• An important undesirable effect of immunity is the development of:
  • Allergy
  • Other types of immune hypersensitivity
• There are several types of allergies and hypersensitivity reactions.
• Some types occur only in people with a specific allergic tendency.

Allergy Caused by Activated T Cells: Delayed-Reaction Allergy

• Delayed-reaction allergy is caused by activated T cells.
• It is not caused by antibodies.
• In poison ivy allergy, the poison ivy toxin alone causes very little tissue damage.
• With repeated exposure, the toxin stimulates the formation of:
  • Activated helper T cells
  • Activated cytotoxic T cells
• After another exposure to the poison ivy toxin, within about one day, large numbers of activated T cells leave the circulating blood.
• These activated T cells move into the skin.
• The T cells respond specifically to the poison ivy toxin.
• At the same time, they produce a cell-mediated immune reaction.
• Activated T cells release many toxic substances.
• They also cause extensive invasion of the tissue by macrophages.
• The macrophages produce additional tissue effects.
• Some delayed-reaction allergies can result in severe tissue damage.
• The tissue damage usually occurs where the antigen is present.
• Examples include:
  • Skin damage in poison ivy allergy
  • Lungs, causing pulmonary edema or asthmatic attacks after exposure to some airborne antigens

Key Concept

Allergy and hypersensitivity are undesirable immune responses. Delayed-reaction allergy is mediated by activated T cells rather than antibodies. After repeated exposure to an antigen such as poison ivy, activated helper and cytotoxic T cells migrate to the affected tissue, release toxic substances, recruit macrophages, and produce a cell-mediated immune reaction that can cause significant local tissue damage, including skin inflammation or lung edema and asthma with airborne antigens.

Atopic Allergies Associated With Excess IgE Antibodies

• Some people have a genetic tendency to develop allergies.
• These allergies are called atopic allergies.
• Atopic allergies occur because of an abnormal response of the immune system.
• The allergic tendency is inherited from parents to children.
• People with atopic allergies have large amounts of IgE antibodies in their blood.
• IgE antibodies are also called:
  • Reagins
  • Sensitizing antibodies
• These names distinguish IgE from the more common IgG antibodies.
• An allergen is an antigen that reacts specifically with a particular IgE (reagin) antibody.
• When an allergen enters the body, an allergen–reagin reaction occurs.
• This reaction produces an allergic response.
• A special feature of IgE antibodies is their strong ability to attach to:
  • Mast cells
  • Basophils
• A single mast cell or basophil can bind up to 500,000 IgE antibody molecules.
• When an allergen with multiple binding sites binds to several IgE antibodies attached to a mast cell or basophil, the cell membrane changes immediately.
• This membrane change may result from physical distortion caused by the bound antibody molecules.
• Many mast cells and basophils rupture.
• Other mast cells and basophils release chemical mediators immediately or shortly afterward.
• These released substances include:
  • Histamine
  • Protease
  • Slow-reacting substance of anaphylaxis (mixture of leukotrienes)
  • Eosinophil chemotactic substance
  • Neutrophil chemotactic substance
  • Heparin
  • Platelet-activating factors
• These substances cause:
  • Dilation of local blood vessels
  • Attraction of eosinophils and neutrophils to the reaction site
  • Increased capillary permeability, allowing fluid to leak into tissues
  • Contraction of local smooth muscle
• The final allergic response depends on which tissue contains the allergen–reagin reaction.
• Different tissues produce different types of allergic reactions.

Figure Number

• Figure 35.10: Shows:
  • Mechanism of mRNA vaccines
  • Entry of mRNA into antigen-presenting cells
  • Antigen production
  • Presentation by MHC I and MHC II
  • Activation of:
    • Cytotoxic T cells
    • Helper T cells
    • B cells
    • Macrophages
  • Production of neutralizing antibodies
  • Release of perforins and inflammatory cytokines

Mathematical Equations

• No mathematical equation is present in the provided text.

Key Concept

Atopic allergies are inherited allergic disorders associated with excessive IgE (reagin) antibodies. IgE binds strongly to mast cells and basophils. When an allergen cross-links these IgE molecules, the cells rupture or degranulate, releasing histamine, leukotrienes, heparin, chemotactic factors, and other mediators. These substances produce vasodilation, increased capillary permeability, inflammatory cell recruitment, and smooth muscle contraction, resulting in tissue-specific allergic reactions.

Anaphylaxis—Widespread Allergic Reaction

• Anaphylaxis is a widespread allergic reaction.
• It occurs when a specific allergen is injected directly into the bloodstream.
• The allergen reacts with:
  • Basophils in the blood
  • Mast cells in tissues surrounding small blood vessels
• This reaction occurs only if the basophils and mast cells have been sensitized by IgE (reagin) antibodies.
• As a result, a widespread allergic reaction develops throughout the vascular system and nearby tissues.
• This reaction is called anaphylaxis.
• During anaphylaxis, histamine is released into the bloodstream.
• Histamine causes:
  • Widespread vasodilation
  • Increased capillary permeability
• Increased capillary permeability allows plasma to leak out of the circulation.
• This causes a marked loss of plasma volume.
• In severe cases, the person may develop circulatory shock.
• Without prompt treatment, death can occur within a few minutes.
• Epinephrine is used to counteract the effects of histamine.
• Activated basophils and mast cells also release the slow-reacting substance of anaphylaxis (SRS-A).
• SRS-A is a mixture of leukotrienes.
• These leukotrienes cause spasm of the smooth muscle of the bronchioles.
• Bronchial smooth muscle spasm produces an asthma-like attack.
• Severe bronchospasm may cause death by suffocation.

Key Concept

Anaphylaxis is a severe systemic IgE-mediated allergic reaction that occurs when an allergen enters the bloodstream and activates sensitized mast cells and basophils. Massive release of histamine causes widespread vasodilation, increased capillary permeability, plasma loss, and circulatory shock, while leukotrienes (slow-reacting substance of anaphylaxis) produce bronchospasm that can lead to life-threatening airway obstruction.

Urticaria—Localized Anaphylactoid Reactions

• Urticaria occurs when an antigen enters a specific area of the skin.
• The antigen produces a localized anaphylactoid reaction.
• Histamine is released at the affected site.
• Histamine causes:
  • Vasodilation, producing an immediate red flare.
  • Increased capillary permeability.
• Increased capillary permeability causes localized swelling of the skin within a few minutes.
• These localized swellings are called hives.
• Antihistamine drugs, given before exposure to the antigen, can prevent the formation of hives.

Hay Fever

• In hay fever, the allergen–reagin reaction occurs in the nose.
• Histamine released during the reaction causes:
  • Local vasodilation inside the nose.
  • Increased capillary pressure.
  • Increased capillary permeability.
• These changes cause rapid leakage of fluid into:
  • The nasal cavity.
  • The deeper tissues of the nose.
• As a result, the nasal lining becomes swollen.
• The nasal lining also becomes more secretory.
• Antihistamine drugs can prevent this swelling.
• However, other substances released during the allergen–reagin reaction can still irritate the nose.
• This irritation produces the typical sneezing attacks.

Asthma

• Asthma commonly occurs in hypersensitive allergic individuals.
• In asthma, the allergen–reagin reaction occurs in the bronchioles of the lungs.
• An important substance released from mast cells is the slow-reacting substance of anaphylaxis (SRS-A).
• SRS-A is a mixture of three leukotrienes.
• These leukotrienes cause spasm of the bronchiolar smooth muscle.
• Bronchial smooth muscle spasm makes breathing difficult.
• Breathing improves only after the products of the allergic reaction are removed.
• Antihistamine drugs have little effect on asthma.
• This is because histamine is not the major cause of the asthmatic reaction.

Key Concept

Urticaria, hay fever, and asthma are IgE-mediated allergic reactions that occur in different tissues. Urticaria causes localized skin hives due to histamine-induced vasodilation and increased capillary permeability. Hay fever affects the nasal mucosa, producing swelling, secretions, and sneezing. Asthma affects the bronchioles, where leukotrienes (slow-reacting substance of anaphylaxis) cause bronchial smooth muscle spasm, making breathing difficult; therefore, antihistamines are less effective in asthma than in urticaria or hay fever.

Sex Differences in Innate and Adaptive Immunity

• Sex chromosomes and gonadal hormones (such as testosterone and estrogen) influence:
  • The number of immune cells
  • The function of immune cells
• In females, the activation and phagocytic activity of certain macrophages and monocytes are greater than in males.
• After viral infections, immune cells in females produce more interferons than those in males.
• Interferons are signaling proteins with antiviral activity.
• Females also have a stronger adaptive immune response than males.
• This stronger adaptive immunity includes:
  • Greater expansion of T cells
  • Stronger humoral immune responses
• As a result, females:
  • Eliminate pathogens more rapidly
  • Produce stronger antibody responses after repeated exposure to the same antigen
• Immune responses to vaccines are generally stronger in women than in men.
• Although stronger innate and adaptive immunity provides better protection against pathogens, it can also increase the risk of autoimmune diseases.
• Autoimmune diseases are more common in females than in males.
• Autoimmune diseases affect about 5% of the human population.
• About 80% of people with autoimmune diseases are female.
• Systemic Lupus Erythematosus (SLE) affects women nearly 10 times more often than men.
• The exact reasons for these sex-related differences in immunity are not yet fully understood.
• Better understanding of these differences may improve:
  • Vaccine development
  • Treatment of immune-mediated diseases

Key Concept

Sex chromosomes and hormones influence both innate and adaptive immunity. Females generally have stronger macrophage activity, greater interferon production, more robust T-cell and antibody responses, and stronger vaccine responses than males. However, this enhanced immunity is also associated with a higher prevalence of autoimmune diseases, with women accounting for about 80% of autoimmune cases and experiencing diseases such as systemic lupus erythematosus much more frequently than men.

Allergy, Hypersensitivity, and Sex Differences in Immunity ( Summary)

Allergy is an undesirable effect of the immune system in which the body reacts excessively to substances that are normally harmless. These substances, called allergens, may include pollen, dust, certain foods, medicines, insect venom, or plant toxins. Instead of protecting the body, the immune system produces an exaggerated response that damages normal tissues. This exaggerated immune response is known as hypersensitivity. Different types of hypersensitivity exist, and they occur through different immune mechanisms.

One important type is delayed-reaction allergy, also called cell-mediated hypersensitivity. Unlike most allergies, this reaction is caused by activated T lymphocytes rather than antibodies. A classic example is poison ivy allergy. During the first exposure, the poison ivy toxin does not cause significant tissue damage, but it sensitizes the immune system by activating helper T cells and cytotoxic T cells. When the person is exposed again, these activated T cells rapidly migrate to the affected skin and release inflammatory chemicals that attract macrophages and other immune cells. This causes redness, swelling, itching, and tissue damage. Similar delayed reactions can also occur in the lungs after inhalation of certain allergens, leading to lung inflammation, edema, or asthma attacks. Because the reaction takes several hours to develop, it is called a delayed hypersensitivity reaction.

Another common form of allergy is atopic allergy, which is caused by excessive production of IgE antibodies. Some people inherit a genetic tendency to produce unusually high levels of IgE antibodies, making them more susceptible to allergies. These IgE antibodies, also called reagin antibodies, attach firmly to the surface of mast cells and basophils. When the same allergen enters the body again, it binds to these IgE antibodies and triggers the mast cells and basophils to release several powerful chemical mediators, including histamine, leukotrienes (also called the slow-reacting substance of anaphylaxis), heparin, platelet-activating factor, and substances that attract eosinophils and neutrophils. These chemicals produce the typical features of allergy, such as widening of blood vessels, increased capillary permeability, leakage of fluid into tissues, swelling, redness, itching, mucus secretion, and contraction of smooth muscles.

The most severe allergic reaction is anaphylaxis, which occurs when an allergen enters the bloodstream and causes widespread activation of mast cells and basophils throughout the body. Large amounts of histamine are released, causing marked vasodilation and increased capillary permeability. As fluid leaks out of the blood vessels, blood pressure falls rapidly, leading to circulatory shock, which can be fatal if not treated immediately. At the same time, leukotrienes cause severe contraction of the bronchiolar smooth muscles, producing intense bronchospasm that may result in suffocation. Because of its rapid onset and life-threatening nature, anaphylaxis requires immediate treatment with epinephrine, which reverses the effects of histamine and improves breathing and blood pressure.

A milder localized allergic reaction is urticaria, commonly known as hives. In this condition, allergens act only on specific areas of the skin. Histamine released from mast cells causes local dilation of blood vessels and increased capillary permeability, producing red, itchy, swollen patches on the skin. These swellings usually develop within minutes and can often be prevented or reduced by antihistamine drugs, which block the action of histamine.

Hay fever, also called allergic rhinitis, occurs when allergens such as pollen trigger an IgE-mediated reaction in the lining of the nose. Histamine causes dilation of nasal blood vessels and increases capillary permeability, leading to swelling of the nasal mucosa, excessive mucus secretion, nasal congestion, and a runny nose. Although antihistamines reduce swelling and mucus production, they may not completely prevent sneezing because other inflammatory chemicals also contribute to nasal irritation.

Asthma is another common allergic disorder in hypersensitive individuals. In allergic asthma, the allergen-IgE reaction occurs in the bronchioles of the lungs. The most important chemical responsible for the symptoms is the slow-reacting substance of anaphylaxis, a mixture of leukotrienes that causes prolonged contraction of bronchiolar smooth muscles. As the airways become narrow, the patient experiences wheezing, shortness of breath, chest tightness, and difficulty breathing. Since leukotrienes play a greater role than histamine in asthma, antihistamines alone are usually not very effective in controlling asthmatic attacks.

The immune system also differs between males and females. Sex chromosomes and sex hormones, particularly estrogen and testosterone, influence both innate and adaptive immunity. In general, females have a stronger immune response than males. Their macrophages and monocytes show greater phagocytic activity, and they produce higher levels of interferons, which are proteins that help fight viral infections. Females also develop stronger T-cell responses and produce more antibodies after exposure to infections or vaccines. As a result, they often clear infections more rapidly and develop stronger immunity following vaccination.

However, a stronger immune system also has disadvantages. Because females mount more vigorous immune responses, they are more likely to develop autoimmune diseases, in which the immune system mistakenly attacks the body’s own tissues. Approximately 80% of autoimmune diseases occur in women, and diseases such as systemic lupus erythematosus (SLE) are nearly ten times more common in females than in males. Researchers continue to study these sex-related differences because understanding them may improve future vaccine development and lead to better treatments for autoimmune and immune-mediated diseases.

In summary, allergies are exaggerated immune responses against harmless substances. Delayed hypersensitivity is mediated by activated T cells, whereas atopic allergies are mediated by IgE antibodies attached to mast cells and basophils. Release of histamine and other inflammatory mediators produces allergic diseases such as anaphylaxis, urticaria, hay fever, and asthma. In addition, females generally have stronger innate and adaptive immune responses than males, resulting in better protection against infections but also a greater risk of developing autoimmune diseases.