6: Hypersensitivity

Overview of the Immune System

• Focus on non-desirable functions of the immune system.

• Terms:

  • Immunodeficiency: Immune system not functioning properly.

  • Immunocompromised: A component of the immune system is incapacitated.

Immunodeficiency and Immunocompromised States

• Definition: Immunodeficiency refers to the failure of the immune system to function adequately.

  • Can be due to:

  • Viral infections (e.g., HIV leading to AIDS).

  • Genetic conditions (e.g., X-linked Severe Combined Immunodeficiency - XSCID).

• Consequences:

  • Loss of memory and immunity responses.

  • Inability to develop new immunity leads to recurrent infections.

Causes of Immunodeficiency

• Viral Infections:

  • HIV attacks the adaptive immune system's cells.

• Genetic Conditions:

  • Mutations preventing proper immune system functionality.

  • Example: XSCID affects long-term immune memory.

• Immune Exhaustion:

  • Overactivation leads to neutrophil exhaustion and subsequent immunodeficiency.

• Stress Impact:

  • Elevation of cortisol suppresses immune responses.

Autoimmune Disorders

• Definition: Immune system incorrectly targets self-antigens, leading to tissue damage.

• Key Concept: Inappropriate immunotolerance.

  • Immunotolerance: The ability of the immune system to not attack the body’s own cells.

• Consequences:

  • Immune responses generated against self-antigens, causing conditions such as:

  • Multiple Sclerosis (MS): T cells destroy the myelin sheath.

  • Systemic Lupus Erythematosus: Antibodies attack self-components, resulting in inflammation.

• Mechanisms:

  • Activating Antibodies: E.g., in Graves' Disease, antibodies mimic Thyroid-Stimulating Hormone (TSH), causing hyperthyroidism.

Hypersensitivity Reactions

• Definition: Inappropriate immune responses that cause tissue damage.

• Mechanisms: Triggered by sensitization followed by excessive immune response.

• Classification: Four types of hypersensitivity reactions based on response type (humoral vs. cell-mediated).

Type 1 Hypersensitivity (Allergic)

• Characteristics:

  • IgE mediated.

  • Rapid onset (within an hour).

• Responses:

  • Local or systemic reactions (e.g., anaphylaxis).

  • Eosinophil activation and histamine release.

  • Histamine drives inflammation, airway constriction, etc.

• Processes:

  • Sensitization Stage: Initial exposure activates B cells, leading to IgE production.

  • IgE antibodies attach to mast cells and eosinophils.

  • Subsequent antigen exposure leads to histamine release and allergic responses.

• Identification: Skin prick tests and blood tests for IgE levels.

• Treatment:

  • Allergen avoidance, pharmacological controls (antihistamines), and immunotherapy.

Type 2 Hypersensitivity (Cytotoxic)

• Characteristics:

  • Antibody-mediated cellular destruction.

  • Can occur through complement activation leading to cell lysis.

• Common Instances:

  • Blood transfusion reactions due to incompatible blood types.

  • Antibodies recognize and mark cells for destruction.

Type 3 Hypersensitivity (Immune Complex-Mediated)

• Characteristics:

  • Mediated by immune complexes (antibody:antigen combinations).

• Impact:

  • Immune complexes can deposit in tissues, leading to inflammatory responses.

• Associations:

  • Commonly seen in autoimmune diseases like rheumatoid arthritis and systemic lupus erythematosus.

Type 4 Hypersensitivity (Delayed Type)

• Characteristics:

  • Cell-mediated response by T cells; no antibodies involved.

  • Peak response occurs days after exposure.

• Common Instances:

  • Contact dermatitis, graft-versus-host disease, transplant rejection.

  • Granuloma formation seen in tuberculosis response.

Conclusion

• The immune system's complexities involve interactions that can lead to unwanted states such as immunodeficiency, autoimmune disorders, and hypersensitivity reactions.

• Understanding each type of response and condition is crucial for diagnosis and treatment.