Congenital defects of leukocyte number and function II Flashcards
What are the 2 examples of SCID?
-gamma chain deficiency
-adenosine deaminase (ADA) deficiency
is the most common form of SCID and is caused by mutations in the IL2RG gene located at Xq13.1.
Gamma chain deficiency, or X-linked SCID
Circulating T and
natural killer (NK) lymphocytes are nearly absent. B cells are
adequate in number but are dysfunctional.
Gamma chain deficiency, or X-linked SCID
Adenosine deaminase is a key component of the
metabolic breakdown of
ATP AND RNA
accumulation of adenosine, which is lymphotoxic, leading to
profound decreases in T, B, and NK cells.
ADA deficiency
there are skeletal
abnormalities, neurologic deficits, and skin rashes.
ADA deficiency
is important in cytoskeletal remodeling and nuclear transcription in hematopoietic
cells.
WASp
T cells are decreased;
B cells, T cells and NK cells, neutrophils and monocytes are dysfunctional which leads to bacterial,
viral and fungal infections.
Wiskott-Aldrich Syndrome
There is a risk of bleeding due to thrombocytopenia and small abnormal platelets.
Wiskott-Aldrich Syndrome
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.
TBX1
The 22q11 deletion is associated with a broad range of problems such as:
cardiac defects
palatal abnormalities
distinctive facial features, developmental delays,
psychiatric disorders,
short stature,
kidney disease,
hypocalcemia
Risk of fungal and viral (except enterovirus) infection is low because of normal T cell function.
Bruton Tyrosine Kinase Deficiency
Shortly after birth, patients suffer from recurrent infections, often affecting skin and mucosal infections. Lymphadenopathy, splenomegaly, and neutrophilia are common findings
LAD 1.
The clinical severity of LAD, including number of infections and survival, depends on the amount of _____
produced
b2 integrins
presents in a similar manner as LAD 1, however leukocytes have normal b2 integrins
LAD II
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.
LAD I is caused by a mutation in ITGB2
There are molecular defects
in LAD 2________ which codes for a fucose transporter that moves
fucose from the endoplasmic reticulum to the Golgi region.
SLC35C1, in LAD II
is needed for posttranslational fucosylation of glycoconjugates, which are required for synthesis of selectin ligand
Fucose
selectin synthesis is compromised
LAD II
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
LAD II
Protein along with talin are required for activation of b integrin and leukocyte rolling
Kindlin-3 In LAD 3
leukocytes and platelets have
normal expression of integrins; however, there is failure in response to external signals that normally results in leukocyte
activation.
LAD III
leukocytes and platelets have
normal expression of integrins; however, there is failure in response to external signals that normally results in leukocyte
activation
LAD III
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.
LAD III
is a defect in leukocyte motility. SDS is a rare autosomal recessive disease caused by mutations in the SBDS gene located at
7q11.22.
LAD, Shwachman-Diamond syndrome (SDS)
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
SBDS protein
has additional regulatory functions in the generation of other antimicrobial agents
NADPH
Most cases of——are due to
mutations in gp91phox or p47.
Defects of Respiratory Burst OR
Chronic granulomatous disease (CGD)
is diagnosed through a test
that uses a fluorescent probe dihydrorhodamine to measure
intracellular production of reactive oxygen species
CGD
Neutrophils accumulate in the bone marrow which results in low numbers of circulating neutrophils
(myelokathexis)
The retained neutrophils in the marrow exhibit degenerative, pyknotic,
morphologic changes
WHIM Syndrome
IN WHIM Syndrome CXCR4 receptor
antagonist is a targeted treatment proving to be effective at increasing neutrophil and lymphocyte counts.
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