Immunodeficiencies

Question 1

immunodeficiencies of phagocyte dysfunction

Answer 1

*leukocyte adhesion deficiency
*Chediak-Hagashi syndrome
*chronic granulomatous disease

Question 2

immunodeficiencies of B-cell dysfunction

Answer 2

*X-linked agammaglobulinemia (Btk deficiency)
*selective IgA deficiency
*common variable immunodeficiency

Question 3

immunodeficiencies of T-cell dysfunction

Answer 3

*thymic aplasia (diGeorge syndrome)
*IL-12 receptor deficiency
*Job syndrome
*chronic mucocutaneous candidiasis

Question 4

immunodeficiencies of B- AND T-cell dysfunction

Answer 4

*severe combined immunodeficiency (SCID)
*ataxia-telangectasia
*hyper IgM syndrome
*Wiskott-Aldrich syndrome

Question 5

leukocyte adhesion deficiency - pathogenesis

Answer 5

*defect in LFA-1 integrin (CD18) on phagocytes
autosomal recessive
**leads to impaired migration and chemotaxis
*PHAGOCYTE DYSFUNCTION immunodeficiency

Question 6

leukocyte adhesion deficiency - presentation

Answer 6

*recurrent skin and mucosal bacterial infections
*NO PUS formation
*impaired wound healing
*delayed detachment of umbilical cord

Question 7

leukocyte adhesion deficiency - findings

Answer 7

*increased neutrophils in BLOOD (lack of neutrophil migration)
*ABSENT NEUTROPHILS AT INFECTION SITES

Question 8

Chediak-Hagashi syndrome - pathogenesis

Answer 8

*autosomal recessive defect in LYST (lysosomal trafficking regulator gene)
*MICROTUBULE DYSFUNCTION in phagosome-lysosome fustion
*PHAGOCYTE DYSFUNCTION immunodeficiency

Question 9

Chediak-Hagashi syndrome - findings

Answer 9

*GIANT GRANULES in platelets and PMNs
*pancytopenia
*mild coagulation defects

Question 10

Chediak-Hagashi syndrome - presentation

Answer 10

*recurrent staph and strep infections
*partial albinism
*peripheral neuropathy
*progressive neurodegeneration

Question 11

IL-12 receptor deficiency - pathogenesis

Answer 11

*autosomal recessive deficiency in IL-12 receptor, leading to LACK OF Th1 CELL RESPONSE
*T-CELL DYSFUNCTION immunodeficiency

Question 12

IL-12 receptor deficiency - presentation

Answer 12

*recurrent, disseminated MYCOBACTERIAL and fungal infections

Question 13

IL-12 receptor deficiency - findings

Answer 13

low levels of IFN-gamma

Question 14

Job syndrome - pathogenesis

Answer 14

*aka autosomal dominant hyper-IgE syndrome
*Th17 deficiency - leads to an impaired ability to recruit neutrophils to a site of infection

Question 15

Job syndrome - presentation

Answer 15

FATED:
*coarse facies
*staph abscesses
*retained primary teeth
*hyper-IgE
*dermatologic issues (ex. eczema)

Question 16

Job syndrome - findings

Answer 16

*elevated IgE and eosinophils
*decreased IFN-gamma

Question 17

chronic mucocutaneous candidiasis - pathogenesis

Answer 17

*T-cell dysfunction (multiple causes, though often due to a defect in the IL-17 pathway)

Question 18

chronic mucocutaneous candidiasis - presentation

Answer 18

*noninvasive candida infections of the skin and mucous membranes

Question 19

chronic mucocutaneous candidiasis - findings

Answer 19

*absent in vitro or cutaneous response to candida infections

Question 20

severe combined immunodeficiency (SCID) - pathogenesis

Answer 20

*defective IL-2 receptor (X-linked)
OR
*defective adenosine deaminase (ADA) [autosomal recessive]
*B AND T CELL DYSFUNCTION immunodeficiency

Question 21

severe combined immunodeficiency (SCID) - presentation

Answer 21

***failure to thrive, chronic diarrhea
*thrush, recurrent viral, fungal, bacterial, and protozoal infections

Question 22

severe combined immunodeficiency (SCID) - findings

Answer 22

*absent thymic shadow
*absent germinal centers
*scanty lymph nodes
*absent T cells

Question 23

severe combined immunodeficiency (SCID) - treatment

Answer 23

*BONE MARROW TRANSPLANT IS CURATIVE
*avoid live vaccines
*give prophylactic antibiotics
*environmental sterilization (bubble boy)

Question 24

ataxia-telangiectasia - pathogenesis

Answer 24

*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

Question 25

ataxia-telangiectasia - findings

Answer 25

*increased AFP *decreased IgA, IgG, and IgE *lymphopenia *cerebellar atrophy *increased risk of lymphoma and leukemia

Question 25

ataxia-telangiectasia - presentation

Answer 25

CLASSIC TRIAD = 1) ataxia (cerebellar defects) 2) angiomas (telangiectasias) 3) IgA deficiency

Question 26

Wiskott-Aldrich syndrome - pathogenesis

Answer 26

*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

Question 27

Wiskott-Aldrich syndrome - results in higher risk of?

Answer 27

autoimmune disease and malignancy

Question 28

Wiskott-Aldrich syndrome - presentation

Answer 28

WATER: *thrombocytopenia *eczema *recurrent pyogenic infections

Question 29

Wiskott-Aldrich syndrome - findings

Answer 29

*elevated IgE and IgA *fewer and smaller platelets on blood smear

Question 30

thymic aplasia (diGeorge syndrome) - pathogenesis

Answer 30

22q11 deletion *leads to failure to develop the 3rd and 4th pharyngeal pouches *results in an absent thymus and parathyroids *T CELL DYSFUNCTION immunodeficiency

Question 31

thymic aplasia (diGeorge syndrome) - findings

Answer 31

**LOW Ca2+ *decreased T cells *low PTH *ABSENT THYMIC SHADOW on CXR

Question 32

thymic aplasia (diGeorge syndrome) - presentation

Answer 32

CATCH-22: *cleft palate *abnormal facies *thymic aplasia *conotruncal abnormalities *hypocalcemia *22q11 deletion

Question 33

chronic granulomatous disease (CGD) - pathogenesis

Answer 33

*autosomal or X-linked mutation causing DEFECTIVE NADPH OXIDASE *leads to failure to generate oxygen radicals for respiratory burst in neutrophils *PHAGOCYTE DYSFUNCTION immunodeficiency

Question 34

chronic granulomatous disease (CGD) - presentation

Answer 34

heightened susceptibility to infection during the first year of life (pneumonia and abscesses of the skin) *especially to CATALASE POSITIVE organisms

Question 35

chronic granulomatous disease (CGD) - findings

Answer 35

*neutrophils and macrophages fail to reduce NBT when a respiratory burst stimulus is applied *altered flow cytometry results

Question 36

X-linked (Bruton's) agammaglobulinemia - pathogenesis

Answer 36

*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

Question 37

X-linked (Bruton's) agammaglobulinemia - presentation

Answer 37

*recurrent bacterial and enteroviral infections AFTER 6 MONTHS OF AGE note - presents after 6 months because of decreased IgG from breastfeeding

Question 38

X-linked (Bruton's) agammaglobulinemia - findings

Answer 38

*absent B cells in peripheral blood *decreases in ALL immunoglobulin isotypes *absent/scanty lymph nodes and tonsils

Question 39

selective IgA deficiency - presentation

Answer 39

*many patients are asymptomatic *can present with airway and GI infections, atopy, autoimmune disease, and anaphylaxis to IgA-containing products *B CELL DYSFUNCTION immunodeficiency

Question 40

selective IgA deficiency - findings

Answer 40

*low levels of IgA but normal levels of other immunoglobulins *infections of the respiratory and GI tracts are common *susceptible to GIARDIASIS

Question 41

hyper-IgM syndrome - pathogenesis

Answer 41

*due to mutated CD40L on helper T cells, leading to lack of class switching *X-linked recessive *B AND T CELL DYSFUNCTION immunodeficiency

Question 42

hyper-IgM syndrome - presentation

Answer 42

*severe pyogenic infections in early life *susceptible to opportunistic infections

Question 43

hyper-IgM syndrome - findings

Answer 43

*normal or increased IgM *severely decreased IgG, IgA, and IgE *absence of germinal centers on lymph node biopsy

Question 44

common variable immunodeficiency - pathogenesis

Answer 44

defect in B-cell differentiation

Question 45

common variable immunodeficiency - presentation

Answer 45

*low plasma cells *low immunoglobulins *delayed presentation (> 2 yr old) *increased risk of autoimmune disease, infection, and lymphoma