Primary Immunodeficiency Syndromes

Primary Immunodeficiency Syndromes

  • Types of Immunodeficiency
      - Primary (congenital) immunodeficiencies: Caused by single-gene defects.
      - Secondary (acquired) immunodeficiencies: Due to cancers, infections, malnutrition, or immunosuppression treatments.

  • Learning Objectives
      - Understand classifications of immunodeficiency syndromes.
      - Recognize molecular pathogenesis, clinical presentations, and laboratory diagnostics.

Innate vs Adaptive Immunity

  • Innate Immunity
      - Affected by defects in phagocytes, leukocytes, or complement.
      - Increases vulnerability to recurrent infections.

  • Adaptive Immunity
      - Involves T and B lymphocytes. Deficiencies lead to poor antibody response.

Key Syndromes and Pathologies

  • Leukocyte Adhesion Deficiency (LAD)
      - Defects in surface proteins (e.g., integrins) leading to impaired leukocyte function.
      - Autosomal recessive, marked by delayed umbilical cord separation and recurrent infections.

  • Chédiak-Higashi Syndrome
      - Autosomal recessive: Defective fusion of lysosomes and phagosomes.
      - Clinical features include albinism, neurologic deficits, recurrent bacterial infections.

  • Chronic Granulomatous Disease (CGD)
      - X-linked or autosomal recessive: Defect in NADPH oxidase function.
      - Patients experience recurrent bacterial infections.

  • Defects in Complement System
      - Hereditary deficiencies affecting complement components (e.g., C2, C3).
      - Increased risk of infections and autoimmune diseases.

Adaptive Immune Deficiencies

  • Severe Combined Immunodeficiency (SCID)
      - X-linked or autosomal recessive: Affects T and B cell maturation due to cytokine receptor mutation.

  • X-linked Agammaglobulinemia
      - Failure of B cell maturation due to mutations in Bruton tyrosine kinase.
      - Presents with recurrent bacterial infections after depletion of maternal immunoglobulins.

  • Common Variable Immunodeficiency
      - Hypogammaglobulinemia affecting antibody class differentiation.
      - Recurrent infections noted, particularly respiratory.

  • DiGeorge Syndrome
      - Thymic hypoplasia leads to T cell deficiency, congenital heart defects, and facial anomalies.

Systemic Disorders and Syndromes

  • Wiskott-Aldrich Syndrome
      - X-linked: Characterized by eczema, thrombocytopenia, and recurrent infections.

  • Ataxia Telangiectasia
      - Autosomal recessive: Presents with ataxia, vascular malformations, and increased tumor risk.

Summary of Immune Deficiencies

  • Defects in Innate Immunity lead to recurrent bacterial infections and abscess formation.

  • Adaptive Immunity defects primarily cause severe infections, particularly by fungi and opportunistic pathogens.

  • Clinical management often involves frequent monitoring and treatment of infections.