The need to evaluate immunologic function has become a part of the standard practice of clinical medicine, resulting at least in part from the secondary immunodeficiency produced by human immunodeficiency virus (HIV) infection. In addition, since the early 1990s the molecular basis of primary immunodeficiency disorders has evolved, with now more than 120 genetic defects identified and an expanded range of clinical phenotypes associated with immune dysfunction. This chapter presents the general methods available to assess immune function linking these to the clinical infection scenaria that suggest specific types of immunodeficiency.

The primary clinical problem that sets the stage for initiating an immunologic evaluation is a history of increased susceptibility to infection. In general, the specific characteristics of the recurrent and/or chronic infections, including organism(s), sites, and response to therapy, provide critical insights into the most likely source of the immunodeficiency.

Defects in adaptive immunity involving antibody production (humoral immunity) lead to recurrent infections with high-grade encapsulated extracellular bacteria such as Haemophilus influenzae and Streptococcus pneumoniae usually affecting the sinopulmonary tract. The protective immune response depends on the production of antibodies against the capsular carbohydrate antigens present on these organisms. In contrast, the clinical picture of patients with defective T-cell (cellular) immunity typically consists of recurrent infections with opportunistic organisms, including Pneumocystis jiroveci (formerly Pneumocystis carinii), Candida species, and cytomegalovirus. This demonstrates that functional T cells are required to prevent or clear infection with these opportunistic intracellular micro organisms.