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Primary immunodeficiency diseases result from genetic defects affecting the development and/or the function of immune system components.1-5 They frequently manifest soon after birth, although some become evident later in life. Recurrent infections are the hallmark of immunodeficiency syndromes, with the types of infections reflecting the nature of the defect. Autoimmune disorders and certain malignancies occur more frequently in individuals with immunodeficiency diseases.

Primary immunodeficiency diseases may affect either acquired immunity, as seen in cellular and humoral deficiency diseases, or innate immunity, such as seen in deficiencies of the various complement components and phagocytic cell deficiencies. This chapter reviews representative immunodeficiency diseases of altered development and function of T and B cells. These defects have served as experiments of nature to unravel the complexities of T-cell and B-cell development and function. T-cell immunodeficiencies resulting from defects affecting T-cell development and activation are shown in Figure 188-1, and B-cell immunodeficiencies due to abnormalities in B-cell development and differentiation are shown in Figure 188-2. Diseases of the innate immune system are reviewed in Chapter 187. Disorders of phagocytosis and other granulocyte disorders including Chediak-Higashi syndrome, cartilage-hair hypoplasia syndrome, myelokathexis, specific granule deficiency, leukocyte adhesion deficiency, chronic granulomatous disease and myeloperoxidase deficiency are discussed in Chapter 442.

Figure 188-1.

Schematic representation of T-cell immunodeficiencies resulting from defects affecting T-cell development and activation. Bars indicate a block in cell development or function. CLP and CMP, common lymphoid and myeloid progenitors, respectively; DPT, double-positive thymocytes; HSCs, hematopoietic stem cells; NKT, natural killer cell; PreT, pre-T cells; SCID, severe combined immunodeficiency.

Figure 188-2.

B-cell immunodeficiencies due to abnormalities in B-cell development and differentiation. AID, activation-induced cytidine deaminase; BLNK, B cell LINKer protein; CD, cluster of differentiation; CSR, class switch recombination; HSCs, hematopoietic stem cells; IGLL1, immunoglobulin lambda-like polypeptide 1; μ HC, Ig membrane µ heavy chain; NEMO, NF-κB essential modulator; PreB, pre-B cells; ProB, pro-B cells; SHM, somatic hypermutation; TACI, transmembrane activator and CAML interactor; Tfh, T follicular helper B cells; UNG, uracil-DNA glycosylase; XLA, X-linked agammaglobulinemia.

Because of the role of the T lymphocyte in supporting B lymphocyte function, abnormalities affecting T cells alone or in combination with B lymphocytes frequently lead to states of combined immunodeficiency, the severity of which depends on the extent of the T-cell defect. In contrast to combined immunodeficiency diseases, where both T-cell and B-cell compartments are affected, T-cell function in isolated B-cell immunodeficiency syndromes, such as X-linked agammaglobulinemia, remains intact.

Severe combined immunodeficiency (SCID) is characterized by the breakdown of both cellular and humoral adaptive immunity. The reported incidence is approximately 1 per 100,000.6,7 It is caused by a heterogeneous group of at least 15 known genetic abnormalities that result in severe T-cell depletion (or dysfunction) with either primary ...

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