Immuno 2: Disease and Lab Diagnosis

which category of PID refers to predominantly antibody deficiencies?

3

which category of PID refers to purine-nucleoside-phosphorylase (PNP) deficiency?

1

which category of PID refers to combined immunodeficiencies with associated or syndromic features?

2

what condition has the following characteristics:

• rare autosomal recessive trait

• presents in infancy (pulmonary infections, UTI)

• affects an enzymes involved in the metabolism of purines

• moderate to severe defect in CMI with normal or only mildly impaired HMI

PNP deficiency 

what condition refers to a progressive decline in T cell number due to accumulation of toxic dGTP?

PNP deficiency 

what condition may be confused with neonatal HIV and needs to be differentiated using specific tests?

PNP deficiency 

what category has the following characteristics:

• nonimmunologic features in addition to the combined immunodeficiency 

• affect CMI (T cells) and indirectly other branches of immune response

• increased risk of GVHD

2

what category includes the following:

• wiskott aldrich syndrome (WAS)

• 22q11.2 deletion syndrome (DiGeorge syndrome)

• ataxia-telangiectasia (AT)

2

what condition refers to a rare X-linked recessive syndrome that is defined by the triad of

• immunodeficiency

• eczema

• thrombocytopenia

WAS

what condition is often fatal in childhood because of infection, hemorhage, or malignancy?

WAS

what condition has the following lab picture

• thrombocytopenia, prolonged BT (PFA-100), very low isohemagglutinins (especially IgM diagnostic), increased serum AFP (diagnostic)

• shortened half-life of PLTs, T lymphs affected, B lymphs appear to function normally

WAS

B lymphocytes appear to function normally in WAS. true or false?

true

a mutation in the ____ gene which encodes WASp required for actin polymerization in hematopoietic cells.

WAS

a mutation in the ____ gene results in defective signal transduction in lymphocytes and platelets.

WAS

in WAS, abnormal integral membrane protein _____ is due to the mutated WAS gene on the X chromosome.

CD43

the following characteristics are associated with ____:

• thrombocytopenia = increased bleeding time

• small PLTs

• infections

• eczema

• absence of isohemagglutinins

• autoimmunity and/or malignancies

WAS

the following characteristics are associated with ____:

• autosomal dominant 

• deleted genes affect thymus development in embryo

• deletion of q11.2 on chromosome 22

DiGeorge syndrome

if there is partial 22q11.2 deletion, there is near normal immune function. true or false? 

true

around 20% of children with 22q11.2 deletion syndrome have severe ____ deficiency.

T cell

what condition is associated with the following:

• severe, recurrent viral and fungal infections

• tetany due to hypocalcemia resulting from hypoparathyroidism

DiGeorge syndrome

what condition is associated with the following: 

• a complex, autosomal recessive syndrome 

• combined defect of humoral and cellular immunity

ataxia telangiectasia 

what condition is characterized by involuntary muscle movements and capillary swelling that results in red blotches on the skin?

ataxia telangiectasia 

what term refers to involuntary muscle movements?

cerebellar ataxia

what term refers to capillary swelling that results in red blotches on the skin?

telangiectasia 

ataxia telangiectasia will have a(n) increased/decreased serum alpha-fetoprotein (AFP) level (pick one).

increased

ataxia telangiectasia will have a defect in the ____ gene on chromosome 11, region 22.

ATM

what gene is required for recombination process for genes in the immunoglobulin superfamily?

ATM

in ataxia telangiectasia, the ____ gene abnormality results in a defective kinase involved in DNA repair and cell cycle control (high risk of developing lymphoid malignancies).

ATM

what term refers to a loss of motor control?

ataxia

what term refers to spider veins?

telangiectasia

what condition is associated with the following:

• neurodegenerative, inherited disease

• causes tumor formation

• impairs cerebellum

• prevents repair of broken DNA

ataxia telangiectasia 

what condition is associated with the following:

• nystagmus (rapid involuntary eye movement)

• ocular telangiectasia 

ataxia telangiectasia 

which category of PID refers to diseases of immune dysregulation?

4

which category of PID includes many diseases with normal numbers of T or B cells but with reduced control over their functions?

4

many diseases of category 4 have features of autoimmunity. true or false?

true

what category 4 condition refers to mutations in genes controlling apoptosis in the thymus that may lead to autoreactive cells in circulation?

autoimmune lymphoproliferative syndrome

what category 4 condition refers to a lack of T regulatory (Treg) cells that may lead to lymphoproliferation and autoimmunity?

CD25 deficiency; mutation of FOXP3 gene

what category 4 condition refers to a mutation in the LYST gene and is characterized by a reduced number of NK cells and neutrophils as well as an increased production of inflammatory proteins?

chediak higashi 

which category of PID refers to congenital defects of phagocyte number, function, or both?

5

what category 5 condition is associated with the following:

• group of disorders that involve abnormality in neutrophil microbicidal function

• 70% cases x-lnked (more severe)

• symptoms

  • recurrent suppurative infections

  • pneumonia

  • osteomyelitis

  • draining adenopathy

  • liver abscess

  • dermatitis

  • hypergammaglobulinemia

• infections usually begin before 1 year of age and the syndrome is often fatal in childhood

CGD

what category 5 condition refers to when phagocytic cells ingest but do not kill bacteria due to failure to form oxygen radicals (no NADPH oxidative)?

CGD

what category 5 condition typically has catalase positive organisms (e.g., staphylococcus aureus) and fungi (aspergillus and nocardia)?

CGD

in CGD, infections usually begin before 1 year of age, but the syndrome is often treatable in childhood. true or false?

false

mutations in any of these 5 components of NADPH oxidase for are associated with which condition?

• p22 phox

• p40 phox

• p47 phox

• p67 phox

• gp91 phox

CGD

for CGD lab diagnosis by flow cytometry using dihydrorhodamine (DHR), DHR will allow DHR to fluoresce when it is ____.

reduced 

for CGD lab diagnosis by flow cytometry using dihydrorhodamine (DHR), what cells are activated using phorbol myristate acetate (PMA)?

neutrophils

phorbol myristate acetate (PMA) is mitogenic for what cells?

neutrophils

neutrophils from CGD patients are unable to undergo oxidative burst and will show less fluorescence than normal neutrophils when performing flow cytometry using dihydrorhodamine (DHR). true or false?

true

for CGD diagnosis, what test measures the ability of a patient’s neutrophils to reduce the yellow dye nitroblue tetrazolium to a deep blue produce (formazan) precipitated in neutrophils that could be detected microscopically in a PBS?

NBT dye test

for a nitroblue tetrazolium (NBT) dye test for CGD, what term refers to the deep blue produce created based on the ability of a patient’s neutrophils to reduce the yellow dye?

formazan

this is an image of the results of 2 different patient samples that underwent the NBT dye test. which one is of the normal patient (no CGD)?

1

this is an image of the results of 2 different patient samples that underwent the NBT dye test. which one is of the patient with CGD?

2

what condition refers to an absent beta subunit (CD18) on neutrophils for 3 cell surface integrin complexes on neutrophils?

leukocyte adhesion deficiency

what gene defect on chromosome location 21q22.3 encodes CD18 is associated with leukocyte adhesion deficiency?

ITGB2

what refers to a common protein that forms part of the β2 integrins needed for white blood cells to adhere to blood vessel walls?

CD18

in leukocyte adhesion deficiency, without CD18, there is ineffective adhesion. true or false?

true

in leukocyte adhesion deficiency, CD11a/CD18 are beta2 integrins found on what cells?

T cells

in leukocyte adhesion deficiency, CD11b/CD18 and CD11c/CD18 are beta2 integrins found on what cells?

PMNs/Mono

in leukocyte adhesion deficiency, what cells cannot migrate toward inflammatory stimuli or adhere to vascular endothelium?

neutrophils

what diagnosis is suggested by these features:

• recurrent soft tissue infections, periodontal

• delayed wound healing

• delayed umbilical cord separation 

• no pus formation despite high WBC counts

leukocyte adhesion deficiency

what category of PIDs refer to complement deficiencies?

8

what category of PIDs are associated with early complement components deficiency associated with recurrent pyogenic infection and also connective tissue disease (especially C2 and C4)?

8

for category 8, complement deficiency of components 5 through 8 are associated with recurrent ____ species infection.

neisseria

for category 8, deficiency of the complement regulatory protein _____ is associated with angioedema (hereditary angioedema).

C1 esterase inhibitor 

which group of category 8 PIDs refers to immune complex disease?

I

which group of category 8 PIDs refers to angioedema?

II

which group of category 8 PIDs refers to recurrent pyogenic infections?

III

which group of category 8 PIDs refers to recurrent neisseria infections?

IV

which group of category 8 PIDs refers to asymptomatic?

V

which group of category 8 PIDs is associated with the following deficiencies:

• C1q

• C1s, or C1r + C1s

• C2

• C4

I

which group of category 8 PIDs is associated with the following deficiencies:

• C1 inhibitor

II

which group of category 8 PIDs is associated with the following deficiencies:

• C3

• factor H

• factor I

III

which group of category 8 PIDs is associated with the following deficiencies:

• C5

• C6

• C7

• C8

• properdin 

• factor D

IV

which group of category 8 PIDs is associated with the following deficiencies:

• C9

V

when performing diagnostic testing for immunodeficiency, it is important for laboratorians to compare the results for a patient with appropriate age-matched controls. true or false?

true

in tests of cellular function, the patient’s cells need to be tested in parallel with cells from a abnormal control. true or false?

false

when an abnormal test result is obtained with evaluation immune dysfunction, it should be confirmed by repeat testing. true or false?

true

____ with small PLTs can be detected in WAS. 

thrombocytopenia

by the age of ____, an individual should have naturally-occurring IgM antibodies against ABO blood group antigens.

2

the absence of IgM antibodies against ABO blood group antigens suggest an abnormal IgG response. true or false?

false

an overall assessment of ____ immunity can be made by measuring antibody responses to antigens to which the population is exposed normally or following vaccination.

antibody-mediated

which IgG subclass(es) normally respond to protein antigens, such as those found in tetanus and diphtheria vaccines?

IgG1; IgG3

which IgG subclass(es) normally responds to polysaccharide antigens such as those in the H. influenzae and S. pneumoniae vaccines?

IgG2

screening for complement deficiencies usually begins with a ____ assay, which determines functional complement level in an individual.

CH50

undetectable ____ levels may indicate a deficiency in a specific component of the classical pathway of complement (but could also indicate consumption of C components).

CH50

what is the best confirmatory test when evaluating immune dysfunction?

flow cytometry

in flow cytometry, what cell type refers to CD19+?

B cells

in flow cytometry, what cell type refers to CD3+?

T cells

in flow cytometry, what cell type refers to CD3+/CD4+?

t helper cells

in flow cytometry, what cell type refers to CD3+/CD8+?

cytotoxic t cells

in flow cytometry, what cell type refers to CD16+ or CD56+?

NK cells

an absence of or profound decrease in the number of CD3+ cells would be consistent with _____.

digeorge syndrome

an absence of CD19+ B cells suggests _____.

Btk deficiency

_____ function can be measured by assessing the ability of isolated T cells to proliferate in response to an antigenic stimulus or to T-cell mitogens in culture, such as phytohemagglutinin (PHA) or Concanavalin A (Con A). 

t cells

what refers to a substance that stimulated mitosis in all T cells or all B cells, regardless of antigen specificity?

mitogen

for QuantiFERON-TB assays and T-SPOT assays, IFNy is secreted by activated ____ and is quantitated by either an enzyme-linked immunosorbent assay (ELISA) or ELISPOT procedure.

Th1 cells

all states in the U.S. include PID testing as part of their newborn screening programs. true or false?

true

TCR excision circles (TRECs) in newborn blood for PID testing is identified by quantitative ____.

PCR

____ are present in T cells that have undergone alpha-beta receptor gene rearrangements.

TRECs

what refers to genetic material that has been removed from the germline DNA during alpha V-J and beta V-D-J recombination?

TRECs