Term
What type of immunodeficiency is "DiGeorge" and how does it present?
How would you treat? |
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Definition
T cell deficiency (22Q11.2 deletions)
1) Conotruncal defect due to neural crest development (3rd and 4th pharyngeal pouch) leading to aplasia/HYPOPLASIA of thymus.
Cardiac- interrupted aortic arch, TOF, VSD
Thymus- low/absent T cells
Parathyroid- Hypocalcemia (early)
Facial Dsymorphia
Low T-cell mitogen response
2) Thymic transplant and Calcium supplementation, as well as prophylactic antibiotics. |
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Term
A patient is severely deficient in CD8 T cells, suffering from chronic upper respiratory diseases (no opportunistic infections).
What is going on? |
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Definition
Probably Bare Lymphocyte Syndrome 1 "The TAP problem"
1) Lack of MHC1 expression in TAP1, TAP2 or tapasin genes in thymus, leading to lack of intrathymic CD8 T cell maturation. |
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Term
| A patient presents with mild SCID and defective CD4+ T-cell maturation. Whats going on? |
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Definition
Could be Bare Lymphocyte Syndrome II
Defect in t-factors important for MHC-II expression, meaning no T cell presentation and no CD4+ maturation. |
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Term
| How are Severe Combined Immunodeficiency classified? |
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Definition
Cell counts
1) T-B+NK+ (IL-7R, CD3)
2) T-B+NK- (JAK3, IL-2R- common gamma chain)
50% of SCID is X-linked due to y-chain defects.
3) T-B-NK+
RAG1, RAG2, artemia, Cernunnos (B and T cell rearrangement)
4) T-B-NK-
ADA, Reticular dysgenesis, PNP
Purine salvage pathway defects leading to lymphocytotoxic accumulation of adenosine and deoxyadenosene in metabolites, which inhibit DNA synthesis and repair. |
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Term
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Definition
No eyebrows and Skin issues
RAG1/2, ARTEMIS, IL-7R defect
SCID phenotype with erythroderma, lymphadenopathy, hepatosplenomegaly, eosinophelia and high IgE
Oligoclonal T cells (makes WBC count look normal) |
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Term
| What is Wiskott-Aldrich Disease? |
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Definition
X-linked defect in WASP gene (actin cytoskeleton) leads to TCR signaling issues and T:B cell interaction issues
Petechia (thrombocytopenia)
Eczema (starts in infancy)
Sinopulmonary and opportunistic infections
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Term
A patient presents with abnormal gait, progressive cerebellar ataxia (early), Oculocutaneous telangiectasia (late) and Radiation Sensitivity. You notice elevated serum AFP as well.
What is going on? |
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Definition
Ataxia-Telangiectasia Combined Immunodeficiency
DNA-repair defect (ATM) |
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Term
| What is the cause of X-linked SCID? |
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Definition
50% of SCID cases are X-linked
Mutations in y-subunit of Cytokine Receptor (shared by IL-2, IL-4, IL-7, IL-9 and IL-15).
Problems with BOTH B and T cell maturation from pro- forms |
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Term
| What is the cause of autosomal SCID? |
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Definition
Adenosine deaminase (ADA) mutations, which prevents ADA from breaking down purines.
Build-up of toxic purine metabolites blocks T cell maturation more than B cell maturation
Can also involve RAG1 or RAG2 (BCR and TCR gene recombination), as well as signal associated with y-chain of cytokine receptor |
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Term
| How can you distinguish between bare lymphocyte syndrome 2 and SCID? |
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Definition
| BOTH involve defective T-cells, but SCID how NO normal cells, while BLS2 has some normal T cells. |
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Term
| What is the most common form of SCID? |
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Definition
All have missing/dysplastic thymus
T-B+NK- (gamma common chain) accounts for 50%
the y-chain is common to IL-2, IL-9, IL-15 and IL-7
In this case, IL-2 is important for T-cells and IL-15 for NK cells. |
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Term
| Which SCID form is associated with IL-2-alpha mutations and CD3 mutations? |
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Definition
Both are associated with T-cells specifically.
So T-B+NK+. Impacts T-cell proliferation |
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Term
| Which SCID form is associated with RAG1, RAG2, Artemis and Cernunnos mutations? |
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Definition
These are involved in BCR and TCR rearrangement (somatic recombination), so T-B-NK+
RAGs cleave and Artemis/Cernunnos repairs |
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Term
| Which SCID form is associated with ADA and PNP? |
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Definition
ADA is important for purine salvage metabolism. Without it, you can't synthesize DNA, and uou can make any lymphocytes!
T-B-NK- (skeletal findings, hearing loss, behavioral issues) |
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Term
| Why might you measure TRECS? |
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Definition
| To check for SCID. If T cell receptor excision circles (during TCR rearrangement) are not present, it means that T-cell counts are low and probably indicates SCID. |
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Term
| In what combined immunodeficiency might you see normal WBC counts? |
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Definition
| Omenn Syndrome, because of Oligoclonal T cells. |
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Term
| A patient presents with petichiae, bloody poo and eczema. What might they have? |
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Definition
| Wiskott-Aldrich (x-linked WASP defect that affects T:B cell interaction and TCR signaling) |
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Term
| What unique feature can you look for to diagnose Ataxia-Telangiectasia? |
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Definition
high AFP!
Also, gait issues, red stripes on the eyes (telangiectasia of the eyes and radiation sensitivity). |
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