In the human body, the immune system plays a vital role in the identification and removal of antigens such as viruses, bacteria, fungi, toxins, and other harmful foreign bodies. The main function of the immune system is to protect the body against these harmful invaders. Autoimmunity is a state when an individual’s immune system starts reacting against the body’s own normal components and, thereby, producing many diseases.
Autoimmune Disease. Image Credit: Kateryna Kon/Shutterstock.com
Autoimmunity is present across all age groups; however, a higher frequency has been observed among normal elderly people. To date, scientists have discovered more than 80 autoimmune diseases. There are different types of autoimmune diseases, some of which can be easily diagnosed while others with unusual symptoms remain undetected for many years.
Certain infections and tissue damages from trauma or ischemia caused due to autoimmunity often go undetected because of the difficulty in determining whether organ damage is mediated by autoreactivity or pathogens. Generally, an individual with autoimmune disease (AD) may have numerous autoantibodies, among which the majority can be nonpathogenic.
Determinants and General Mechanisms of Various Autoimmune Diseases:
Researchers have reported that autoimmunity is linked to an encounter with a specific pathogen, drugs, toxins, chemicals, or hormones. A complex genetic pattern of AD susceptible alleles and haplotypes also determines the malfunction of immune mechanisms.
However, some factors and their mechanisms that lead to the onset of AD are discussed below:
Genetic Factors
Scientists have developed several successful mouse models for a better understanding of autoimmune diseases. They have reported the importance of immunoregulation, pathways of tolerance induction, and the role of immune signaling in autoimmunity. An important genetic factor associated with human autoimmune diseases is leukocyte antigen (HLA) allele(s).
Additionally, owing to the direct association to the T cell responses, the most important gene that is responsible for autoimmunity in both animals and humans is the major histocompatibility complex (MHC). Researchers have reported that ankylosing spondylitis (AS), in over 90% of Caucasians, is due to the expression of an allele belonging to the HLA-B27 family.
Similarly, many other AD show strong associations with specific HLA allele families, e.g., expression of HLA-DR3, -DR4, -DQ2, and -DQ8 is responsible for the development of type 1 diabetes mellitus. Likewise, expression of HLA-DR4 indicates rheumatoid arthritis and HLA-DR3 for primary Sjogren’s syndrome.
Environmental Factors
The role of several environmental factors in causing AD was first observed while studying the disease concordance rate between monozygotic twins. Various animal models suggested that environmental triggers such as pathogenic infestations, and chemicals or pharmaceutical agents are significantly linked to the onset of AD.
For instance, heavy metal (mercuric-chloride) or polyvinylchloride can cause systemic sclerosis, immune complex nephritis, and can produce autoantibodies. Other chemical agents such as hair dyes containing aromatic amines, glue-sniffing, smoking, exposure to silica dust in the manufacturing or mining sites, can cause Graves’ disease (GD), or scleroderma.
Industrial workers who are involved with spray-painting, furniture refinishing, and cosmetic manufacturing are reported to be at a higher risk of developing AD. In vitro studies have proved that exposure to UV-B rays causes conformational changes to DNA and small nuclear ribonucleoproteins (snRNPs), that may induce autoreactive lymphocyte.
Mechanisms such as DNA methylation and histone modification induce autoimmunity by generating novel antigens and abnormal cell death by releasing cellular material. This leads to inflammasome activation, which produces pro-inflammatory cytokines.
Drugs may also induce AD, for example, thiol-containing drugs, sulfonamide derivatives, antibiotics, and non-steroidal anti-inflammatory drugs. Researchers have also associated AD with pathogenic infection by Epstein-Barr virus (EBV), HSV-1, human immunodeficiency virus (HIV), Coxsackie virus, human papillomavirus (HPV), and influenza virus.
Hormonal influences
Two types of AD, namely, Hashimoto’s thyroiditis and Graves’ disease occur predominantly in women. These diseases primarily occur in the postpartum period indicating that they are linked with hormonal imbalances. In animal models, researchers found that hypothyroidism and estrogen aggravate Hashimoto’s thyroiditis symptoms while testosterone reverses it. Additionally, defects in the hypothalamic-pituitary-adrenal (HPA) axis increase susceptibility to AD.
Autoimmune diseases can be categorized into two classes, namely, organ-specific and systemic. For organ-specific diseases, the immune response is targeted towards antigens in a single organ, e.g., Addison disease, in which autoantibodies attack the adrenal cortex. In systemic diseases, the immune system attacks self-antigens in several organs, e.g., Systemic lupus erythematosus, which brings about an inflammation of the skin, joints, and kidneys, and other organs.
Some Autoimmune Diseases
Most autoimmune diseases have no permanent cure and require prolonged treatment to abate symptoms. Some of the common autoimmune diseases are discussed below:
- Rheumatologic diseases: There are many types of rheumatologic diseases, for example, rheumatoid arthritis causes multiple joints to become inflamed, stiff, and painful. Inflammation in other organs, such as the lungs or eye, may also develop. Other rheumatologic diseases are lupus, Sjögren's syndrome, Polymyalgia rheumatic, Ankylosing spondylitis, and Vasculitis.
- Multiple sclerosis – In this disease, the lining of axons (myelin) is damaged by an immune attack that results in a malfunction in the brain and spinal cord leading to impaired movement, problems in the vision, etc.
- Celiac disease – This disease leads to an immune reaction that harms the small intestine and damages the normal digestion process on gluten ingestion. The common symptoms are rash, joint pain, and fatigue.
- Alopecia areata – This results in an immune attack on the hair follicles that leads to patchy hair loss, especially on the scalp.
Common Treatments of Autoimmune Diseases
Commonly, autoimmune diseases are treated with medications that inhibit or alter the immune system. The treatment generally depends on the condition or extent of the disease. One of the effective treatments has been discovered by accident, i.e., gold salt injections.
In 1920, gold salt injections were first used for the treatment of rheumatoid arthritis, during that time gold was used to treat tuberculosis since it possesses antibiotic properties. More recently, the approach involves the identification of immune cells or chemical factors responsible for the autoimmune disease. Subsequently, therapies such as rituximab, anti-B-cell treatment, etc., are used to inhibit or alter the triggering factors.
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