Primary Immunodeficiency

Question 1

Top 6 antibody defiencies

Answer 1

1. Agammaglobuinemia (x-linked and AR) 2. Hyper-IgM Syndrome 3. IgA deficiency 4. Common variable immunodeficiency 5. Specific antibody deficiency 6. Transient hypogammaglobulinemia of infancy

Question 2

Agammaglobulinemias

Answer 2

Caused by defects in B-cell development. Germinal center formation in these patients is defective (underdevelopment of lymphoid tissues, lymph nodes, peyer’s patches, spleen, tonsils, adenoids)

Question 3

Enzyme associated in lyonized boys/females with agamaglobulinemias?

Answer 3

B cell tyrosine kinase

Question 4

Mode of inheritance for agammaglobulinemia?

Answer 4

85% x-linked

Question 5

Role of BTK?

Answer 5

Associated with pre-B cell receptor and is required for transducing signals downstrream=Stimulate B-cell maturation

Question 6

Characterisitics of X-linked agammaglbulinemia

Answer 6

Approximately half are due to positive family history. IgG is usually<100 mg/dl; B-cells<2% of lymphocytes (usually 0.05-0.3%), and NORMAL T-CELL FUNCTION AND NUMBER

Question 7

Hyper-IgM Syndrome characteristics

Answer 7

Defects in B-cell isotype switching. Normal numbers of B-cells, but express elevated levels of IgM with low IgG, IgE, and IgA

Question 8

Mutant proteins in Hyper-IgM syndrome

Answer 8

CD40, CD40L, IKK-gamma (NEMO), AID, UNG

Question 9

IgA Deficiency Characteristics

Answer 9

Most common primary immunodeficiency (1:500 healthy blood donors); IgA<5-7 mg/dl; Usually asymptomatic (occasionally increased sinopulmonary infections, diarrhea, autoimmune disease

Question 10

Common Variable Immunodeficiency characteristics

Answer 10

2nd most frequent PID in humans after IgA. Most prevalent PID. Recurrent infections (sinusitis most common followed by pneumonia, life threatening infections). Granulomatous disease, autoimmune disorders, splenomegaly, and certain malignancies (300x LYMPHOMA RISK), REDUCED SERUM IgG, IgA, and/or IgM, Abset or impaired specific antibody responses to previous infection or vaccination

Question 11

Specific antibody deficiency

Answer 11

Recurrent sinopulmonary infections; Normal IgG, IgA, IgM; Normal B-cell number and Normal T-cell number and function; Impaired vaccine response (polysaccharide); Impaired antibody response to natural infection with encapsulated bacteria

Question 12

Encapsulated organisms

Answer 12

Streptococcus pneumoniae and pyogenes; Staph aureus; Klebsiella; Haemophilus influenzae; Pseudomonas aeruginosa; Neisseria menigngitidis; Cryptococcus neoformans (Mycoplasma, bordetella pertussis, some e coli, streptococcus agalactiae, Yersinia Pestis (F1 envelope)

Question 13

Transient Hypogammaglublinemia of infancy

Answer 13

Recurrent sinopulmonary infections, low IgG, NORMAL SPECIFIC ANTIBODIES, normal lymphocyte number and function, delay in maturation of T-cell help for antibody production, Onset of about 6 months of age, resolve by age 4

Question 14

Types of SCID And Lymphocyte development deficiencies

Answer 14

1. Adenosine deaminase deficiency (worst case)/PNP Deficiency 2. Gamma-c? Deficiency 3. DiGeorge syndrome 4. RAG Deficiency

Question 15

Mode of inheritance Adenosine deaminase deficiency; step involved

Answer 15

autosomal; stem cell to pro-B cell AND stem cell to Pro-T-cell

Question 16

Mode of inheritance PNP Deficiency; step involved

Answer 16

autosomal; stem cell to pro-B cell AND stem cell to Pro-T-cell

Question 17

Mode of inheritance RAG deficiency; step involved

Answer 17

autosomal; Pro-B cell to Pre-B cell AND Pro-Tcell to Pre-T cell

Question 18

Mode of inheritance with gamma c deficiency; step involved with gamma c and digeorge syndrome

Answer 18

X-linked; Stem cell to pro-t cell

Question 19

Omenn syndrome characteristics

Answer 19

Hypomorphic mutations (most common in RAG genes); Low to normal number of T-cells but oligoclonal T-cell population; early onset (<3 months) of a diffuse exudative erythroderma; lymphadenopathy; hepatosplenomegaly; chronic persistent diarrhea; failure to thrive; elevated IgE and eosinophili (can be confused with normal baby eczema); “leaky SCID”

Question 20

Digeorge syndrome characteristics

Answer 20

Defect in embryogenesis 3rd and 4th pharyngeal pouches. Most have deletion of chromosome 22q11.2. Dysmorphic faces (micrognathia, low set ears), hypocalcemia (lack of parathyroids, hypoplastic to aplastic thymus, congenital heart disease (aortic defects, VSD), presents in first few days of life. Affects both males and females

Question 21

Diagnosing of digeorge syndrome

Answer 21

Diagnosed immediately by lateral chest x-ray (absence of thymic shadow)

Question 22

Partial DiGeorge Syndrome

Answer 22

More frequent; thymic hypoplasia (normal corticomedullary differentiation, presence of Hassall’s corpuscles, normal thymic function); CD4 cells>400/mm3; T-cell function adequate, B-cell numbers and function normal, usually free of infections

Question 23

Complete Digeorge Syndrome

Answer 23

Uncommon; thymic apalsia, CD4 cells<400mm3, B-cells numbers normal; antibody response decreased; susceptible to infections; susceptible to GVHD

Question 24

Wiskott Aldrich Syndrome

Answer 24

Eczema; THROMBOCYTOPENIA WITH SMALL PLATELETS (look for low MPV); immunodeficiency; Inovlved with actin polymerization

Question 25

Types of lymphocyte mitogen proliferation assays

Answer 25

Nonspecific mitogens phytohemagglutin (PHA), concanavalin (Con A), and pokeweek determined by 3H-thymidine incorporation

Question 26

Chronic granulomatous disease

Answer 26

Recurrent bacterial infection with catalase positive organisms (staph, serratia, aspergillus); pathognomic organism (chromobacterium violaceum), granulomas of skin, liver, lungs, lymph nodes, phagocytic cells ingest but do not kill bacteria due to failure to form oxygen radicals

Question 27

Gene defects in CGD

Answer 27

Gene defects interruprs electron transfer necessary to produce superoxide. GP91 phox (XL), p22 phox (AR), p47 (AR), p67 (AR)

Question 28

Diagnosing CGD

Answer 28

1 Nitroblue tetrazolium dye test, 2. superoxide radical formation (chemiluminescene test). 3. Flow cytometry (dihydorhodamine 123 assay)

Question 29

Leukocyte adhesion deficiency-1

Answer 29

Absent beta subunit (CD18) of 3 cell surface glycoproteins (CD11 family) B2 integrins, Neutrophils CANNOT MIGRATE toward inflammatory stimuli or ADHERE to vaascular endothelium

Question 30

Diagnosis of Leukocyte adhesion deficiency-1

Answer 30

Recurrent soft tissue infections, DELAYED UMBILICAL CORD SEPARATION, severe periodontal disease, No pus formation despite high white blood counts

Question 31

Hyper IgE syndrome (Job syndrome)

Answer 31

Recurrent staphylococcal abscesses, sinopulmonary infections, and severe eczema; retained primary teeth; recurrent candida; recurrent bone fractures; very elevated IgE level >2000, peripheral eosinophila

Question 32

Diagnosis of Primary Immunodeficiency

Answer 32

Birth to 3 months (phagocytic cell defects, complement defects, digeorge syndrome); 3 to 6 months (severe combined immunodicieincy SCID); 6 to 18 months (X-linked agammaglobulinemia, transient hypogam); 18 months through adulthood (common variable immunodeficiency, complement defects

Question 33

Treatment for combined immunodeficiency

Answer 33

stem cell transplant, enzyme replacement (PEG-ADA), thymic transplant for digeorge, gene therapy (ADA, XL-SCID), IVID, avoidance live viral vaccines, irradiation blood products, prophylactic antibiotics

Question 34

Defects of phagocytic cell treatment

Answer 34

Prophylactic abx, avoidance of live viral vaccines in some patients, gamam interferon in CGD, bone marrow transplant in some

Question 35

Complement immunodeficiency treatment

Answer 35

symptomatic care, frequent use of abx, immunizations with bacterial polysaccharide vaccines

Question 36

Primary immunodeficiency

Answer 36

Caused by genetic abnormality that can occur at any phase of the immune response