B3.060 Prework 2 Immune Deficiency Examples

Question 1

X-linked (Bruton) agammaglobulinemia defect

Answer 1

defect in MTK, a tyrosine kinase gene which prevents maturation of B cells
X linked recessive

Question 2

X-linked (Bruton) agammaglobulinemia presentation

Answer 2

recurrent bacterial and enteroviral infections after 6 months

Question 3

X-linked (Bruton) agammaglobulinemia findings

Answer 3

no B cells in peripheral blood
all Ig classes reduced/absent
absent or scanty lymph nodes and tonsils

Question 4

IPEX

Answer 4

immune dysregulation, polyendocrinopathy, enteropathy, x-linked

Question 5

IPEX defect

Answer 5

mutations in FOXP3 gene required for regulatory T cell development

Question 6

IPEX presentation

Answer 6

chronic, life threatening diarrhea due to autoimmune enteropathy, neonatal type 1 diabetes, eczema, severe food allergies

Question 7

IPEX findings

Answer 7

normal T and B cell numbers
normal response to mitogen and antigen stimulation
Th2 skewing
Higher IgE, high IgA (normal M and G)
elevated glucose

Question 8

hyper IgM syndrome defect

Answer 8

most commonly dye to defective CD40L on T helper cells leading to a class switching defect
X linked recessive

Question 9

hyper IgM syndrome presentation

Answer 9

severe pyogenic infections early in life

opportunistic infections

Question 10

hyper IgM syndrome findings

Answer 10

high IgM, low IgG, A, E

Question 11

WAS defect

Answer 11

mutations in the WAS gene
X linked recessive
T cells unable to reorganize cytoskeleton

Question 12

WAS presentation

Answer 12

thrombocytopenia with small platelets, eczema, recurrent bacterial and viral infections
increased risk of autoimmune disease and malignancy

Question 13

WAS findings

Answer 13

low to normal IgG, IgM

high IgE, IgA

Question 14

autosomal dominant hyper IgE syndrome (Job syndrome) defect

Answer 14

deficiency in Th17 cells due to STAT3 mutation leading to impaired neutrophil recruitment to sites of infection

Question 15

autosomal dominant hyper IgE syndrome (Job syndrome) presentation

Answer 15

coarse facies, non-inflamed staph abscesses, retained primary teeth, increased IgE, eczema, no food allergies

Question 16

autosomal dominant hyper IgE syndrome (Job syndrome) findings

Answer 16

high IgE, low IFNy, low TNFa, low CD8+ memory cells
peripheral eosinophilia
normal platelets

Question 17

IL12 receptor beta 1 deficiency defect

Answer 17

mutation in the IL12RB1 gene leading to a premature stop codon in the sequence coding for the extracellular domain of receptor
prevents receptor expression on the cell surface and therefore prevents IL12 signaling

Question 18

IL12 receptor beta 1 deficiency presentation

Answer 18

disseminated salmonella and nontuberculous mycobacterial infection or disseminated BCG infection following inoculation with the vaccine

Question 19

IL12 receptor beta 1 deficiency findings

Answer 19

normal T and NK cell numbers with impaired IFNy secretion

Question 20

X linked severe combined immunodeficiency (SCID) defect

Answer 20

due to mutations in the common gamma chain aka IL2RG gene

receptor utilized by many different cytokines

Question 21

SCID presentation

Answer 21

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

Question 22

SCID findings

Answer 22

decreased T cell receptor excision circles (TRECs), absence of thymic shadow, germinal centers, and T cells

Question 23

Omenn syndrome defect

Answer 23

RAG1 RAG2 mutations

Question 24

Omenn syndrome presentation

Answer 24

erythroderma, desquamation, alopecia, chronic diarrhea, failure to thrive, lymphadenopathy, eosinophilia, hepatosplenomegaly

Question 25

Omenn syndrome findings

Answer 25

elevated IgE, low IgG,A,M
limited to no T and B cells
if present, non functional
NK cells normal