Immune Deficiencies

Question 1

Bruton’s Agammaglobulinemia

Answer 1

Inheritance: X-linked recessive
Defect: in BTK (a tyrosine kinase)
S/S: Recurrent bacT infections after 6 months due to oponsization defect
Labs: Normal pro-B, decreased Maturation, decreased #B-cells, decrease in all immunoglobulins

Question 2

Hyper-IgM Syndrome

Answer 2

Defect: CD40L on helper T-cells leads to an inability to class switch
S/S: severe pyogenic infections early in life
Labs: increased IgM, decrease IgG/A/E

Question 3

Selective Ig Deficiency

Answer 3

Defect: isotype switching - usually in a specific class (IgA most common)
S/S: sinus, lung infection, milk allergies, and diarrhea - anaphylaxis on exposure to blood products with IgA
Labs: failure to mature into plasma cells, decreased secretory IgA

Question 4

Common variable immunodeficiency (CVID)

Answer 4

Defect: in B-cell maturation (many causes)
S/S: increased risk AI disease, lymphoma, sinopulmonary infections
Labs: normal number of B-cells, decreased plasma cells, decreased immunoglobulin

Question 5

Thymic aplasia (DiGeorge syndrome)

Answer 5

Defect: 22q11 deletion; failure to develop 3rd and 4th pharyngeal pouches
S/S: tetany (hypocalcemia), recurrent viral/fungal infections (t-cell deficiency), congenital heart and great vessel defects
Labs: decreased t-cells, decreased PTH and calcium; absent thymic shadow on CXR

Question 6

IL-12 receptor deficiency

Answer 6

Defect: decreased TH1 response
S/S: disseminated mycobacterial infection
Labs: decreased IFN-gamma

Question 7

Hyper-IgE syndrome (Job’s syndrome)

Answer 7

Defect: TH cells fail to produce IFN-gamma leading to an inability of neutrophils to response to chemotactic stimuli
S/S: “FATED” - course FACIES, cold staph ABSCESSES, retained primary TEETH, increase IGEEEE, DERM problems (eczema)
Labs: increased IgE

Question 8

Chronic mucocutaneous candidiasis

Answer 8

Defect: T-cell dysfunction

S/S: candida albicans infections of skin and mucous membranes

Question 9

Severe combined immunodeficiency (SCID)

Answer 9

Defects (multiple): 1 - defective IL-2 receptor (most common/X-linked); 2 - adenosince deaminase deficiency; 3 - failure to synthesize MHC II antigens
S/S: recurrent viral bacterial, fungal and protozoal infections due to both B/T-cell deficiencies
Labs: if decrease IL-2 then decrease T-cell activation; increased adenosine is toxic to B and T cells; absence of thymic shadow, germinal centers (lymph node bx) and B cells (on peripheral blood smear)
TX: bone marrow transplant (no allograft rejection)

Question 10

Ataxia-telangiectasia

Answer 10

Defect: in the ATM gene (which codes for DNA repair enzymes)
S/S: (triad) - cerebellar defects (ataxia), spider angiomas (telangiectasia), IgA deficiency
Labs: IgA deficiency

Question 11

Wiskott-Aldrich syndrome

Answer 11

Defect: progressive deletion of B and T cells (X-linked recessive)
S/S: ‘TIE’ triad - thrombocytopenic purpura, infections and eczema
Labs: increased IgE/A and decreased IgM

Question 12

Leukocyte adhesion deficiency (type 1)

Answer 12

Defect: in LFA-1 integrin (CD18) protein on phagocytes
S/S: recurrent bacT infections, absent pus formation, delayed separation of umbilical cord
Labs: neutrophilia

Question 13

Chediak-Higashi Syndrome

Answer 13

Defect: in lysosomal regulator trafficking (LYST) - microtubule dysfunction in phagosome-lysosome fusion (autosomal recessive)
S/S: recurrent pyogenic infections by staph and strep; partial ALBINISM; peripheral neuropathy

Question 14

Chronic granulomatous disease

Answer 14

Defect: lack of NADPH oxidase leads to decrease in reactive oxygen species (i.e. superoxide) and absent respiratory burst in neutrophils
S/S: increased susceptibility to catalase positive organisms (i.e. staph aureus, ecoli, aspergillus)
Labs: negative nitroblue tetrazolium dye reduction test