Secondary immunodeficiencies, including HIV infection

Abstract

Extrinsic factors can adversely affect immune responses, producing states of secondary immunodeficiency and consequent increased risk of infections. These immunodeficiencies, which can be encountered in routine clinical practice, arise from a number of conditions, such as treatment with glucocorticoids and immunomodulatory drugs, surgery and trauma, extreme environmental conditions, and chronic infections, such as those caused by HIV. The most common cause of immunodeficiency is malnutrition, affecting many communities around the world with restricted access to food resources. Protein-calorie deficiency and micronutrient deficiencies have been shown to alter immune responses; of note, recent progress has been made in the influence of vitamin D deficiency in causing failure of immune activation. Other categories of disease that might present with secondary immunodeficiency include metabolic diseases and genetic multisystemic syndromes. The immune defects observed in secondary immunodeficiency are usually heterogeneous in their clinical presentation, and their prognosis depends on the severity of the immune defect. Management of the primary condition often results in improvement of the immunodeficiency; however, this is sometimes not possible, and the risk of infections can be reduced with prompt antimicrobial treatment and prophylaxis.

FIG 1.

Extrinsic factors leading to defects of immune function.

FIG 2.

Role of vitamin D (VitD) in macrophage activation. Toll-like receptor 2 (TLR2) activation increases expression of CYP21B1, a mitochondrial enzyme that converts vitamin D into its active form, 1,25OH vitamin D, and vitamin D nuclear receptor (VDR) expression, which when bound to 1,25OH vitamin D promotes cathelicidin synthesis. Cathelicidins are intracellular bactericidal proteins.

FIG 3.

Molecular mechanism of action of glucocorticoids. A cytosolic receptor binds glucocorticoids and translocates them to the nucleus, where they either activate anti-inflammatory genes or inhibit proinflammatory genes. At high doses, corticosteroids can also affect cell function by non–receptor-dependent mechanisms.

FIG 4.

Effect of cyclosporine on T cells. Inhibition of calcineurin activity by cyclosporine results in decreased activation of IL-2 transcription. TCR, T-cell receptor; NFAT, nuclear factor of activated T cells; NFATc, cytoplasmic monomer; NFATn, nuclear monomer.

FIG 5.

Human model to test the effects of microgravity. Volunteers are maintained in bedrest position for 60 days to mimic the affects of microgravity in space. Exercise is used as a countermeasure.

FIG 6.

Worldwide prevalence of HIV infection. Adapted from the United Nations Programme on HIV/AIDS.