Hypersensitivity Reactions: Types, Mechanisms and Clinical Examples

Understanding Hypersensitivity Reactions: Mechanisms, Types and Clinical Implications

Introduction

Hypersensitivity reactions are exaggerated immune responses that cause tissue damage and clinical disease. These reactions occur when the immune system overreacts to an antigen, leading to inflammatory processes that may harm the host. Understanding these reactions is critical for diagnosing and managing allergic and autoimmune diseases.

Types of Hypersensitivity Reactions

Hypersensitivity reactions are classified into four main types based on their immune mechanisms, as outlined by Coombs and Gell:

1. Type I Hypersensitivity (Immediate Hypersensitivity)

• Mechanism:
  • Involves IgE antibodies binding to mast cells and basophils.
  • Upon subsequent exposure to the same allergen, cross-linking of IgE occurs, leading to the release of histamines, prostaglandins, and leukotrienes.
• Clinical Examples:
  • Allergic Rhinitis (hay fever)
  • Asthma
  • Anaphylaxis (severe, life-threatening reaction)
• Symptoms:
  • Itching, swelling, wheezing, and anaphylactic shock in severe cases.

2. Type II Hypersensitivity (Cytotoxic Hypersensitivity)

• Mechanism:
  • Mediated by IgG or IgM antibodies directed against cell surface antigens.
  • Leads to cell destruction via complement activation or antibody-dependent cell-mediated cytotoxicity (ADCC).
• Clinical Examples:
  • Hemolytic Disease of the Newborn (HDN)
  • Goodpasture Syndrome
  • Myasthenia Gravis (autoimmune disorder affecting neuromuscular transmission)
• Symptoms:
  • Tissue inflammation, anemia, muscle weakness, and renal dysfunction.

3. Type III Hypersensitivity (Immune Complex-Mediated Hypersensitivity)

• Mechanism:
  • Antigen-antibody complexes (IgG or IgM) form in circulation and deposit in tissues, triggering complement activation and neutrophil recruitment.
• Clinical Examples:
  • Systemic Lupus Erythematosus (SLE)
  • Rheumatoid Arthritis
  • Serum Sickness (reaction to foreign proteins in vaccines or antiserum)
• Symptoms:
  • Joint pain, rashes, fever, and inflammation in affected organs.

4. Type IV Hypersensitivity (Delayed-Type Hypersensitivity, DTH)

• Mechanism:
  • Mediated by T cells, rather than antibodies.
  • Involves activation of macrophages and cytokines, leading to inflammation and tissue damage.
• Clinical Examples:
  • Tuberculosis Skin Test (Mantoux test)
  • Contact Dermatitis (poison ivy, nickel allergy)
  • Type 1 Diabetes Mellitus (autoimmune destruction of pancreatic cells)
• Symptoms:
  • Redness, swelling, induration, and in chronic cases, tissue necrosis.

Mechanisms of Hypersensitivity Reactions

Each hypersensitivity reaction follows a unique pathophysiological mechanism:

• Type I: IgE and mast cell degranulation.
• Type II: Antibody-mediated cytotoxicity.
• Type III: Immune complex deposition and inflammation.
• Type IV: T-cell activation and delayed inflammatory response.

Common Pathways Involved:

• Histamine Release: Causes vasodilation and bronchoconstriction (Type I).
• Complement Activation: Leads to cell lysis and inflammation (Type II & III).
• Cytokine Secretion: Induces chronic inflammation and tissue destruction (Type IV).

Clinical Management and Treatment Strategies

The approach to managing hypersensitivity reactions depends on the type and severity of the condition.

General Treatment Strategies:

• Avoidance of allergens (e.g., dust, pollen, food allergens)
• Immunotherapy (Allergy shots) for desensitization
• Use of corticosteroids to control inflammation
• Plasmapheresis in severe autoimmune diseases

Type-Specific Treatments:

• Type I: Antihistamines, epinephrine (for anaphylaxis), and bronchodilators
• Type II: Immunosuppressive therapy, corticosteroids
• Type III: NSAIDs, corticosteroids, and immune-modulating drugs
• Type IV: Topical steroids, immunosuppressants

Clinical Examples and Case Studies

Case Study 1: Anaphylaxis After Peanut Ingestion

• Patient: 12-year-old male with a history of peanut allergy.
• Symptoms: Severe difficulty breathing, swelling of the face, hypotension.
• Management: Immediate administration of epinephrine and oxygen therapy.

Case Study 2: Rheumatoid Arthritis (RA) and Joint Damage

• Patient: 45-year-old female with chronic joint pain and morning stiffness.
• Diagnosis: Elevated rheumatoid factor, inflammation of joints.
• Treatment: Disease-modifying antirheumatic drugs (DMARDs) and NSAIDs.

Website URL Links Related to the Topic

• National Institute of Allergy and Infectious Diseases (NIAID): https://www.niaid.nih.gov
• American Academy of Allergy, Asthma & Immunology (AAAAI): https://www.aaaai.org
• World Allergy Organization (WAO): https://www.worldallergy.org

Further Reading and References

• Mayo Clinic – Hypersensitivity Disorders: https://www.mayoclinic.org
• Johns Hopkins Medicine – Allergy & Immunology: https://www.hopkinsmedicine.org
• UpToDate – Hypersensitivity Reactions: https://www.uptodate.com

Conclusion

Hypersensitivity reactions play a significant role in allergic and autoimmune diseases. Their classification into four types helps in understanding their mechanisms and developing effective treatment strategies. Proper diagnosis and targeted therapies can significantly improve patient outcomes.

MCQs on Hypersensitivity Reactions

1. Which of the following best defines hypersensitivity reactions?

A) Immune responses that protect the body from infections
B) Exaggerated immune responses that cause tissue damage
C) Immune reactions that occur only in autoimmune diseases
D) Mild allergic reactions that do not affect the body

Answer: B) Exaggerated immune responses that cause tissue damage
Explanation: Hypersensitivity reactions occur when the immune system overreacts, leading to harmful effects on tissues and organs.

2. Type I hypersensitivity reactions are primarily mediated by which antibody?

A) IgA
B) IgG
C) IgE
D) IgM

Answer: C) IgE
Explanation: Type I hypersensitivity (immediate hypersensitivity) involves IgE binding to mast cells and basophils, leading to histamine release.

3. Which of the following is an example of Type II hypersensitivity?

A) Anaphylaxis
B) Hemolytic disease of the newborn
C) Contact dermatitis
D) Serum sickness

Answer: B) Hemolytic disease of the newborn
Explanation: Type II hypersensitivity involves antibody-mediated cytotoxicity, as seen in hemolytic disease of the newborn caused by Rh incompatibility.

4. Type III hypersensitivity involves the deposition of:

A) Immune complexes
B) T lymphocytes
C) Complement proteins
D) Eosinophils

Answer: A) Immune complexes
Explanation: In Type III hypersensitivity, antigen-antibody immune complexes deposit in tissues, leading to inflammation and damage.

5. Delayed-type hypersensitivity (Type IV) is mediated by:

A) B cells
B) Cytotoxic T cells and macrophages
C) IgE
D) Complement system

Answer: B) Cytotoxic T cells and macrophages
Explanation: Type IV hypersensitivity is a T-cell-mediated immune response that takes time to develop (e.g., tuberculin skin test).

6. Which hypersensitivity reaction is responsible for anaphylaxis?

A) Type I
B) Type II
C) Type III
D) Type IV

Answer: A) Type I
Explanation: Anaphylaxis is a severe, rapid allergic reaction caused by IgE-mediated mast cell degranulation.

7. The Arthus reaction is an example of which type of hypersensitivity?

A) Type I
B) Type II
C) Type III
D) Type IV

Answer: C) Type III
Explanation: The Arthus reaction occurs due to immune complex deposition in blood vessel walls, leading to local inflammation.

8. Contact dermatitis is an example of which type of hypersensitivity reaction?

A) Type I
B) Type II
C) Type III
D) Type IV

Answer: D) Type IV
Explanation: Contact dermatitis is mediated by T cells and occurs after exposure to allergens like poison ivy.

9. Which cells play a crucial role in Type I hypersensitivity reactions?

A) Neutrophils
B) Mast cells
C) Cytotoxic T cells
D) Dendritic cells

Answer: B) Mast cells
Explanation: Mast cells degranulate upon IgE cross-linking, releasing histamine and causing allergic symptoms.

10. Goodpasture syndrome is an example of:

A) Type I hypersensitivity
B) Type II hypersensitivity
C) Type III hypersensitivity
D) Type IV hypersensitivity

Answer: B) Type II hypersensitivity
Explanation: Goodpasture syndrome involves autoantibodies against the basement membrane, leading to lung and kidney damage.