Primary Immunodeficiency Diseases Affecting Innate Immunity (NK-cell immune deficiency due to phagocyte dysfunction, lack of complement factors).
Primary immunodeficiencies affecting innate immunity involve defects in the body’s first-line defense, such as phagocytes (neutrophils, macrophages), natural killer (NK) cells, and the complement system.
Key Features
- Early onset of infections.
- Frequent, recurrent bacterial and fungal infections.
- Poor wound healing (in some phagocyte disorders).
1 NK Cell Deficiency
Role of NK cells
- Early defense against viral-infected cells and tumor cells.
- Kill targets by releasing perforin and granzymes.
Deficiency
- Rare, but documented.
- Clinical features:
- Severe, recurrent viral infections (e.g., herpesviruses, HPV).
- Increased risk of certain cancers.
- Mechanism:
- Genetic defects affecting NK cell development or function (e.g., GATA2 mutations).
- Diagnosis:
- Low or absent NK cells on lymphocyte subset analysis.
- Functional assays (reduced cytotoxic activity).
2 Phagocyte Dysfunction Disorders
a) Chronic Granulomatous Disease (CGD)
- Etiology:
- Mutation in genes encoding subunits of NADPH oxidase complex (most commonly X-linked).
- Pathogenesis:
- Defective generation of reactive oxygen species → impaired intracellular killing.
- Clinical features:
- Recurrent bacterial (e.g., Staphylococcus aureus) and fungal infections (e.g., Aspergillus).
- Granuloma formation in response to persistent pathogens.
Diagnosis:
- Nitroblue tetrazolium (NBT) test: negative (cells fail to reduce dye).
- Dihydrorhodamine (DHR) flow cytometry assay.
b) Leukocyte Adhesion Deficiency (LAD)
Etiology:
- Mutation in genes encoding integrins (CD18 subunit in LAD-1).
Pathogenesis:
- Defective leukocyte adhesion and migration → impaired recruitment to infection sites.
Clinical features:
- Recurrent bacterial infections without pus.
- Delayed separation of umbilical cord.
- Poor wound healing.
Diagnosis:
- Flow cytometry: absence or reduction of CD18.
c) Chediak-Higashi Syndrome
Etiology:
- Mutation in LYST gene→ defective lysosomal trafficking.
Pathogenesis:
- Impaired phagosome-lysosome fusion → defective killing.
Clinical features:
- Recurrent pyogenic infections.
- Partial albinism.
- Peripheral neuropathy.
- Giant granules in leukocytes (pathognomonic).
Diagnosis:
- Microscopic examination: giant azurophilic granules.
d) Myeloperoxidase (MPO) deficiency
Common, often asymptomatic.
Pathogenesis:
- Defect in myeloperoxidase enzyme → reduced microbial killing in phagosomes.
Clinical features:
- Mild increased risk of Candida infections.