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Flashcards in Primary Immunodeficiencies Deck (45):
1

List warning signs of primary immunodeficiency

4+ ear infections in a year
2+ sinus infections in a year
2 months of antibiotics without effect
2+ pneumonias per year
Failure to thrive
Recurrent deep abscesses
Persistent thrush or fungal infection
Need for IV antibiotics to clear infections
Two or more deep infections incl septicemia
Family history of PI

2

List signs of B cell deficiency

Recurrent sinopulmonary infections or sepsis
Infections with encapsulated organisms
Chronic enteroviral meningoencephalitis

3

What lab tests are used to work up B cell deficiencies

Ig levels
Specific antibody titers
Flow cytometry

4

What disease states present with B cell deficiencies?

X linked agammaglobulinemia
Common variable immunodeficiency
Selective IgA deficiency

5

List signs of T cell deficiency

Opportunistic infections
Recurrent and severe common infections
Failure to thrive

6

List lab tests used to work up T cell deficiencies

CBC with differential
Flow cytometry
T cell functional study
Ig levels

7

List disease states associated with T cell deficiency

DiGeorge syndrome
Wiskott Aldrich syndrome
SCID (B and T cell)
CID

8

List signs of phagocyte deficiency

Soft tissue abscess or lymphadenitis
Infection with catalase + organisms (staph, serratia, aspergillus)
Poor wound healing

9

List lab test used to work up phagocyte deficiency

CBC with differential
Neutorphil oxidative burst assay
Flow cytometry for adhesion molecules

10

List disease states associated with phagocyte deficiency

Chronic granulomatous disease
Leukocyte adhesion defecit

11

List signs of complement deficiency

Recurrent disseminated Neisseria infection
Autoimmune disease
Bacterial sepsis

12

List lab tests used to work up complement deficiency

CH50 measures entire complement cascade
AH50

13

List disease states associated with complement deficiency

Classical complement deficiency
Alternative complement defect

14

List presenting signs of innate immune defects

Septicemia
Poor inflammatory response

15

List lab tests used to work up innate immune defects

TLR signaling

16

List disease states associated with innate immune defects

IRAK 4 mutation
NEMO mutation
MyD88 mutation

17

The majority of primary immune deficiencies are due to deficiency in ______

antibodies

#2: combined cellular and antibody
#3: phagocytic
#4: cellular
#5: complement

18

Describe the rationale for SCID screening on the newborn screening panel

- many genotypes, many mutations
- diagnosis often not apparent on exam
- treatable but life threatening
- early treatment associated with better outcomes
- cost effective

19

T cell recombination in the thymus creates ______ as a byproduct. They are stable and can be detected by PCR in newly formed T cells but are diluted out as T cells undergo successive division

TRECs- TCRa rearrangement excision circles

20

Newborn screening for SCID involves quantitative PCR to determine the number of ______ present and is confirmed with ______

TRECs
Flow cytometry

21

What findings will be present on flow cytometry of a child with SCID?

Low absolute lymphocytes
Low CD3
Low CD19
Normal NK cells

22

How is SCID treated?

immune reconstitution: bone marrow transplant, gene therapy, PEG-ADA, thymic transplant

23

What is the classic triad of DiGeorge syndrome?

Conotruncal cardiac anomaly
Hypoplastic thymus
Hypocalcemia

24

Describe the pathophysiology of DiGeorge syndrome

Deletions in chromosomes 22 (or 10)

teratogens that presumably inhibit neural crest cell migration at critical times during development result in chromosomal defects. Examples: accutane, EtOH, maternal diabetes.

25

How can DiGeorge syndrome be diagnosed?

FISH

26

How can DiGeorge syndrome be treated?

Immunologic monitoring
Guidance re: live vaccines
Thymic transplantation if complete syndrome

27

_______ is the most common humoral immune deficiency but is poorly understood at the molecular level.

Common variable immunodeficiency

28

What is the main defect in CVID?

Primarily a defect in B cell differentiation or function
Also often involves autoimmunity

29

What age is most commonly affected by CVID?

Bimodal age of onset- first and third decades of life

30

Lis three diagnostic criteria for CVID

Male or female with marked decrease in IgG, IgM, IgA PLUS
1. Onset greater than 2 years of age
2 .Absence of isohemagglutinins or poor response to vaccines
3. Defined causes of hypogammaglobulinemia have been excluded

31

There is increased incidence of _____, _____, and ___ in CVID

lymphoid malignancy, autoimmune disease, atopy

32

List some autoimmune manifestations of CVID

Hematologic: autoimmune cytopenias
GI: pernicious anemia,celiac, IBD
Rheumatologic: SLE, RA, JRA, vasculitis
Endocrine: Hashimoto’s, Type 1 DM
Dermatologic: vitiligo, alopecia
Neurologic: Guillain-Barre

33

What treatments are used for CVID?

Gammaglobuline therapy
Aggressive antibiotics for bacterial infections
Immunosuppression ofr autoimmunity
BMT????

34

Wiskott Aldrich Syndrome shows ________ inheritance and typically presents with recurrent infections, thrombocytopenia, and eczema

X linked

35

What is the normal role of the Wiskott Aldrich protein

actin cytoskeleton modulation

36

Describe lab findings in WAS

Low platelets with low volume
Lymphopenia
Increased IgA, IgE and normal- low IgM and IgG

37

List treatments of WAS

- possible prophylactic antibiotics against PCP
- acyclovir to prevent HSV
- gammaglobulin replacement therapy
- curative options: HSCT, gene therapy trials underway

38

_________ is a primary immune deficiency characterized by severe immune dysregulation after EBV infection.

X linked lymphoproliferative disorder, XLP

39

Describe the clinical phenotype of XLP

fatal mononucleosis, hemophagocytic lymphohistiocytosis, lymphoma, aplastic anemia

40

What is the genetic defect in XLP?

Genetic mutation in SH2D1A gene which encodes intracellular signaling protein, SLAM associated protein. SAP is necessary for NK cell development, CD8 response to EBV

41

How is XLP treated?

Bone marrow transplant
B cell depletion early in EBV infection course

42

Chronic granulomatous disease shows _____ inheritance and involves disruption of NADPH oxidase complex formation

X linked

43

What are the clinical manifestations of chronic granulomatous disease?

Recurrent abscess, pneumonia, osteomyelitis, gingivitis, poor wound healing, colitis, GI obstruction.
Susceptibility to catalase positive organisms

44

How is chronic granulomatous disease treated

Antibacterial and antifungal prophylaxis
Interferon gamma prophylaxis
Steroid therapy for dysregulated inflammatory responses
Bone marrow transplant
Gene therapy

45

Summarize the genetics of the diseases presented in lecture

X linked: WAS, XLP, CGD
SDID: various, can be X linked, AR, mitochondrial
DiGeorge: chromosomal deletion
CVID: