Congenital defects of leukocyte number and function II

Question 1

What are the 2 examples of SCID?

Answer 1

-gamma chain deficiency
-adenosine deaminase (ADA) deficiency

Question 2

is the most common form of SCID and is caused by mutations in the IL2RG gene located at Xq13.1.

Answer 2

Gamma chain deficiency, or X-linked SCID

Question 3

Circulating T and
natural killer (NK) lymphocytes are nearly absent. B cells are
adequate in number but are dysfunctional.

Answer 3

Gamma chain deficiency, or X-linked SCID

Question 4

Adenosine deaminase is a key component of the
metabolic breakdown of

Answer 4

ATP AND RNA

Question 5

accumulation of adenosine, which is lymphotoxic, leading to
profound decreases in T, B, and NK cells.

Answer 5

ADA deficiency

Question 6

there are skeletal
abnormalities, neurologic deficits, and skin rashes.

Answer 6

ADA deficiency

Question 7

is important in cytoskeletal remodeling and nuclear transcription in hematopoietic
cells.

Answer 7

WASp

Question 8

T cells are decreased;
B cells, T cells and NK cells, neutrophils and monocytes are dysfunctional which leads to bacterial,
viral and fungal infections.

Answer 8

Wiskott-Aldrich Syndrome

Question 9

There is a risk of bleeding due to thrombocytopenia and small abnormal platelets.

Answer 9

Wiskott-Aldrich Syndrome

Question 10

IN 22Q11 syndrome the underlying genetic abnormality is a microdeletion in chromosome band 22q11.2, most likely involving ___ and occurs in approximately 1 in 3000 to 6000 births.

Answer 10

TBX1

Question 11

The 22q11 deletion is associated with a broad range of problems such as:

Answer 11

cardiac defects
palatal abnormalities
distinctive facial features, developmental delays,
psychiatric disorders,
short stature,
kidney disease,
hypocalcemia

Question 12

Risk of fungal and viral (except enterovirus) infection is low because of normal T cell function.

Answer 12

Bruton Tyrosine Kinase Deficiency

Question 13

Shortly after birth, patients suffer from recurrent infections, often affecting skin and mucosal infections. Lymphadenopathy, splenomegaly, and neutrophilia are common findings

Answer 13

LAD 1.

Question 14

The clinical severity of LAD, including number of infections and survival, depends on the amount of _____
produced

Answer 14

b2 integrins

Question 15

presents in a similar manner as LAD 1, however leukocytes have normal b2 integrins

Answer 15

LAD II

Question 16

the gene encoding the CD18 subunit of b2 integrins, resulting in either a decreased or truncated form of the b2 integrin, which is necessary for
adhesion to endothelial cells, recognition of bacteria, and outside-in signaling.

Answer 16

LAD I is caused by a mutation in ITGB2

Question 17

There are molecular defects
in LAD 2________ which codes for a fucose transporter that moves
fucose from the endoplasmic reticulum to the Golgi region.

Answer 17

SLC35C1, in LAD II

Question 18

is needed for posttranslational fucosylation of glycoconjugates, which are required for synthesis of selectin ligand

Answer 18

Fucose

Question 19

selectin synthesis is compromised

Answer 19

LAD II

Question 20

the defective fucose transporter leads to an inability to produce functional selectins and defective leukocyte recruitment, which
leads to recurring infections. Other clinical findings related to defective fucose transport are absence of blood group H antigen, growth retardation, and neurologic defect

Answer 20

LAD II

Question 21

Protein along with talin are required for activation of b integrin and leukocyte rolling

Answer 21

Kindlin-3 In LAD 3

Question 22

leukocytes and platelets have
normal expression of integrins; however, there is failure in response to external signals that normally results in leukocyte
activation.

Answer 22

LAD III

Question 23

leukocytes and platelets have
normal expression of integrins; however, there is failure in response to external signals that normally results in leukocyte
activation

Answer 23

LAD III

Question 24

patients experience a mild LAD
I-like immunodeficiency with recurrent infections. Additionally, there is decreased platelet integrin GPIIbb3 (glycoprotein
IIb/IIIa), resulting in bleeding similar to that seen in Glanzmann thrombasthenia.

Answer 24

LAD III

Question 25

is a defect in leukocyte motility. SDS is a rare autosomal recessive disease caused by mutations in the SBDS gene located at
7q11.22.

Answer 25

LAD, Shwachman-Diamond syndrome (SDS)

Question 26

This affects the ——–product which has an
important role in ribosomal maturation, cell proliferation and bone marrow microenvironment. Patients are usually diagnosed in infancy with exocrine pancreatic insufficiency associated malabsorption, malnutrition, chronic steatorrhea, and failure to thrive

Answer 26

SBDS protein

Question 27

has additional regulatory functions in the generation of other antimicrobial agents

Answer 27

NADPH

Question 28

Most cases of——are due to
mutations in gp91phox or p47.

Answer 28

Defects of Respiratory Burst OR
Chronic granulomatous disease (CGD)

Question 29

is diagnosed through a test
that uses a fluorescent probe dihydrorhodamine to measure
intracellular production of reactive oxygen species

Answer 29

CGD

Question 30

Neutrophils accumulate in the bone marrow which results in low numbers of circulating neutrophils

Answer 30

(myelokathexis)

Question 31

The retained neutrophils in the marrow exhibit degenerative, pyknotic,
morphologic changes

Answer 31

WHIM Syndrome

Question 32

IN WHIM Syndrome CXCR4 receptor
antagonist is a targeted treatment proving to be effective at increasing neutrophil and lymphocyte counts.

Answer 32

TAKE NOTE