Immunodeficiencies Flashcards
immunodeficiencies of phagocyte dysfunction
*leukocyte adhesion deficiency
*Chediak-Hagashi syndrome
*chronic granulomatous disease
immunodeficiencies of B-cell dysfunction
*X-linked agammaglobulinemia (Btk deficiency)
*selective IgA deficiency
*common variable immunodeficiency
immunodeficiencies of T-cell dysfunction
*thymic aplasia (diGeorge syndrome)
*IL-12 receptor deficiency
*Job syndrome
*chronic mucocutaneous candidiasis
immunodeficiencies of B- AND T-cell dysfunction
*severe combined immunodeficiency (SCID)
*ataxia-telangectasia
*hyper IgM syndrome
*Wiskott-Aldrich syndrome
leukocyte adhesion deficiency - pathogenesis
*defect in LFA-1 integrin (CD18) on phagocytes
autosomal recessive
**leads to impaired migration and chemotaxis
*PHAGOCYTE DYSFUNCTION immunodeficiency
leukocyte adhesion deficiency - presentation
*recurrent skin and mucosal bacterial infections
*NO PUS formation
*impaired wound healing
*delayed detachment of umbilical cord
leukocyte adhesion deficiency - findings
*increased neutrophils in BLOOD (lack of neutrophil migration)
*ABSENT NEUTROPHILS AT INFECTION SITES
Chediak-Hagashi syndrome - pathogenesis
*autosomal recessive defect in LYST (lysosomal trafficking regulator gene)
*MICROTUBULE DYSFUNCTION in phagosome-lysosome fustion
*PHAGOCYTE DYSFUNCTION immunodeficiency
Chediak-Hagashi syndrome - findings
*GIANT GRANULES in platelets and PMNs
*pancytopenia
*mild coagulation defects
Chediak-Hagashi syndrome - presentation
*recurrent staph and strep infections
*partial albinism
*peripheral neuropathy
*progressive neurodegeneration
IL-12 receptor deficiency - pathogenesis
*autosomal recessive deficiency in IL-12 receptor, leading to LACK OF Th1 CELL RESPONSE
*T-CELL DYSFUNCTION immunodeficiency
IL-12 receptor deficiency - presentation
*recurrent, disseminated MYCOBACTERIAL and fungal infections
IL-12 receptor deficiency - findings
low levels of IFN-gamma
Job syndrome - pathogenesis
*aka autosomal dominant hyper-IgE syndrome
*Th17 deficiency - leads to an impaired ability to recruit neutrophils to a site of infection
Job syndrome - presentation
FATED:
*coarse facies
*staph abscesses
*retained primary teeth
*hyper-IgE
*dermatologic issues (ex. eczema)
Job syndrome - findings
*elevated IgE and eosinophils
*decreased IFN-gamma
chronic mucocutaneous candidiasis - pathogenesis
*T-cell dysfunction (multiple causes, though often due to a defect in the IL-17 pathway)
chronic mucocutaneous candidiasis - presentation
*noninvasive candida infections of the skin and mucous membranes
chronic mucocutaneous candidiasis - findings
*absent in vitro or cutaneous response to candida infections
severe combined immunodeficiency (SCID) - pathogenesis
*defective IL-2 receptor (X-linked)
OR
*defective adenosine deaminase (ADA) [autosomal recessive]
*B AND T CELL DYSFUNCTION immunodeficiency
severe combined immunodeficiency (SCID) - presentation
***failure to thrive, chronic diarrhea
*thrush, recurrent viral, fungal, bacterial, and protozoal infections
severe combined immunodeficiency (SCID) - findings
*absent thymic shadow
*absent germinal centers
*scanty lymph nodes
*absent T cells
severe combined immunodeficiency (SCID) - treatment
*BONE MARROW TRANSPLANT IS CURATIVE
*avoid live vaccines
*give prophylactic antibiotics
*environmental sterilization (bubble boy)
ataxia-telangiectasia - pathogenesis
*autosomal recessive defect in the ATM gene, leading to an INABILITY TO REPAIR dsDNA BREAKS (lead to cell cycle arrest)
**B AND T CELL DYSFUNCTION immunodeficiency
ataxia-telangiectasia - presentation
CLASSIC TRIAD =
1) ataxia (cerebellar defects)
2) angiomas (telangiectasias)
3) IgA deficiency
Wiskott-Aldrich syndrome - pathogenesis
*X-linked recessive mutation in the WASp gene
*leads to an inability of leukocytes and platelets to reorganize the actin cytoskeleton, causing:
1) defective antigen presentation
2) defective platelets
*B AND T CELL DYSFUNCTION immunodeficiency
Wiskott-Aldrich syndrome - results in higher risk of?
autoimmune disease and malignancy
Wiskott-Aldrich syndrome - presentation
WATER:
*thrombocytopenia
*eczema
*recurrent pyogenic infections
Wiskott-Aldrich syndrome - findings
*elevated IgE and IgA
*fewer and smaller platelets on blood smear
thymic aplasia (diGeorge syndrome) - pathogenesis
22q11 deletion
*leads to failure to develop the 3rd and 4th pharyngeal pouches
*results in an absent thymus and parathyroids
*T CELL DYSFUNCTION immunodeficiency
thymic aplasia (diGeorge syndrome) - findings
**LOW Ca2+
*decreased T cells
*low PTH
*ABSENT THYMIC SHADOW on CXR
thymic aplasia (diGeorge syndrome) - presentation
CATCH-22:
*cleft palate
*abnormal facies
*thymic aplasia
*conotruncal abnormalities
*hypocalcemia
*22q11 deletion
chronic granulomatous disease (CGD) - pathogenesis
*autosomal or X-linked mutation causing DEFECTIVE NADPH OXIDASE
*leads to failure to generate oxygen radicals for respiratory burst in neutrophils
*PHAGOCYTE DYSFUNCTION immunodeficiency
chronic granulomatous disease (CGD) - presentation
heightened susceptibility to infection during the first year of life (pneumonia and abscesses of the skin)
*especially to CATALASE POSITIVE organisms
chronic granulomatous disease (CGD) - findings
*neutrophils and macrophages fail to reduce NBT when a respiratory burst stimulus is applied
*altered flow cytometry results
X-linked (Bruton’s) agammaglobulinemia - pathogenesis
*X-linked recessive defect in the BTK gene
*leads to lack of B-cell maturation
*B CELL DYSFUNCTION immunodeficiency
*do NOT give patients live vaccines
X-linked (Bruton’s) agammaglobulinemia - presentation
*recurrent bacterial and enteroviral infections AFTER 6 MONTHS OF AGE
note - presents after 6 months because of decreased IgG from breastfeeding
X-linked (Bruton’s) agammaglobulinemia - findings
*absent B cells in peripheral blood
*decreases in ALL immunoglobulin isotypes
*absent/scanty lymph nodes and tonsils
selective IgA deficiency - presentation
*many patients are asymptomatic
*can present with airway and GI infections, atopy, autoimmune disease, and anaphylaxis to IgA-containing products
*B CELL DYSFUNCTION immunodeficiency
selective IgA deficiency - findings
*low levels of IgA but normal levels of other immunoglobulins
*infections of the respiratory and GI tracts are common
*susceptible to GIARDIASIS
hyper-IgM syndrome - pathogenesis
*due to mutated CD40L on helper T cells, leading to lack of class switching
*X-linked recessive
*B AND T CELL DYSFUNCTION immunodeficiency
hyper-IgM syndrome - presentation
*severe pyogenic infections in early life
*susceptible to opportunistic infections
hyper-IgM syndrome - findings
*normal or increased IgM
*severely decreased IgG, IgA, and IgE
*absence of germinal centers on lymph node biopsy
common variable immunodeficiency - pathogenesis
defect in B-cell differentiation
common variable immunodeficiency - presentation
*low plasma cells
*low immunoglobulins
*delayed presentation (> 2 yr old)
*increased risk of autoimmune disease, infection, and lymphoma
ataxia-telangiectasia - findings
*increased AFP
*decreased IgA, IgG, and IgE
*lymphopenia
*cerebellar atrophy
*increased risk of lymphoma and leukemia
