Causes (see Table: Causes of Secondary Immunodeficiency) include

Secondary immunodeficiency also occurs among critically ill, older, or hospitalized patients. Prolonged serious illness may impair immune responses; impairment is often reversible if the underlying illness resolves.

Immunodeficiency can result from loss of serum proteins (particularly IgG and albumin) through the following:

Enteropathy may also lead to lymphocyte loss, resulting in lymphopenia. All of these disorders can mimic B- and T-cell defects. Treatment focuses on the underlying disorder; a diet high in medium-chain triglycerides may decrease loss of immunoglobulins (Igs) and lymphocytes from the GI tract and be remarkably beneficial.

If a specific secondary immunodeficiency disorder is suspected clinically, testing should focus on that disorder (eg, diabetes, HIV infection, cystic fibrosis, primary ciliary dyskinesia).

These disorders are genetically determined; they may occur alone or as part of a syndrome. More than 100 of these disorders have been described, and heterogeneity within each disorder may be considerable. The molecular basis for about 80% is known.

Primary immunodeficiencies typically manifest during infancy and childhood as abnormally frequent (recurrent) or unusual infections. About 70% of patients are < 20 yr at onset; because transmission is often X-linked, 60% are male. Overall incidence of symptomatic disease is about 1/280 people.

Primary immunodeficiencies are classified by the main component of the immune system that is deficient, absent, or defective:

As more molecular defects are defined, classifying immunodeficiencies by their molecular defects will become more appropriate.

Primary immunodeficiency syndromes are genetically determined immunodeficiencies with immune and nonimmune defects. Nonimmune manifestations are often more easily recognized than those of the immunodeficiency. Examples are ataxia-telangiectasia, cartilage-hair hypoplasia, DiGeorge syndrome, hyper-IgE syndrome, and Wiskott-Aldrich syndrome.

Immunodeficiency typically manifests as recurrent infections. The age at which recurrent infections began provides a clue as to which component of the immune system is affected. Other characteristic findings tentatively suggest a clinical diagnosis (see Table: Characteristic Clinical Findings in Some Primary Immunodeficiency Disorders). However, tests are needed to confirm a diagnosis of immunodeficiency (see Table: Initial and Additional Laboratory Tests for Immunodeficiency). If clinical findings or initial tests suggest a specific disorder of immune cell or complement function, additional tests are indicated (see Table: Specific and Advanced Laboratory Tests for Immunodeficiency*).

The prognosis in primary immunodeficiency disorders depends on the specific disorder.

Some decrease in immunity occurs with aging. For example, in the elderly, the thymus tends to produce fewer naive T cells; thus, fewer T cells are available to respond to new antigens. The number of T cells does not decrease (because of oligoclonality), but these cells can recognize only a limited number of antigens.

Signal transduction (transmission of antigen-binding signal across the cell membrane into the cell) is impaired, making T cells less likely to respond to antigens. Also, helper T cells may be less likely to signal B cells to produce antibodies.

The number of neutrophils does not decrease, but these cells become less effective in phagocytosis and microbicidal action.

Undernutrition, common among the elderly, impairs immune responses. Calcium, zinc, and vitamin E are particularly important to immunity. Risk of calcium deficiency is increased in the elderly, partly because with aging, the intestine becomes less able to absorb calcium. Also, the elderly may not ingest enough calcium in their diet. Zinc deficiency is very common among the institutionalized elderly and homebound patients.

Certain disorders (eg, diabetes, chronic kidney disease, undernutrition), which are more common among the elderly, and certain therapies (eg, immunosuppressants, immunomodulatory drugs and treatments), which the elderly are more likely to use, can also impair immunity.