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20.6: Disorders of the Immune System

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  • Allergy Eyes

    Eyes that are red, watery, and itchy are typical of an allergic reaction known as allergic rhinitis. Commonly called hay fever, allergic rhinitis is an immune system reaction typically to the pollen of certain plants. Your immune system usually protects you from pathogens and keeps you well. However, like any other body system, the immune system itself can develop problems. Sometimes it responds to harmless foreign substances as though they were pathogens. That’s the basis of allergies such as hay fever.

    red eye
    Figure \(\PageIndex{1}\): (By Championswimmer (Own work) [Public domain], via Wikimedia Commons; Oedem.jpg)


    An allergy is a disorder in which the immune system makes an inflammatory response to a harmless antigen. It occurs when the immune system is hypersensitive to an antigen in the environment that causes little or no response in most people. Allergies are strongly familial: allergic parents are more likely to have allergic children and those children’s allergies are likely to be more severe. This is evidence that there is a heritable tendency to develop allergies. Allergies are more common in children than adults because many children outgrow their allergies by adulthood.



    Figure \(\PageIndex{2}\): (Hans; CC BY-NC 3.0;

    Any antigen that causes an allergy is called an allergen. Common allergens are plant pollens, dust mites, mold, specific foods (such as peanuts or shellfish), insect stings, and certain common medications (such as aspirin and penicillin). Allergens may be inhaled or ingested, or they may come into contact with the skin or eyes. Symptoms vary depending on the type of exposure and the severity of the immune system response. Two common causes of allergies are shown in the figures \(\PageIndex{2}\) and \(\PageIndex{3}\): ragweed and poison ivy, respectively. Inhaling ragweed pollen may cause symptoms of allergic rhinitis, such as sneezing and red itchy eyes. Skin contact with oils in poison ivy may cause an itchy rash. This type of allergy is called contact dermatitis.

    eastern poison ivy
    Figure \(\PageIndex{3}\): Common causes of allergies include pollen (top) and poison ivy (bottom). (By Sam Fraser-Smith from Brisbane, Australia [CC BY 2.0], via Wikimedia Commons; poison ivy)

    Prevalence of Allergies

    There has been a significant increase in the prevalence of allergies over the past several decades, especially in the rich nations of the world, where allergies are now very common disorders. In the developed countries, about 20 percent of people have or have had hay fever, another 20 percent have had contact dermatitis, and about 6 percent have food allergies. In the poorer nations of the world, on the other hand, allergies of all types are much less common.

    One explanation for the rise in allergies in the developed world is called the hygiene hypothesis. According to this hypothesis, people in developed countries live in relatively sterile environments because of hygienic practices and sanitation systems. As a result, people in these countries are exposed to fewer pathogens than their immune system evolved to cope with. To compensate, their immune system “keeps busy” by attacking harmless antigens in allergic responses.

    How Allergies Occur

    Mast cells allergic reaction mechanism
    Figure \(\PageIndex{4}\): This diagram shows how the adaptive immune system is activated by an otherwise harmless antigen on ragweed pollen, responding to the allergen as though it was a pathogen. (By DO11.10 [Public domain] via Wikimedia Commons; Mast cells.jpg)

    The diagram below shows how an allergic reaction occurs. At the first exposure to an allergen, B cells are activated to form plasma cells that produce large amounts of antibodies to the allergen. These antibodies attach to leukocytes called mast cells. Subsequently, every time the person encounters the allergen again, the mast cells are already primed and ready to deal with it. The primed mast cells immediately release cytokines and histamines, which in turn cause inflammation and recruitment of leukocytes, among other responses. These responses are responsible for the signs and symptoms of allergies.

    Treating Allergies

    The symptoms of allergies can range from mild to life-threatening. Mild allergy symptoms are often treated with antihistamines. These are drugs that reduce or eliminate the effects of the histamines that produce allergy symptoms.

    Signs and symptoms of anaphylaxis
    Figure \(\PageIndex{5}\): Anaphylaxis is a rapid, systemic reaction to allergens that may lead to life-threatening symptoms. (By Mikael Häggström (Own work) [CC0], via Wikimedia Commons; Signs and symptoms of anaphylaxis.png)

    Treating Anaphylaxis

    The most severe allergic reaction is a systemic reaction called anaphylaxis. This is a life-threatening response caused by a massive release of histamines. Many of the signs and symptoms of anaphylaxis are shown in the figure below. Some of them include a drop in blood pressure, changes in heart rate, shortness of breath, and swelling of the tongue and throat, which may threaten the patient with suffocation unless emergency treatment is given. People who have had anaphylactic reactions may carry an epinephrine autoinjector (widely known by its brand name EpiPen®) so they can inject themselves with epinephrine if they start to experience an anaphylactic response. The epinephrine helps to control the immune reaction until medical care can be provided. Epinephrine constricts blood vessels to increase blood pressure, relaxes smooth muscles in the lungs to reduce wheezing and improve breathing, modulates heart rate, and works to reduce swelling that may otherwise block the airways.

    Immunotherapy for Allergies

    Another way to treat allergies is called immunotherapy, commonly called “allergy shots.” This approach may actually cure specific allergies, at least for several years if not lifelong. It may be particularly beneficial for allergens such as pollen that are difficult or impossible to avoid. First, however, patients must be tested to identify the specific allergens that are causing their allergies. As shown in the photo below, this may involve scratching tiny amounts of common allergens into the skin and then observing whether there is a localized reaction to any of them. Each allergen is applied in a different numbered location on the skin so if there is a reaction, such as redness or swelling, the responsible allergens can be identified. Then, through periodic injections (usually weekly or monthly), patients are gradually exposed to larger and larger amounts of the allergens. Over time, generally from months to years, the immune system becomes desensitized to the allergens. This method of treating allergies is often effective for allergies to pollen or insect stings, but its usefulness for allergies to food is unclear.

    Skin prick testing for allergies
    Figure \(\PageIndex{6}\): Skin testing for common allergens is one way to identify the cause(s) of a patient’s allergic symptoms. (Public Domain; NIH via Wikimedia Commons; Skin prick testing for allergies.jpg).

    Autoimmune Diseases

    Symptoms of SLE
    Figure \(\PageIndex{7}\): Systemic lupus erythematosus is an autoimmune disease that may cause symptoms of body-wide tissue damage. (By Mikael Häggström, 2014, Medical gallery [Public domain], via Wikimedia Commons; Symptoms of SLE.png)

    Autoimmune diseases occur when the immune system fails to recognize the body’s own molecules as self. As a result, instead of ignoring the body’s healthy cells, it attacks them, causing damage to tissues and altered organ growth and function. Most often, it is B cells that are at fault in autoimmune responses. They are generally the cells that lose tolerance for self. Why does this occur? Some autoimmune diseases are thought to be caused by exposure to pathogens that have antigens similar to the body’s own molecules. After this exposure, the immune system responds to body cells as though they were pathogens as well.

    Certain individuals are genetically susceptible to developing autoimmune diseases. These individuals are also more likely to develop more than one such disease. Gender is also a risk factor for autoimmunity. Females are much more likely than males to develop autoimmune diseases, probably in part because of gender differences in sex hormones.

    At a population level, autoimmune diseases are less common where infectious diseases are more common. The hygiene hypothesis has been proposed to explain the inverse relationship between infectious and autoimmune diseases as well as the prevalence of allergies. According to the hypothesis, without infectious diseases to “keep it busy,” the immune system may attack the body’s own cells instead.

    Common Autoimmune Diseases

    An estimated 15 million or more people worldwide have one or more autoimmune diseases. Two of the most common autoimmune diseases are type I diabetes and multiple sclerosis. Both are localized diseases in terms of the specific body cells that are attacked by the immune system. In the case of type I diabetes, the immune system attacks and destroys insulin-secreting islet cells in the pancreas. In the case of multiple sclerosis, the immune system attacks and destroys the myelin sheaths that normally insulate the axons of neurons and allow rapid transmission of nerve impulses.

    Some relatively common autoimmune diseases are systemic, or body-wide, diseases. They include rheumatoid arthritis and systemic lupus erythematosus (SLE). In these diseases, many tissues and organs may be attacked and injured by the immune system. For example, as you can see in the figure below, symptoms of SLE may involve the muscular, skeletal, integumentary, respiratory, and cardiovascular systems.

    Treatment for Autoimmune Diseases

    None of these common autoimmune diseases can be cured, although all of them have treatments that may help relieve symptoms and prevent some of the long-term damage they may cause. Traditional treatments for autoimmune diseases include immunosuppressive drugs to block the immune response and anti-inflammatory drugs to quell inflammation. Hormone replacement may be another option. For example, type I diabetes is treated with injections of the hormone insulin because islet cells in the pancreas can no longer secrete it.


    Immunodeficiency occurs when the immune system is not working properly, generally because one or more components of the immune system are inactive. As a result, the immune system may be unable to fight off pathogens or cancers that a normal immune system would be able to resist. Immunodeficiency may occur for a variety of reasons.

    Causes of Immunodeficiency

    Dozens of rare genetic diseases can result in a defective immune system. This type of immunodeficiency is called primary immunodeficiency. One is born with one of these diseases rather than acquiring it after birth. Probably the best known of these primary immunodeficiency diseases is severe combined immunodeficiency (SCID). It is also known as “bubble boy disease” because people with this disorder are extremely vulnerable to infectious diseases and some of them have become well known for living inside a bubble that provides a sterile environment. SCID is most often caused by an X-linked recessive mutation that interferes with normal B cell and T cell production.

    Other types of immunodeficiency are not present at birth but acquired due to experiences or exposures that occur after birth. Acquired immunodeficiency is called secondary immunodeficiency because it is secondary to some other event or exposure. Secondary immunodeficiency may occur for a number of different reasons:

    • The immune system naturally becomes less effective as people get older. This age-related decline, called immunosenescence, generally begins at about age 50 and worsens with increasing age. Immunosenescence is why older people are generally more susceptible to disease than younger people.
    • The immune system may be damaged by another disorder, such as obesity, alcoholism, or the abuse of other drugs.
    • In developing countries, malnutrition is the most common cause of immune system damage and immunodeficiency. Inadequate protein intake is especially damaging to the immune system. It can lead to impaired complement system activity, phagocyte malfunction, and lower-than-normal production of antibodies and cytokines.
    • Surgical removal or disease of the thymus, where T lymphocytes normally mature, results in severe immunodeficiency. People without a functioning thymus are extremely susceptible to infections.
    • Certain medications can suppress the immune system. This is the intended effect of immunosuppressant drugs given to people with transplanted organs so they do not reject them. In many cases, however, immunosuppression is an unwanted side effect of drugs used to treat other disorders.
    • Some pathogens attack and destroy cells of the immune system. An example is a virus known as HIV, which attacks and destroys T cells.

    Focus on HIV

    Human immunodeficiency virus (HIV) is the most common cause of immunodeficiency in the world today, so it is the focus of the rest of this concept. It is also covered in the concept HIV and AIDS. HIV infections of human hosts are a relatively recent phenomenon. Scientists think that the virus originally infected monkeys but then jumped to human populations, probably sometime during the early to mid-1900s. This most likely occurred in West Africa, but the virus soon spread around the world. HIV was first identified by medical researchers in 1981. Since then, HIV has killed almost 40 million people worldwide, and its economic toll has also been enormous. The hardest hit countries are in Africa, where the virus has infected human populations the longest and medications to control the virus are least available.

    HIV Transmission

    HIV is transmitted through direct contact of mucous membranes or body fluids such as blood, semen, or breast milk. As shown in the figure below, the transmission of the virus can occur through sexual contact or the use of contaminated hypodermic needles. It can also be transmitted from an infected mother’s blood during late pregnancy or childbirth or through breast milk after birth. In the past, HIV was also transmitted occasionally through blood transfusions. Because donated blood is now screened for HIV, the virus is no longer transmitted this way.

    HIV infection
    Figure \(\PageIndex{8}\): HIV may be transmitted in all of the ways shown here. (Hana Zavadska and Laura Guerin; CC BY 3.0; CK-12 foundation)

    HIV and the Immune System

    AIDS life cycle illustration

    Figure \(\PageIndex{9}\): The human immunodeficiency virus (HIV-I) enters the T-lymphocyte where the virus loses its outer envelope, releasing its RNA and its reverse transcriptase. The reverse transcriptase builds a complementary DNA strand from the viral RNA template. The DNA helix is inserted into the host genome. When this is transcribed by the infected cell, the new viral RNA and proteins are produced to form new viruses that then bud from the cell membrane, thus completing the life cycle of the virus. (Trudy Nicholson (Illustrator) [Public domain]; via AIDS life cycle illustration.jpg)

    HIV infects and destroys helper T cells, the type of lymphocytes that regulate the immune response. How this occurs is shown in Figure \(\PageIndex{9}\). The virus injects its own DNA into a helper T cell and uses the T cell’s “machinery” to make copies of itself. In the process, the helper T cell is destroyed, and the virus copies go on to infect other helper T cells. HIV is able to evade the immune system and keep destroying helper T cells by mutating frequently so its surface antigens keep changing and by using the host cell’s membrane to hide its own antigens.

    HIV destroying T cells
    Figure \(\PageIndex{10}\): This diagram shows how HIV infects and destroys helper T cells. (Rupali Raju; CC BY 3.0: CK-12 foundation).

    Acquired immunodeficiency syndrome (AIDS) may result from years of damage to the immune system by HIV. It occurs when helper T cells fall to a very low level and opportunistic diseases occur (see the graph below). Opportunistic diseases are infections and tumors that are rare except in people with a damaged immune system. The diseases take advantage of the “opportunity” presented by people whose immune system cannot fight back. Opportunistic diseases are usually the direct cause of death of people with AIDS.

     HIV early and late opportunistic infections
    Figure \(\PageIndex{11}\): It typically takes several years after infection with HIV for the drop in helper T cells to damage the immune system to the point where opportunistic infections start to appear. Note that the y-axis is labeled CD4+ cells, which is another designation for helper T cells. (Hana Zavadska; CC BY 3.0; CK-12 foundation)

    Treating HIV/AIDS

    For patients who have access to HIV medications, infection with the virus has ceased to be the death sentence that it once was. By 1995, combinations of drugs called “highly active antiretroviral therapy” were developed. For some patients, these drugs can reduce the amount of virus they are carrying to undetectable levels. However, some amount of virus always hides in the body’s immune cells and will multiply again if a patient stops taking the medications. Researchers are trying to develop drugs to kill these hidden viruses as well. If their efforts are successful, it could bring an end to AIDS.

    Feature: Human Biology in the News

    EpiPens® and their sole manufacturer, pharmaceutical company Mylan, were featured in the news headlines in 2016 but not for a good reason. A drastic price hike in EpiPens® and Mylan’s apparent greed triggered the media outburst.

    EpiPens® are auto-injectable syringes preloaded with a measured dose of epinephrine, a drug that can rapidly stop a life-threatening anaphylactic response to an allergen. Using the device is easy and does not require any special training. The injector just needs to be jammed against the thigh, which can be done through clothing or on bare skin. Each year, doctors write millions of prescriptions for EpiPens®. Many people with severe allergies always carry two of the devices with them just in case they experience anaphylaxis, although most of them never need to use them. Other people with severe allergies have literally had their lives saved multiple times by EpiPens® when they had anaphylactic reactions. Even when the devices haven’t been used, they must be replaced each year due to the expiration of the epinephrine.

    You might think that EpiPens® would be relatively inexpensive, given their life-saving potential. As recently as 2009, a two-pack of EpiPens® cost about $100. However, in just 7 years, the cost of the same two-pack of EpiPens® skyrocketed by an incredible 400 percent! By 2016, the cost was $600 or more. Mylan apparently raised the price for the sole purpose of increasing profits. The company also raised prices significantly on many other drugs. The price hike in EpiPens® alone was certainly profitable. In 2015, the sale of EpiPens® earned Mylan $1 billion. Mylan’s CEO took home almost $19 million the same year, which was an increase of more than 600 percent over her prior salary.

    News coverage of the price hike in EpiPens® began in the summer of 2016 after a price increase in May of that year. Both private citizens and elected officials expressed outrage over the price increase, especially when coupled with the gluttonous profits of the company and its CEO. By late August, Mylan responded to the backlash by offering discount coupons for EpiPens®. A few days later, the company promised to introduce a cheaper, generic version of the device. Analysts quickly determined that selling a generic version would allow Mylan to make more money on the product than reducing the price of the name-brand device, which they still declined to do. By September of 2016, Mylan was being investigated for antitrust violations relating to sales of EpiPens® to public schools in New York City.

    The Mylan/EpiPen® story may still be making the news. But whatever its outcome, the story has already added fuel to public and private debates about important ethical issues — issues such as the excessive costs of life-saving drugs and the huge profits of big pharma. What is the most recent news on EpiPens® and Mylan? If you are interested, you can check the headlines online to find out. What are your views on the ethical issues they raise?


    • An allergy is a disorder in which the immune system makes an inflammatory response to a harmless antigen. Any antigen that causes allergies is called an allergen. Common allergens include pollen, dust mites, mold, specific foods such as peanuts, insect stings, and certain medications such as aspirin.
    • The prevalence of allergies has been increasing for decades, especially in developed countries where they are much more common than in developing countries. The hygiene hypothesis posits that this has occurred because humans evolved to cope with more pathogens than we now typically face in our relatively sterile environments in developed countries. As a result, the immune system “keeps busy” by attacking harmless antigens.
    • Allergies occur when B cells are first activated to produce large amounts of antibodies to an otherwise harmless allergen and the antibodies attach to mast cells. On subsequent exposures to the allergen, the mast cells immediately release cytokines and histamines that cause inflammation.
    • Mild allergy symptoms are frequently treated with antihistamines that counter histamines and reduce allergy symptoms. A severe systemic allergic reaction, called anaphylaxis, is a medical emergency that is usually treated with injections of epinephrine. Immunotherapy for allergies involves injecting increasing amounts of allergens to desensitize the immune system to them.
    • Autoimmune diseases occur when the immune system fails to recognize the body’s own molecules as self and attacks them, causing damage to tissues and organs. A family history of autoimmunity and female gender are risk factors for autoimmune diseases.
    • In some autoimmune diseases, such as type I diabetes, the immune system attacks and damages specific body cells. In other autoimmune diseases, such as systemic lupus erythematosus, many different tissues and organs may be attacked and injured. Autoimmune diseases generally cannot be cured, but their symptoms can often be managed with drugs or other treatments.
    • Immunodeficiency occurs when the immune system is not working properly, generally because one or more of its components are inactive. As a result, the immune system is unable to fight off pathogens or cancers that a normal immune system would be able to resist.
    • Primary immunodeficiency is present at birth and caused by rare genetic diseases. An example is severe combined immunodeficiency. Secondary immunodeficiency occurs because of some event or exposure experienced after birth. Possible causes include aging, certain medications, infections with pathogens, and other disorders, such as obesity or malnutrition.
    • The most common cause of immunodeficiency in the world today is the human immunodeficiency virus (HIV), which infects and destroys helper T cells. HIV is transmitted through mucous membranes or body fluids. The virus may eventually lead to such low levels of helper T cells that opportunistic infections occur. When this happens, the patient is diagnosed with acquired immunodeficiency syndrome (AIDS). Medications can control the multiplication of HIV in the human body but not eliminate the virus completely.


    1. What are allergies? What causes them?
    2. Compare the prevalence of allergies in developed and developing countries. How does the hygiene hypothesis explain the differences in prevalence?
    3. How do allergies occur?
    4. How are mild allergy symptoms treated?
    5. What is anaphylaxis, and how is it treated?
    6. How does immunotherapy for allergies work?
    7. What are autoimmune diseases?
    8. Identify two risk factors for autoimmune diseases.
    9. Autoimmune diseases may be specific to particular tissues, or they may be systemic. Give an example of each type of autoimmune disease.
    10. What is immunodeficiency?
    11. Compare and contrast primary and secondary immunodeficiency, and give an example of each.
    12. What is the most common cause of immunodeficiency in the world today? How does this cause affect the immune system?
    13. Distinguish between HIV and AIDS.
    14. True or False. Allergies and autoimmune diseases both result from an over-reactive immune system.

    15. True or False. An anaphylactic reaction can be stopped by administering a shot of histamine.

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