Primary immunodeficiency diseases (PIDs) are inherited genetic disorders of the immune system affecting its development or function, leading to increased susceptibility to infections, autoimmunity, and malignancy. B-cell (humoral) deficiencies account for approximately 50% of PIDs and present with recurrent sinopulmonary infections from encapsulated bacteria (Streptococcus pneumoniae, Haemophilus influenzae). Selective IgA deficiency is the most common PID (1:500 prevalence), often asymptomatic but associated with recurrent mucosal infections and autoimmune diseases. Common Variable Immunodeficiency (CVID) causes low immunoglobulin levels with recurrent infections typically presenting in the 2nd-3rd decade. T-cell deficiencies present with opportunistic infections (Pneumocystis, Candida, viruses). Severe Combined Immunodeficiency (SCID) affects both B and T cells, presenting in infancy with failure to thrive, chronic diarrhea, and recurrent severe infections requiring hematopoietic stem cell transplant. Warning signs include 4+ ear infections/year, 2+ serious sinus infections/year, recurrent deep tissue infections, and family history of immunodeficiency.