The primary immunodeficiencies have taught us much about the biology of specific proteins of the immune system. Fortunately, these conditions are rare. In contrast, secondary immunodeficiency is relatively common. Malnutrition devastates many populations around the world, and a major feature of malnutrition is secondary immunodeficiency. This particularly affects cellmediated immunity, and death in famines is frequently caused by infection. Measles, which itself causes immunosuppression, is an important cause of death in malnourished children. In the developed world, measles is an unpleasant illness but major complications are uncommon. In contrast, measles in the malnourished has a high mortality. Tuberculosis is another important infection in the malnourished. In mice, protein starvation causes immunodeficiency by affecting antigenpresenting cell function, but in humans it is not clear how malnourishment specifically affects immune responses. Links between the endocrine and immune systems may provide part of the answer.
Adipocytes (fat cells) produce the hormone leptin, levels of which are related directly to the amount of fat present in the body; leptin levels therefore fall during starvation when fat is consumed. Both mice and humans with genetic leptin deficiency have reduced Tcell responses, and in mice the thymus atrophies. In both starved mice and those with inherited leptin deficiency, these abnormalities can be reversed by the administration of leptin.
Secondary immunodeficiency states are also associated with hematopoietic tumors such as leukemia and lymphomas. Myeloproliferative diseases, such as leukemia, can be associated with deficiencies of neutrophils (neutropenia) or an excess of immature myeloid progenitors that lack functional properties of mature neutrophils, either of which increases susceptibility to bacterial and fungal infections. Destruction or invasion of peripheral lymphoid tissue by lymphomas or metastases from other cancers can promote opportunistic infections.
Congenital asplenia (a rare inherited absence of the spleen), surgical removal of the spleen, and destruction of spleen function by certain diseases are associated with a lifelong predisposition to overwhelming infection by S. pneumoniae, graphically illustrating the role of mononuclear phagocytic cells within the spleen in the clearance of this organism from blood. Patients who have lost spleen function should be vaccinated against pneumococcal infection and are often recommended to take prophylactic antibiotics throughout their life.
Secondary immunodeficiency is also a complication of certain medical therapies. A major complication of cytotoxic drugs used to treat cancer is immunosuppression and increased susceptibility to infection. Many of these drugs kill all dividing cells, including normal cells of the bone marrow and lymphoid systems. Infection is thus one of the major side effects of cytotoxic drug therapy. Immune suppression to induce host tolerance of solid organ allografts, such as kidney or heart transplants, also carries a substantial increased risk for infection and even for malignancy. The recent introduction of biologic therapies for some forms of autoimmunity has led to an increased risk of infection because of their immunosuppressive effects. For example, administration of antibodies that block TNFα in patients with rheumatoid arthritis or other forms of autoimmunity has been associated with infrequent, but increased, instances of infectious complications.
Summary.