK)

                                                                         British Society of Inmunology, NCBI - 2020

                                                                               Resumido por: Herba El Wassef


Our immune system is our army against any molecule that wants to invade our bodies like viruses, bacteria, and cancer. It is responsible for our protection. Just like an army, it has the ability to recognize foreign invaders and distinguish them from any normal body constituent. This unique ability of the immune system makes it able to differentiate between self and non-self antigens, "molecules that are presented to the immune cells"  so as not to attack the body itself by mistake.

Imagine what would happen if something disrupted that marvelous ability and the immune system couldn't differentiate anymore between normal body constituents and foreign invaders. It will make it go awry and start attacking the body itself; this is Autoimmunity.

It is still unclear what makes the immune system behaves this way, but some research shows that a genetic factor is involved in addition to environmental factors. Some autoimmune diseases are hereditary and run in the family, like type-1 Diabetes and Lupus.

Apparently, autoimmunity is more common in women than men; a study showed that the chances of developing autoimmune disease in women are 2:1 compared to men, another syudy showed that 75% of those suffering from autoimmune diseases are women

The immune system comprises different cells and components that interact together in a sequence of events to recognize a foreign invader and start fighting it. They start with recognizing a foreign antigen, that is a molecule or a molecular structure that can induce an immune response. The mechanism by which the immune cells differentiate between self and non-self antigens "Foreign antigens" is by specific recognition molecules present on the surface of some immune cells as B and T cell lymphocytes. 

A disruption in those recognition molecules or some immune components may lead to Autoimmunity where the immune system starts attacking self-antigens; start attacking the body's organs and tissues causing a disease.

An autoimmune response can be produced against a specific organ causing damage in that organ as Type-1 Diabetes where the pancreas is affected or can produce a systematic response affecting the whole body as Systemic Lupus erythematosus (SLE).

Some of the most common autoimmune diseases are:

1- Type-1 Diabetes: The immune system attacks and destroys the insulin-producing cells in the pancreas making the body lose its ability to regulate sugar levels in the blood.

2-  Rheumatoid arthritis (RA): The immune system attacks the joints causing stiffness, redness, and soreness. 

3- Multiple sclerosis (MS): The immune system attacks and damages the myelin sheath; the protective covering surrounding nerve cells in the central nervous system, affecting the communication between the brain and spinal cord to and from the rest of the body. 

4- Systemic lupus erythematosus (SLE): The immune response is systemic affecting different parts of the body like joints, skin, kidneys, and the brain.

5- Addison’s disease: The adrenal glands are affected. Adrenal glands produce cortisol, aldosterone, and androgen hormones. Deficiency in these hormones affects the body, like a deficiency in the aldosterone hormone causes disruption to the regulation of salt and water which affects blood pressure.

The immune response in autoimmune disease recapitulates that of responses directed against infection, except that self antigens are, or become, the target of the adaptive immune system. These self antigens may drive a process that is localised within a specific organ, such as the thyroid gland (Grave’s disease, Hashimoto’s thyroiditis) or brain (multiple sclerosis). Or responses to them may lead to a more general inflammatory condition (e.g. systemic lupus erythematosus [SLE]). Following initiation and trafficking, local damage can amplify disease, while the balance of this by regulation determines whether relapse or remission dominate as the disease progresses.

Autoimmune disease occurs when an immune response attacks our own tissues. Like all adaptive immune responses, it is focused on specific antigens by T-cell receptors and B-cell receptors. In contrast to infection, the antigens that these cells recognise are processed from proteins within the target organ and this drives a chronic inflammatory process that disrupts the normal function of the tissue.

In human diseases the trigger for this process cannot usually be determined. There is evidence that autoimmunity can follow infection, but that more than one infection can initiate disease. Other environmental factors are also relevant but are not well defined.

There has been a lot of recent progress in understanding the influence of inheritance on autoimmune disease. A key observation is that susceptibility to autoimmune disease is influenced by a large number of polymorphic genes. These have small effects on their own, but in aggregate they determine an underlying susceptibility to autoimmunity. Many of these genes are clearly implicated in setting a threshold for an immune response, but clarifying the detail of these processes is an ongoing challenge.

The clinical course of autoimmunity is often marked by a relapsing and remitting course. This arises because there is both a continuing pro-inflammatory, disease-causing, drive (in the form of persistent antigen) and opposing this an anti-inflammatory regulatory aspect. The natural regulation of the autoimmune process is known to involve antigen-specific regulatory cells as well as anti-inflammatory cytokines such as IL-10 and TGF-beta. To date, therapies that exploit natural immune regulation have been less successful in the clinic than treatment that blocks the immune response. Blocking the immune response can be effective in autoimmunity, but is accompanied by adverse effects due to immunosuppression. This can allow the reactivation of latent infection and reduce the immuno-surveillance of transformed cells. Therefore antigen-specific immune therapy, targeted at a specific immune response, rather than general therapies targeted at the whole immune system, remains a critical goal for the treatment of these chronic debilitating diseases.

Most autoimmune diseases are chronic but their symptoms can be managed with treatment. Treatment will not cure the diseases but helps the patients live a full life with less pain and managed symptoms.