Monday Article #7: Autoimmune Diseases- Our Immune System: Friend or Foe?
~ A disorder where the human immune system attacks its own organs~
What are autoimmune diseases
Our immune system protects us from the outside environment by recognizing foreign substances in our body and degrade them. This happens all the time such as when pathogens get into a cut or during an infection. Immune cells recognize the foreign substances via a receptor on its cell surface which binds to surface protein (antigen) of the pathogens. Therefore, the immune system has to differentiate between self-antigen and nonself-antigen so it does not randomly attack the normal cells.
The immune system has a built-in system to tolerate normal cells. This happens via central tolerance when the immune cells such as T cells and B cells (lymphocytes) are in development in the lymphoid tissues i.e., bone marrow, thymus and lymph nodes. Lymphocytes that recognize self-antigens will be degraded via programmed cell death (apoptosis). Peripheral tolerance occurs in the bloodstream where lymphocytes that recognizes self-antigens are inactivated. (Figure 1)
Figure 1. This shows how immune tolerance occurs via central and peripheral tolerance.
However, there are instances where the immune cells can bypass the tolerance checkpoint resulting in recognizing and attacking own cells. B cells that recognizes self-antigen will produce antibodies (known as autoantibodies) against it hence attacking normal cells. This is known as autoimmune diseases (AD).
The causes of ADs are still unknown by researchers although there are several risk factors that can contribute to the development of ADs. Such risk factors include:
Genetics Majority of ADs have no direct link between the disease and specific genetic mutation. This is known as polymorphism where multiple genes are involved in the development of ADs. One such gene that can be involved is the major histocompatibility complex (MHC) gene that encode for human leucocyte antigens (HLA) variants.
Diet Researchers have found that vitamin D could act as an immune modulator where lack of vitamin D can result in increased risk for loss of immune tolerance.
Examples of autoimmune diseases
ADs can be classified as organ specific or non-organ specific (systemic). Organ specific means that the immune system target only one specific organ whereas the immune system can target any organ in systemic AD. Examples of organ specific ADs are type 1 diabetes, rheumatoid arthritis (RA) and multiple sclerosis (MS) while systemic AD is systemic lupus erythematosus (SLE).
Type 1 diabetes
Autoantibodies attack the insulin-producing β cells of the pancreas leading to insufficient production of insulin to convert glucose into glycogen after a meal. Symptoms of type 1 diabetes include increased thirst, extreme hunger and fatigue. Patients with type 1 diabetes will require insulin injection to survive.
Rheumatoid arthritis (RA):
Autoantibodies attack the synovium fluid and lining of joints, resulting in inflammation, swelling and painful joints. These symptoms can be reduced by taking non-steroidal anti-inflammatory (NSAIDS) drugs to reduce inflammation and swelling.
Multiple Sclerosis (MS):
Autoantibodies attack the myelin sheath of neurons that assist in the insulation of nerve cells for quick transmission between nerve cells. As a result of decreased myelin sheath, the transmission speed within the brain and spinal cord decreases leading to poor coordination, weakness and muscle spasms.
Systemic lupus erythematosus (SLE):
Autoantibodies can attack any part of the body including joints, skin, kidneys, blood vessels and nervous system. The symptoms depend on where the autoantibodies attack, but the most common symptoms are joint pain, fatigue and skin rashes.
Diagnosis and Treatment
Clinically, ADs can be diagnosed by performing antinuclear antibody test (ANA). This is to test for the presence of autoantibodies in the bloodstream. Positive test results indicate the diagnosis of AD and further testing will need to be done to confirm the specific type of disease.
ADs can be treated with immunosuppressive drugs to dampen down the immune system. Corticosteroids such as prednisone is an anti-inflammatory drug that can inhibit the activation of T cells thus, decreasing the stimulation of autoantibodies production. NSAIDs can also be taken to treat the symptoms of ADs such as pain and swelling.
In addition, targeted therapy such as monoclonal antibodies can be used to target the specific immune cells so it does not produce autoantibodies against the organs. Examples of monoclonal antibodies are daclizumab and alemtuzumab to treat MS, rituximab to treat RA and belimumab to treat SLE.
Figure 1- ResearchGate
Hafeez U, Gan HK, Scott AM. Monoclonal antibodies as immunomodulatory therapy against cancer and autoimmune diseases. Curr Opin Pharmacol. 2018 Aug;41:114-121. doi: 10.1016/j.coph.2018.05.010. Epub 2018 Jun 5. PMID: 29883853.
Wang L, Wang FS, Gershwin ME. Human autoimmune diseases: a comprehensive update. J Intern Med. 2015 Oct;278(4):369-95. doi: 10.1111/joim.12395. Epub 2015 Jul 25. PMID: 26212387.