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Immune Cells as Villains: Misdirected Immune Attack During Autoimmune Diseases
The body should operate at an equilibrium. The immune system has cells that play a heroic role in protecting the body against infections or diseases in the state. However, in some cases, the same cells expected to play the heroic role become “villainous.” The T cells and antibodies start attacking the same cells and tissues they are expected to protect from infections and diseases in the state. They create a state of autoimmunity, a misdirected attack on the body’s cells and tissues. When this occurs, experts claim that the person has an autoimmune disease. Various situations arise that result in the immune system becoming a villain instead of a hero. First, one could be born with a weak immune system, referred to as a primary immune deficiency. Secondly, a person could develop a condition that that weakens the immune system (a situation known as the acquired immune deficiency). Thirdly, one can have a too active immune system, such as in a case of allergic reactions. Finally, the body’s immune system can just turn against the healthy body in the event of an autoimmune disease. Although the immune system cells are expected to fight against infections and diseases, the protective cells can become villains when a person’s autoimmune system fails to function optimally.
Autoimmune diseases happen when the body’s natural defense system (the immune system) begins to attack healthy tissues. However, situations occur in which particular adaptive immune responses are targeted towards self-antigens. Typically, the adaptive immune response appears to fight against and eliminate an antigen from the body. For instance, cytotoxic T cells destroy virus-infected cells while antibody and antigen’s immune complexes occur to clear soluble antigens. Nonetheless, in some cases, an adaptive immune response emerges to fight against self-antigens, making it hard for the immune effector mechanisms to get rid of antigens effectively, causing a sustained reaction (Mackay & Rose, 2014). The situation leads to chronic inflammatory injury to tissues caused by the immunity’s effector pathways. The tissue damage mechanism, in this case, is the same as occurs in protective immunity. Individuals can develop defects in the immune system, making it incapable of playing its defensive role and even attacking the same systems it is expected to protect.
Autoimmune disease is an abnormality that can even be fatal. Experts have used different theories to explain the reason for the occurrence of this abnormality. The human body perceives a danger from an infection, such as a virus or bacteria, causing the immune system to respond by attacking the disease. The process is referred to as an immune response. In some cases, healthy cells and tissues are affected in the immune response, leading to autoimmune disease (Kumar et al., 2019). Some scientists are convinced that the process results from rheumatoid arthritis, a kind of autoimmune disease. The condition is known to attack joints and commonly occurs following strep throat. Other kinds of autoimmune conditions emerge as the body tries to respond to cells, such a cancerous cells. Another potential condition is Orbai points to scleroderma, which leads to skin and connective tissues thickening (Latorre et al., 2018). In such conditions, the immune system gets to an inflammatory response because of fighting after getting rid of the cancerous cells.
While some people could be born with genetic defects increasing the susceptibility of autoimmune disease, some environmental conditions may trigger autoimmune attacks on the body. Antigen-specific T cells’ activation initiates the adaptive immune response. According to Mackay and Rose (2014), the activation of autoimmunity occurs in the same manner as the antigen-specific T cells’ activation. People have an underlying genetic susceptibility to autoimmune disease and the body’s attack against itself, as evidenced in family studies, particularly on twins. Researchers compare monozygotic and dizygotic twins in terms of the proportion of the susceptibility to certain conditions, such as autoimmune disease. Diseases that show a high prevalence in all twins reveals common genetic and environmental causes. The explanation is the typical environmental conditions in which all twins grow up. However, in situations where the prevalence rate is limited to monozygotic, genetic factors play a more significant role than environmental factors in the occurrence of the disease.
Studies have been conducted to show the connection between environmental factors and the development of autoimmune conditions, such as rheumatoid arthritis, type I IDDM, multiple sclerosis, and SLE. In most cases, about 20% of monozygotic twins reveal disease concordance. The percentage differs from less than 5% shown in dizygotic twins (Janeway Jr, et al., 2001). The results indicate the possibility of inheritability of the conditions from parents. Nonetheless, regardless of the genetic susceptibility of the autoimmune disease, common environmental factors have been implicated in developing the state in which the body turns against itself. Studies from twin and family studies have revealed the importance of genetic and environmental factors in diseases involving the autoimmune system attacking healthy cells and tissues. To some extent, autoimmunity is evidence in everyone but does not exist in a harmful manner. However, cases occur when autoimmunity develops to a pathogenic state involving the entire immune system: “antigens, antigen-presenting cells, T and B lymphocytes, messenger molecules, cytokines, chemokines and their receptors, and signaling and co-stimulatory molecules” (Brower, 2004). In such cases, some external influences could be responsible for developing an autoimmune disease in already vulnerable individuals.
One of the challenging dimensions of autoimmune disease is identifying the initial events triggering immune dysregulation and autoimmunity. Current evidence indicates that environmental agents (such as “solvents, crystalline silica, mercury, pesticides, pristine, and cigarette smoking”) are responsible for up to 70% of all autoimmune diseases (Vojdani, 2014; Khan & Wang, 2018, 22). The gut microbiome has also been implicated in the development of autoimmunity. Dysbiosis of the gut, oral, and skin microbiome has been revealed to cause the conditions in vulnerable people (Dehner et al., 2019). Changes in the microbiome can lead to autoimmunity since changes in microbial compositions can cause inflammations and reduced immune tolerance. Dysbiosis can even lead to multiple immune diseases since the stability and composition of the gut microbiome helps absorb nutrients and regulate the mucosal immune system (Khan & Wang, 2020). Such changes caused by environmental factors can cause autoimmune disease.
Differences in prevalence
Another source of evidence to indicate the role of environmental factors in developing an autoimmune disease is the higher prevalence in some countries than others. The rate of autoimmune disease has been revealed to be higher in countries with developed economies, indicating the potential implications of environmental conditions in developing the condition. The US National Institutes of Health (NIH) reveals an estimated 80 autoimmune diseases, affecting “14–22 million Americans, or 5%–8% of the population” (Brower, 2004, 758). Unfortunately, the rate of conditions in the country is increasing. Women are shown to have a higher rate of the infection than men (“a female to male ratio of 50:1 in Hashimoto’s syndrome (hypothyroiditis), 9:1 in lupus, primary biliary cirrhosis and antiphospholipid syndrome, 7:1 in Graves’ disease, 4:1 in RA and 2:1 in multiple sclerosis (MS) and myasthenia gravis” (Brower, 2004, 758). The higher rate of the condition in women shows that sex hormones could play a key role in the development and progression. Another trend in the conditions is ethnic disparities, with “lupus being three times as common in African Americans and Latinos/Hispanics, whereas MS and type 1 diabetes are seen more frequently in Caucasians” (Brower, 2004, 758). The differences in prevalence reveal a genetic susceptibility that is worsened by environmental factors.
The primary role of sex hormones in the development of autoimmune disease is quite evident. The hormones are important in modulating T-cell receptor signalling, activating “cytokine genes and lymphocyte homing” (Brower, 2004). An Albert Einstein College of Medicine-based study by Betty Diamond revealed that estrogen potentially predisposes women to SLE since they reduce B-cell tolerance and dampens apoptotic processes. Another research at the Baylor College of Dentistry revealed that low estrogen levels cause a reaction chain of inflammations (Brower, 2004). The study and others revealed the role of estrogen receptors in mediating various autoimmune diseases. Furthermore, researchers have established that autoimmune conditions such as lupus and RA have common susceptibility genes. However, their prevalence rates differ from one region to another indicates a potential role of environmental factors.
Apart from sex hormones, infectious diseases are another potential underlying cause of the high prevalence of an autoimmune disease. The pathogenesis of autoimmune diseases can be activated in the effort of the body to wade off infections. Cells in the immune system that fights infections can cross-react with normal tissues. Some conditions, such as the COVID-19 infections, have some implications in the development of autoimmune disease. Experts continually understand the contribution of the immune system to the defenses against the new strain of coronavirus. Autoantibodies (immune system proteins) that attack the healthy tissues could be implicated with the progression of COVID-19. Those present before the infection could be responsible for 20% or more of severe or fatal COVID-19 cases (Autoimmune response found in many with COVID-19, 2021). However, research remains inconclusive in establishing whether SARS-CoV-2 could be responsible for the production of autoantibodies. According to Michael Oldstone, head of the Viral Immunobiology Laboratory at the Scripps Research Institute, “in molecular mimicry, a small number of self-reactive T-cells are expanded with cross-reactive epitopes to produce a quantity of T-cells sufficient to create disease,” he said. “The initial insult is often an infection, which affects a target tissue, such as the brain or pancreas, but does not cause disease. The infection may be cleared, but when the insult is repeated, self-reactive cells are expanded from a few autoreactive cells” (Brower, 2004, 759). For instance, there is a potential connection between lymphocytic choriomeningitis virus and type 1 diabetes.
The body’s immune system plays a vital role in protecting the body against pathogens and infections. When the system senses such invasions, the immune response mode is activated to fight and eliminate the infections or diseases. However, a condition occurs where the immune system attacks itself and other healthy cells and tissues instead of focusing on infections. The situation occurs if the immune system suffers from an autoimmune condition that distracts the normal functioning. Understanding the genetic and environmental factors that cause the state is essential in addressing the early onset and progression of autoimmune disease.
Autoimmune response found in many with COVID-19 (2021). Retrieved from https://www.nih.gov/news-events/nih-research-matters/autoimmune-response-found-many-covid-19#:~:text=A%20recent%20study%20found%20that,them%20before%20they%20got%20sick.
Dehner, C., Fine, R., & Kriegel, M. A. (2019). The Microbiome in Systemic Autoimmune Disease–Mechanistic Insights from Recent Studies. Current Opinion in Rheumatology, 31(2), 201.
Janeway Jr, C. A., Travers, P., Walport, M., & Shlomchik, M. J. (2001). Autoimmune responses are directed against self antigens. In Immunobiology: The Immune System in Health and Disease. 5th edition. Garland Science.
Khan, M. F., & Wang, G. (2018). Environmental agents, oxidative stress and autoimmunity. Current opinion in Toxicology, 7, 22-27.
Khan, M. F., & Wang, H. (2020). Environmental exposures and autoimmune diseases: Contribution of gut microbiome. Frontiers in Immunology, 10, 3094.
Kumar, P., Saini, S., Khan, S., Lele, S. S., & Prabhakar, B. S. (2019). Restoring self-tolerance in autoimmune diseases by enhancing regulatory T-cells. Cellular Immunology, 339, 41-49.
Latorre, D., Kallweit, U., Armentani, E., Foglierini, M., Mele, F., Cassotta, A., … & Sallusto, F. (2018). T cells in patients with narcolepsy target self-antigens of hypocretin neurons. Nature, 562(7725), 63-68.
Mackay, I. R., & Rose, N. R. (2014). The autoimmune diseases. Elsevier Inc..
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