Autoimmunity: What Really Happens When the Body Turns on Itself

Anna Slezak

Dr. Hubert Bray

Math 89s

6 December 2016

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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

received by surrounding cell’s pattern recognition receptors (PRRs). Cells such as macrophages,

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”).

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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.

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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.3 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).

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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).

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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.

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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 insulin-

producing 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

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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).

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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.

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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.

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"Type 1 Diabetes Facts - JDRF." JDRF. Juvenile Diabetes Research Foundation, 2016. Web. 28

Nov. 2016.

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