First Aid, Chapter 8, Immunologic Disorders, SCID Flashcards by Geeta Bhargave | Brainscape

Q

What is the lymphocyte phenotype in X-linked SCID caused by the mutation in the γc chain?

A

T–B+NK–

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Q

Which type of SCID can most easily be missed by newborn TRECs (Tcell receptor excision circles) screening?

A

ADA deficiency

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Q

What is the most common form of SCID? Who is most often diagnosed?

A

X-linked SCID (γc chain defect) and, therefore, most cases will be diagnosed in male infants.

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Q

What type of SCIDs experience the following infections/clinical findings: FTT, rash, chronic diarrhea, GVHD (maternal T lymphocytes), and absent lymphoid tissue; Opportunistic and live vaccine infections?

A

X-linked SCID (yc chain), AR SCID (JAK-d deficiency, IL-7Ra (CD127), IL-2Ra (CD25), CD45, CD3δεζ, RAG 1/2

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Q

What are the infections/clinical findings in X-linked SCID (yc chain)?

A

FTT, rash, chronic diarrhea, GVHD (maternal T lymphocytes), and absent lymphoid tissue; Opportunistic and live vaccine infections

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Q

What are the infections/clinical findings in JAK-3 deficiency?

A

FTT, rash, chronic diarrhea, GVHD (maternal T lymphocytes), and absent lymphoid tissue; Opportunistic and live vaccine infections

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Q

What are the infections/clinical findings in IL-7Rα (CD127)?

A

FTT, rash, chronic diarrhea, GVHD (maternal T lymphocytes), and absent lymphoid tissue; Opportunistic and live vaccine infections

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Q

What are the infections/clinical findings in IL-2Rα (CD25)?

A

FTT, rash, chronic diarrhea, GVHD (maternal T lymphocytes), and absent lymphoid tissue; Opportunistic and live vaccine infections

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Q

What are the infections/clinical findings in CD45?

A

FTT, rash, chronic diarrhea, GVHD (maternal T lymphocytes), and absent lymphoid tissue; Opportunistic and live vaccine infections

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Q

What are the infections/clinical findings in CD3δεζ?

A

FTT, rash, chronic diarrhea, GVHD (maternal T lymphocytes), and absent lymphoid tissue; Opportunistic and live vaccine infections

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Q

What are the infections/clinical findings in RAG1/2?

A

FTT, rash, chronic diarrhea, GVHD (maternal T lymphocytes), and absent lymphoid tissue; Opportunistic and live vaccine infections

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Q

Why do JAK-3 deficiency and yc chain SCID have the same phenotype?

A

JAK-3 is a signaling protein of γc chain, therefore both have the same phenotype

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Q

What cytokine signalling defects is yc chain SCID involved in?

A

γc chain involves in IL-2, 4, 7, 9, 15, 21 receptor signaling

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Q

Why is IL-7Ra SCID B+N+?

A

IL-7Rα is specific for only T-cell development

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Q

Why are CD45 and CD3δεζ SCID B+NK+?

A

CD45 tyrosine phosphatase and CD3 subunits involve in only TCR signaling, therefore B+ NK+

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Q

Why are RAG 1/2 SCID NK+?

A

RAG1/2 involves in VDR rearrangement of T- and B-cell Ag receptor formation, therefore NK+.

(Proteins are unique to immune cells, no radiation sensitivity)

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Q

What gene is defective in yc x-linked SCID? What is the lymphocyte phenotype?

A

IL-2RG

T-B+NK-

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Q

What gene is defective in JAK-3 deficiency SCID? What is the lymphocyte phenotype?

A

Gene: JAK-3

Lymphocyte phenotype: T-B+NK-

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Q

What gene is defective in IL-7Ra(CD127) SCID? What is the lymphocyte phenotype?

A

Gene: IL-7Ra

Lymphocyte phenotype: T-B+NK+

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Q

What gene is defective in IL-2Ra(CD25) SCID? What is the lymphocyte phenotype?

A

Gene: IL-2Ra

Lymphocyte phenotype: T-B+NK+

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Q

What gene is defective in CD45 SCID? What is the lymphocyte phenotype?

A

Gene: CD45

Lymphocyte phenotype: T-B+NK+

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Q

What gene is defective in CD3δεζ SCID? What is the lymphocyte phenotype?

A

Gene: CD3δεζ

Lymphocyte phenotype: T-B+NK+

Q

What gene is defective in RAG 1/2 SCID? What is the lymphocyte phenotype?

A

Gene: RAG 1/2

Lymphocyte phenotype: T-B-NK+

Q

What is the inheritance of Omenn’s syndrome? What are the infections/clinical manifestations?

A

Autosomal Recessive

Infections/Clinical findings:
rythroderma, increased lymphoid tissues, alopecia, recurrent infections, eosinophilia, high IgE

Q

What are the defects in Omenn’s syndrome?

A

Hypomorphic defects in RAG1/2. Also IL-7RA, ADA, Artemis, RNA component of RNAse mitochondrial RNA, and leaky phenotype

Q

What is the gene that is defective in Omenn’s syndrome?

A

Gene: RAG 1/2

Q

What is the lymphocyte phenotype of Omenn’s syndrome?

A

B-NK+

T lymphocytes in Omenn’s are oligoclonal, CD45RO+, and TREC–.

Q

What are the clinical findings and infections in ADA deficiency SCID?

A

Skeletal abnormalities: “rachitic rosary” ribcage and abnormal iliac bone, deafness

Q

What is the lymphocyte phenotype in ADA deficiency SCID?

A

T-B-NK-

Q

What is the defect in ADA deficiency SCID?

A

Premature lymphoid progenitor cell death from accumulating toxic metabolites, therefore all negative phenotypes.

(Defective nucleotide salvage pathway) (Defective purine nucleotide metabolism) (Defective hematopoietic energy metabolism)

Q

What are the clinical findings and infections in PNP deficiency SCID?

A

Lymphoreticular disease and autoimmune disease

Q

What is the lymphocyte phenotype in PNP deficiency SCID?

A

T-B+NK+/-

Q

What are the clinical findings and infections in reticular dysgenesis SCID?

A

Severe neutropenia and sensorineural deafness

Q

What is the lymphocyte phenotype in reticular dysgenesis SCID?

A

T-B-NK-

Q

What kinds of infections/clinical findings occur in artemis SCID?

A

Diarrhea and candidiasis Athebascan-speaking Navajo/Apache

Q

What is the defect in artemis SCID?

A

Recombinase DNA repair protein defect

- Defective receptor formation

Q

What is the gene involved in artemis SCID?

A

artemis

Q

What is the lymphocyte phenotype in artemis SCID?

A

T-B-NK+

Q

What are the radiosensitive SCIDs?

A

Artemis, Cernunnon, Ligase IV, Nijimegen breakage syndrome

Q

What are the infections/clinical findings in cernunnos SCID?

A

Developmental delay, growth failure, and bird-like facies

Microcephaly

Q

What is the defect in cernunnos SCID?

A

Recombinase DNA repair protein defect Hypogammaglobulinemia

Q

What is the gene that is defective in Cernunnos SCID?

A

Cernunnos

Q

What is the lymphocyte phenotype in cernunnos SCID?

A

T-B-NK+

Q

What are the infections/clinical findings in ligase IV SCID?

A

Developmental delay, FTT, Bird-like facies Microcephaly, photosensitivity Pancytopenia and malignancy

Q

What is the defect in ligase IV SCID?

A

Recombinase DNA repair protein defect
Pancytopenia
↓CD4/CD8

Q

What is the gene that is defective in ligase IV SCID?

A

Ligase IV

Q

What is the lymphocyte phenotype of ligase IV SCID?

A

T-B-NK+

Q

What are the infections/clinical findings in Nijimegen breakage syndrome?

A

Microcephaly, recurrent infections, bird-like facies, developmental delay, lymphoma, short stature, clinodactyly,syndactyly, and radiatiosensitive

Q

What is the defect in Nijimegen breakage syndrome?

A

Class switching recombination defect ↓CD4/CD8
↓proliferation
Can have hypogammaglobulinemia and IgA deficiency.
Elevated IgM
Defect in specific antibody response
Absence of Hassel’s corpuscles on thymic biopsy

Q

What is the gene in Nijimegen breakage syndrome?

A

NBS1 (substrate for ATM)

Q

What is the lymphocyte phenotype in Nijimegen breakage syndrome SCID?

A

T-B-NK+

Q

What is the treatment of SCID?

A

Preventing infections with intravenous immunoglobulin (IVIG), prophylactic antibiotics (sulfamethoxazole/trimethoprim), antifungals, withholding live immunizations, and isolation in the sterile environment
Improving nutritional status
Hematopoietic stem cell transplantation
Gene therapy
Enzyme replacement; pegdemase bovine ADA (ADA-PEG)
Avoid breast feeding
CMV negative, irradiated blood products

Q

What conditions cause CD8 lymphopenia? CD4 lymphopenia?

A

CD 8 lymphopenia can be caused by MHC class I deficiency (TAP1/2 deficiencies, tapasin deficiency) and ZAP70 deficiency (lack of blood CD8 lymphocyte).
CD4 lymphopenia can be caused by bare lymphocyte syndrome (MHC class II deficiency), LCK deficiency, and HIV infection.