Immuno - Immune Responses (Immune deficiencies)

Question 1

Name 3 immune deficiencies that are classified as B-cell disorders.

Answer 1

(1) X-linked (Bruton) agammaglobulinemia (2) Selective IgA deficiency (3) Common variable immunodeficiency

Question 2

What is another name for X-linked agammaglobulinemia? What is the defect in it? What is its mode of inheritance?

Answer 2

X-linked (Bruton) agammaglobulinemia; Defect in BTK, a tyrosine kinase gene –> no B cell maturation. X-linked recessive (increased in Boys); Think: “B’s: BTK, no B cell maturation, increased in Boys”

Question 3

What is the presentation of X-linked (Bruton) agammaglobulinemia?

Answer 3

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

Question 4

What are the lab values associated with X-linked (Bruton) agammaglobulinemia? What is the histological finding associated with X-linked (Bruton) agammaglobulinemia?

Answer 4

Absent CD19+ B cells, decreased pro-B, decreased Ig of all classes; Absent/Scanty lymph nodes and tonsils

Question 5

What is the most common primary immunodeficiency?

Answer 5

Selective IgA deficiency

Question 6

What is the defect in selective IgA deficiency?

Answer 6

Unknown

Question 7

What is the presentation of selective IgA deficiency?

Answer 7

Majority Asymptomatic. Can see Airway and GI infections, Autoimmune disease, Atopy, Anaphylaxis to IgA-containing products

Question 8

What are the lab findings associated with Selective IgA deficiency?

Answer 8

IgA < 7 mg/dL with normal IgG, IgM levels

Question 9

What is the defect in common variable immunodeficiency?

Answer 9

Defect in B-cell differentiation. Many causes.

Question 10

In what age group can common variable immunodeficiency present? What are 4 conditions for which these patients are at an increased risk?

Answer 10

Can be acquired in 20s-30s; Increased risk of autoimmune disease, bronchiectasis, lymphoma, sinopulmonary infections

Question 11

What are the lab findings associated with common variable immunodeficiency?

Answer 11

Decreased plasma cells, Decreased immunoglobulins

Question 12

Name 4 immune deficiencies classified as T-cell disorders.

Answer 12

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

Question 13

What is the another name for thymic aplasia? What are the genetic and phenotypic defects in this deficiency?

Answer 13

Thymic aplasia (DiGeorge syndrome); 22q11 deletion; Failure to develop 3rd and 4th pharyngeal pouches –> absent thymus and parathyroids

Question 14

What are 3 parts of the presentation of thymic aplasia (DiGeorge syndrome)?

Answer 14

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

Question 15

What are the lab findings associated with Thymic aplasia (DiGeorge syndrome)? What is found on imaging? What is found on FISH?

Answer 15

Decreased T cells, PTH, and Ca2+; Absent thymic shadow on CXR; 22q11 deletion detected by FISH

Question 16

What is the defect in IL-12 receptor deficiency? What is the mode of inheritance of this deficiency?

Answer 16

Decreased Th1 response; Autosomal recessive

Question 17

What is the presentation of IL-12 receptor deficiency? In what context may a patient present with this disorder?

Answer 17

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

Question 18

What is a lab finding associated with IL-12 receptor deficiency?

Answer 18

Decreased IFN-gamma

Question 19

What is another name for Autosomal dominant hyper-IgE syndrome? What are the genotypic and phenotypic effects associated with this syndrome?

Answer 19

Autosomal dominant hyper-IgE syndrome (Job syndrome); Deficiency of Th17 cells due to STAT3 mutation –> impaired recruitment of neutrophils to sites of infection

Question 20

What is the presentation of Autosomal dominant hyper-IgE syndrome (Job syndrome)?

Answer 20

FATED: coarse Facies, cold (noninflamed) staphylococcal Abscesses, retained primary Teeth, high IgE, Dermatologic problems (eczema)

Question 21

What are lab findings associated with Autosomal dominant hyper-IgE syndrome (Job syndrome)?

Answer 21

Increased IgE, decreased IFN-gamma

Question 22

What is the defect in chronic mucocutaneous candidiasis?

Answer 22

T-cell dysfunction. Many causes.

Question 23

What is the presentation of chronic mucocutaneous candidiasis?

Answer 23

Noninvasive Candida albicans infections of skin and mucous membranes

Question 24

What are lab findings associated with chronic mucocutaneous candidiasis?

Answer 24

Absent in vitro T cell proliferation in response to Candida antigens. Absent cutaneous reaction to Candidia antigens.

Question 25

Name 4 immune deficiencies that can be classified as B- and T- cell disorders.

Answer 25

(1) Severe combined immunodeficiency (SCID) (2) Ataxia-telangiectasia (3) Hyper-IgM syndrome (4) Wiskott-Aldrich syndrome

Question 26

What is the most common defect leading to severe combined immunodeficiency (SCID)? What is another example of a defect leading to SCID? What is the mode of inheritance for both of these defects?

Answer 26

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

Question 27

What is the presentation of SCID?

Answer 27

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

Question 28

What is the treatment for SCID?

Answer 28

Treatment: bone marrow transplant (no concern for rejection)

Question 29

What are histology, lab, and imaging findings associated with SCID?

Answer 29

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

Question 30

What are the genotypic and phenotypic defects associated with ataxia-telangiectasia?

Answer 30

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

Question 31

What is the presentation of ataxia-telangiectasia?

Answer 31

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

Question 32

What are lab/histology findings associated with ataxia-telangiectasia?

Answer 32

Increased AFP. Decreased IgA, IgG, and IgE. Lymphopenia, cerebellar atrophy.

Question 33

What is the most common defect causing Hyper-IgM syndrome? What is its mode of inheritance?

Answer 33

Most commonly due to defective CD40L on Th cells = class switching defects; X-linked recessive

Question 34

What is the presentation of Hyper-IgM syndrome? What are 3 opportunistic infections that target these patients?

Answer 34

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

Question 35

What are the lab findings associated with Hyper-IgM syndrome?

Answer 35

Increased IgM, Very Decreased IgG, IgA, IgE

Question 36

What is the defect in Wiskott-Aldrich syndrome? What is the mode of inheritance?

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, Thrombocytopenic purpura, Eczema, Recurrent infections

Question 38

For what 2 conditions do Wiskott-Aldrich patients have increased risk?

Answer 38

Increased risk of autoimmune disease and malignancy

Question 39

What are the lab findings associated with Wiskott-Aldrich syndrome?

Answer 39

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

Question 40

What are 3 immune deficiencies that are classified as phagocyte dysfunction?

Answer 40

(1) Leukocyte adhesion deficiency (type I) (2) Chediak-Higashi syndrome (3) Chronic granulomatous disease

Question 41

What is the defect in Leukocyte adhesion deficiency (type 1)? What is its mode of inheritance?

Answer 41

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

Question 42

What are 3 components of the presentation of Leukocyte adhesion deficiency (type 1)?

Answer 42

(1) Recurrent bacterial skin and mucosal infections, absent pus formation, (2) impaired wound healing, (3) delayed separation of umbilical cord (>30 days)

Question 43

What are the labs associated with leukocyte adhesion deficiency (type 1)?

Answer 43

Increased neutrophils. Absence of neutrophils at infection sights.

Question 44

What is the defect in Chediak-Higashi syndrome? What is its mode of inheritance?

Answer 44

Defect in lysosomal trafficking regulator gene (LYST); Microtubule dysfunction in phagosome-lysosome fusion; autosomal recessive

Question 45

What are 5 components of the presentation of Chediak-Higashi syndrome?

Answer 45

(1) Recurrent pyogenic infections by staphylococci and streptococci, (2) partial albinism, (3) peripheral neuropathy, (4) progressive neurodegeneration, (5) infiltrative lymphohistiocytosis

Question 46

What are lab/hematological findings associated with Chediak-Higashi syndrome?

Answer 46

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

Question 47

What is the defect in Chronic granulomatous disease? What is its mode of inheritance?

Answer 47

Defect of NADPH oxidase --> decreased reactive oxygen species (e.g., superoxide) and absent respiratory burst in neutrophils; X-linked recessive

Question 48

What is the presentation of Chronic granulomatous disease?

Answer 48

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

Question 49

What lab findings are associated with Chronic granulomatous disease?

Answer 49

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