Primary immune deficiencies

Question 1

Associated with recurrent respiratory and gastrointestinal infections in 30%

Answer 1

A. IgA deficiency

Affects 1 in 600 Caucasians

Question 2

These two infections commonly follow antibiotic use

Answer 2

A. Candida and Clostridium difficile

Question 3

Failure of stem cells to differentiate along myeloid or lymphoid lineage - fatal in early life unless corrected with BMT

Answer 3

A. Reticular dysgenesis

AR severe SCID is the most severe form - mutation in adenylate kinase 2

Question 4

Neutrophil count <500, normal leukocyte adhesion markers, absent/normal NBT, no pus

Answer 4

A. Kostmann syndrome (severe congenital neutropenia)

Classical form due to mutation in HAX1

Question 5

Normal neutrophil count, absent leukocyte adhesion markers, normal NBT (turns blue), no pus

Answer 5

A. Leukocyte adhesion deficiency (CD11a/CD18 and CD11b/18)

Characterised by v high neutrophil count, no pus formation and delayed separation of umbilical cord

Question 6

Normal neutrophil count, normal leukocyte adhesion markers, negative NBT (stays yellow), pus formation

Answer 6

A. Chronic granulomatous disease
- Deficiency in a component of NADPH oxidase leads to inability to generate free radicals and engage in oxidative killing –> excessive inflammation and pus, HSmegaly, catalase +ve organism infection

Mx. INFy

Question 7

What does PLACESS stand for?

Answer 7

A. Catalse positive organisms (infection associated with chronic granulomatous disease)

Pseudomonas
Listeria
Aspergillus
Candida
E. coli 
Staph aureus
Serratia

Question 8

Susceptibility to infection with mycobacteria (TB and atypical), BCG and salmonella

Answer 8

A. MSMD (Mendelian Susceptibility to Mycobacterial Disease)

Deficiency of IL-12 and IFNy and their receptors - inability to form granulomas

Question 9

VERY RARE inability to mobilise complement rapidly in response to bacterial infection

Normal C3/4, AP50 reduced, CH50 normal

Answer 9

A. Factor B, I, or P deficiency

Susceptible to infection with encapsulated bacteria (as in any complement deficiency)

Question 10

Increased susceptibility to infection with encapsulated bacteria AND increased load of self-antigens which may promote auto-immunity (SLE)

Reduced CH50 and normal AP50, normal C3/4

Answer 10

A. Deficiency in early classical pathway (C1/2/4)

C2 deficiency most common and almost all patients have SLE

Question 11

Associated with increased infection in patients with another cause of immunosuppression e.g. premature infant or chemotherapy

Answer 11

A. MBL deficiency

30% of all individuals are heterozygote for mutant protein
6-10% have no circulating MBL

Question 12

Severe susceptibility to bacterial infections - especially encapsulated AND increased risk of developing connective tissue disease

Answer 12

A. C3 deficiency (all pathways converge on C3)

Encapsulated bacteria = SHiNE SKiS

Strep pnemoniae
Haemophilus 
Neisseria meningitides
E. coli 
Salmonella
Klebsiella
Strep (Group B Strep) 

2o C3 deficiency is associated with membranoproliferative glomerulonephritis

Question 13

Presents at 3 months of age with infections of all types, faltering growth and persistent diarrhoea +/- unusual skin disease

FHx of early infant death

Answer 13

A. SCID

Protected until 3 months old with maternal IgG. There is colonosiation of infant’s empty bone marrow by maternal lymphocytes which may result in GVHD.

Question 14

Mutation of gamma chain IL-2RG on chromosone Xq13.1

Answer 14

A. X-linked SCID

45% of all SCID is X-linked. Inability to respond to cytokines causes early arrest of T cell and NK cell development and production of immature B cells.

Question 15

Normal numbers of B cells and reduced numbers of T cells.

Answer 15

A. DiGeorge syndrome (22q11.2)

No IgG as CD4 T cells needed for class switching.

CATCH-22
T- Thymic aplasia

Question 16

Defect in one of the regulatory proteins involved in HLA gene expression leads to either low CD4 T cell or low CD8 T cell

Answer 16

A. Bare lymphocyte syndrome

Type II (deficiency of CD4 cells) is more common

Both present at 3 months with infection and faltering growth - association with slerosing cholangitis and FHx of early infant death

Question 17

Mostly X-linked recessive failure of expression of CD40L on activated T cells

Answer 17

A. Hyper IgM syndrome

Normal T cells and B cells, with massively raised IgM and no other Ig present due to failure of class switching.

Typically boys present with faltering growth and infection with Pneumocystis jiroveci (honeycomb appearance on H&E)

Question 18

Defective B cell tyrosine kinase gene (BTK)

Answer 18

A. Bruton’s X-linked hypogammaglobulinaemia

B cells can’t mature –> no IgG after 3 months
Recurrent infections with bacteria and enterovirus

Question 19

Low IgG, IgA and IgE

Presents with recurrent bacterial infections with severe end-organ damage

Answer 19

A. CVID (common variable immune deficiency)

• Associated with autoimmune disease and granulomatous disease