How does sarcoidosis develop?
An antigen enters the body. It is a foreign molecule that, once inside, activates a whole series of defence mechanisms provided by our innate or acquired immune system.
The activation of these defence mechanisms in response to a foreign body (an antigen) is called a trigger.
The trigger for a viral infection is a virus, for a bacterial infection a bacterium, and for an allergy an allergen.
In sarcoidosis, studies of immune defence mechanisms indicate that the trigger is most likely a bacterium, virus or toxin.
Our immune cells, including macrophages and dendritic cells, present the antigen to the immune system as a danger and release cytokines that activate the immune response.
In sarcoidosis, an unknown reaction occurs: defence cells present information at the site of the antigen that tells the immune system that the body’s own cells are foreign. Inflammation then develops as clusters of immune lymphocytes form granulomas. These granulomas can develop in any organ.
Thus, this inflammatory disease, caused by external factors and genetic predisposition, behaves in some respects like an autoimmune disease.
Modern research links high levels of stress with inflammatory and autoimmune diseases as one possible co-trigger.
Stress raises cortisol levels. If they remain high for too long, this may weaken the immune system. Stress can also damage the body’s own cells and stimulate immune reactions, including increased inflammation, making a person more vulnerable to viruses and infections.
The restoration of normal cortisol production may therefore be linked to an immune reaction that contributes to the development of autoimmune diseases.
Specific biomarkers such as ACE and chitotriosidase, measured in blood, may support a diagnosis of sarcoidosis.
A granuloma biopsy may also show an increased CD4-to-CD8 lymphocyte ratio, supporting the diagnosis of sarcoidosis.
In most people living with sarcoidosis, the lungs are affected. Bilateral hilar lymphadenopathy in the mediastinum may therefore already be visible on an X-ray.
Symptoms may include shortness of breath, fatigue, chest pain and cough.
In most people living with sarcoidosis, the lungs are affected. Bilateral hilar lymphadenopathy in the mediastinum may therefore already be visible on an X-ray.
Symptoms may include shortness of breath, fatigue, chest pain and cough.
A common presentation of pulmonary sarcoidosis is Löfgren syndrome, in which granulomas occur in the lungs, skin and joints. It is also generally considered a more favourable form of sarcoidosis.
Dino-Josip Ključarić, Master of Theology
Schematic representation of the causes of sarcoidosis at the cellular level
Schematic representation of the lymphatic system
(click to enlarge the image)
How sarcoidosis develops and progresses at the cellular level
In simple terms:
1. A foreign body enters the body.
This body is called an antigen.
It most likely enters through the airways.
2. The immune system responds “too aggressively.”
Small cells called macrophages are responsible for “eating” foreign material. Together, they form an inflammatory cluster and create granulomas.
During the defence process, these macrophages may contribute to calcification of healthy tissue. For this reason:
DO NOT TAKE CALCIUM OR VITAMIN D WITHOUT MEDICAL SUPERVISION, AND DO NOT TRY TO BOOST THE IMMUNE SYSTEM.
Lymphatic vessels, whose role is to remove toxins and reduce inflammation, become swollen as they encounter granulomas.
Treatment with glucocorticosteroids aims to reduce inflammation, while treatment with cytotoxic or immunosuppressive medicines such as methotrexate slows the immune response.
Exposure to an unknown sarcoidosis antigen activates T cells and antigen-presenting cells (APCs), leading to the release of cytokines.
CD4 activation can skew the immune system towards a Th1 or Th2 response, which in turn induces granuloma formation.
At later stages, granuloma formation may be followed by resolution or by a chronic state of disease with fibrosis.
A granuloma is a term used to describe a type of inflammation that occurs in response to different triggers, such as infections, foreign bodies or autoimmune disorders.
It is characterised by small clusters of cells that may develop in different parts of the body, including the lungs, skin and digestive system.
Granulomas consist of immune cells, such as macrophages, which accumulate in a particular area in response to a stimulus.
Sarcoid granuloma:
It can develop in several organs, including the lungs, lymph nodes and skin. The cause of sarcoidosis is not fully understood, but it is believed to involve an abnormal immune response in which the immune system attacks the body’s own tissues. Sarcoid granulomas can cause symptoms such as cough, breathing difficulties and skin lesions.
Macrophages are a type of leukocyte found in humans and animals. They are microscopically larger than neutrophils and their main task is to clear waste from the body and fight foreign substances (antigens).
They develop from blood monocytes, which are produced in the bone marrow, and have characteristic morphological features. Unfortunately, macrophages contribute to anthracosis and asbestosis because they move towards inflammatory interleukins, such as IL-1, and areas of inflammation, where they “eat” foreign particles. This can lead to pulmonary anthracosis when the material cannot be broken down. Macrophages also participate in atherosclerosis, where they become “foam cells”. They are present in many organs. Their main function is to engulf foreign substances, a process called phagocytosis.
TNF-alpha
Macrophages release plasminogen activator, which is important in blood clotting. They also release serine proteases, other enzymes, various interleukins and tumour necrosis factor alpha (TNF-alpha).
Dino-Josip Ključarić, Master of Theology
Source: https://hemed.hr/Default.aspx?sid=15908