Immune deficiencies

Question 1

2 T cell deficiencies, and their consequences

Answer 1

Bare Lymphocyte Syndrome,
DiGeorge’s Syndrome.
More viral and fungal infections, and early malignancies.

Question 2

B cell deficiencies (4)

Answer 2

Bruton's agammaglobulinaemia, 
Common variable immune deficiency, 
Selective IgA deficiency, 
Hyper-IgM syndrome. 
More bacterial infections, and some toxins.

Question 3

Phagocyte deficiencies (4)

Answer 3

Kostmann syndrome, 
Leukocyte adhesion defiency, 
Chronic granulomatous disease, 
Cyclic neutropaenia. 
More bacterial and fungal infections, more abscesses.

Question 4

Bare Lymphocyte Syndrome

Answer 4

No HLA in thymus, so T cells. (Type 1 lacks MHC I, so no CD8, and 2, II (CD4).)
Type 2 more common.
B cell class switch needs CD4, so less IgA and IgG.
Associated with Primary Sclerosing Cholangitis.
Unwell by 3 months old.

Question 5

DiGeorge’s Syndrome

Answer 5

Cardiac abnormality (tetralogy), 
Abnormal face, 
Thymic aplasia, 
Cleft palate/lip and low set ears, 
Hypocalcaemia / hypoparathyroidism. 
22q11.2 deletion (75% sporadic). 
3rd and 4th pharyngeal pouches don't develop. 
Tx: thymus transplant.

Question 6

Bruton’s agammaglobulinaemia

Answer 6

X-linked Tyrosine kinase defect.
No mature B cells, so no Abs.
Symptoms after 3-6 months old.

Question 7

Common Variable Immune Deficiency

Answer 7

Low IgG, IgA and IgE.
Many genetic causes, including MHC III deficiency.
Failure to thrive, recurrent infections, autoimmune and granuomatous disaeases.

Question 8

Selective IgA Deficiency

Answer 8

Affects 1 in 600 Cauasians, 70% asymptomatic.

Recurrent gastro and respiratory infections.

Question 9

Hyper-IgM Syndrome

Answer 9

Xq26 (boys). Defect in CD40, CD40L, CD154 or AICDA.
Baby boys with recurrent bacerial infections (Pneumocytis carinii) and FTT.
T cells can’t communicate with B cells, so no class switching, so IgM only.
Less lymphoid tissue: no germinal centre development.
Risk of autoimmunity and malignancy.

Question 10

Tx for B cell deficiencies

Answer 10

Ig replacement,
?BMT.
Vaccines in IgA def only.

Question 11

Severe Combined Immune Deficiency

Answer 11

Lymphoid precursor problem:
- X-linked: IL2-Receptor mutn;
- Adenosine deaminse deficiency;
- Adenylate kinase 2 malfunction: Reticular dysgenesis.
Recurrent infections (bubble babies), FTT, persistent diarrhoea, early death.
T cells low, B cells low or normal, Abs low.
Tx: BMT.

Question 12

Kostmann Syndrome

Answer 12

Severe congenital neutropaenia.
Autosomal recessive, HAX-1.
Dx: Chronically low neut, arrested neut precursor maturation in BM.
Tx: G-CSF, Abx, ?BMT.

Question 13

Leukocyte Adhesion Deficiency

Answer 13

No Leukocyte adhesion markers.
- LAD 1: deficiency of beta 2 integrin subunit (CD18);
- LAD 2: much rarer. severe growth restriction, mental retardation.
Life threatening neonatal bacterial infections.
High neutrophil count. Delayed umbilical cord separation.
Tx: BMT.

Question 14

Chronic Granumlomatous Disease

Answer 14

Usually X-linked, many mutns.
Failure of oxidative killing:
- negative Nitro-Blue Tetrazolium as no H2O2 (stays yellow);
- dihydrorhodamine (DHR) not oxidised to rhodamine.
Pneumonia, abscesses, suppurative arthritis.
Can resist catalase -ve bacteria.
Tx: trimethorpim, itraconazole, interferon, ?SCT.

Question 15

Cyclic neutropaenia

Answer 15

Every 3 weeks, a few days of neutropaenia.
ELA1 mutns.
Tx: G-CSF.

Question 16

Reticular Dysgenesis

Answer 16

Most severe form of SCID (adenylate kinase 2).
Missing all blood cells but RBCs.
Fatal v early unless BMT.

Question 17

Wiskott-Aldrich Syndrome

Answer 17

Low platelets, so brusing and bloody diarrhoea.

Low IgM, so recurrent infections.

Question 18

Cytokine deficiencies

Answer 18

Can be low in IFN-g, IFN-g-Receptor, IL-12 or IL-12-Receptor.
No signalling between T cells and macrophages, so no TNF or NADPH oxidase.
Salmonella, and TB (inclusing atypical Mycobacteria).
Can’t form granulomata.