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
