Immune System Malfunctions: Allergies and Autoimmunity

An allergy is an overreaction of the immune system to a harmless substance (an allergen), while an autoimmune disease occurs when the immune system mistakenly attacks the body’s own healthy tissues. In brief: in an allergy, antibodies of the IgE class cause mast cells to release histamine, which leads to sneezing, itching, swelling or, in severe cases, anaphylaxis. In autoimmune diseases such as type 1 diabetes and rheumatoid arthritis, the loss of self-tolerance causes immune cells or antibodies to damage the body’s own cells.

These disorders affect many people, and they show what happens when the immune system’s balance between defense and restraint is lost. This guide explains what happens in an allergic reaction, how severe reactions are treated, how autoimmunity arises, gives examples, compares the two problems, works through a diagnostic example and corrects common mistakes.

What is an allergy?

An allergy (hypersensitivity) is an exaggerated immune response to a substance that is normally harmless. The substance is called an allergen. Common allergens include pollen, house dust mites, pet dander, mold spores, foods (peanuts, milk, eggs, shellfish), insect stings, and drugs such as penicillin. Allergic diseases include hay fever (allergic rhinitis), allergic asthma, eczema and food allergies. In many countries, up to 20 to 30 percent of people suffer from some allergic disease, and the numbers have increased over the last decades. The reasons are not completely understood, and one hypothesis is that less exposure to microbes in childhood may affect the development of the immune system (the hygiene hypothesis).

How does an allergic reaction happen?

1. Sensitization: on first exposure, the allergen is taken up by antigen-presenting cells, and helper T cells stimulate B cells to produce IgE antibodies against it. The IgE attaches to the surface of mast cells (in tissue) and basophils (in blood). There are usually no symptoms at this stage.
2. Re-exposure: the allergen binds to IgE on the mast cells and links several of them together.
3. Release of mediators: the mast cells release histamine and other chemicals within minutes.
4. Symptoms: histamine widens blood vessels and makes them leaky (redness, swelling, runny nose), contracts smooth muscle in the airways (wheezing), stimulates mucus production and nerve endings (itching, sneezing).

Antihistamines block histamine receptors and reduce these symptoms. Some reactions have a delayed phase, with more inflammation hours later.

What is anaphylaxis?

Anaphylaxis is a severe, whole-body allergic reaction that can be life-threatening. Large amounts of histamine and other mediators cause blood vessels to widen and leak, so blood pressure falls sharply, the airways narrow and the throat and tongue may swell. Symptoms may include difficulty in breathing, dizziness, rapid pulse, hives and vomiting. Common triggers are foods such as peanuts, insect stings and drugs.

The emergency treatment is an injection of adrenaline (epinephrine) into the thigh muscle, which constricts blood vessels, raises blood pressure and opens the airways. People with serious allergies carry an auto-injector, and emergency medical help should always be called.

What is an autoimmune disease?

Normally, the immune system distinguishes self from non-self, a property called self-tolerance. In an autoimmune disease, this tolerance fails, and lymphocytes or autoantibodies attack the body’s own tissues. The exact causes are not fully known. They involve a combination of genes (certain MHC types increase the risk), environmental triggers (infections, some drugs, smoking) and hormones, since many autoimmune diseases are more common in women.

• Type 1 diabetes: T cells destroy the insulin-producing beta cells of the pancreas, so people need insulin for life.
• Rheumatoid arthritis: the immune system attacks the lining of the joints and causes pain, swelling and damage.
• Multiple sclerosis: immune cells attack the myelin sheath of nerves in the brain and spinal cord, which slows or blocks the nerve signals.
• Systemic lupus erythematosus: autoantibodies attack many tissues, including skin, joints and kidneys.
• Celiac disease: gluten triggers an immune attack on the lining of the small intestine.
• Graves’ disease and Hashimoto’s thyroiditis: autoantibodies or immune cells affect the thyroid gland.

A related problem is immunodeficiency, in which part of the immune system is weak or missing, as in AIDS or some inherited conditions. Transplant rejection is also an immune response, in which T cells attack foreign tissue, so transplant patients take drugs that suppress the immune system.

Allergies and autoimmune diseases compared

Worked example: interpreting immune test results

Two patients visit a clinic. Patient 1 sneezes and has itchy eyes each spring and has a positive skin prick test for birch pollen: a drop of allergen extract is placed on the skin and the skin is pricked. A raised, red, itchy bump (wheal) appears within 15 to 20 minutes. Patient 2 has fatigue, joint pain and a blood test that shows autoantibodies against cell nuclei and a high level of inflammation markers.

1. Patient 1: the rapid wheal-and-flare reaction is typical for IgE-mediated allergy to birch pollen (hay fever). Management: avoid pollen when levels are high, use antihistamines or nasal steroids, or consider immunotherapy with gradually increasing doses of allergen.
2. Patient 2: autoantibodies and symptoms in several tissues suggest an autoimmune disease such as lupus, and further tests are needed. Management: drugs that reduce the activity of the immune system.

The two cases show the key differences. For the first, the target is a foreign substance, and the response is quick and mediated by IgE. For the second, the target is the body’s own tissue, and the disease is chronic. Doctors rely on the history and on confirmed tests, as symptoms alone can be misleading.

How are these conditions managed?

For allergies: identifying and avoiding triggers, antihistamines, corticosteroids to reduce inflammation, and allergen immunotherapy, which gradually builds tolerance. Early introduction of peanuts to infants at high risk has been shown in trials to reduce the risk of peanut allergy. For autoimmune diseases, there is generally no cure. Treatments reduce symptoms and slow the damage, using anti-inflammatory drugs, immunosuppressants and biologic drugs, which are antibodies that block specific immune signals, and replacing what is lost, such as insulin in type 1 diabetes.

How were these disorders discovered?

Charles Richet and Paul Portier discovered anaphylaxis in 1902, when dogs given a second dose of sea anemone toxin reacted severely, and Richet received the 1913 Nobel Prize in Physiology or Medicine. The antibody IgE was identified by Kimishige and Teruko Ishizaka in 1966. Paul Ehrlich proposed the idea of “horror autotoxicus” in 1900, that the body should not attack itself. Autoimmune thyroiditis was described by Hakaru Hashimoto in 1912.

Which mistakes are common?

Mistake 1: Saying that allergies are caused by weak immunity

They are caused by an overreaction of the immune system.

Mistake 2: Confusing food allergy with food intolerance

An allergy involves the immune system and can be dangerous. Intolerance, such as lactose intolerance, is a digestive problem without immune involvement.

Mistake 3: Thinking autoimmune diseases are infectious

They do not spread from person to person.

Mistake 4: Treating a severe allergic reaction with an antihistamine alone

Anaphylaxis requires adrenaline and emergency care.