BL - Immunodeficiency

Question 1

DiGeorge syndrome

Answer 1

DiGeorge syndrome: abnormality in pharyngeal pouches forming thymus (and other associated structures)

Question 2

Infections expected in pure B-cell vs pure T-cell deficiency

Answer 2

Pure B cell = high grade pathogens, extracellular, pyogenic bacteria: Staph aureus, Haemophilus influenza, Streptococcus pneumoniae
Pure T cell = intracellular pathogens: viruses, some bacteria, yeasts, fungi, Candida albicans, Pneumocystis jirovecii

Question 3

Clinical features of DiGeorge syndrome

Answer 3

CATCH-22: cardiovascular issues, abnormal facial features, thymic aplasia, cleft palate, hypocalcemia/hypoparathyroidism, chromosome 22q deletion.

Question 4

Selective IgA deficiency

Answer 4

Incidence about 1/500 people. Patients are often relatively asymptomatic other than diarrhea and sinopulmonary infections, or increased frequency and severity of allergies. 10-15x more frequent in individuals with celiac.

Question 5

Enzyme-deficient SCID

Answer 5

Missing ADA – adenosine deaminase enzyme. Autosomal recessive inheritance. Can be transfused via irradiated RBCs – must be irradiated to kill all lymphocytes so as not to cause a reaction in an immunocompromised patient. Purified ADA can be administered as a drug when stabilized with PEG.

Question 6

T- and B-cell areas in lymph node

Answer 6

B cells in lymphoid follicles (primary and secondary)

T cells in interfollicular area - paracortex

Question 7

IVIG as treatment

Answer 7

IgG pooled from many donors, usually about 99% IgG. IVIG is administered monthly and has a half life of 3 weeks. Standard treatment is an IV administration (effective but expensive and short supply), slow subcutaneous infusion (SCIG) has been approved and can be done at home.
Useful in conditions where B-cell function is deficient: ex. Bruton’s agammaglobulinemia

Question 8

Tests to determine type of immunodeficiency

Answer 8

B cells: serum protein electrophoresis, quantative Ab levels, specific Abs to prior immunizations, ABO isohemagglutinins
T cells: skin test with recall Ag panel, total lymphocyte count
Phagocytes: WBC count, differential, morphology; NBT test, oxidative burst
Complement: CH50, assay for C1 inhibitor

Question 9

Transplantation therapy

Answer 9

Fetal thymus or cultured thymic stromal cells in DiGeorge to minimize GvH. 
Bone marrow transplant has about 50% success rate in SCID – donor must match recipient at at least one MHC class I locus and one MHC class II.

Question 10

SCID

Answer 10

Abnormality of production in bone marrow. Neither pre-T nor pre-B cells are produced

Question 11

X-linked (Bruton) hypogammaglobulinemia

Answer 11

Abnormality of production in bone marrow. Pre-B cells can’t be converted into B cells because of defect in btk gene

Question 12

CVID

Answer 12

Abnormality of production in lymph node. B cells not triggered to make antibody properly

Question 13

Hyper IgM syndrome

Answer 13

Defect in class switching from IgM -> IgG. T-cells stimulate B-cells to switch but process can’t be carried out properly