Types and Causes of Immunodeficiency and Hypersensitivity Reactions

Disorders of the Immune System

• The immune system is divided into three broad categories:
  • Hypersensitivity reactions (immunologically mediated tissue injury)
  • Autoimmune diseases
  • Immunodeficiency diseases

Immunodeficiency

• Definition: inability to mount an effective immune response
• Primary immunodeficiency: genetically determined, inherited genetic disorders
• Secondary immunodeficiency: acquired, may arise from various diseases, infections, malnutrition, or side effects of treatments

Primary Immunodeficiency

• Impair mechanisms of innate immunity (phagocytes, NK cells, or complement) or adaptive immunity (B lymphocytes and T lymphocytes)
• Usually detected in infancy (6 months to 2 years)
• Signs: recurrent infections
• Examples:
  • Severe combined immunodeficiency (SCID)
  • Common variable immunodeficiency (CVID)
  • X-linked agammaglobulinemia (XLA)

Severe Combined Immunodeficiency (SCID)

• Combination of genetically distinct syndromes
• Impaired development of mature T lymphocytes and/or B lymphocytes
• Defects in both humoral and cell-mediated immunity
• Signs: thrush (oral candidiasis), severe diaper rash, failure to thrive
• Susceptible to recurrent, severe infections

X-Linked Agammaglobulinemia (XLA)

• Failure of pre–B cells to differentiate into mature B cells
• Resultant absence of antibodies (gamma globulin) in the blood
• Frequency: about 1 in 100,000 male infants

Common Variable Immunodeficiency (CVID)

• Heterogeneous group of disorders
• Hypogammaglobulinemia affecting all antibody classes (sometimes only IgG)
• Normal numbers of mature B cells, but plasma cells are absent
• B cell areas of lymphoid tissues tend to be hyperplastic

Causes of Primary Immunodeficiency

• Genetic mutations affecting immune cell development, function, or regulation
• Defects in specific components of the immune system (T cells, B cells, phagocytes)
• Inherited disorders of immune regulation (autoimmune lymphoproliferative syndrome, hyper-IgE syndrome)

Secondary Immunodeficiency

• Acquired conditions that compromise immune function due to external factors or underlying diseases
• Examples:
  • Protein deficiency
  • Hematologic malignancies (leukemia, lymphoma)
  • Acute viral infections (infectious mononucleosis)
  • Chronic renal failure
  • Iatrogenic (steroids, cytotoxic drugs, radiotherapy)
  • Splenectomy
  • Acquired Immunodeficiency Syndrome (AIDS)

Hypersensitivity Reactions

• Exaggerated or inappropriate immune responses to harmless antigens
• Overview of four types of hypersensitivity reactions (I-IV) and their underlying mechanisms

Type I Hypersensitivity

• Immediate hypersensitivity, mediated by IgE antibodies and mast cell activation
• Reaction occurs rapidly (within minutes) after the interaction of antigen with IgE antibody bound to the surface of mast cells
• Examples: seasonal rhinitis, hay fever, asthma, anaphylaxis

Type II Hypersensitivity

• Antibody-mediated hypersensitivity disorders
• Mechanisms:
  • Opsonization and phagocytosis
  • Inflammation
  • Antibody-mediated cellular dysfunction
• Examples:
  • Transfusion reactions
  • Hemolytic disease of the newborn
  • Autoimmune hemolytic anemia, agranulocytosis, and thrombocytopenia
  • Certain drug reactions

Type III Hypersensitivity

• Immune complex-mediated hypersensitivity reactions
• Characterized by immune complex deposition and tissue damage
• Examples:
  • Serum sickness
  • Arthus reaction
  • Rheumatoid arthritis
  • Systemic lupus erythematosus

Type IV Hypersensitivity

• Delayed-type hypersensitivity reactions
• Mediated by CD4+ T cells and cytokines
• Characterized by chronic inflammation
• Examples:
  • Contact dermatitis
  • Tuberculin reaction
  • Granulomatous reactions
  • Chronic inflammatory diseases