Immuno - deficiencies Flashcards
Recurrent bacterial/enterovial infections after age of 6mos (after loss of maternal IgG), young boys
X-linked agammaglobulinemia
B’s! Defect in BTK, no B-cell maturation, X-linked recessive (more common in Boys)
Look for absent B cells in peripheral blood and low number of all immunoglobulins
Absent lymph nodes!
Airway/Gi infections, Autoimmune disease, Atopy (though often asymptomatic!)
Selective IgA deficiency
Anaphylaxis to IgA-containing products
Look for selectively decreased IgA levels
Autoimmune diseases, brochiectasis, lymphoma, sinopulmonary infections, acquired in 20s-30s
Common variable immunodeficiency
Defect in B-cell differentiation
Decreased plasma cells and decreased immunoglobulins
Tetany, recurrent viral/fungal infections, conotruncal abnormalities (Tetralogy of Fallot, truncus arteriosus), absent thymus/parathyroids (no appearance on CXR)
Thmyic aplasia (DiGeorge) - 22q11 deletion, detected by FISH
failure to develop 3rd and 4th branchial pouches
T cell disorder
Decreased T cells, PTH, Ca2+
Disseminated mycobacterial and fungal infections; appears after BCG vaccine (decreased Th1 response)
IL-12 deficiency
Decreased Th1 response. Autosomal recessive.
Decreased IFN-y
coarse Facies, Abscesses, Teeth, increased igE, Derm lesions (FATED), seen in babies!
hyper-IgE syndrome (Jobs)
deficiency of Th17 cells due to STAT3 defect –> impaired neutrophil recruitment to site of infection
autosomal dominant
Noninvasive Candidal infections of the skin and mucus membranes
Chronic mucocutaneous candidiasis
T-cell dysfunction, absent T cell proliferation to Candidal antigens
Failure to thrive, chronic diarrhea, thrush, absence of thymus/lymph node germinal centers/T cells
Recurrent bacterial, viral, fungal infections, esp. opportunistic infxns
Severe combined immunodeficiency (SCID)
Major types: IL-2R deficiency, adenosine deaminase deficiency (decr. purine salvage)
tx: bone marrow transplant (no concern for rejection)
Triad of : Cerebellar defects, spider angiomas/telengiectasias, IgA deficiency
Also, lymphopenia, decr. immunoglobulins
Ataxia-telengiectasia
Defects in ATM gene –> failure to repair DNA double stand breaks –> cell cycle arrest
incr. AFP, decr. IgA/G/E, lymphopenia
Also, hypersensitivity to ionizing radiation
Severe pyogenic infections, opportunistic infections (Candida, PCP, CMV), only IgM present, Early in life!
Hyper-IgM syndrome
Defective CD40L on T cell leads to inability for B cells to undergo class-switching
Thrombocytopenic purpura, eczema, recurrent infections
Incr. risk of autoimmune disease and malignancy
Wiskott-Aldrich (WATER)
Mutation in WAS gene = T cells unable to reorganize actin cytoskeleton
Fewer and smaller platelets
Absent pus, impaired wound healing, delayed separation of umbilical cord
Leukocyte Adhesion Deficiency type 1
Defect in LFA-1 integrin (CD18) on phagocytes –> impaired migration and chemotaxis
Increased neutrophils, but absence at infection sites
Recurrent staph/strep infections, partial albinism, peripheral neuropathy, neurodegeneration
Chediak-Higashi
Defect in lysosomal trafficking regular gene (LYST)
Microtubule dysfunction in phagosome-lysosome fusion
Look for giant granules in granulocytes and platelets
Increased susceptibility to catalase + organisms (Nocardia, Pseudomonas, Listeria, Aspergillus, Candida, E. coli, S. aureus, Serratia)
Chronic granulomatous disease
Defect of NADPH oxidase –> decreased ROS/respiratory burst in neutrophils
Abnormal dihydrorhodamine test
Transplant rejections
widespread thrombosis/ischemia/necrosis…
dense interstitial lymphocytic infiltrate…
vascular smooth muscle growth and parenchymal fibrosis…
Hyperacute
- type II hypersensivity
- widespread thrombosis/ischemia/necrosis
Acute
- CD8 T cells activate against donor MHCs
- vasculitis with dense interstitial lymphocytic infiltrate. Prevent with immunosuppressives!
Chronic
- CD4 T cells respond to recipient APCs presenting donor peptides, secrete cytokines, leads to proliferation of vascular smooth muscle and parenchymal fibrosis
