Immune Deficiencies

Question 1

What are the B cell disorders?

Answer 1

X-Linked (Bruton) agammaglobulinemia, Selective IgA deficiency, Common Variable immunodeficiency

Question 2

What is the defect in X-linked agammaglobulinemia?

Answer 2

Defect in BTK, a tyrosine kinase gene (no B cell maturation). x-linked, therefore greater incidence in boys

Question 3

What is the clinical presentation of X-linked agammaglobulinemia?

Answer 3

Recurrent bacterial and enteroviral infections after 6 months (due to decreased maternal IgG)

Question 4

What are the findings in X-linked agammaglobulinemia?

Answer 4

Normal CD19+ B cell count, Decreased pro-B, decreased Ig of all classes. Absent/scanty lymph nodes and tonsils

Question 5

Selective IgA deficiency defect?

Answer 5

Unknown. most common immunodeficiency

Question 6

What is the presentation of IgA deficiency/

Answer 6

Majority Asymptomatic. Can cause Airway and Gi infections, Autoimmune disease, Atopy, Anaphylaxis to IgA containing products

Question 7

Findings in selective IgA deficiency

Answer 7

IgA

Question 8

What is the defect in common variable immunodeficiency

Answer 8

Defect in B-cell differentiation. Many causes

Question 9

What is the presentation of common variable immunodeficiency?

Answer 9

Can be acquired in 20s or 30s; increased risk of autoimmune disease, brochiectasis, lymphoma, sinopulmonary infetions. Multiple joint pain, fatigue, weight loss

Question 10

what are the findinds of common variable immunodeficiency?

Answer 10

decrease plasma cells, decrease immunoglobulins

Question 11

What are the (4) T cell disorders?

Answer 11

1) Thymic aplasia (DiGeorge syndrome) 2) IL-12 receptor deficiency 3) Autosomal dominant hyper-IgE syndrome (Job Syndrome) 4) Chronic mucocutaneous candidiasis

Question 12

Thymic aplasia (DiGeorge Syndrome) defect?

Answer 12

22q11 deletion; failure to develop 3rd and 4th pharyngeal pouches - absent thymus and parathyroids

Question 13

Thymic aplasia (DiGeorge) presentation?

Answer 13

Tetany (hypocalcemia), recurrent viral/fungal infections (T-cell deficiency), coonotruncal abnormalities (i.e. tetralogy of Fallot, truncus arteriosus)

Question 14

Thymic aplasia (DiGeorge) Findings

Answer 14

Decreased T cells, Decreased PTH, Decreased Ca++, Absent thymic shadow on CXR. 22q11 deletion by FISH.

Question 15

IL-12 receptor deficiency

Answer 15

decreased Th1 response. Autosomal recessive

Question 16

IL-12 receptor deficiency presentation

Answer 16

Disseminated mycobacterial and fungal infections; may present after administration of BCG vaccine.

Question 17

IL-12 receptor deficiency findings

Answer 17

decreased IFN-gamma

Question 18

Autosomal dominant hyper-IgE syndrome (JOB syndrome) Defect?

Answer 18

Deficiency of Th17 cells due to STAT3 mutation - impaired recruitment of neutrophils to sites of infection

Question 19

what is the clinical presentation in hyper-IgE syndrome (Job)

Answer 19

FATED: coarse Facies, cold (noninflamed) staphylococcal Abscesses, retained primary Teeth, increased IgE, dermatologic problems (eczema).

Question 20

Autosomal dominant hyper-IgE syndrome (Job Syndrome)

Answer 20

increased IgE, decreased IFN-gamma

Question 21

Chronic mucocutaneous candidiasis defect?

Answer 21

T-cell dysfunction. many causes

Question 22

presentation of chronic mucocutaneous candidiasis?

Answer 22

noninvasive candidia albican infections of skin and mucous membranes

Question 23

chronic mucocutaneous candidiasis presentation

Answer 23

absent in vitro T-cell proliferation in response to candida antigens. absent cutaneous reaction to candida antigens

Question 24

What are the B & T cell disorders?

Answer 24

SCID, Ataxia-telangiectasia, Hyper-IgM syndrome, Wiskott-Aldrich Syndrome

Question 25

What is the defect in SCID?

Answer 25

Several types including defective IL-2R gamma chain (most common, X-linked), adenosine deaminase deficiency (autosomal recessive

Question 26

What is the presentation of SCID?

Answer 26

Failure to thrive, chronic diarrhea, thrush. Recurrent viral, bacterial, fungal, and protozoal infections.

Question 27

What is the treatment of SCID?

Answer 27

Bone marrow transplant (no concern for rejection)

Question 28

What are the findings in SCID?

Answer 28

Decreased T cell receptor excision circles (TRECS). Absence of thymic shadow (CXR), germinal centers (lymph node biopsy), and T cells (flow cytometry). Absence of tonsils. absence of T and B cells.

Question 29

What is the defect in Ataxia Telangiectasia?

Answer 29

Defects in ATM gene - DNA double strand breaks - cell cycle arrest

Question 30

What is the clinical presentation in Ataxia Telangiectasia?

Answer 30

Triad: cerebellar defects (Atazia), spider Angiomas (telangiectasia), IgA deficiency

Question 31

What are the findings in Ataxia Telangiectasia?

Answer 31

Increased AFP, decreased IgA, IgG, IgE. Lymphopenia, cerebellar atrophy

Question 32

What is the defect in Hyper-IgM syndrome

Answer 32

Most commonly due to defective CD40L on Th cells = class switching defect

Question 33

What is the inheritance of Hyper-IgM syndrome?

Answer 33

X-linked recessive

Question 34

What is the presentation of Hyper-IgM syndrome?

Answer 34

Severe pyogenic infections early in life; opportunistic infection with Pneumocystis, Cryptosporidium, CMV

Question 35

What are the findings of Hyper-IgM syndrome?

Answer 35

Increased IgM. Decreased IgG, IgA, IgE

Question 36

What is the defect in Wiskott-Aldrix Syndrome?

Answer 36

Mutation in WAS gene (X-linked recessive); T cells unable to reorganize actin cytoskeleton.

Question 37

What is the presentation of Wiskott-Aldrich Syndrome?

Answer 37

WATER: Wiskott-Aldrich: Thrombocytopenia purpura, Eczema, Recurrent infections. Increased Risk of autoimmune disease and malignancy

Question 38

What are the findings in Wiskott-Aldrich Syndrome?

Answer 38

Decreased to normal IgG, IgM. Increased IgE, IgA. Fewer and smaller platelets

Question 39

What are the immune diseases with phagocyte dysfunction?

Answer 39

Leukocyte adhesion deficiency (type I), Chediak-Higashi syndrome, Chronic granulomatous disease

Question 40

What defect is seen in Leukocyte adhesion deficiency (type I)?

Answer 40

Defect in LFA-1 integrin (CD18) protein on phagocytes; impaired migration and chemotaxis; autosomal recessive

Question 41

What is the presentation of Leukocyte adhesion deficiency?

Answer 41

Recurrent bacterial skin and mucosal infections, absent pus formation, impaired wound healing, delayed umbilical cord seperation (

Question 42

What are the findings in leukocyte adhesion deficiency?

Answer 42

1) increased neutrophils 2) absent of neutrophils at infection sites

Question 43

What is the defect in Chediak Higashi syndrome?

Answer 43

Defect in lysosomal trafficking regulator gene (LYST). Microtubule dysfunction in phagosome-lysosome fusion

Question 44

What is the presentation in Chediak Higashi syndrome?

Answer 44

Recurrent pyogenic infection by staph and strep, partial albinism, peripheral neuropathy, progressive neurodegeneration, infiltrative lymphohistiocytosis.

Question 45

What are the findings in Chediak Higashi syndrome?

Answer 45

giant granules in neutrophils and platelets. Pancytopenia. Mild coagulation defects.

Question 46

What is the defect in Chronic Granulomatoux Disease?

Answer 46

Defect in NADPH oxidase which leads to decrease in ROS (superoxide) and absent respiratory burst in neutrophils

Question 47

What is the inheritance of Chronic Granulomatoux disease?

Answer 47

X-Linked Recessive

Question 48

What is the inheritance of Chediak Higashi Syndrome?

Answer 48

Autosomal Recessive

Question 49

What is the presentation of CGD?

Answer 49

Increased susceptibility to catalase + organisms (PLACESS): Pseudomonas, Listeria, Aspergillus, Candida, E. Coli, S. Aures. Serratia

Question 50

What are the findings in CGD?

Answer 50

Abnormal dihydrorhodamine (flow cytometry) test. Nitroblue tetrazolium dye reduction test is negative (test out of favor).