Immunodeficiencies Flashcards
What is the molecular defect in chronic granulomatous disease (CGD)?
Deficiency of NADPH oxidase (any one of 4 complement proteins)
Failure to generate superoxide and other O2 radicals
What are the symptoms of CGD?
Recurrent infections with catalase-positive bacteria and fungi
What is the molecular defect of Leukocyte adhesion deficiency (LAD)?
Absence of CD18- common beta chain of the leukocyte integrins
The 3 integrins that contain CD18: LFA-1, MAC-1 and gp 150/95
What are the symptoms of LAD?
Recurrent and chronic infections, failure to form pus, and delayed separation of umbilical cord stump
What is the defect in LAD-2?
L-selectin
What is the molecular defect of Chediak-Higashi syndrome?
Nonsense mutation in the lysosomal trafficking regulator, CHS1/LYST protein, leads to aberrant fusion of vesicles
What are the symptoms of Chediak-Higashi syndrome?
Recurrent infection with bacteria: chemotactic and degranulation defects; absent NK activity partial albinism
What is the molecular defect of Glucose-6-phosphate dehydrogenase (G6PD) deficiency?
Deficiency of essential enzyme in hexose monophosphate shunt
What are the symptoms of Glucose-6-phosphate dehydrogenase (G6PD) deficiency?
Same as CGD, with associated anemia
What is the molecular defect of Myeloperoxidase deficiency?
Defect in MPO affects the ability to convert hydrogen peroxide to hypochlorite
What are the symptoms of MPO?
Mild or none
what is the molecular defect of hyperimmunoglobulin E syndrome (formerly Job syndrome)?
Defects in JAK/STAT signaling pathway leading to impaired Th17 function: decreased IFN-gamma production
What are the symptoms of hyperimmunoglobulin E syndrome (formerly Job syndrome)?
Characteristic facies, severe, recurrent sinusopulmonary infections, pathologic bone fractures, retention of primary teeth, increased IgE, eczematous rash
What is the molecular defect of Bruton (X-linked) agammaglobulinemia?
Deficiency of the Bruton tyrosine kinase (btk) which promotes pre-B cell expansion; faulty B-cell development
What are the signs and symptoms of Bruton (X-linked) agammaglobulinemia?
Increased susceptibility to encapsulated bacteria and bloodborne viruses, low immunoglobulin of all isotypes, absent or low levels of circulating B-cells. B-cell maturation does not progress past the pre-B cell stage while maintaining cell-mediated immunity
What is the molecular defect of X-linked hyper-IgM syndrome?
Deficiency of CD40L on activated T cells
What are the signs and symptoms of X-linked hyper-IgM syndrome?
High serum titers of IgM without other isotypes, normal B and T-cell numbers, susceptibility to encapsulated bacteria and opportunistic pathogens
What is the molecular defect of selective IgA deficiency?
Multiple genetic causes
What are the signs and symptoms of selective IgA deficiency?
Decreased levels of IgA level and normal IgM and IgG with elevation of IgE. Repeated sinopulmonary and gastrointestinal infections, increased atopy
What is the molecular defect of common variable immunodeficiency?
Collection of syndromes; several associated genetic defects
What are the signs and symptoms of common variable immunodeficiency?
Onsets in late teens, early twenties
B-cells present in peripheral blood, immunoglobulin levels decrease with time; increase autoimmunity
What is the molecular defect in transient hypogammaglobulinemia of infancy?
Delayed onset of normal IgG synthesis
What are the signs and symptoms of transient hypogammaglobulinemia of infancy
Detected in 5th to 6th month of life, resolves by 16-30 months; susceptibility to pyogenic bacteria
What is the deficiency in hereditary angioedema?
Deficient in C1-INH
C1 inhibitor that turns off complement
What are the signs of hereditary angioedema?
Overuse of C1, C4 or C2, edema at mucosal surfaces
What is the defect in DiGeorge syndrome?
Heterozygous deletion of chromosome 22q11. Failure of formation of 3rd and 4th pharyngeal pouches, thymis aplasia.
What are the clinical manifestations of DiGeorge syndrome?
Characteristic facies and a clinical triad of cardiac malformations, hypocalcemia and hypoplastic thymus
What is the defect in MHC class I deficiency?
Failure of TAP 1 molecules to transport peptides to endoplasmic reticulum
What are the clinical manifestations of MHC class 1 deficiency?
CD8+ T cells deficient, CD4+ T cells normal, recurring viral infections, normal DTH, normal Ab production
What is the defect in Wiskott-Aldrich syndrome?
Defect in WAS protein which plays a critical role in actin cytoskeleton rearrangement
What are the clinical manifestations of Wiskott-Aldrich syndrome?
Defective responses to bacterial polysaccharides and depressed IgM, gradual loss of humoral and cellular responses, thrombocytopenia, and eczema
IgA and IgE may be elevated
What is the defect in Ataxia telangiectasia?
Defect in ATM kinase involved in the detection of DNA damage and progression through the cell cycle
Ds DNA defect
What are the clinical manifestations of Ataxia telangiectasia?
Ataxia (gait abnormalities), telangiectasia (capillary distortions in the eye), deficiency of IgA and IgE production
What is the defect in bare lymphocyte syndrome/MHC class II deficiency?
Failure of MHC class II expression, defects in transcription factors
What are the clinical manifestations of bare lymphocyte syndrome/MHC class II deficiency?
T cells present and responsive to nonspecific mitogens, no GVHD, deficient in CD4+ T cells, hypogammaglobulinemia. Clinically observed as a severe combined immunodeficiency
What is the defect in severe combined immunodeficiency (SCID)?
Defects in common gamma chain of IL-2 receptor (present in receptors for IL-4, -7, -9, -15)
X-linked Male>female
What are the clinical manifestations of SCID?
Chronic diarrhea; skin, mouth, and throat lesions; opportunistic (fungal) infections; low levels of circulating lymphocytes; cells unresponsive to mitogens
What is the defect of ADA?
Adenosine deaminase deficiency
What are the clincal manifestations of ADA?
Clinical overlap with X-linked SCID plus neurologic deficiency
What is the defect in Rag SCID?
rag1 or rag2 gene nonsense mutations
What are the clinical correlates of Rag SCID
Total absence of B+ T cells
