Our immune system comprises specialized cells, tissues, and organs that works together to protect the body against foreign invaders.
However, problem arises when the immune system is compromised or mistakenly attacks the body’s own cells, that can trigger a range of diseases including allergy, AIDS, or life-threatening giant cell myocarditis.
So, what could possibly go wrong that makes immune system behaves in a destructive way?
Common risk factors
Primary immunodeficiencies
Primary immunodeficiency disorders are usually inherited genetic disorders – passed down either from father or mother or both. There are now more than 400 unique disorders recognized under primary immunodeficiencies [3], where part of the body’s immune system is either missing or dysfunctional.
Primary immunodeficiency disorders are frequently accompanied by autoimmune diseases [2].
Primary immunodeficiencies are broadly classified into following categories based on the immune components that is primarily affected [4]:
Defects in the innate immune components:
i) Phagocytes
ii) Complement components
iii) Toll-like receptor-mediated signaling
Defects in parts of adaptive immune responses:
i) T cell deficiencies
ii) B cell or antibody deficiencies
iii) Combined T and B cell deficiencies
In combined immunodeficiency (CID) disorder, both T cell function and antibody production is impaired, while in its severe form – called ‘severe combined immunodeficiency (SCID)’ – T cells are completely missing.
Children with primary immunodeficiencies are highly susceptible to recurrent, long-lasting, or severe infections with various pathogens depending on the type of immune defects [4].
The ‘bubble boy disease’ is an extraordinary example of SCID. It was named affectionately after David Vetter (1971-1984), who was born with SCID and had to live within a plastic bubble to maintain a sterile or germ-free environment. Bone marrow transplant with an exact tissue matched donor was the only available treatment for him at that time. Sadly, bone marrow treatment failed, and David died four months later following transplantation because of lymphoma – a cancer develops in lymphocytes, which is later found to be introduced in his system by Epstein-Barr virus.
Secondary/Acquired immunodeficiencies
Secondary immunodeficiency disorders occur when the immune system is weakened by external sources, including –
-Surgery and trauma
-Chemotherapy
-Radiation
-Treatments with glucocorticoids
-Immunomodulatory drugs
-environmental factors, such as toxic chemicals, sunburn
-chronic infections
-Metabolic diseases and
-Malnutrition
The defects in the components of immune system due to secondary immunodeficiencies are heterogeneous and prognosis depends on the severity of defects of the immune system [5].
AIDS caused by HIV is an example of secondary or acquired immunodeficiencies. HIV attacks CD4 positive T cell (also called T-helper cells), make many more copies of themselves inside it and then kills it. The new copies of HIV then find and attack other CD4 positive T cells and the cycle continues.
Managing the primary cause can sometimes alleviate the progression of secondary immunodeficiencies; the risk of infections may also be mitigated by prompt antimicrobial treatment or prophylaxis [5].
Hypersensitivity
Some allergens, such as dirt, household dust, or pollen may trigger hypersensitivity reaction which is an undesirable immune response. If body is sensitive to these usual harmless substances, then the immune system may mistakenly think of these allergens as a threat and therefore raise immune responses.
Immunoglobulin E or IgE antibody is associated with allergic reactions. Each IgE is specific for only one type of allergens; the IgE produced by Ragweed is different from the IgE produced by Pigweed [1].
The typical allergic reactions (runny nose, mucus production, sneezing, coughing, tear production, bronchoconstriction, vomiting, and diarrhea) stimulated by IgE antibody is thought to be beneficial for the host, since these responses help to drive out the allergenic proteins from the host’s body [1].
Autoimmunity
The immune system acts on recognizing cells or molecules within the body and distinguishes them as self from non-self.
In autoimmune condition, the immune system behaves as if a tissue is infected with foreign pathogens or have some kind of injury to resolve, so it triggers inflammation when the tissue is practically healthy and there is no injury or pathogens to fight off.
For example, T cell attacks pancreas and destroys beta cells, thus little to no insulin production by pancreas, results in type 1 diabetes.
Consequences of autoimmune disorders:
-Changes in organ function
-Tissue destruction, or
-Tissue overgrowth
Types of autoimmune diseases:
So far more than 80 different types of autoimmune diseases have been identified. Some common autoimmune conditions are-
-Rheumatoid arthritis
-Celiac disease
-Type 1 diabetes
-Graves’ disease
-Scleroderma
-Psoriasis
-Multiple sclerosis
-Systemic lupus erythematosus
Causes:
Science still cannot explain what exactly triggers autoimmune disorders. It is believed that, one or more of the following risk factors could be associated with autoimmune conditions.
Inheritance-
Animal studies as well as the clinical and epidemiologic data demonstrated a link between genetics and autoimmune diseases. That means, autoimmunity can run in families and the close relatives (e.g., siblings) are more prone to develop autoimmune disorders. However, identical twins of patients usually do not develop the disease, which suggests that environmental components could be a combined risk factor.
Ironically, mothers can get autoimmune diseases in response to the fetal cells (produces auto-antibody) that remain in their body for years or even decades after childbirth.
Sex-
Among the individuals with autoimmune diseases, 78% are women. Women are more susceptible to autoimmune diseases, partly due to the second ‘X’ chromosome that carries many immune related genes.
Personal health & hygiene-
Cigarette smoking is a known factor that triggers inflammatory response, disrupts cytokine balance, and causes cell and DNA damage. Research studies evidenced its high association with developing rheumatoid arthritis, systemic lupus erythematosus, Graves’s disease, multiple sclerosis, and others. It also interacts with genetic materials and becomes combined risk factor for the disease.
Environmental factors-
Environmental factors (from industrial toxic chemicals to some dietary components) may promote autoimmune diseases by altering gene expression via epigenetic mechanisms.
Infection-
Some bacterial or viral infections may cause certain changes that imbalance immune system, leading to autoimmunity. This is more common in individuals who are genetically predisposed to autoimmune disorders.
Medication-
Certain medications may cause autoimmune disease. For instance, minocycline, a widely used medication to treat acne and rheumatoid arthritis triggers drug-induced lupus erythematosus.
Symptoms:
Some common symptoms of autoimmune disorders at early stages are-
-Fatigue
-Recurring low-grade fever
-Muscle pain or weakness
-Swelling
-Numbness and tingling feeling in the hands and feet
-Skin problems
-Unhealthy hair or hair loss
-Sudden weight loss or weight gain
And if you are diagnosed with one type of autoimmune disease, then the chances of you developing other types of autoimmune diseases is very likely. Lifestyle changes can greatly reduce the risk of developing autoimmune disorders or disease progression.
References
2. Amaya-Uribe, L., Rojas, M., Azizi, G., Anaya, J. M., & Gershwin, M. E. (2019). Primary immunodeficiency and autoimmunity: a comprehensive review. Journal of autoimmunity, 99, 52-72.
3. Gruber, C., & Bogunovic, D. (2020). Incomplete penetrance in primary immunodeficiency: a skeleton in the closet. Human Genetics, 1-13.
4. Notarangelo, L. D. (2010). Primary immunodeficiencies. Journal of Allergy and Clinical Immunology, 125(2), S182-S194.
5. Chinen, J., & Shearer, W. T. (2010). Secondary immunodeficiencies, including HIV infection. Journal of Allergy and Clinical Immunology, 125(2), S195-S203.
6. Fairweather, D., & Rose, N. R. (2004). Women and autoimmune diseases. Emerging infectious diseases, 10(11), 2005.
7. Costenbader, K. H., & Karlson, E. W. (2006). Cigarette smoking and autoimmune disease: what can we learn from epidemiology?. Lupus, 15(11), 737-745.
8. Harel-Meir, M., Sherer, Y., & Shoenfeld, Y. (2007). Tobacco smoking and autoimmune rheumatic diseases. Nature clinical practice Rheumatology, 3(12), 707-715.
9. Hewagama, A., & Richardson, B. (2009). The genetics and epigenetics of autoimmune diseases. Journal of autoimmunity, 33(1), 3-11.
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