Defects In Activation Of T Cells

Question 1

What is common gamma chain deficiency?

Answer 1

T-B+NK-
IgM+, low everything else
X linked recessive
Defect in gene encoding gamma chain which is shared by IL-2R

Question 2

Pts with common gamma chain deficiency present with what?

Answer 2

Failure to thrive, severe thrush, opportunistic infections and chronic diarrhea

Question 3

With which deficiencies should live/viral vaccines be avoided?

Answer 3

Common gamma chain, IL-7R alpha chain, BLS II and CD3 deficiencies

Question 4

For which deficiencies is HSCT appropriate?

Answer 4

Common gamma chain, IL-7R, BLS II, CD3 complex deficiency and IPEX

Question 5

What is IL-7R alpha chain deficiency?

Answer 5

T-B+NK+
IgM+, low everything else
No costimulation from T cell to B cells
Pts present with cadidiasis, chronic diarrhea, pneu jiroveci and severe viral infections during infancy

Question 6

What is bare lymphocyte syndrome II (BLS II)?

Answer 6

Normal Ig levels
No MHC class II expression on APCs resulting in CD4 deficiency
Leads to recurrent respiratory, GI and UTIs, death in childhood

Question 7

What is MHC class I deficiency?

Answer 7

CD8 low and normal Ig levels
Caused by mutation in TAP molecules to transfer peptides to the ER
Recurrent viral infections
Symptomatic Tx, no vaccine restrictions

Question 8

What is CD3 complex deficiency?

Answer 8

T-B+NK+
IgM+, low everything else
Presents in infancy w/ lymphopenia, decreased T cell #s, failure to thrive, chronic diarrhea and opportunistic and viral infections
Specific Ab responses decreased

Question 9

What happens in pts with IPEX?

Answer 9

Self reactive effector T cells aren’t inhibited because of a mutation in FOXP3
Tx = HSCT

Question 10

What happens in pts with ALPs?

Answer 10

Defects in either Fas/FasL, caspase 8 or 10 genes results in abrogated formation of death induced signaling complex (DISC) and resistance of effector T cells to apoptosis
HSCT not recommended

Question 11

What is Wiskott-Aldrich syndrome (WAS)?

Answer 11

T-B+NK-
Low IgM, normal IgG, high IgA and IgE
X liked disorder characterized by thrombocytopenia, eczema, cellular and humoral immune deficiency, autoimmune disease and malignancy
Caused by mutations in the WAS protein (WASP)

Question 12

Describe pts with WAS

Answer 12

They develop a combined immunodeficiency with low IgM, normal IgG and high IgA and IgE, T cell lymphopenia and decreased NK cell cytotoxicity
Have recurrent bacterial infections with encapsulated bacteria, viral infections and opportunistic infections with jiroveci and candidiasis

Question 13

Pts with defects in the IFN-gamma and IL-12 axis loop present with what?

Answer 13

Selective susceptibility to intracellular pathogens such as atypical mycobacteria, candida and salmonella

Question 14

What is Th17 deficiency?

Answer 14

Susceptibility to mococutaneous candidiasis

Associated with mutations in genes encoding for IL-17, IL-17R, TF STAT 1, 3 or AIRE

Question 15

Many pts with Th17 deficiency are characterized as having what?

Answer 15

Autosomal recessive hyper IgE syndrome with severe atopic disease (atopic dermatitis, food allergies and asthma) as well as recurrent staph aureus skin abscesses

Question 16

What is NK cell deficiency (NKD)?

Answer 16

Two major types: classical and functional NKD
Presents with multiple severe or disseminated viral infections including herpesvirus infections including varicella pneumonia, cytomegalovirus (CMV) and HSV

Question 17

In order to be considered a NKD what what needs to be observed?

Answer 17

NK cells should represent the major immune abnormality

Question 18

What is classical NKD (CNKD)?

Answer 18

Defined as an absence of NK cells

Ex. GATA2 deficiency with NK cell lymphopenia

Question 19

What is functional NKD (FNKD)?

Answer 19

Defined as the presence of NK cells exhibition defective NK cell activity without NK cell lymphopenia
Ex. Perforin deficiency