Immunodeficiencies

Question 1

primary immunodeficiency

Answer 1

genetic or developmental disorders manifesting early in infancy or early childhood

Question 2

secondary immunodeficiency

Answer 2

more common than primary; acquired, as result of some other disease process (protein-calorie malnutrition, irradiation, chemotherapy, bone cancer, immunosuppressive drugs, splenectomy, infections)

Question 3

Protein-Calorie malnutrition

Answer 3

most common cause of immunodeficiency worldwide; lack of nutrients prevents immune system maturation, changes response from Th1 to Th2

Question 4

Cyclosporin

Answer 4

calcineurin inhibitor; binds cyclophilin and prevents IL-2 transcription; side effects include nephrotoxicity, hypertension, gingival hyperplasia

Question 5

Tacrolimus (FK506)

Answer 5

calcineurin inhibitor; binds FK506 binding protein and prevents IL-2 transcription; similar side effects as cyclosporin except no gingival hyperplasia and hirsutism

Question 6

Glucocorticoids

Answer 6

inhibit NF-kB and suppresses both B and T cell function by decreasing transcription of many cytokines

Question 7

X-linked agammaglobulinemia

Answer 7

humoral deficiency; defect in BTK (B cell tyrosine kinase) which is expressed in all stages of B cell differentiation and is required for maturation) -> only pre-B cells in BM, no B cells in the periphery, T cells normal

Question 8

Hyper-IgM syndrome

Answer 8

humoral deficiency; defect in CD40L gene on T cells (X-linked recessive) or CD40 on B cells/APC; no memory B cells or class switching -> elevated levels of IgM, low levels of IgG, IgA, IgE

Question 9

Selective Ig deficiencies

Answer 9

humoral deficiency; unknown cause, IgA deficiency most common primary immunodeficiency; majority asymptomatic and if not condition usually is not severe, can see airway and GI infections, autoimmune disease, atopy, anaphylaxis to IgA-containing products; low IgA levels but all other Ig’s normal

Question 10

Common variable immunodeficiency

Answer 10

humoral deficiency; many causes (TACI mutation) but there is a defect at stage where B cells become plasma cells -> low #s of plasma cells and reduced serums levels of IgG, IgA, and IgM

Question 11

Severe Combined immunodeficiency disease (SCID)

Answer 11

cellular deficiency; most common causes is defective IL-2R gamma chain (X-linked) and adensoine deaminase (autosomal recessive) -> lack of thymus, low T cell # and function, failure to thrive, recurrent infections, absence germinal centers

Question 12

ZAP-70 deficiency

Answer 12

SCID-like deficiency; ZAP-70 binds ITAMs during TCR signaling -> normal levels of Ig and CD4+ lymphocytes but their CD4+ T cells are nonfunctional

Question 13

Bare lymphocyte syndrome

Answer 13

SCID-like deficiency; defects in MHC expression; MHC I -> TAP mutations; MHC II -> impairment of MHC gene transcription

Question 14

Wiskott-Aldrich syndrome

Answer 14

cellular deficiency; mutation in WAS gene (X-linked recessive) where T cells are unable to reorganize actin cytoskeleton; WATER (Wiskott, Aldrich, TTP, Eczema, Recurrent infections)

Question 15

DiGeorge syndrome

Answer 15

cellular deficiency; 22q11 deletion with a failure to develop 3rd and 4th pharyngeal pouches -> absent thymus and parathyroids -> few T cells, low PTH, low serum Ca, tetany, recurrent viral/ fungal infections (but not bacterial -> T-cell deficiency), facial abnormalities

Question 16

Chronic granulomatous disease (CGD)

Answer 16

phagocytic disorder; X-linked (70%), AR (30%); defect of NADPH oxidase, can not convert O2 to superoxdie, decreasing respiratory burst of neutrophils -> NBT is negative, susceptible to catalase positive bacteria (in catalase negative, cells use H2O2 from bacteria to make HOCl -> kills; but in catalase positive H2O2 gets converted to water and O2)

Question 17

Nitroblue tetrazolium test (NBT)

Answer 17

Used to screen for CGD; NBT dye turns blue if NADPH oxidase can convert O2 to superoxide; remains colorless if NADPH is defective

Question 18

Chediak-Higashi syndrome

Answer 18

phagocytic disorder; autosomal recessive; defect in lysosomal trafficking regulator gene (LYST) causing microtubule dysfunction so phagosome and lysosome can not fuse -> giant granules and platelets, pancytopenia, partial albinism, peripheral neuropathy, defective primary hemostasis, recurrent pyogenic infections

Question 19

Classical pathway deficiency (C1, C2, C4)

Answer 19

immune complex disease

Question 20

MBL pathway deficiency (MBL, MASP1, MASP2, C2, C4)

Answer 20

bacterial infections, mainly in childhood

Question 21

Alternative pathway deficiency (Factor D, Factor P)

Answer 21

infection with pyogenic bacteria and Neisseria spp. but no immune-complex disease

Question 22

C3b deposition deficiency

Answer 22

infection with pyogenic bacteria and Neisseria spp. with sometimes immune-complex disease

Question 23

Membrane attack component deficiency (C5, C6, C7, C8, C9)

Answer 23

infection with Neiseeria spp.

Question 24

Hereditary angioneurotic edema

Answer 24

complement disorder; low levels or improper function of C1 inhibitor -> swelling of face and airways, abdominal cramping

Question 25

IL-12 receptor deficiency

Answer 25

T cell deficiency; autosomal recessive, decreased Th1 response, decreased IFN-g; disseminated Mycobacterial and fungal infections, may present after administration of BCG vaccine

Question 26

Autosomal dominant hyper-IgE syndrome (Job syndrome)

Answer 26

T cell deficiency; deficiency of Th17 cells due to STAT3 mutation -> impaired recruitment of neutrophils to sites of infection; FATED (coarse Facies, cold (non-inflammed) staphylococcal Abcesses, retained primary Teeth, increase IgE, Dermatologic problems (eczema)); increased IgE, decreased IFN-g

Question 27

Chronic mucocutaneous candidiasis

Answer 27

T cell deficiency; many causes resulting in T cell dysfunction; characterized by noninvasive Candida albicans infections of skin and mucous membranes

Question 28

Ataxia-telangiectasia

Answer 28

Defects in ATM gene -> failure to repair DNA double strand breaks -> cell cycle arrest; Triad: cerebellar defects (Ataxia), spider Angiomas (telangiectasia), IgA deficiency; lymphopenia, cerebellar atropy, increased AFP, increased IgA, IgM, IgE

Question 29

Leukocyte adhesion deficiency (type I)

Answer 29

phagocytic disorder; autosomal recessive, defect in LFA-1 integrin (CD18) protein on phagocytes -> impaired migration and chemotaxis; delayed separation of umbilical cord, increased circulating neutrophils, recurrent bacterial infections that lack pus

Question 30

Myeloperoxidase (MPO) deficiency

Answer 30

results in defective conversion of H2O2 to HOCl-; increased risk of Candida infections however most patients are asymptomatic; NBT test is normal