Immunology 6b - Immune deficiencies

Question 1

Clinical features of T cell deficiencies

Answer 1

Viral infecitons (CMV)
Fungal infections (pneumocystis - CD4 cells needed to control PCP, cryptosporidium)
Bacterial infections (Esp. intracellular e.g. M.tb, salmonella)
Early malignancy

Question 2

What is a functional test of B cell activation/proliferation?

Answer 2

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

Question 3

Mx of ADA-SCID

Answer 3

PEG-ADA (ENZyme replacement therapy)

Question 4

BLS type II mx

Answer 4

replace abnormal cell populations e.g. class II deficient APCs

Question 5

DiGeorge syndrome mx

Answer 5

Thymus transplantation in to recipient quadriceps muscle

Question 6

The “Combined” component of SCID

Answer 6

Both B and T lymphocytes

Question 7

Most common form of SCID

Answer 7

X-linked SCID

Question 8

most severe form of SCID

Answer 8

Reticular dysgenesis (AK2 mutation)

Question 9

Pathogenesis of X-linked SCID

Answer 9

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

Question 10

Phenotype of X-linked SCID

Answer 10

V low T cells (ARrest)
V low NK cells (ARrest)
Normal/elevated B cells (immature, cannot make Ig)
Very low Ig
BOYS

Question 11

ADA deficiency

Answer 11

AR
Deficiency in adenosine deaminase
Inability to response to cytokines - boys AND girls

Question 12

Adenosine deaminase function

Answer 12

An enzyme needed by lymphocytes for cell metabolism

Question 13

ADA deficiency phenotype

Answer 13

V low or absent T cells, NK cells, B cells, v low Ig

Question 14

Key difference between ADA and X-linked SCID

Answer 14

In ADA you have V LOW OR ABSENT B CELL NUMBERS

Question 15

Clinical phenotype of SCID in general

Answer 15

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

Question 16

The deletion in DiGeorge

Answer 16

22q11.2 deletion syndrome

Question 17

Describe DiGeorge syndrome

• Mnemonic for clinical features?
• B and T cell levels?
• Does immunity change with age?

Answer 17

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

Question 18

Gene involved in DiGeorge

Answer 18

TBX1

Question 19

hOW IS THE DELETION DETECTED IN dIgEORGE?

Answer 19

FISH cytogenetics analysis

Question 20

V low CD4 count
Normal CD8 cell count
Low IgG, low IgA

Answer 20

Bare lymphocyte syndrome type II

• Due to absent MHC II gene expression so no CD4+ T cells

Question 21

4 Hx features of bare lymphocyte syndrome

Answer 21

3 months:
FTT
Infections of all types
FH of early infant death 
Prone to sclerosing cholangitis --> hepatosplenomegaly and jaundice

Question 22

Features of B cell (or CD4+ T cell) deficiency

Answer 22

Bacterial infections (staph, strep)
Toxins e.g. tetanus, diphtheria
Some viral infections e.g. enterovirus

Question 23

Ix for B cell deficiencies

Answer 23

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

Question 24

Management of immunodeficiency involving b cells

Answer 24

Prophylaxis / treatment of infection
IVIG
Immunisations only in SELECTIVE IgA DEFICIENCY OTHERWISE REDUNDANT AS CANNOT MAKE ANTIBODIES

Question 25

Most severe B-cell deficiency? Aetiology? Ix results? Presentation?

Answer 25

Bruton’s X-linked hypogammaglobulinaemia
Due to BTK gene defect
Arrest of B-cell maturation
- Low B cells and ALL Igs
Recurrent infection in childhood, bacterial, enterovirus, absence of lymphoid tissue (Adenoids, tonsils)

Question 26

B-cell deficiency where class switch is affected?
Aetiology?
Presentation - any specific pathogens?

Answer 26

X-linked recessive Hyper-IgM syndrome
Defect in CD40L gene (ChrXq26) is mutated on T HELPER CELLS
B cells are not activated to class switch
Boys presenti n first few years of life:
recurrent bacterial infections esp PCP
also autoimmunity and malignancy esp NHL

Question 27

Phenotype in HyperIgM

Answer 27

Normal B cells
Normal T cells
No germinal centre development within LNs
IgM high
IgG,IgA, IgE undetectable

Question 28

Heterogenous group of disorders where disease mechanism is unknown
Low IgG, IgA and IgG

Answer 28

Common variable immune deficiency

Question 29

3 main clinical features of common variable immune deficiency w egs

Answer 29

1. V severe recurrent bacterial infections (w end organ damage)- bronchiectasis, sinusitis, GI infection
2. Autoimmune disease e.g. atypical SLE
3. Granulomatous disease

Question 30

Results on electrophoresis in Bruton’s

Answer 30

No signal for gamma

Question 31

Adult with bronchiectasis, recurrent sinusitis and development of atypical SLE - which B-cell deficiency?

Answer 31

Common variable immune deficiency - combination of infection and autoimmunity

Question 32

Recurrent respiratory tract infections, absent IgA, normal IgM and IgG

Answer 32

Selective IgA deficiency

Question 33

Specific management of IgA deficiency

Answer 33

Immunisation