Immunodeficiencies Flashcards
Bruton agammaglobulinemia - defect
defect in BTK, a tyrosine kinase gene -> no B-cell maturation
insufficient opsonization of pathogens with IgG
X-linked recessive
Bruton agammaglobulinemia - presentation
recurrent extracellular encapsulated bacterial and enteroviral infections after 6mo (decrease maternal IgG)
Bruton agammaglobulinemia - findings
absent B cells in peripheral blood
decrease Ig of all classes
Absent/scanty lymph nodes and tonsils
LIVE VACCINES CONTRAINDICATED
Selective IgA deficiency - defect
unknown
most common primary immunodeficiency
Selective IgA deficiency - presentation
majority: asymptomatic can see airway and GI infections autoimmune disease atopy anaphylaxis to IgA-containing products
Selective IgA deficiency - findings
decrease IgA with normal IgG, IgM levels
increase susceptibility to GIARDIASIS
Common variable immunodeficiency - defect
defect in B-cell differentiation
cause is unknown in most cases
Common variable immunodeficiency - presentation
usually presents after age 2 and may be considered delayed
increase risk of autoimmune disease, bronchiectasis, lymphoma, sinopulmonary infections
Common variable immunodeficiency - findings
decrease plasma cells
decrease immunoglobulins
thymic aplasia (DiGeorge syndrome) - defect
22q11 deletion
failure to develop 3rd and 4th pharyngeal pouches -> absent thymus and parathyroids
thymic aplasia (DiGeorge syndrome) - presentation
tetany (hypocalcemia) recurrent viral/fungal infections, intracellular bacteria (T-cell deficiency) cotruncal abnormalities (tetralogy of Fallot, truncus arteriosus)
thymic aplasia (DiGeorge syndrome) - findings
decrease T cells, decrease PTH, decrease Ca2+
thyme shadow absent on CXR
IL-12 receptor deficiency - defect
decrease Th1 response
autosomal recessive
IL-12 receptor deficiency - presentation
disseminated mycobacterial and fungal infections
may present after administration of BCG vax
IL-12 receptor deficiency - findings
decrease IFN-gamma
autosomal dominant hyper-IgE syndrome (Job syndrome) - defects
deficiency of Th17 cells due to STAT3 mutation -> impaired recruitment of neutrophils to sites of infection
autosomal dominant hyper-IgE syndrome (Job syndrome) - presentation
FATED: coarse Facies cold (non inflamed) staphylococcal Abscesses retained primary Teeth increased IgE Dermatologic problems (eczema)
bone fractures from minor trauma
autosomal dominant hyper-IgE syndrome (Job syndrome) - findings
increase IgE
increase eosinophils
chronic mucocutaneous candidiasis - defect
T-cell dysfunction
can result from congenital genetic defects in IL-17 or IL-17 receptors
chronic mucocutaneous candidiasis - presentation
noninvasive Candida albicans infections of skin and mucous membranes
chronic mucocutaneous candidiasis - findings
absent in vitro T-cell proliferation in response to candida antigens
absent cutaneous reaction to candida antigens
severe combined immunodeficiency - defect
several types including:
defective IL-2R gamma chain (most common, XR)
adenosine deaminase deficiency (AR)
severe combined immunodeficiency - presentation
failure to thrive, chronic diarrhea, thrush
recurrent viral, bacterial, fungal, and protozoal infections
treatment: avoid live vax, give antimicrobial prophylaxis and IVIG; BONE MARROW TRANSPLANT = curative
severe combined immunodeficiency - findings
decrease T-cell receptor excision circles (TRECs)
absence of thymic shadow (CXR), germinal centers (lymph node biopsy), and T cells (flow cytometry)
ataxia-telangiectasia - defect
defects in ATM gene -> failure to detect DNA damage -> failure to halt progression of cell cycle -> mutations accumulate
AR
defect in DNA ds repair enzyme
ataxia-telangiectasia - presentation
triad: cerebellar defects (ataxia) spider angiomas (telangiectasia) IgA deficiency
ataxia-telangiectasia - findings
increase AFP
decrease IgA, IgG, and IgE
lymphopenia, cerebellar atrophy
increase risk of lymphoma and leukemia
Hyper-IgM syndrome - defect
most commonly due to defective CD40L on Th cells -> class switching defect XR
Hyper-IgM syndrome - presentation
severe pyogenic infections early in life
opportunistic infection with Pneumocystis (fungal), cryptosporidium, CMV
Hyper-IgM syndrome - findings
normal or increase IgM
marked decrease IgG, IgA, IgE
failure to make germinal centers
Wiskott-Aldrich syndrome - defect
mutation in WASp gene
leukocytes and platelets unable to reorganize actin cytoskeleton -> defective antigen presentation
XR
Wiskott-Aldrich syndrome - presentation
WATER: Wiskott-Aldrich: Thrombocytopenia Eczema Recurrent (pyogenic) infections increase risk of autoimmune disease and malignancy
Wiskott-Aldrich syndrome - findings
decrease to normal IgG, IgM
increase IgE, IgA
fewer and smaller platelets
Leukocyte adhesion deficiency type 1 - defect
Defect in LFA-1 integrin (CD18) protein on phagocytes
impaired migration and chemotaxis
AR
Leukocyte adhesion deficiency type 1 - presentation
recurrent skin and mucosal bacterial infections, absent pus, impaired wound healing, delayed (>30d) separation of umbilical cord
Leukocyte adhesion deficiency type 1 - findings
increase neutrophils in blood
absence of neutrophils at infection sites
Chediak-Higashi syndrome - defect
defect in lysosomal trafficking regulator gene (LYST)
microtubule dysfunction in phagosome-lysosome fusion
AR
decrease phagocytosis
Chediak-Higashi syndrome - presentation
PLAIN: Progressive neurodegeneration Lymphobistiocytosis Albinism (partial) recurrent pyogenic Infections by staphylococci and streptococci (gram +, gram -, fungal) peripheral Neuropathy
Chediak-Higashi syndrome - findings
giant granules in granulocytes and platelets
pancytopenia
mild coagulation defects
chronic granulomatous disease - defect
defect in NADPH oxidase -> decrease ROS (e.g. superoxide) and decrease respiratory burst in neutrophils
X-linked most common
chronic granulomatous disease - presentation
increase susceptibility to catalase + organisms
- staph aureus, pseudomonas, klebsiella, aspergillus
chronic granulomatous disease - findings
abnormal dihydrorhodamine (flow cytometry) test (decrease green fluorescence) nitroblue tetrazolium dye reduction test (obsolete) fails to turn blue
early complement deficiencies
C1-C4
increased risk of severe, recurrent pyogenic sinus and respiratory tract infections
increased risk of SLE
terminal complement deficiencies
C5-C9
increased susceptibility to recurrent Neisseria bacteremia
C1 esterase inhibitor deficiency
causes hereditary angioedema d/t unregulated activation of kallikrein -> increase bradykinin
characterized by decreased C4 levels
ACEi CONTRAINDICATED
paroxysmal nocturnal hemoglobinuria
defect in PIGA gene preventing the formation of anchors for complement inhibitors (decay-accelerating factor [DAF/CD55] and membrane inhibitor of reactive lysis [MIRL/CD59])
causes complement-mediated lysis of RBCs
