Immune System Disorders

Immune Disorders

• Disorders associated with the immune system:
  • Immunodeficiencies: Lack of a properly functioning immune system.
  • Autoimmunity: Immune responses directed toward “self”.
  • Hypersensitivities: Excessive or inappropriately directed immune responses.

Immunodeficiencies

• Primary Immunodeficiencies:
  • Present from birth.
  • Genetic in nature.
  • Rare.
  • Deficiencies in humoral, cellular, and/or innate responses.
• Secondary Immunodeficiencies (acquired):
  • Infections (AIDS, hepatitis, EBV, measles).
  • Chronic illnesses (diabetes, some cancers).
  • Medications & Treatments (cancer chemotherapy & radiation therapy, immunosuppressive drugs).
  • Environmental or lifestyle factors (malnutrition, alcoholism).
  • Aging.

Autoimmune Disorders

• Failure of self-tolerance leads to immune responses against tissues, causing chronic conditions.
• Multi-factorial causes and risk factors:
  • Genetic pre-disposition.
  • Exposure to certain infectious agents.
  • Sex (women have a higher rate of some).
  • Environmental Factors (Vitamin D deficiency).
• Diagnosis is often difficult due to generalized symptoms and varied disorders.
• Detection of autoantibodies may suggest an autoimmune disease.
• Managing autoimmune disorders:
  • Immunosuppressive drugs.
  • Replacement (insulin for Type 1 Diabetes).
  • Monoclonal Antibodies (biologics, generic drug name often ends in “mab”).

Hypersensitivities

• Inappropriate, exaggerated immune response to harmless antigens.
• Classified into 4 categories:
  • 3 are antibody-based (humoral).
  • 1 is T-cell based (cellular).

Type I Hypersensitivity

• Commonly called “allergies”.
• Involves overproduction of IgE antibodies against harmless substances (allergens).
• Excessive histamine production by mast cells and basophils.
• Onset is immediate upon exposure.
• Sensitization: Prior exposure to the allergen is required.
• Systemic anaphylaxis:
  • System-wide allergic reaction, can be rapidly fatal.
  • Treatment: Epinephrine, Benadryl.
  • Medical emergency.
• Diagnosis: Challenge tests identify specific triggers.
• Management:
  • Over-the-counter medications.
  • Desensitization immunotherapy (trigger IgG production).
• Increasing due to genetic component, industrialized countries, hygiene hypothesis.
• Intolerances: Lactose, gluten.

Type II Hypersensitivity

• “Cytotoxic” reactions.
• IgG binding to cell surfaces triggers complement system or NK cells for destruction.
• Examples: myasthenia gravis, Graves disease.
• ABO Blood Transfusion Reactions:
  • Antibodies against blood types you don’t have.
  • Transfusion reaction if wrong type is given, often fatal.
• Hemolytic Disease of the Newborn:
  • Rh incompatibility between mother and fetus.
  • Preventable: Rh- mothers treated with Rhogam.

Type III Hypersensitivity

• Immune Complex (soluble antigens + IgM/IgG antibodies).
• Complexes block capillaries and deposit into tissues, triggering complement and inflammation.
• Serum sickness: complication of artificial passive immunization.
• Examples of Autoimmune Type III Hypersensitivities: Systemic Lupus Erythematosus, Rheumatoid Arthritis, Scleroderma.

Type IV Hypersensitivity

• Delayed hypersensitivity.
• Delayed onset (12-72 hours after antigen exposure).
• Involves T cells reacting to harmless substance or self.
• Examples: contact dermatitis, TB skin test, multiple sclerosis.