Inherited and Acquired immunodeficiencies

1. Overview

Immunodeficiencies can be primary (inherited) or secondary (acquired). Both cause ↑ susceptibility to infections and some cancers. The pattern of infection points to the arm affected: antibody/complement defects → pyogenic encapsulated bacteria; T-cell defects → viral/fungal/opportunistic.

2. Primary (inherited) immunodeficiency

Mostly genetic; may affect innate (complement, NK, phagocytes) or adaptive (humoral/cellular) immunity.

Disease	Defect	Key features
SCID	Both humoral + cellular (T and B). X-linked: IL-2/4/7/9/15 receptor γ-chain (IL-7 key); AR: ADA deficiency → toxic adenosine	Severe recurrent infections (Candida, Pseudomonas, CMV, varicella); hypoplastic thymus, atrophic lymphoid tissue. Tx: bone-marrow transplant
X-linked agammaglobulinemia (Bruton)	BTK mutation → pre-B cells can’t mature → no Ig	Boys only; onset ~6 mo (after maternal Ig wanes); recurrent pyogenic infection (S. aureus, S. pneumoniae, H. influenzae). Tx: IVIG
DiGeorge (thymic hypoplasia)	22q11 deletion → 3rd/4th pharyngeal pouch failure	No T cells; hypocalcemia (no parathyroids), facial/aortic arch anomalies
Selective IgA deficiency	Block in terminal differentiation of IgA B cells	Most common PID; recurrent sinopulmonary/GI infections; autoimmune association; anaphylaxis to blood products

3. Secondary (acquired) immunodeficiency

• Much more common than primary.
• Causes: cancer, infection (AIDS), malnutrition, renal disease, sarcoidosis, diabetes, aging.
• Iatrogenic: immunosuppressive/cytotoxic therapy (transplant, autoimmune, chemo).
• Asplenia → susceptibility to encapsulated bacteria.
• The most important is AIDS (next topic).

💡 High-yield: SCID = T + B defect (ADA / γ-chain) → BMT. Bruton XLA = BTK, boys, no B cells/Ig, after 6 mo. DiGeorge = 22q11, no thymus, hypocalcemia. Selective IgA deficiency = most common PID, anaphylaxis to transfusion. Secondary >> primary; AIDS is the most important.