Immunology 6b - Immune deficiencies Flashcards
Clinical features of T cell deficiencies
Viral infecitons (CMV) Fungal infections (pneumocystis - CD4 cells needed to control PCP, cryptosporidium) Bacterial infections (Esp. intracellular e.g. M.tb, salmonella) Early malignancy
What is a functional test of B cell activation/proliferation?
Specific AB responses to known pathogens e.g. IgG to Hib, tetanus, strep
If specific AB low, vaccinate with killed vaccine and measure AB 6-8 weeks later
Mx of ADA-SCID
PEG-ADA (ENZyme replacement therapy)
BLS type II mx
replace abnormal cell populations e.g. class II deficient APCs
DiGeorge syndrome mx
Thymus transplantation in to recipient quadriceps muscle
The “Combined” component of SCID
Both B and T lymphocytes
Most common form of SCID
X-linked SCID
most severe form of SCID
Reticular dysgenesis (AK2 mutation)
Pathogenesis of X-linked SCID
Inability to respond to cytokines due to mutation of gamma chain of IL2 receptor (common gamma chain) on ChrXq13.1
Inability to respond to cytokines –> early arrest of T and NK cell development and production of immature B cells
Phenotype of X-linked SCID
V low T cells (ARrest) V low NK cells (ARrest) Normal/elevated B cells (immature, cannot make Ig) Very low Ig BOYS
ADA deficiency
AR
Deficiency in adenosine deaminase
Inability to response to cytokines - boys AND girls
Adenosine deaminase function
An enzyme needed by lymphocytes for cell metabolism
ADA deficiency phenotype
V low or absent T cells, NK cells, B cells, v low Ig
Key difference between ADA and X-linked SCID
In ADA you have V LOW OR ABSENT B CELL NUMBERS
Clinical phenotype of SCID in general
Unwell from 3 months of life as in the first 3 months of life protected by IgG from mother across placenta and colostrum
Presentatino: infectino of all types FTT Persistent diarrhoea Unusual skin disease Colonisation of infant's empty BM by maternal lymphocytes GvHD
The deletion in DiGeorge
22q11.2 deletion syndrome
Describe DiGeorge syndrome
- Mnemonic for clinical features?
- B and T cell levels?
- Does immunity change with age?
Cardiac abnormalities (Tetralogy of Fallot)
Abnormal facies (high forehead and low set ears)
Thymic aplasia
Cleft palate
Hypocalcaemia/hypoparathyroidism
22q11.2 deletion
Normal B cell levels but Low IgG and IgA
Low T cell levels
Homeostatic proliferation with age so immune function improves with age
Gene involved in DiGeorge
TBX1
hOW IS THE DELETION DETECTED IN dIgEORGE?
FISH cytogenetics analysis
V low CD4 count
Normal CD8 cell count
Low IgG, low IgA
Bare lymphocyte syndrome type II
- Due to absent MHC II gene expression so no CD4+ T cells
4 Hx features of bare lymphocyte syndrome
3 months: FTT Infections of all types FH of early infant death Prone to sclerosing cholangitis --> hepatosplenomegaly and jaundice
Features of B cell (or CD4+ T cell) deficiency
Bacterial infections (staph, strep)
Toxins e.g. tetanus, diphtheria
Some viral infections e.g. enterovirus
Ix for B cell deficiencies
Total WCC
Lymphocyte subsets
Ig and protein elevtrophoresis (IgG is a surrogate marker for CD4+T cell function)
Functional tests of B cell activation/prolferation
Management of immunodeficiency involving b cells
Prophylaxis / treatment of infection
IVIG
Immunisations only in SELECTIVE IgA DEFICIENCY OTHERWISE REDUNDANT AS CANNOT MAKE ANTIBODIES
