12.5: Immunity Disorders: Autoimmune Diseases - Biology

12.5: Immunity Disorders: Autoimmune Diseases

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. This is the basis of allergies like hay fever.

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, which 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.


Lymphocytes enable the body to remember antigens and to distinguish self from harmful nonself (including viruses and bacteria). Lymphocytes circulate in the bloodstream and lymphatic system and move into tissues as needed.

The immune system can remember every antigen encountered because after an encounter, some lymphocytes develop into memory cells. These cells live a long time—for years or even decades. When memory cells encounter an antigen for the second time, they recognize it immediately and respond quickly, vigorously, and specifically to that particular antigen. This specific immune response is the reason that people do not contract chickenpox or measles more than once and that vaccination can prevent certain disorders.

Lymphocytes may be T cells or B cells. T cells and B cells work together to destroy invaders.

T cells

T cells develop from stem cells in the bone marrow that have travelled to an organ in the chest called the thymus. There, they learn how to distinguish self from nonself antigens so that they do not attack the body's own tissues. Normally, only the T cells that learn to ignore the body's own antigens (self-antigens) are allowed to mature and leave the thymus.

T cells can potentially recognize an almost limitless number of different antigens.

Mature T cells are stored in secondary lymphoid organs (lymph nodes, spleen, tonsils, appendix, and Peyer patches in the small intestine). These cells circulate in the bloodstream and the lymphatic system. After they first encounter an infected or abnormal cell, they are activated and search for those particular cells.

Usually, to be activated, T cells require the help of another immune cell, which breaks antigens into fragments (called antigen processing) and then presents antigen from the infected or abnormal cell to the T cell. The T cell then multiplies and specializes into different types of T cells. These types include

Killer (cytotoxic) T cells attach to antigens on infected or abnormal (for example, cancerous) cells. Killer T cells then kill these cells by making holes in their cell membrane and injecting enzymes into the cells.

Helper T cells help other immune cells. Some helper T cells help B cells produce antibodies against foreign antigens. Others help activate killer T cells to kill infected or abnormal cells or help activate macrophages, enabling them to ingest infected or abnormal cells more efficiently.

Suppressor (regulatory) T cells produce substances that help end the immune response or sometimes prevent certain harmful responses from occurring.

When T cells initially encounter an antigen, most of them perform their designated function, but some of them develop into memory cells, which remember the antigen and respond to it more vigorously when they encounter it again.

Sometimes T cells—for reasons that are not completely understood—do not distinguish self from nonself. This malfunction can result in an autoimmune disorder, in which the body attacks its own tissues.

B cells

B cells are formed in the bone marrow. B cells have particular sites (receptors) on their surface where antigens can attach. B cells can learn to recognize an almost limitless number of different antigens.

The main purpose of B cells is to produce antibodies, which tag an antigen for attack or directly neutralize it. B cells can also present antigen to T cells, which then become activated.

The B-cell response to antigens has two stages:

Primary immune response: When B cells first encounter an antigen, the antigen attaches to a receptor, stimulating the B cells. Some B cells change into memory cells, which remember that specific antigen, and others change into plasma cells. Helper T cells help B cells in this process. Plasma cells produce antibodies that are specific to the antigen that stimulated their production. After the first encounter with an antigen, production of enough of the specific antibody takes several days. Thus, the primary immune response is slow.

Secondary immune response: But thereafter, whenever B cells encounter the antigen again, memory B cells very rapidly recognize the antigen, multiply, change into plasma cells, and produce antibodies. This response is quick and very effective.

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Plan of Action

A successful immune response to invaders requires

Activation and mobilization


To be able to destroy invaders, the immune system must first recognize them. That is, the immune system must be able to distinguish what is nonself (foreign) from what is self. The immune system can make this distinction because all cells have identification molecules (antigens) on their surface. Microorganisms are recognized because the identification molecules on their surface are foreign.

In people, the most important self-identification molecules are called

Human leukocyte antigens (HLA), or the major histocompatibility complex (MHC)

HLA molecules are called antigens because if transplanted, as in a kidney or skin graft, they can provoke an immune response in another person (normally, they do not provoke an immune response in the person who has them). Each person has an almost unique combination of HLAs. Each person’s immune system normally recognizes this unique combination as self. A cell with molecules on its surface that are not identical to those on the body’s own cells is identified as being foreign. The immune system then attacks that cell. Such a cell may be a cell from transplanted tissue or one of the body’s cells that has been infected by an invading microorganism or altered by cancer. (HLA molecules are what doctors try to match when a person needs an organ transplant.)

T cells (T lymphocytes), as part of the immune surveillance system, must be able to recognize substances that do not belong to the body (foreign antigens). However, they cannot directly recognize an antigen. They need the help of an antigen-presenting cell (such as a macrophage or dendritic cell).

The antigen-presenting cell engulfs the antigen. Then enzymes in the cell break the antigen into fragments, which are combined with the cell's identification molecules—called major histocompatibility complex molecules, or human leukocyte antigens (HLAs). The combined HLA and antigen fragment moves to the surface of the antigen-presenting cell where it is recognized by receptors on the T cell.

Some white blood cells—B cells (B lymphocytes)—can recognize invaders directly. But others—T cells (T lymphocytes)—need help from cells called antigen-presenting cells:

Antigen-presenting cells ingest an invader and break it into fragments.

The antigen-presenting cell then combines antigen fragments from the invader with the cell's own HLA molecules.

The combination of antigen fragments and HLA molecules is moved to the cell’s surface.

A T cell with a matching receptor on its surface can attach to part of the HLA molecule presenting the antigen fragment, as a key fits into a lock.

The T cell is then activated and begins fighting the invaders that have that antigen.

How T Cells Recognize Antigens

T cells are part of the immune surveillance system. They travel through the bloodstream and lymphatic system. When they reach the lymph nodes or another secondary lymphoid organ, they look for foreign substances (antigens) in the body. However, before they can fully recognize and respond to a foreign antigen, the antigen must be processed and presented to the T cell by another white blood cell, called an antigen-presenting cell. Antigen-presenting cells consist of dendritic cells (which are the most effective), macrophages, and B cells.

Activation and mobilization

White blood cells are activated when they recognize invaders. For example, when the antigen-presenting cell presents antigen fragments bound to HLA to a T cell, the T cell attaches to the fragments and is activated. B cells can be activated directly by invaders. Once activated, white blood cells ingest or kill the invader or do both. Usually, more than one type of white blood cell is needed to kill an invader.

Immune cells, such as macrophages and activated T cells, release substances that attract other immune cells to the trouble spot, thus mobilizing defenses. The invader itself may release substances that attract immune cells.


The immune response must be regulated to prevent extensive damage to the body, as occurs in autoimmune disorders. Regulatory (suppressor) T cells help control the response by secreting cytokines (chemical messengers of the immune system) that inhibit immune responses. These cells prevent the immune response from continuing indefinitely.


Resolution involves confining the invader and eliminating it from the body. After the invader is eliminated, most white blood cells self-destruct and are ingested. Those that are spared are called memory cells. The body retains memory cells, which are part of acquired immunity, to remember specific invaders and respond more vigorously to them at the next encounter.

There are two major classes of lymphocytes involved with specific defenses: B cells and T cells.

Immature T cells are produced in the bone marrow, but they subsequently migrate to the thymus, where they mature and develop the ability to recognize specific antigens. T cells are responsible for cell-mediated immunity.

B cells, which mature in the bone marrow, are responsible for antibody-mediated immunity.

The cell-mediated response begins when a pathogen is engulfed by an antigen-presenting cell, in this case a macrophage. After the microbe is broken down by lysosomal enzymes, antigenic fragments are displayed with MHC molecules on the surface of the macrophage.

T cells recognize the combination of the MHC molecule and an antigenic fragment and are activated to multiply rapidly into an army of specialized T cells.

One member of this army is the cytotoxic T cell. Cytotoxic T cells recognize and destroy foreign cells and tissues or virus-infected cells.

Another T cell is the memory cytotoxic T lymphocyte, which remains in reserve in the body. If, sometime in the future, these T cells re-encounter this specific antigen, they will rapidly differentiate into cytotoxic T cells, providing a speedy and effective defense.

Helper T cells coordinate specific and nonspecific defenses. In large part by releasing chemicals that stimulate T cell and B cell growth and differentiation.

Suppressor T cells inhibit the immune response so that it ends when the infection has been controlled. Whereas the number of helper T cells increases almost at once, the number of suppressor T cells increases slowly, allowing time for an effective first response.

Clinical Implications

The increasing knowledge on the potential involvement of inflammatory processes in mental disorders and the associations found between autoimmunity and psychotic disorders can help the expanding field of immuno-psychiatry and have impact on the outcome of patients. In the last couple of years, researchers have focused on the role of infections, autoantibodies and other immune components that plays a major role in autoimmune diseases. Potentially this might also be the case for mental disorders. Risk factors for both autoimmune diseases and schizophrenia includes an interaction between environmental factors, such as infections and stress, with genetic factors involving the HLA region. Autoimmune reactions with activation of immune components and the production of NSAbs can induce a broad spectrum of psychiatric symptoms, hereunder psychosis. The potential autoimmune-mediated psychosis group might only be a small part of a broader immune-related psychosis group, and an even smaller fraction of the overall psychosis group. However, identification of this subgroup might allow for precision medicine strategies where immune-based treatment could possibly improve the psychotic symptoms. A quick discovery and treatment of autoimmune encephalitis markedly reduces the neuropsychiatric sequelae, and intensive immunotherapy in lupus patients with psychosis massively benefits psychiatric symptoms (42, 121).

Focus on the association between autoimmunity and psychosis, regardless of etiology, is important, not only for researchers but also for the individual patient. It is known that patients suffering from schizophrenia have an excess early mortality, with a life expectancy up to 13.5 years shorter than the general population, primarily due to physical diseases (122). Bearing this in mind and considering that patients with psychotic disorders might struggle with reporting on somatic symptoms, it is important for clinicians to be aware of an increased prevalence of autoimmune disease in this group. Symptoms from a disease such as celiac disease or rheumatoid arthritis might very well be overlooked and cast aside as a part of the patient's psychosis, or possibly adverse events caused by their treatment. With increasingly sufficient treatment strategies in autoimmune diseases, overlooking and therefore not treating these diseases, increases the health gap between those with schizophrenia and the general population even further. Therefore, patients with a psychotic disorder need to be thoroughly and frequently examined when presenting with symptoms possibly related to autoimmunity or other health problems.

Treatment depends on the type of autoimmune disease. In most cases, your doctor will prescribe medications to reduce redness, pain, and swelling.

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Centers for Disease Control and Prevention, National Center for Health Statistics

National Institute of Allergy and Infectious Diseases, National Institutes of Health

American Autoimmune-Related Diseases Association, Inc.

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If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

  • To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from MedlinePlus Genetics.

Some obesity may be caused by a faulty immune system

Immune cells are usually described as soldiers fighting invading viruses and bacteria. But they may also be waging another battle: the war against fat. When mice lack a specific type of immune cell, researchers have discovered, they become obese and show signs of high blood pressure, high cholesterol, and diabetes. The findings have yet to be replicated in humans, but they are already helping scientists understand the triggers of metabolic syndrome, a cluster of conditions associated with obesity.

The new study “definitely moves the field forward,” says immunologist Vishwa Deep Dixit of the Yale School of Medicine, who was not involved in the work. “The data seem really solid.”

Scientists already know that there is a correlation between inflammation—a heightened immune response—and obesity. But because fat cells themselves can produce inflammatory molecules, distinguishing whether the inflammation causes weight gain or is just a side effect has been tricky.

When he stumbled on this new cellular link between obesity and the immune system, immunologist Yair Reisner of the Weizmann Institute of Science in Rehovot, Israel, was studying something completely different: autoimmune diseases. An immune molecule called perforin had already been shown to kill diseased cells by boring a hole in their outer membrane. Reisner’s group suspected that dendritic cells containing perforin might also be destroying the body’s own cells in some autoimmune diseases. To test the idea, Reisner and his colleagues engineered mice to lack perforin-wielding dendritic cells, and then waited to see whether they developed any autoimmune conditions.

“We were looking for conventional autoimmune diseases,” Reisner says. “Quite surprisingly, we found that the mice gained weight and developed metabolic syndrome.”

Mice lacking the dendritic cells with perforin had high levels of cholesterol, early signs of insulin resistance, and molecular markers in their bloodstreams associated with heart disease and high blood pressure. And a look at the immune systems of the mice revealed that they also had a different balance of T cells—a type of white blood cell that directs immune responses—than normal, Reisner and his colleagues report online today in Immunity. When the researchers removed these T cells from the mice, however, the lack of the dendritic cells no longer caused the animals to become obese or develop metabolic syndrome.

The results, Reisner says, suggest that the normal role of the perforin-positive dendritic cells is to keep certain populations of T cells under control. Just as perforin acts to kill cells infected with viruses, it can be directed to kill subsets of unnecessary T cells, he thinks. When the brakes are taken off those T cells, they cause inflammation in fat cells, which leads to altered metabolism and weight gain.

“We are now working in human cells to see if there is something similar going on there,” Reisner says. “I think this is the beginning of a new focus on a new regulatory cell.” If the results hold true in humans, he says, he could point toward a way to use the immune system to treat obesity and metabolic disease.

Daniel Winer, an endocrine pathologist at the University of Toronto in Canada and the lead author of a January Diabetes paper linking perforin to insulin resistance, says the new results overlap with his study. His group had found that mice lacking perforin—throughout their whole immune system, not just in dendritic cells—and fed a high-fat diet developed the early stages of diabetes. The new paper builds on that by homing in on perforin-positive dendritic cells and showing the link even in the absence of a high-fat diet. “It provides further evidence that the immune system has an important role in the regulation of both obesity and insulin resistance.”

Even if the results hold true in humans, however, the research is still far from leading to treatments for obesity or metabolic disease, Dixit says. “Talking about therapeutics at this point would be a bit of a stretch.” After all, injecting perforin into the body could kill cells beyond the T cell ones promoting obesity, he points out. Moreover, we can’t live without any T cells at all—they are vital for immunity against disease. But research on what the T cells are recognizing when they seek out fat cells and cause inflammation in fat tissue could eventually reveal drug targets.