The immune system is a complicated web of defenses needed to protect the human body. It can be broadly divided into four categories: cellular (affecting T cell function), humoral (affecting B cell function, most notably antibody production), phagocytic, and complement. Even though defects in humoral immunity are most common, deficiencies can occur in isolation or combination in any of the four categories. The type, severity, and number of infections that a child has all provide clues as to which part of the immune system is deficient. Multiple parts of the immune system may need to be evaluated, however, because overlap does exist.

Patients with an isolated humoral immunodeficiency usually present after 6 months of age, when placentally transferred maternal antibody levels start to decline. Recurrent bacterial respiratory tract infections (≥8 episodes of otitis media or ≥2 severe episodes of sinusitis or pneumonia in 1 year), enteroviral infections, or serious bacterial infections (including sepsis) are hallmarks of defects in humoral immunity. Isolated cellular immune defects most commonly present with Salmonella or nontuberculous Mycobacterium infections, although other intracellularly dividing organisms can also be involved. Recurrent fungal infections or Pneumocystis carinii also suggest a cellular immune defect. A combination of defects in cellular and humoral immunity represents the most serious type of immunodeficiency; it is commonly known as severe combined immunodeficiency (SCID). In most cases, SCID presents with failure to thrive, chronic diarrhea, opportunistic infections (Pneumocystis jiroveci [previously known as Pneumocystis carinii] pneumonia [PCP] and disseminated cytomegalovirus), and chronic respiratory infections.