Immuno - primary immune def Flashcards
A 4-month-old girl, recurrent candida on skin and mouth. Blood tests reveal a diminished T-cell count;
further lymphocyte testing demonstrates non-functional B cells.
SCID
Severe combined immunodeficiency causes defects in both T cells and B cells. Present young with failure to thrive.
Defects in lymphoid precursors - lymphocytes can never mature. The most common subtypes can be categorized into
an X-linked disease (mutation of IL-2 receptor) or an autosomal recessive condition - adenosine deaminase
Atrophy of thymus and MALT
include diarrhoea, failure to thrive and skin disease (graft-versus-host
induced, secondary to transplacental maternal T cells or blood transfusion-
related caused by donor T cells).
A 5-month-old boy is referred to a paediatrician after suffering with recurrent
infections since his birth. His mother has noticed increased irritability. Blood
tests reveal a neutrophil count of 350/μL. NBT test is normal.
Kostmann Syndrome
Severe congenital neutropenia, so look for very low neutrophil count in an infant. <500/ul is very severe.
NBT test is normal as neutrophils are still functional - there’s just none of them.
A 4-year-old girl is referred to a paediatrician after experiencing recurrent
chest infections. Blood tests demonstrate a reduced B-cell count as well as low
IgA, IgM and IgG levels
Bruton’s Agammaglobinaemia
X-linked tyrosine kinase defect
Mutation in BTK gene (bruton’s tyrosine kinase)
Failed production of any B cells
Therefore, B cell count is low, including all Ig variants. Presents fairly young.
A 3-year-old girl is seen by a GP due to recurrent mild chest infections. The
doctor notices the girl has a cleft lip. Blood tests reveal a reduced T-cell count
as well as hypocalcaemia.
Di George Syndrome
22q11.2 deletion
Low set ears, cleft lip and palate
Low calcium
As there is impaired development of 3rd and 4th pharyngeal pouch (head and neck essentially), the thymus is aberrant, meaning very low T-cell count.
A 20-year-old man presents to his GP with signs of a mild pneumonia. The
patient states he has had several similar episodes in the past. Further investigations
by an immunologist reveal the patient has a genetic condition caused by a
mutation of MHC III.
Common Variable Deficiency
Defect in B-cell differentiation, class switching gone wrong - low IgG, IgE and IgA but normal IgM
B cell count is usually reduced a little.
Can be caused by MHC III mutation but there are many genetic causes
Failure to thrive, recurrent infections including autoimmune and granulomatous disease.
A 3-year-old girl is referred to a paediatrician after concerns about recurrent
skin infections she has suffered from since birth. A nitro-blue-tetrazolium test
is negative (remains colourless).
Chronic Granulomatous Disease
Failure of oxidative killing, but normal or raised neutrophil count.
Negative NBT and DHR test - which test for oxidation of hydrogen peroxide.
Pneumonia and abscess common due to inability to remove bugs. Catalase positive (PLACESS) especially bad.
A 4-year-old boy is referred to a paediatrician after a period of mild but
chronic
diarrhoea. On examination the child is found to have icteric sclera and
hepatomegaly. Following blood tests, the doctor has a high suspicion that the
child could have a defect in MHC I.
Bare Lymphocyte Syndrome
Absent expression of HLA within thymus - therefore T cells cannot mature. Can have defect in MHC I (type 1) or MHC II (type 2) which leads to deficiency in respective T cells. Type 2 is more common
↓CD4 means no class switching so there is ALSO ↓IgA and ↓IgM
Associated with sclerosing cholangitis, hence the hepatomegaly and jaundice
A 22-year-old woman visits her GP after several chest infections in the past few
years. As well as the chest infections, the patient reports that she has had several
bouts of diarrhoea over the same time period.
Selective IgA deficiency
↓IgA, nothing else to it. Common, 70% asymptomatic. More infections on mucusal surface, hence chest infection and diarrhoea
A young boy presents with recurrent opportunistic infection and failure to thrive.
↑IgM ↓IgG ↓IgA, normal T-cell count
Hyper-IgM Syndrome
Inability for T helper cells to interact with B cells, meaning no class switching. Usually an issue with co-stimulation
Can be caused by defect in CD40L, CD40
Life threatening neonatal bacterial infections. Neutrophil count high
Leukocyte adhesion deficiency
Neutrophils cannot migrate to infected tissue as chemokines not working. Deficiency of Beta-2 integrin subunit (CD18) of leukocyte adhesion molecule (LAD1).
There is also LAD 2 which is less common and presents with growth restriction and mental retardation
Rx: BMT
Episodic neutropenia every 3 weeks
Cyclic neutropenia
ELA-1 gene mutation
Low T cell and B cells. You take a further look and there’s also pancytopenia everywhere. Pt dies in front of you.
Reticular Dysgenesis
Most severe form of SCID (AK2). Absolute deficiencies in everything.
BMT or fatal
