Immunodeficiencies Flashcards
(39 cards)
DiGeorge Syndromes
T cell deficiency (lack of T cells)
Parathyroid , thymic, hypoplasia and malformation of outflow vessels of the heart, facial abnormalities, recurrent infections
Key feature is HYPOCALCEMIA
Tetany, seizures in infants
22q11 chromosome deletion
WHN
Congenital alopecia and nail dystrophy
CD3 Deficiency
Autoimmune hemolytic anemia and severe infections, recurrent hemophilus influenza pneumonia and otitis media
MHC I Deficiency
Decreased number of CD8+
Inability of Tap1 to transfer peptides to the ER
Recurring VIRAL infections
Normal CD4+, Ab production and DTH
MHC II Deficiency (Bare Lymphocyte Syndrome)
Persistent diarrhea, bacterial pneumonia, viral and candidal infections, low CD4+ cells/no MHC II on pro APCs
Genes for MHC II on Chrom. 6 intact
Variable hypogammaglobulinemia (IgA and IgG2)
Mutations in genes encoding for transcription factors that regulate expression of MHCII genes
LCK Deficiency
Bacterial, viral, fungal infections, lymphopenia and hypogammaglobulinaemia
ZAP70 Deficiency
Decreased CD4/CD8+ and severe recurrent infections
CD8 Deficiency
No CD8+, recurrent respiratory infections
HIGM1
Pneumonia, pyogenic infections, bacterial infections
Normal response to encapsulated infections
High IgM, low or absence of serum IgG, IgA, IgE
Impaired class switching, somatic hypermutation
Normal peripheral B cells, LOW MEMORY CELLS
X-linked CD40L (2/3 of cases, male only), autosomal CD40 Deficiency (M & F, 1/3 of cases)
Common Gamma Chain Deficiency (yc or IL-2Ry)
Most common SCID
X-linked recessive, only males
T-, B+, NK-
No functional B cells since T cells unable to help
Fungal infections, chronic diarrhea, skin, mouth and throat lesions
Jak 3 Deficiency
T-, B+, NK-
Autosomal Recessive
Defect in IL-2 receptor signaling
Fungal infections, chronic diarrhea, skin, mouth and throat lesions
Wiskott-Aldrich Syndrome
X-links recessive, progressive decrease in T cells
Defect in WASP - cytoskeleton protein
Only expressed on hematopoietic lineage
Low IgM, Normal IgG, elevate IgA/IgE
Thrombocytopenia, small platelets/dysfunction, Eczema, recurrent infections from encapsulated bacteria, (infants have longer bleeding after circumcision, bloody diarrhea, bruising)
IPEX (Immunodysregulation, Polyendocrinopathy and Enteropathy)
X-linked defect in T cell function after maturation
Self reactive T Effector Cells are not inhibited
Mutations in FOXP3
Loss of CD4/CD25 Treg cells
ALPS (Autoimmune Lymphoproliferative Syndrome)
Defects in Fas/FasL, Caspase 8, 10 genes
Abrogate Formation of death inducing signaling complex (DISC)
Interferes with apoptosis of T effector cells
X Linked Briton Agammaglobulinemia (affects males only)
Low/absent IgG, IgA, IgM
Mutation in BTK gene
Diagnosis 5-6 months old
Defect in rearrangement of Ig heavy chain genes
Early B cell development arrested at Pre-B cell stage (never mature)
NO PLASMA CELLS
Secondary Lymph organs poorly developed
Severe bacterial infections
Autosomal Recessive Agammaglobulinemia (affects males and females)
Low/absent IgG, IgA, IgM
Mutations in u, Igalpha, delta5, BLNK
BLNK: amplifies signal transduction
Delta 5: encodes surrogate light chain
Pre B cells do not mature
Common Variable Immune Deficiencies
Associated with hypogammaglobulinemia
Low IgG, IgA
Normal/low IgM
Males and females equally affected
Diagnosed at 2 years, Onset after 4-5 years
Some have low B cells, defects in their formation or Abs against B cells (inherited vs. acquired)
Recurrent bacterial infections
IgA Deficiency
Low IgA, normal IgG/IgM
Prevalence may be higher in male
Disorder of maturation or terminal differentiation of secreting B cells
Prone to infections in GI tract in epithelial areas, mom with this will have child with higher rate of disease
Isolated IgG Subclass Deficiency
Decreased concentrations of one or more IgG subclass
Total IgG, IgM, IgA, IgE are normal
Low IgG2 frequent in children (poor response to polysaccharide Ags)
IgG4 levels vary widely
Recurrent viral/bacterial infection in respiratory tract
Transient Hypogammaglobulinemia of Infancy
Low IgA/IgG
Normal IgM
Intrinsic Ig production delayed up to 36 months
Increased sinopulmonary infections
Ig concentrations normalize by 2-4 years
Severe Chronic Neutropenia
Defect in life cycle and anatomy of neutrophils
Decreased absolute neutrophil count (<500 cells/mm^3)
Suppressed inflammation
Increased susceptibility to severe bacterial and fungal infections
Chronic Granulomatous Disease (CGD)
Tendency to form granulomas
Most frequent phagocytic primary immunodeficiency
More common in males
NADPH oxidase Deficiency, failure to generate superoxide anion and O2 radicals
Defective elimination of extracellular pathogens i.e. bacteria and fungi
Recurrent infection with catalase positive organisms
Myeloperoxidase Deficiency (MPO)
Autosomal recessive
Most common phagocyte DISORDER
Diagnosis by staining neutrophils for MPO activity
Almost exclusively seen in setting of diabetes
Neutrophils cant kill Candida in vitro
Defect in the IFN-y-IL-12 Axis
POSITIVE REGULATORY LOOP
Normally, IL-12 from macrophage binds IL-12R, stimulates IFN-y release by T cells and NK Cells
Macrophage binds IFN-yR, produces H2O2 and TNF-alpha and IL-12
Increased susceptibility to nontuberculous mycobacteria from mutations in: IFN-y RC, IL-12 Rc, p40 subunit of IL-12.
