Acquired immunodeficiency syndrome (AIDS) Monoclonal gammopathy

T cells (destroyed by virus) B cells (multiply out of control)

eukaryotic pathogens, such as Pneumocystis carinii and other fungi, as well as viruses and obligate intracellular bacteria. ■ Pneumocystis carinii, p. 754

Severe combined immunodeficiency (SCID) results when neither T nor B lymphocytes are produced from bone marrow stem cells. Children with SCID die of infectious diseases at an early age unless they are successfully treated by receiving a bone marrow transplant to reconstitute the bone marrow with healthy cells. There are a variety of gene defects that can cause SCID. One defect is in an enzyme necessary for V, D, and J chain recombination to form B- and T-cell receptors for antigen. Without these receptors, there are no functioning B and T cells. SCID has also been shown to result from mutation in a gene for the interleukin-2 receptor on lymphocytes, such that the cells could not receive the signal to proliferate. Other individuals with SCID lack adenosine deaminase, an enzyme important in the proliferation of B and T cells. A number of these people have responded well to repeated replacement of the adenosine deaminase enzyme. It has been possible to correct this condition temporarily in a few children by collecting their own defective T cells, inserting the adenosine deaminase gene linked to a retrovirus vector, and returning the cells to them. Unfortunately, the genetically altered cells do not live long, and the treatment must be repeated. Still, these results are promising, and there is much excitement about the possibility of treating other severe disorders with gene therapy. Many of the gene defects that cause primary immunological disorders are known and work is under way to correct them. Table 18.6 lists some of the primary immunodeficiencies for which gene defects have been identified. As the table indicates, deficiencies and defects can occur at any point in the complex steps that lead to an effective immune response. ■ interleukin-2, p. 380 ■ antigen receptors on B and T cells, p. 394 ■ gene therapy, p. 367

Chronic granulomatous disease involves the phagocytes, which fail to produce hydrogen peroxide and certain other active products of oxygen metabolism, due to a defect in an oxidase system normally activated by phagocytosis. Hence, the phagocytes are defective in their ability to kill some organisms, especially the catalase-positive Staphylococcus aureus. In Chediak-Higashi disease, the phagocyte lysosomes are deficient in certain enzymes and thus cannot destroy phagocytized bacteria. People with this condition suffer from recurring pyogenic bacterial infections. ■ pyogenic bacterial infections, p. 693

Secondary Immunodeficiencies

Secondary, or acquired, immunodeficiency diseases result from environmental rather than genetic factors. Malignancies, advanced age, certain infections (especially viral infections), immunosuppressive drugs, or malnutrition may all lead to secondary immunodeficiencies. Often, an infection will cause a depletion of certain cells of the immune system. The measles virus, for example, replicates in lymphoid cells, killing many of them and leaving the body temporarily open to other infections. Syphilis, leprosy, and malaria affect the T-cell population and

Table 18.6 Some Primary Immunodeficiency Diseases for Which Genetic Defects Are Known

Severe combined immunodeficiency (SCID)

X-linked SCID MHC class II deficiency CD3 deficiency CD8 deficiency

X-linked agammaglobulinemia

X-linked hyper-IgM syndrome Wiscott-Aldrich syndrome Ataxia telangiectasia Chronic granulomatous disease Leukocyte adhesion deficiency Many complement deficiencies

456 Chapter 18 Immunologic Disorders also macrophage function, causing defects in cell-mediated immunity. Malnutrition also causes decreased immune responses, especially the cell-mediated response.

Malignancies involving the lymphoid system often decrease effective antibody-mediated immunity. For example, multiple myeloma is a malignancy arising from a single plasma cell that proliferates out of control and produces large quantities of its specific immunoglobulin. This overproduction of a single kind of molecule results in the body using its resources to produce a single specificity of immunoglobulin at the expense of those needed to fight infection. The result is an overall immunodeficiency. Other lymphoid disorders include macroglobulinemia (overproduction of IgM) and some forms of leukemia.

One of the most serious and widespread secondary immunodeficiencies is AIDS (acquired immunodeficiency syndrome), caused by human immunodeficiency virus (HIV). This RNA virus of the retrovirus group infects and destroys helper T cells, leaving the affected person highly susceptible to infections, especially with opportunistic agents. AIDS and opportunistic infections are covered in chapter 29. ■ retrovirus, p. 356

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