Primary Immunodeficiencies

Question 1

DiGeorge Syndrome

Answer 1

22q11 micro deletion (detected by FISH) –> developmental failure of 3rd and 4th pharyngeal pouches –> absent thymus and parathyroids.
Presentation:
-T-cell deficiency (recurrent viral/fungal infections)
-Hypocalcemia (tetany)
-Abnormalities of heart, great vessels, face
Dec T cells, PTH, Ca2+.
Absent thymic shadow on CXR.

CATCH-22: Conotruncal cardiac abnormalities (tetralogy of fallot, etc), Abnormal facies, Thymic aplasia, Cleft palate, Hypocalcemia/hypoparathyroidism, 22 chromosome.

Question 2

Severe Combined Immunodeficiency (SCID)

Answer 2

Defective cell-mediated and humoral immunity.
Etiologies:
-Cytokine receptor defects - necessary for maturation and proliferation of B and T cells. Most common is defective IL-2R gamma chain. X-linked.
-Adenosine deaminase (ADA) deficiency - can’t excrete adenosine and deoxyadenosine and buildup is toxic to lymphocytes. Auto recessive.
-MHC class II deficiency - necessary for CD4+ helper T cell activation and cytokine production.
Susceptible to fungal, viral, bacterial, protozoal infections.
Tx: sterile isolation (bubble baby) and stem cell transplantation.
Findings: dec T-cell receptor excision circles. Absent thymic shadow, germinal centers, and T cells.

Question 3

X-linked Agammaglobulinemia

Answer 3

Complete lack immunoglobulin.
Due to disordered B-cell maturation.
Mutated Bruton tyrosine kinase (BTK).
X-linked.
Presents after 6 months (mom’s antibodies).
Bacterial, enterovirus, Giardia infections.
Absent B cells in peripheral blood, dec Ig of all classes, absent/scanty lymph nodes and tonsils.

Question 4

Common Variable Immunodeficiency (CVID)

Answer 4

Low immunoglobulin.
Due to B-cell or helper T-cell defects.
Late childhood.
Bacterial, enterovirus, Giardia infections.
^ risk autoimmune disease and lymphoma.

Question 5

IgA Deficiency

Answer 5

Low serum and mucosal IgA.
Most common immunoglobulin deficiency.
^ risk mucosal infection, esp viral.
Celiac disease associated w it.

Question 6

Hyper IgM Syndrome

Answer 6

Elevated IgM.
Due to mutated CD40L (on helper T cells) or CD40R (on B cells).
Therefore second signal can’t be delivered to helper T cells during B cell activation –> T cells don’t activate B cells –> B cells can’t produce IL4 and IL5 for class switching –> only IgM producing B cells made.
Low IgA, IgG, IgE.
Recurrent pyogenic infections (bc poor opsonization w/o those Igs), esp at mucosal sites, opportunistic infections with CMV, cryptosporidium, pneumocystis.

Question 7

Wiskott-Aldrich Syndrome

Answer 7

WATER:
WA syndrome –> Thrombocytopenia, Eczema, Recurrent infections (defective humoral and cellular immunity).
Bleeding can –> death.
Mutation in WASP gene. T cells unable to reorganize actin cytoskeleton –> problems w receptors and recognizing foreign antigen and signaling/synapse with APC.
X-linked recessive.
dec-normal IgG, IgM.
^ IgE, IgA.
Fewer and smaller platelets.
^ risk autoimmune disease and malignancy.

Question 8

C5-C9 deficiencies

Answer 8

^ risk Neisseria infection

Question 9

C1 inhibitor deficiency

Answer 9

Over-activation of complement –> hereditary angioedema - edema of skin and mucosa

Question 10

Leukocyte Adhesion Deficiency type 1 (LAD-1)

Answer 10

Defect in LFA-1 integrin (CD18) protein on phagocytes.
Impaired migration and chemotaxis.
Autosomal recessive.
Recurrent bacterial skin and mucosal infections.
No pus.
Impaired wound healing.
Delayed separation of umbilical cord.
^^^ neutrophils, but absence at infection sites (enter blood stream, but can’t leave blood vessels).

Question 11

Chronic Granulomatous Disease

Answer 11

Defect in NADPH oxidase –> dec reactive oxygen species and dec respiratory burst in neutrophils.
X-linked recessive usu.
^ susceptibility to catalase + (Cats Need PLACESS to Belch their Hairballs)
Catalase, Nocardia, Pseudomonas, Listeria, Aspergillus, Candida, E coli, Staphylococci, Serratia, B cepacia, H pylori.
Abnormal dihydrorhodamine test (dec green fluorescence).