Immunodeficiency Disorders: Pathological High-Yield
Immunodeficiencies arise from defects in either innate or adaptive immunity. For board examinations, these are organized by the primary component affected: Humoral (B-cell), Cellular (T-cell), Combined, or Phagocytic.
1. Humoral (B-Cell) Deficiencies
Predispose patients to recurrent infections with encapsulated bacteria (e.g., S. pneumoniae, H. influenzae) and enteroviruses.
| Disorder | Key Features |
|---|---|
| X-linked agammaglobulinemia (Bruton) | Defect in BTK kinase; low/absent B-cells and all Ig classes. Present after 6 months of age. |
| Selective IgA Deficiency | Most common primary immunodeficiency. Often asymptomatic, but can present with recurrent sinopulmonary infections and anaphylaxis if given blood with IgA. |
| Common Variable Immunodeficiency (CVID) | B-cell differentiation defect. Normal B-cell numbers, but low plasma cells and Igs. Increased risk of autoimmune disease and lymphoma. |
2. Cellular (T-Cell) & Combined Deficiencies
Predispose patients to fungal, viral, protozoal, and intracellular bacterial infections.
- DiGeorge Syndrome: Failure of 3rd/4th pharyngeal pouches (22q11 deletion). Thymic hypoplasia (T-cell loss) and parathyroid hypoplasia (hypocalcemia).
- Severe Combined Immunodeficiency (SCID): Most commonly X-linked IL-2 receptor deficiency or Adenosine Deaminase (ADA) deficiency. Failure to thrive, chronic diarrhea, and recurrent infections starting in infancy. Requires a stem cell transplant.
- Wiskott-Aldrich Syndrome: Triad of Thrombocytopenia, Eczema, and Recurrent Infections (WATER). X-linked defect in the WAS gene.
3. Phagocytic & Complement Deficiencies
Pathology Pearl: Chronic Granulomatous Disease (CGD) is caused by NADPH oxidase deficiency. Patients cannot produce superoxide, leading to recurrent infections with catalase-positive organisms (S. aureus, Nocardia, Aspergillus, Pseudomonas, Serratia). Screen with Nitroblue Tetrazolium (NBT) test.
- Chediak-Higashi Syndrome: Defect in lysosomal trafficking (LYST gene). Presents with partial albinism, peripheral neuropathy, and giant cytoplasmic granules in neutrophils.
- Complement Deficiencies: Early components (C1-C4) increase risk of SLE. Late components (C5-C9) increase the risk of recurrent Neisseria species (meningococcal) infections.