AIDS and Other Immunodeficiencies CHAPTER 19 433 TABLE 19-1 Some primary human immunodeficiency diseases and underlying genetic defects Immunodeficiency Inheritance Chromosomal disease Specific defect mpaired function Severe combined RAG-1/RAG-2 deficiency No TCR or lg gene 11p13 immunodeficiency rearrangement ADA deficiency Toxic metabolite in T 20q13 PNP deficiency 14q13 JAK-3 deficiency Defective signals from 19p13 IL-2Ry-deficiency lL2,4,7.9.15 Xq13 ZAP-70 deficiency Defective signal from 2q12 Bare lymphocyte Defect in MHc class ll No class I mHc 6p13 Wiskott-Aldrich Cytoskeletal protein(CD43) Defective T cells and A platelets Interferon gamma IFN-y-receptor defect Impaired immunity to q23 DiGeorge syndrome Thymic aplasia T-and B-cell development 22q11 Ataxia telangiectasia Defective cell-cycle kinase Low IgA, igE 11q22 ammaglobulinemias X-linked gammaglobulin Btk): no mature B cells X-linked hyper-IgM Defective CD40 ligand syndrome Common variable Low IgG, IgA; variable immunodeficiency Selective IgA deficiency Low or no IgA Complex Chronic granulomatous Cyt p67 No oxidative burst Cyt p22 for bacterial killing Chediak-Higashi syndrome Defective intracellular Inability to lyse bacteria transport protein(LYST) Leukocyte-adhesion defect Defective integrinβ2 Leukocyte extravasation 21q22 .AR= autosomal recessive: AD= autosomal dominant; XL= x linked; Complex "indicates conditions for which precise genetic data are not available and that may involve several interacting loci Lymphoid Immunodeficiencies May immunoglobulins. Patients with these disorders usually are Involve b cells T Cells, or Both subject to recurrent bacterial infections but display normal immunity to most viral and fungal infections, because the t- The combined forms of lymphoid immunodeficiency affect cell branch of the immune system is largely unaffected. Most both lineages and are generally lethal within the first few common in patients with humoral immunodeficiencies are years of life; these arise from defects early in developmental infections by such encapsulated bacteria as staphylococci, pathways. They are less common than conditions, usually less streptococci, and pneumococci, because antibody is critical severe, that result from defects in more highly differentiated for the opsonization and clearance of these organisms lymphoid cells Because of the central role of t cells in the immune B-cell immunodeficiency disorders make up a diverse tem, a T-cell deficiency can affect both the humoral and the spectrum of diseases ranging from the complete absence of cell-mediated responses. The impact on the cell-mediated mature recirculating B cells, plasma cells, and immuno- system can be severe, with a reduction in both delayed-type globulin to the selective absence of only certain classes of hypersensitive responses and cell-mediated cytotoxicityLymphoid Immunodeficiencies May Involve B Cells, T Cells, or Both The combined forms of lymphoid immunodeficiency affect both lineages and are generally lethal within the first few years of life; these arise from defects early in developmental pathways. They are less common than conditions, usually less severe, that result from defects in more highly differentiated lymphoid cells. B-cell immunodeficiency disorders make up a diverse spectrum of diseases ranging from the complete absence of mature recirculating B cells, plasma cells, and immuno￾globulin to the selective absence of only certain classes of AIDS and Other Immunodeficiencies CHAPTER 19 433 immunoglobulins. Patients with these disorders usually are subject to recurrent bacterial infections but display normal immunity to most viral and fungal infections, because the T￾cell branch of the immune system is largely unaffected. Most common in patients with humoral immunodeficiencies are infections by such encapsulated bacteria as staphylococci, streptococci, and pneumococci, because antibody is critical for the opsonization and clearance of these organisms. Because of the central role of T cells in the immune sys￾tem, a T-cell deficiency can affect both the humoral and the cell-mediated responses. The impact on the cell-mediated system can be severe, with a reduction in both delayed-type hypersensitive responses and cell-mediated cytotoxicity. TABLE 19-1 Some primary human immunodeficiency diseases and underlying genetic defects Immunodeficiency Inheritance Chromosomal disease Specific defect Impaired function mode* defect Severe combined RAG-1/RAG-2 deficiency No TCR or Ig gene AR 11p13 immunodeficiency rearrangement (SCID) ADA deficiency Toxic metabolite in T AR 20q13 PNP deficiency and B cells AR 14q13 JAK-3 deficiency Defective signals from AR 19p13 IL-2R-deficiency IL-2, 4, 7, 9, 15, XL Xq13 ZAP-70 deficiency Defective signal from AR 2q12 TCR Bare lymphocyte Defect in MHC class II No class II MHC AR 16p13 syndrome gene promoter molecules Wiskott-Aldrich Cytoskeletal protein (CD43) Defective T cells and XL Xp11 syndrome (WAS) platelets Interferon gamma IFN-–receptor defect Impaired immunity to AR 6q23 receptor mycobacteria DiGeorge syndrome Thymic aplasia T- and B-cell development AD 22q11 Ataxia telangiectasia Defective cell-cycle kinase Low IgA, IgE AR 11q22 Gammaglobulinemias X-linked Bruton’s tyrosine kinase XL Xq21 agammaglobulinemia (Btk); no mature B cells X-linked hyper-IgM Defective CD40 ligand XL Xq26 syndrome Common variable Low IgG, IgA; variable Complex immunodeficiency IgM Selective IgA deficiency Low or no IgA Complex Chronic granulomatous Cyt p91phox XL Xp21 disease Cyt p67phox No oxidative burst AR 1q25 Cyt p22phox for bacterial killing AR 16q24 Chediak-Higashi syndrome Defective intracellular Inability to lyse bacteria AR 1q42 transport protein (LYST) Leukocyte-adhesion defect Defective integrin 2 Leukocyte extravasation AR 21q22 (CD18) *AR autosomal recessive; AD autosomal dominant; XL X linked; “Complex” indicates conditions for which precise genetic data are not available and that may involve several interacting loci. } } } } } }