Immunodeficiencies Flashcards
primary immunodeficiency
genetic or developmental disorders manifesting early in infancy or early childhood
secondary immunodeficiency
more common than primary; acquired, as result of some other disease process (protein-calorie malnutrition, irradiation, chemotherapy, bone cancer, immunosuppressive drugs, splenectomy, infections)
Protein-Calorie malnutrition
most common cause of immunodeficiency worldwide; lack of nutrients prevents immune system maturation, changes response from Th1 to Th2
Cyclosporin
calcineurin inhibitor; binds cyclophilin and prevents IL-2 transcription; side effects include nephrotoxicity, hypertension, gingival hyperplasia
Tacrolimus (FK506)
calcineurin inhibitor; binds FK506 binding protein and prevents IL-2 transcription; similar side effects as cyclosporin except no gingival hyperplasia and hirsutism
Glucocorticoids
inhibit NF-kB and suppresses both B and T cell function by decreasing transcription of many cytokines
X-linked agammaglobulinemia
humoral deficiency; defect in BTK (B cell tyrosine kinase) which is expressed in all stages of B cell differentiation and is required for maturation) -> only pre-B cells in BM, no B cells in the periphery, T cells normal
Hyper-IgM syndrome
humoral deficiency; defect in CD40L gene on T cells (X-linked recessive) or CD40 on B cells/APC; no memory B cells or class switching -> elevated levels of IgM, low levels of IgG, IgA, IgE
Selective Ig deficiencies
humoral deficiency; unknown cause, IgA deficiency most common primary immunodeficiency; majority asymptomatic and if not condition usually is not severe, can see airway and GI infections, autoimmune disease, atopy, anaphylaxis to IgA-containing products; low IgA levels but all other Ig’s normal
Common variable immunodeficiency
humoral deficiency; many causes (TACI mutation) but there is a defect at stage where B cells become plasma cells -> low #s of plasma cells and reduced serums levels of IgG, IgA, and IgM
Severe Combined immunodeficiency disease (SCID)
cellular deficiency; most common causes is defective IL-2R gamma chain (X-linked) and adensoine deaminase (autosomal recessive) -> lack of thymus, low T cell # and function, failure to thrive, recurrent infections, absence germinal centers
ZAP-70 deficiency
SCID-like deficiency; ZAP-70 binds ITAMs during TCR signaling -> normal levels of Ig and CD4+ lymphocytes but their CD4+ T cells are nonfunctional
Bare lymphocyte syndrome
SCID-like deficiency; defects in MHC expression; MHC I -> TAP mutations; MHC II -> impairment of MHC gene transcription
Wiskott-Aldrich syndrome
cellular deficiency; mutation in WAS gene (X-linked recessive) where T cells are unable to reorganize actin cytoskeleton; WATER (Wiskott, Aldrich, TTP, Eczema, Recurrent infections)
DiGeorge syndrome
cellular deficiency; 22q11 deletion with a failure to develop 3rd and 4th pharyngeal pouches -> absent thymus and parathyroids -> few T cells, low PTH, low serum Ca, tetany, recurrent viral/ fungal infections (but not bacterial -> T-cell deficiency), facial abnormalities
Chronic granulomatous disease (CGD)
phagocytic disorder; X-linked (70%), AR (30%); defect of NADPH oxidase, can not convert O2 to superoxdie, decreasing respiratory burst of neutrophils -> NBT is negative, susceptible to catalase positive bacteria (in catalase negative, cells use H2O2 from bacteria to make HOCl -> kills; but in catalase positive H2O2 gets converted to water and O2)
Nitroblue tetrazolium test (NBT)
Used to screen for CGD; NBT dye turns blue if NADPH oxidase can convert O2 to superoxide; remains colorless if NADPH is defective
Chediak-Higashi syndrome
phagocytic disorder; autosomal recessive; defect in lysosomal trafficking regulator gene (LYST) causing microtubule dysfunction so phagosome and lysosome can not fuse -> giant granules and platelets, pancytopenia, partial albinism, peripheral neuropathy, defective primary hemostasis, recurrent pyogenic infections
Classical pathway deficiency (C1, C2, C4)
immune complex disease
MBL pathway deficiency (MBL, MASP1, MASP2, C2, C4)
bacterial infections, mainly in childhood
Alternative pathway deficiency (Factor D, Factor P)
infection with pyogenic bacteria and Neisseria spp. but no immune-complex disease
C3b deposition deficiency
infection with pyogenic bacteria and Neisseria spp. with sometimes immune-complex disease
Membrane attack component deficiency (C5, C6, C7, C8, C9)
infection with Neiseeria spp.
Hereditary angioneurotic edema
complement disorder; low levels or improper function of C1 inhibitor -> swelling of face and airways, abdominal cramping
