106 Immune Disorders – Overview of Four Types of Hypersensitivity Reactions

Hypersensitivity Reactions – Quick Overview

Hypersensitivity reactions are overreactions of the immune system that lead to tissue irritation and/or damage. There are four types of hypersensitivity reactions.

Type I Hypersensitivity:

An example of Type I hypersensitivity is allergies, such as hay fever, which can lead to anaphylaxis and anaphylactic shock. In this reaction, antigen-presenting cells (APCs) present the allergen to T helper (T_H) cells, which then induce B cells to produce anti-allergen IgE antibodies. These IgE antibodies bind to and sensitize mast cells. Upon subsequent exposure to the allergen, it binds to the IgE on mast cells, leading to their degranulation and the release of histamine, prostaglandins, and leukotrienes. This causes inflammation and pruritus (itching). Symptoms of respiratory allergens include itching, sneezing, watery eyes, and a runny nose, which are often treated with over-the-counter antihistamines. Cutaneous allergens can cause dermatitis, rash, itching, hives, wheal-and-flare reactions, and eczema. Ingested and injected allergens can trigger nausea, vomiting, urticaria, hives, anxiety, respiratory tract swelling, bronchoconstriction, and systemic effects like anaphylactic shock. Anaphylaxis involves massive vasodilation, hypotension, bronchoconstriction, respiratory distress, and hypoxia, with symptoms such as itching, hives, swelling, coughing, difficulty breathing, dizziness, fainting, low blood pressure, and a rapid weak pulse. Treatment includes the immediate administration of epinephrine (EpiPen), calling 911, and providing supportive care. Prevention involves avoiding known allergens, carrying emergency medications, and undergoing allergy testing. Immediate phase reactions cause inflammation (redness, warmth, swelling, itching) within minutes of allergen exposure, while late phase reactions lead to increased inflammation and tissue destruction 8-12 hours after exposure. Extrinsic asthma, triggered by allergens, causes bronchoconstriction, bronchiole swelling, mucus production, coughing, and difficulty breathing, with severe attacks potentially being fatal.

Type II Hypersensitivity:

Examples of Type II hypersensitivity include ABO blood incompatibilities and Hemolytic Disease of the Newborn. This occurs when a person is transfused with the wrong blood type (e.g., Type A receiving Type B). The recipient’s antibodies target the donated red blood cells (RBCs), activating the complement system and leading to the destruction of the RBCs. IgG or IgM antibodies bind to the foreign blood surface and target it for destruction, resulting in hemolysis (RBC lysis) and subsequent phagocytosis of debris. This can potentially cause anemia, hyperbilirubinemia, jaundice, disseminated intravascular coagulation (DIC), and organ failure.

Type III Hypersensitivity:

Type III hypersensitivity reactions are exemplified by autoimmune disorders such as Systemic Lupus Erythematosus and Rheumatoid Arthritis. In these reactions, antigen-antibody complexes deposit in tissues, causing deterioration and cell injury. This leads to inflammation and tissue damage, with affected blood vessels and joints undergoing vasculitis and synovitis, resulting in irritation, inflammation, and possible damage.

Type IV Hypersensitivity:

Examples of Type IV hypersensitivity include contact dermatitis (e.g., reaction to soap), the Tuberculin Skin Test, and delayed transplant rejection. In this reaction, the antigen binds to APCs and T lymphocytes, releasing cytokines, enzymes, and toxins. T cells proliferate and become active, causing inflammation and tissue injury. Prolonged reactions can lead to more tissue damage.  Note that some autoimmune diseases involve more than one hypersensitivity reaction mechanisms.

Another table includes details noted in a recent publication: Li, Sj., Wu, Yl., Chen, Jh. et al. Autoimmune diseases: targets, biology, and drug discovery. Acta Pharmacol Sin 45, 674–685 (2024). https://doi.org/10.1038/s41401-023-01207-2

Summary:

• Overview:
  • Hypersensitivity reactions: overreactions of the immune system leading to tissue irritation and/or damage.
  • Four types of hypersensitivity reactions.
• Type 1:
  • Example: Allergies (e.g., hay fever).
  • Can lead to anaphylaxis and anaphylactic shock.
  • APCs present allergen to T_H cells, which induce B cell production of anti-allergen IgE antibodies
  • Anti-allergen IgE antibodies bind to and sensitize mast cells
  • Subsequent exposure to allergen, results in allergen binding IgE, leading to mast cell degranulation and release of histamine, prostaglandins, and leukotrienes.
  • Causes inflammation and pruritus (itching).
  • Respiratory allergen symptoms: itching, sneezing, watery eyes, runny nose, most often treated with OTC antihistamines
  • Cutaneous allergens can cause dermatitis, rash, itching, hives, wheal-and-flare reactions, eczema
  • Ingested and injected allergens can trigger nausea, vomiting, utricaria, hives, anxiety, respiratory tract swelling, bronchoconstriction, and systemic effects (anaphylactic shock)
  • Anaphylaxis:  Massive vasodilation, hypotension, bronchoconstriction, respiratory distress, hypoxia.  Symptoms: itching, hives, swelling, coughing, difficulty breathing, dizziness, fainting, low blood pressure, rapid weak pulse.
  • Treatment: immediate administration of epinephrine (EpiPen), calling 911, supportive care.
  • Prevention: avoiding known allergens, carrying emergency medications, allergy testing.
  • Immediate and Late Phase Reactions:
    Immediate Phase Signs: inflammation (redness, warmth, swelling, itching).
    Occurs within minutes after allergen exposure.
    Late Phase Signs: increased inflammation, tissue destruction.
    Occurs 8-12 hours after allergen exposure.
  • Extrinsic Asthma: bronchoconstriction, bronchiole swelling, mucus production, coughing, difficulty breathing, severe attacks can be fatal.
• Type 2:
  • Examples: ABO blood incompatibilities and Hemolytic Disease of the Newborn.
  • Occurs when a person is transfused with the wrong blood type (e.g., Type A receives Type B).  Recipient’s antibodies to donated RBCs, activating complement system, and target donated RBCs for destruction.
  • IgG or IgM antibodies bind to foreign blood surface and target it for destruction.
  • Results in hemolysis (red blood cell lysis) and subsequent phagocytosis of debris, potentially anemia, hyperbilirubinemia, jaundice, DIC, organ failure
• Type 3:
  • Example: Autoimmune disorders (e.g., Systemic Lupus Erythematosus, Rheumatoid Arthritis, glomerulonephritis, serum sickness).
  • Antigen-antibody complexes deposit in tissues, causing deterioration and cell injury.
  • Leads to inflammation and tissue damage.
  • Affected blood vessels and joints undergo vasculitis and synovitis (irritation, inflammation, and possible damage).
• Type 4:
  • Examples: Contact dermatitis (e.g., reaction to soap), Tuberculin Skin Test, Delayed transplant rejection.
  • Antigen binds to APCs and T lymphocytes, releasing cytokines, enzymes, toxins.
  • T and B cells proliferate and become active.
  • Causes inflammation and tissue injury.
  • Prolonged reaction leads to more tissue damage.