Monocytes-macrophages have been shown to be abnormal in a variety of diseases (Table 1). The abnormality is partial and no related association with increased susceptibility to infection has been established. In cases of severely depressed migration of monocytes, however, it is likely that this dysfunction predisposes a patient to infection because other defects of host defense coexist in these disorders.

Table1. Primary and Secondary Abnormalities of Monocyte-Macrophage Function

The signs and symptoms of abnormalities of monocyte macrophage function are extremely evident in some conditions. The profound defect of phagocytic killing exhibited by patients with CGD results in the formation of subcutaneous abscesses and abscesses in the liver, lungs, spleen, and lymph nodes. Cancer patients with a defective monocyte cytotoxicity may develop this defect because tumors have the ability to release factors that suppress the generation of toxic oxygen metabolites by macrophages. In newborn infants, depressed chemotaxis, killing, and decreased synthesis of the phagocytosis-promoting factors fibronectin, C3, and complement factor B have been observed. In addition, the newborn’s macrophages may not respond effectively to infection because the lymphocytes have impaired the production of the macrophage activator IFN-γ.

Qualitative disorders of monocytes-macrophages mani fest as lipid storage diseases, including a number of rare autosomal recessive disorders. The expression in macro phages of a systemic enzymatic defect permits the accumulation of cell debris normally cleared by macrophages. The macrophages are particularly prone to accumulate undegraded lipid products. Resistance to infection can be impaired, at least partially, because of a defect in macrophage function. Disorders of this type include Gaucher’s disease and Niemann-Pick disease.

Gaucher’s Disease

 An inherited disease caused by a disturbance in cellular lipid metabolism, Gaucher’s disease most frequently affects children. The prognosis varies; with mild disease, the patient may live a relatively normal life, whereas with severe disease the patient may die prematurely.

The disorder represents a deficiency of β-glucocerebrosidase, the enzyme that normally splits glucose from its parent sphingolipid, glucosylceramide. As a result of this enzyme deficiency, cerebroside accumulates in histiocytes (macro phages). Gaucher’s cells are rarely found in the circulating blood; the typical cell is large, with one to three eccentric nuclei and a characteristically wrinkled cytoplasm. These cells are found in the bone marrow, spleen, and other organs of the mononuclear phagocyte system. Production of erythrocytes and leukocytes decreases as these abnormal cells infiltrate the bone marrow.

Niemann-Pick Disease

 Niemann-Pick disease is similar to Gaucher’s disease, also an inherited abnormality of lipid metabolism. Niemann-Pick dis ease affects infants and children, with an average life expectancy of 5 years.

This disorder represents a rare autosomal recessive deficiency of the enzyme sphingomyelinase, characterized by massive accumulation of sphingomyelin in the mononuclear phagocytes. The characteristic cell in this disorder, Pick’s cell, is similar in appearance to Gaucher’s cell, although the cytoplasm of the cell is foamy.

مواضيع ذات صلة

T Regulatory Lymphocytes

Helper T Lymphocytes

Sites of Lymphocyte Development

Clinical Features of HIV Infection and AIDS

Pathogenesis of AIDS

Congenital Immunodeficiencies : Defects in Lymphocyte Activation and Function

Congenital Immunodeficiencies: Defects in Lymphocyte Maturation

Congenital Immunodeficiencies: Defects in Innate Immunity

Congenital (Primary) Immunodeficiencies

Neuroimmunology: Interactions Between the Immune and Nervous Systems

Disorders of Neutrophils

Cell Surface Receptors