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Autoimmunity: What Really Happens When the Body Turns on Itself Anna Slezak Dr. Hubert Bray Math 89s 6 December 2016 Slezak 2 Introduction The human immune system is constantly responsible for defending our bodies from all sorts of foreign invaders. Generally, it works incredibly well. Occasionally, though, the immune system malfunctions and attacks itself; this is referred to as autoimmunity. In this paper, I will explain the processes that occur in a healthy immune system and then outline the ways in which deviations from these processes occur in a selection of autoimmune conditions. Regular Immune Responses In a healthy human, the immune system works to identify and eradicate pathogens1. The human immune system is divided into two complement parts: the nonspecific or innate immune system and the specific or adaptive immune system. Each functions in a unique way and comprehension of these processes is integral to understanding autoimmunity. The innate immune system can be conceptualized as the “front line” of human immune response. These responses occur immediately or soon after the encounter with a pathogen and are not due to prior sensitization to a pathogen. Components include anatomical barriers, inflammation, and chemicals found in the blood. Each anatomical barrier consists of a physical structure and a biological process that increases its efficacy. For example, the skin is a physical barrier that produces sweat and the eyes produce tears, both of which flush potential invaders from the surface of the body. Inflammation is perhaps the most characteristic aspect of the innate immune system. When cells are damaged, they release chemical signals that are 1 A pathogen is a bacterium, virus, or other microorganism that can cause a disease. Antigens are protein markers found on the surface of pathogens (“How Infection Works”). Slezak 3 received by surrounding cell’s pattern recognition receptors (PRRs). Cells such as macrophages, dendritic cells, and mastocytes have theses PRRs and trigger an inflammatory response. These responses are characterized by redness, heat, swelling, pain, and increased production of mucus. Inflammation functions as an intensified version of the regular anatomical barriers, preventing entry or further motion of a pathogen. Figure 1 diagrams an inflammatory immune response. The final role of the innate immune system is to stimulate the adaptive immune system with chemical signals (Mayer). Figure 1 (https://montereybayholistic.wordpress.com/tag/inflammation/vi) The adaptive immune system is slower to respond than the innate immune system but is far more specialized. Any pathogens that make it past the anatomical barriers of the innate immune system stimulate an antigen-specific immune response. This response is a two-step process carried out by lymphocytes: antibody responses and cell-mediated immune responses. Slezak 4 The antibody response occurs when B cells2 recognize specific antigens and produce antibodies3. The second step, cell-mediated immune response, occurs when activated T cells4 recognize antibodies and attack the antigen, often by killing the infected host cell. In other cases, the T cells receive the antibodies and respond by recruiting macrophages5 (Alberts et al). The adaptive immune system is often referred to as the acquired immune system because antigen-specific receptors are acquired as each pathogen is initially encountered. Immune Malfunctions There are a variety of potential malfunctions of the immune system. Some affect the innate immune system and some affect the adaptive immune system. Allergies are the most common malfunction of the immune system; an allergic reaction occurs when the adaptive immune system mistakes a harmless foreign body as a pathogen. In an autoimmune disorder, the immune system mistakes normal, healthy tissue for foreign bodies and causes harm to the host. Researchers have identified between 80 and 100 unique autoimmune disorders and predict at least 40 more diseases with an autoimmune component. An estimated 5 to 8 percent of people in the United States suffer from these identified autoimmune diseases, and that number is increasing (McCoy). Autoimmune diseases can generally be divided into two categories. Local autoimmune diseases only directly affect specific tissues or organs, whereas 2 B cells are a particular type of white blood cell responsible for the production of antibodies. Antibodies are Y-shaped proteins found in the blood. The immune system uses them to identify and neutralize pathogens like bacteria and viruses (Cashin-Garbutt). 4 T cells are a type of white blood cell. While there are many varieties, all are responsible for the physical attack involved in an adaptive immune response. 5 Macrophages are a type of white blood cell often found at infection sites. Macrophages are generally responsible for phagocytosis of infected host cells (Mosser & Edwards). 3 Slezak 5 systemic autoimmune diseases affect the body as a whole, not just a specific part (“Autoimmune Diseases”). Below is a discussion of several common autoimmune diseases. Rheumatoid Arthritis Rheumatoid Arthritis is the most common autoimmune disease, affecting more than 1.5 million Americans. The systemic disease is characterized by swelling and pain in the joints, most commonly the wrists and hands. As with many other autoimmune diseases, the cause is unknown but is expected to have both genetic and environmental components. The physical mechanism of the disorder involves intense inflammation of the synovium6 caused by excessive release of inflammation-causing chemicals by cells of the innate immune system. The combination of these chemicals and the intense swelling in the joints often leads to permanent cartilage damage. Other side effects of the disease include low red blood cell count, fever, low energy, and inflammation around the heart and lungs. While there is no cure, treatment for rheumatoid arthritis involves anti-inflammatory drugs, pain medications, limiting physical activity, and the use of splints and braces (Ruderman & Tambar). Figure 2 compares the joints of a normal hand to those of a hand with rheumatoid arthritis. 6 The synovium is a specialized connective tissue that lines the joints of the human body (Ruderman & Tambar). Slezak 6 Figure 2 (https://ghr.nlm.nih.gov/art/large/rheumatoid-arthritis-hands.jpeg) Systemic Lupus Erythematosus (SLE) The term lupus actually refers to a collection of autoimmune diseases including systemic, discoid, drug-induced, and neonatal lupus. The most common form is systemic lupus erythematosus, also known as SLE. This condition affects an estimated 1.4 million people in America, 90% of which are women. SLE is a chronic disease that may present itself in a variety of ways, all of which are very difficult to diagnose and treat. While most people who have the disease are able to live normal, healthy lives, the under- and misdiagnosis of the condition can often lead to more serious consequences. One characteristic manifestation of SLE is a malfunction in apoptosis, which refers to programmed cell death that neatly disposes of cells as a function of healthy growth. In general, patients with lupus experience unusually high rates of apoptosis and increased blood concentrations of T and B cells during attacks (Herndon). These episodes include symptoms of severe joint pain and swelling, headaches, rashes, anemia, hair loss, and more. Figure 3 depicts many possible affects lupus can have on the body. Slezak 7 Figure 3 (https://ghr.nlm.nih.gov/condition/systemic-lupus-erythematosus) Type 1 Diabetes Diabetes mellitus type 1, more commonly known as type 1 diabetes (T1D), is a serious condition affecting nearly 1.25 million Americans. While it is considered a local autoimmune disease, it really only involves a single attack by the immune system with lifelong consequences. By an unknown mechanism, the immune system kills the insulinproducing beta cells in the pancreas. Insulin is the hormone that enables the body to absorb glucose from the bloodstream. People who suffer from T1D must closely monitor their blood-glucose levels and ensure they are taking artificial insulin injections as needed. Unlike most autoimmune diseases, T1D is incredibly easy to diagnose with a simple blood-glucose test. Having unhealthy blood-glucose levels results in symptoms of frequent urination, increased thirst, and feeling excessively tired. Long term, complications such as heart disease, kidney failure, and eye damage can occur if the Slezak 8 condition is not managed properly (“Type 1 Diabetes Facts”). Figure 4 shows the differences in insulin and glucose movement in diabetics versus non-diabetics Figure 4 (https://ghr.nlm.nih.gov/condition/type-1-diabetes) One unique aspect of Type 1 Diabetes is its correlation with other, lesser common autoimmune disorders. Both hyper- and hypothyroidism7 are significantly more common in patients with T1D and may also be due to an autoimmune attack. Celiac disease is an autoimmune condition in which the intestine is unable to tolerate gluten. 1 in 20 children with T1D also have celiac, as opposed to 1 in 100 non-diabetic children. Addison’s disease is another local autoimmune disorder that affects the adrenal gland of the endocrine system and is also correlated with Type 1 Diabetes (Dowshen). 7 Hyper- and hypothyroidism refer to over or under production, respectively, of hormones by the thyroid. The thyroid is a part of the endocrine system, just like the pancreas (Dowshen). Slezak 9 Conclusion While there are many different types of autoimmune diseases, they share a shocking number of similarities. For example, nearly all of these conditions are significantly more common in women than men, and very few of them have cures or known causes. As research in immunology continues, it is likely that the answers to each of these questions individually will lead to advances in all other questions. Essentially, as we begin to understand more about malfunction in the autoimmune system, it will lead us to solve not just one disease but give us hints into curing all others. With this perspective, research can continue hopefully as scientists come closer and closer to an answer. Slezak 10 Works Cited Alberts B, Johnson A, Lewis J, et al. Molecular Biology of the Cell. 4th edition. New York: Garland Science; 2002. Chapter 24, The Adaptive Immune System. "Autoimmune Diseases." Australasian Society of Clinical Immunology and Allergy (ASCIA). Health Direct Australia, June 2016. Web. 28 Nov. 2016. Cashin-Garbutt, April. "What Is an Antibody?" News-Medical.net. AZo Network, 13 Oct. 2014. Web. 28 Nov. 2016. Dowshen, Steve, M.D. "Other Diseases That Are More Common in People with Type 1 Diabetes." KidsHealth. The Nemours Foundation, Aug. 2013. Web. 04 Dec. 2016. Herndon, Jamie. "Systemic Lupus Erythematosus (SLE)." Healthline. Healthline Media, 15 Aug. 2016. Web. 01 Dec. 2016. "How Infection Works, How Pathogens Make Us Sick." NAS Need to Know. National Academy of Sciences, 2016. Web. 05 Dec. 2016. Mayer, Gene, Ph.D. "Innate or Nonspecific Immunity." Microbiology and Immunology Online. University of South Carolina School of Medicine, 20 Mar. 2016. Web. 28 Nov. 2016. McCoy, Krisha. "Understanding Autoimmunity." EverydayHealth.com. Everyday Health Media, LLC, 21 Dec. 2015. Web. 28 Nov. 2016. Mosser, David M., and Justin P. Edwards. "Exploring the Full Spectrum of Macrophage Activation." National Center for Biotechnological Information. U.S. National Library of Medical Information, 8 Dec. 2008. Web. 28 Nov. 2016. Ruderman, Eric, M.D., and Siddharth Tambar, M.D. "Rheumatoid Arthritis." American College of Rheumatology. American College of Rheumatology, Aug. 2013. Web. 05 Dec. 2016. Slezak 11 "Type 1 Diabetes Facts - JDRF." JDRF. Juvenile Diabetes Research Foundation, 2016. Web. 28 Nov. 2016.