Hypersensitivities

Hypersensitivities

Introduction

  • Presentation by Dr. Nicholas McCaul on Mechanisms & Pathology of Cancer and Other Chronic Diseases.
  • Date: 27/02/25

Learning Objectives

  • Outline of different types of hypersensitivities.
  • Describe basic aetiology of hypersensitivities.
  • Explain different examples of hypersensitivities.
  • Describe treatments for hypersensitivities.

Causes of Immunological Disorders

  • Multifactorial: caused by a combination of genetic susceptibilities and environmental factors.
  • Factors include diet, infections, and exposure to chemicals.
  • Understanding is still limited and treatment options are often insufficient.

Immune Hypersensitivities

  • Prevalence: Women are affected twice as often as men.
  • Influenced by sex hormones (particularly estrogen).
  • Factors contributing to recent increases include inherited susceptibility and lifestyle changes (e.g., Western diet).
  • The hygiene hypothesis suggests a lack of parasitic infections plays a role.

Types of Immunological Disorders

  • Various types include hypersensitivities, autoimmune diseases, allergies, and immunodeficiencies.
  • Over 80 different hypersensitivities have been documented.

Examples of Hypersensitivities

  • Type 1 diabetes
  • Rheumatoid arthritis (RA)
  • Psoriasis and psoriatic arthritis
  • Multiple sclerosis (MS)
  • Systemic lupus erythematosus (lupus)
  • Inflammatory bowel diseases (Crohn’s disease and ulcerative colitis)

Gell and Coombs Classification of Hypersensitivities

  1. Type I (IgE mediated): Anaphylactic responses.
  2. Type II (IgG mediated): Cytotoxic responses.
  3. Type III (Immune complex mediated): Involves antigen-antibody complexes.
  4. Type IV (Cell-mediated): Delayed-type hypersensitivity.
  • Types I-III are considered immediate responses, while Type IV is delayed.

General Descriptions of the 4 Types of Hypersensitivity

  1. Type I (IgE Meditated): Targets allergens, leading to anaphylaxis and allergies like asthma and hives.
  2. Type II (IgG Mediated): Antibodies destroy target cells, causing reactions like hemolytic anemia.
  3. Type III (Immune Complex-Mediated): Inflammatory responses from deposited immune complexes causing conditions like serum sickness and rheumatoid arthritis.
  4. Type IV (Cell-Mediated): Involves TH1 cells, causing conditions like contact dermatitis and delayed graft rejection.

Type I Hypersensitivity (IgE Mediated)

Mechanism
  1. Initial Exposure: IgE is produced against allergens instead of parasites.
  2. Sensitization: Antigen presented by dendritic cells to T-cells which then stimulate B-cells to produce IgE.
  3. Degranulation: Upon second exposure, allergen cross-links sensitized IgE, resulting in mediator release.
Symptoms & Causes
  • Histamine release causes swelling, redness, and increased mucus.
  • Prostaglandins and leukotrienes contribute to bronchoconstriction and inflammation.
Localized vs Systemic Anaphylaxis
  • Localized: Symptoms include hives, asthma, and allergic rhinitis.
  • Generalized: Can induce shock, with widespread effects, typically occurring from bee stings or certain foods.

Treatments for Type I Hypersensitivity

  • Anaphylaxis: Controlled by adrenaline (epinephrine).
  • Localized Reactions: Treated with antihistamines and corticosteroids.
  • Immunotherapy: Builds tolerance through gradual exposure to allergen.

Type II Hypersensitivity (Cytotoxic)

  1. Characteristics: Fast reaction due to antibodies binding to surface antigens on cells, leading to destruction via complement activation.
  2. Examples: Blood transfusion reactions, autoimmune hemolytic anemia.

Type III Hypersensitivity (Immune Complex Mediated)

  1. Mechanism: Immune complexes induce inflammation by activating neutrophils.
  2. Clinical Conditions: Seen in diseases like systemic lupus erythematosus and rheumatoid arthritis.

Type IV Hypersensitivity

  • Delayed Response: T-cells mediate it, causing tissue damage through inflammation.
  • Contact Hypersensitivity: Occurs with reactions to substances like poison ivy.
  • Phases: Involves sensitization and effector phases post-exposure.

Diagnosis

  • Diagnostic tests include Mantoux test for delayed hypersensitivity and in vitro responses to lymphocytes and cytokines.

Pathology of Specific Hypersensitivities

Disease Specificity
  • Type 1 Diabetes: B-cell autoantibody production.
  • RA: Inflammation of collagen in connective tissues.
  • Multiple Sclerosis: Targets myelin sheath.

Treatments for Type IV Hypersensitivities

  • Treatment is aimed at symptom management with anti-inflammatories and immunosuppressive therapies.
  • New approaches focus on the specific immune response pathway.

Summary of Treatments

  • Immunosuppression: Used cautiously to prevent rejection in organ transplants, with significant side effects on the immune system.
  • Anti-inflammatory Drugs: Includes corticosteroids and NSAIDs for symptom management.

Conclusion

  • Hypersensitivities remain complex and multifactorial.
  • Understanding the genetic and environmental interplay is crucial for developments in therapies aimed at reducing the severity of immune responses without disrupting normal function.