Lecture on Severe Combined Immunodeficiency (SCID)

Overview of Immune System Disorders

• SCID is part of the six branches of immune system disorders.
• Differentiates between primary (genetic, inherited) and secondary (acquired) immunodeficiencies.

Severe Combined Immunodeficiency (SCID)

• Definition: A primary genetic disorder affecting both T and B lymphocytes, along with natural killer cells.
• Characteristics: Increased susceptibility to severe infections; often fatal within the first year of life.

Case Study: David Vetter

• Born in the 1970s, lived in a sterile chamber due to SCID.
• Underwent bone marrow transplantation but died at age 12 due to Epstein-Barr virus infection not being recognized.

Importance of Early Diagnosis

• Methods: Prenatal DNA sequencing, checking lymphocyte levels.
• Symptoms: Appear healthy until about six months due to maternal antibodies.
  • Recurrent infections, failure to thrive, diarrhea, diaper rash, bronchitis, pneumonia, otitis media, liver abscess, morbilliform rash.

Causes of Infections

• Fungal, bacterial, and viral infections.
• Example: Oral candidiasis (whitish plaque in the mouth).

Diagnosis and Morphological Findings

• Hypoplastic Lymphoid Tissues: Depleted zones of T and B lymphocytes in lymph nodes and thymus.
• Thymus: Resembles fetal thymus with less lymphocytes, absence of Hassel's corpuscles.
• X-ray Findings: Absence of thymic shadow.

Types of SCID

• X-linked Recessive: Most common; lack of T cells and natural killer cells, normal B-lymphocyte count but impaired function.
• Autosomal Recessive: Includes adenosine deaminase (ADA) deficiency, purine nucleoside phosphorylase deficiency.
• Genetic Mutations: X chromosome Q13.1 mutation affects interleukin receptors, causing lack of T/NK cells.

Genetic Mechanisms

• Common Gamma Chain Deficiency: Interleukin receptor dysfunction affects IL-2, IL-4, IL-7, IL-9, IL-11, IL-15, IL-21.
• JAK3 Mutation: Blocks signal from receptor, affecting interleukin function.
• ADA Deficiency: Leads to deoxyATP accumulation, blocking ribonucleotide reductase, inhibiting DNA synthesis.
• Purine Nucleoside Phosphorylase Deficiency: Similar pathway, affecting lymphocyte maturation.

Treatments

• Bone Marrow Transplantation: Replaces defective cells; can lead to temporary remission or complications like T-cell leukemia.
• Gene Therapy: Corrects genetic defects in stem cells, using viral vectors.

Key Points to Remember

• Early detection and treatment are critical.
• B-lymphocyte function is impaired without T-cell activation.
• Common genetic deficiencies need targeted therapies.
• SCID is a primary immunodeficiency within genetic disorders.

Conclusion: Understanding SCID involves recognizing genetic mutations, early symptoms, and subsequent therapeutic interventions.