Immunology EMQs Flashcards
A Kostmann syndrome B Severe combined immunodeficiency C Hyper IgM syndrome D Leukocyte adhesion deficiency E Protein-losing enteropathy F Cyclic neutropenia G Bruton’s agammaglobulinaemia H Di George’s syndrome I AIDS
A 4-month-old girl is referred to a paediatrician with failure to thrive, after
suffering from recurrent infections since birth, especially recurrent candida
infections of her skin and mouth. Blood tests reveal a diminished T-cell count;
further lymphocyte testing demonstrates non-functional B cells.
B Severe combined immunodeficiency
Severe combined immunodeficiency (SCID; B) causes defects in both
T cells and B cells. The most common subtypes can be categorized into
an X-linked disease (mutation of IL-2 receptor) or an autosomal recessive
condition (mutation of adenosine deaminase gene which leads to
a build-up of toxins and hence compromised proliferation of lymphocytes).
Characteristically, there is hypoplasia and atrophy of the thymus
and mucosa-associated lymphoid tissue (MALT). Clinical features
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 Kostmann syndrome B Severe combined immunodeficiency C Hyper IgM syndrome D Leukocyte adhesion deficiency E Protein-losing enteropathy F Cyclic neutropenia G Bruton’s agammaglobulinaemia H Di George’s syndrome I AIDS
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.
A Kostmann syndrome
Kostmann syndrome (severe congenital neutropenia; A) is a congenital
neutropenia as a result of failure of neutrophil maturation. This results
in a very low neutrophil count (less than 500/μL indicates severe neutropenia)
and no pus formation. Kostmann syndrome is usually detected
soon after birth. Presenting features may be non-specific in infants,
including fever, irritability and infection. The nitro-blue-tetrazolium
(NBT) test can help with diagnosis; the liquid turns blue due to the normal
presence of NADPH. In Kostmann syndrome, NBT test is positive
and therefore normal.
A Kostmann syndrome B Severe combined immunodeficiency C Hyper IgM syndrome D Leukocyte adhesion deficiency E Protein-losing enteropathy F Cyclic neutropenia G Bruton’s agammaglobulinaemia H Di George’s syndrome I AIDS
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.
G Bruton’s agammaglobulinaemia
Bruton’s agammaglobulinaemia (G) is an X-linked disease that presents
in childhood. It is caused by a mutation of the BTK gene, which
expresses a tyrosine kinase. This mutation inhibits B-cell maturation
and therefore B-cell and immunoglobulin levels are diminished. Blood
tests will reveal a normal T-cell count, but diminished B-cell count as
well as IgA, IgM and IgG levels. Plasma cells will also be absent from
the bone marrow and lymphatics.
A Kostmann syndrome B Severe combined immunodeficiency C Hyper IgM syndrome D Leukocyte adhesion deficiency E Protein-losing enteropathy F Cyclic neutropenia G Bruton’s agammaglobulinaemia H Di George’s syndrome I AIDS
A 48-year-old woman presents to her GP with a history of diarrhoea for
3 weeks, which occasionally contains blood. She has felt increasingly tired and
feverish. The patient has had similar episodes in the past which were treated
with mesalazine. She also reports recurrent chest infections since her first episode
of diarrhoea.
E Protein-losing enteropathy
Protein-losing enteropathy (E) is defined as the severe loss of proteins
via the gastrointestinal tract. The underlying pathophysiology may
relate to mucosal disease, lymphatic obstruction or cell death leading to
increased permeability to proteins. If more proteins are lost than synthesized
in the body, hypoproteinaemia will result. Causes include Crohn’s
disease, coeliac disease and rarely, Menetrier’s disease. Hypoproteinaemia
secondary to such conditions results in fewer immunoglobulins being
formed which diminishes the adaptive immune response.
A Kostmann syndrome B Severe combined immunodeficiency C Hyper IgM syndrome D Leukocyte adhesion deficiency E Protein-losing enteropathy F Cyclic neutropenia G Bruton’s agammaglobulinaemia H Di George’s syndrome I AIDS
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.
H Di George’s syndrome
Di George’s syndrome (H) is caused by an embryological abnormality
in the third and fourth branchial arches (pharyngeal pouches) due to a 22q11 deletion. The result is an absent or hypoplastic thymus, as well
as a deficiency in T cells. There is a reduction or absence of CD4+ and
CD8+ T cells as well as decreased production of IgG and IgA. B cell and
IgM levels are normal. The features of Di George’s syndrome can be
remembered by the mnemonic ‘CATCH’: cardiac abnormalities, atresia
(oesophageal), thymic aplasia, cleft palate and hypocalcaemia.
A Selective IgA deficiency disease B Common variable immunodeficiency C Nephrotic syndrome D Bare lymphocyte syndrome deficiency E Sickle cell anaemia F Chronic granulomatous G Reticular dysgenesis H Wiskott–Aldrich syndrome I Interferon-gamma receptor
A 4-year-old boy is referred to a paediatrician after suffering recurrent chest
infections over the preceding few months. The boy has a history of eczema as
well as recurrent nose bleeds. Blood tests reveal a reduced IgM level but raised
IgA and IgE levels.
H Wiskott–Aldrich syndrome
Wiskott–Aldrich syndrome (WAS; H) is an X-linked condition which is
caused by a mutation in the WASp gene; the WAS protein is expressed
in developing haematopoietic stem cells. WAS is linked to the development
of lymphomas, thrombocytopenia and eczema. Clinical features
include easy bruising, nose bleeds and gastrointestinal bleeds secondary
to thrombocytopenia. Recurrent bacterial infections also result. Blood
tests reveal a reduced IgM level and raised IgA and IgE levels. IgG levels
may be normal, reduced or elevated.
A Selective IgA deficiency disease B Common variable immunodeficiency C Nephrotic syndrome D Bare lymphocyte syndrome deficiency E Sickle cell anaemia F Chronic granulomatous G Reticular dysgenesis H Wiskott–Aldrich syndrome I Interferon-gamma receptor
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.
B Common variable immunodeficiency
Common variable immunodeficiency (CVID; B) presents in adulthood. A
mutation of MHC III causes aberrant class switching, increasing the risk
of lymphoma and granulomas. Patients with CVID also have a predisposition
to developing autoimmune diseases. Recurrent infections caused
by Haemophilus influenzae and Streptococcus pneumoniae are common.
Clinical sequelae include bronchiectasis and sinusitis. Blood tests reveal
a reduced B-cell count, a normal/reduced IgM level and decreased levels
of IgA, IgG and IgE.
A Selective IgA deficiency disease B Common variable immunodeficiency C Nephrotic syndrome D Bare lymphocyte syndrome deficiency E Sickle cell anaemia F Chronic granulomatous G Reticular dysgenesis H Wiskott–Aldrich syndrome I Interferon-gamma receptor
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).
F Chronic granulomatous
Chronic granulomatous disease (F) is an X-linked disorder causing deficiency
of NADPH oxidase. As a result, neutrophils cannot produce the respiratory burst required to clear pathogens. The disease is characterized
by chronic inflammation with non-caseating granulomas. Clinical features
include recurrent skin infections (bacterial) as well as recurrent
fungal infections. The disease is usually detected by the age of 5 and is
diagnosed using the nitro-blue-tetrazolium (NBT) test, which remains
colourless due to NADPH deficiency (if NADPH is present the solution
turns blue). The patient will have a normal neutrophil count as there is
no defect in neutrophil production.
A Selective IgA deficiency disease B Common variable immunodeficiency C Nephrotic syndrome D Bare lymphocyte syndrome deficiency E Sickle cell anaemia F Chronic granulomatous G Reticular dysgenesis H Wiskott–Aldrich syndrome I Interferon-gamma receptor
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.
D Bare lymphocyte syndrome
Bare lymphocyte syndrome (D) is caused by either deficiency in MHC I
(type 1; all T cells become CD4+ T cells) or MHC II (type 2; all T cells
become CD8+ T cells). Clinical manifestations include sclerosing cholangitis
with hepatomegaly and jaundice.
A Selective IgA deficiency disease B Common variable immunodeficiency C Nephrotic syndrome D Bare lymphocyte syndrome deficiency E Sickle cell anaemia F Chronic granulomatous G Reticular dysgenesis H Wiskott–Aldrich syndrome I Interferon-gamma receptor
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.
A Selective IgA deficiency disease
Selective IgA deficiency (A): IgA specifically provides mucosal immunity,
primarily to the respiratory and gastrointestinal systems. Selective
IgA deficiency results from a genetic inability to produce IgA and is
characterized by recurrent mild respiratory and gastrointestinal infections.
Patients with selective IgA deficiency are also at risk of anaphylaxis
to blood transfusions due to the presence of donor IgA. This
occurs especially after a second transfusion; antibodies having been
created against IgA during the primary transfusion. Selective IgA deficiency
is also linked to autoimmune diseases such as rheumatoid arthritis,
systemic lupus erythematosus and coeliac disease.
A HLA-matching B Corticosteroids C Cyclosporine A D Azathioprine E Sirolimus F OKT3 G IL-2 receptor antibody H Tacrolimus I Anti-lymphocyte antibody
A 48-year-old man has undergone a kidney transplant operation as a result
of renal failure caused by long-standing diabetes mellitus. However, despite
immunosuppression,
signs of organ rejection become evident just 1 hour after
the procedure.
A HLA-matching
HLA-matching (tissue typing; A) is a preventative method of limiting
the risk of organ transplant rejection. It is impractical to match all HLA loci and hence tissue typing focuses on major HLA antigens such as
HLA-A and HLA-B. HLA-DR is also now routinely typed due to its role
in activating recipient’s T-helper cells. HLA-matching greatly reduces
the chance of hyperacute rejection caused by the presence of preformed
antibodies against the graft. Pre-formed antibodies may occur as
a result of previous blood transfusion or pregnancy.
A HLA-matching B Corticosteroids C Cyclosporine A D Azathioprine E Sirolimus F OKT3 G IL-2 receptor antibody H Tacrolimus I Anti-lymphocyte antibody
A 45-year-old man undergoes a heart transplant due to end-stage heart failure.
Seventy-two hours after the operation, the patient shows signs of organ rejection
which is resistant to corticosteroid therapy. A mouse monoclonal antibody
is administered to save the transplant.
F OKT3
OKT3 (muromonab-CD3; F) is a mouse monoclonal antibody targeted
at the human CD3 molecule used to treat rejection episodes in patients
who have undergone allograft transplantation. Administration of the
antibody efficiently clears T cells from the recipient’s circulation, T cells
being the major mediator of acute organ rejection. Primary indications
include the acute corticosteroid-resistant rejection of renal, heart
and liver transplants. Anaphylaxis can result given a murine protein
is introduced to the recipient. OKT3 can also bind to CD3 on T cells,
stimulating the release of TNF-α and IFN-γ causing cytokine release
syndrome, which if severe, can be fatal.
A HLA-matching B Corticosteroids C Cyclosporine A D Azathioprine E Sirolimus F OKT3 G IL-2 receptor antibody H Tacrolimus I Anti-lymphocyte antibody
A 32-year-old woman undergoes a bone marrow transplant for chronic lymphoblastic
leukaemia. She is prescribed a medication that inhibits calcineurin. On
examination, the patient has gum hyperplasia.
C Cyclosporine A
Cyclosporine A (C) is an important immunosuppressive agent in the organ
transplant arena, which inhibits the protein phosphatase calcineurin. This in
turn inhibits IL-2 secretion from T cells, a cytokine which stimulates T cell
proliferation. Another proposed mechanism of action involves the stimulation
of TGF-β production. TGF-β is a growth-inhibitory cytokine, the
production of T cells is reduced, hence minimizing organ rejection. Adverse
effects include nephrotoxicity, hepatotoxicity, diarrhoea and pancreatitis.
On examination, patients taking cyclosporine A may have gum hyperplasia.
A HLA-matching B Corticosteroids C Cyclosporine A D Azathioprine E Sirolimus F OKT3 G IL-2 receptor antibody H Tacrolimus I Anti-lymphocyte antibody
A 62-year-old man who has undergone a kidney transplant was started on an
immunosuppressive agent prior to the operation. The patient is warned that he
will only be on the medication for a short period due to long-term side effects
such as osteoporosis.
B Corticosteroids
Corticosteroids (B) are used as an immunosuppressive agent in both the
prevention and treatment of transplant rejection. Corticosteroids inhibit
phospholipase A2 thereby blocking prostaglandin formation as well
as a series of inflammatory mediators. The immunosuppressive effects
of corticosteroids are numerous and include reducing the number of
circulating B cells, inhibiting monocyte trafficking, inhibiting T-cell
proliferation and reducing the expression of a number of cytokines, for
example, IL-1, IL-2 and TNF-α. Prednisolone is used prophylactically
before transplantation to prevent rejection; methylprednisolone is used
in the treatment of rejection. Side effects are frequent, however, and
include osteoporosis, diabetes mellitus and hypertension.
A HLA-matching B Corticosteroids C Cyclosporine A D Azathioprine E Sirolimus F OKT3 G IL-2 receptor antibody H Tacrolimus I Anti-lymphocyte antibody
A 62-year-old man who is undergoing a liver transplant as a result of cirrhosis
is prescribed a medication that inhibits DNA synthesis in an attempt to prevent
proliferation of T cells.
D Azathioprine
Azathioprine (D) is an antimetabolite agent used in immunosuppressive
therapy. Azathioprine is metabolized into 6-mercaptopurine (6-MP), a
purine analogue that prevents DNA synthesis, thereby inhibiting the
proliferation of cells; lymphocytes are most affected. Antigen presenting
cells present non-self proteins (from the allograft) to T cells which
in turn produce IL-2 to stimulate T-cell proliferation. However, 6-MP
inhibits this proliferation and so the reaction between T cells and the
allograft is minimized. Important side effects include hepatotoxicity,
hypersensitivity reactions and myelosuppression.
A Anti-smooth muscle B p-ANCA C Anti-Jo1 D Anti-cyclic citrullinated protein E Anti-centromere F Anti-double stranded DNA G Anti-parietal cell H Anti-thyroid stimulating hormone I Anti-topoisomerase
A 56-year-old woman presents to the rheumatologist with pain in her hands.
On examination there are obvious deformities of her proximal interphalyngeal
joints and metacarpophalyngeal joints. Swan-neck deformities are seen but the
patient has retained functionality of her fingers.
D Anti-cyclic citrullinated protein
Anti-cyclic citrullinated protein (anti-CCP; D) antibody is associated
with rheumatoid arthritis. The antibody is directed at the filament
aggregating protein, filaggrin. Rheumatoid arthritis is a chronic systemic
autoimmune disease that results in a symmetrical deforming polyarthritis.
Clinical features include deformities of the hands (Boutonierre’s
deformity, swan-neck deformity, Z-thumb and ulnar deviation of the
fingers). The proximal interphalangeal joints are affected more than the
distal interphalangeal joints. Extra-articular manifestations include pulmonary
fibrosis, pericardial effusion, rheumatoid nodules and splenomegaly
(Felty’s syndrome). Rheumatoid factor is another antibody measured
in the investigation of rheumatoid arthritis, but is less sensitive
and specific in comparison to anti-CCP.
A Anti-smooth muscle B p-ANCA C Anti-Jo1 D Anti-cyclic citrullinated protein E Anti-centromere F Anti-double stranded DNA G Anti-parietal cell H Anti-thyroid stimulating hormone I Anti-topoisomerase
A 45-year-old woman is referred to a hepatologist after suffering an episode of
jaundice, fatigue and fever. Liver function tests reveal an increased AST. Biopsy
of the liver reveals cirrhosis and an autoimmune pathology is suspected.
A Anti-smooth muscle
Anti-smooth muscle (A) antibody (anti-SMA) suggests the diagnosis of
autoimmune hepatitis, but can also be present in patients with primary
sclerosing cholangitis. Autoimmune hepatitis is characterized by inflammation,
hepatocellular necrosis, fibrosis, with cirrhosis in severe cases.
Diagnosis requires histological confirmation together with the presence
of autoantibodies which may either be non-organ or liver-specific.
Autoimmune hepatitis is classified into two major groups depending on
the autoantibody present: type 1 is defined by the presence of anti-SMA
and/or anti-nuclear antibody, whilst type 2 is characterized by the presence
of anti-liver/kidney microsomal-1 antibody (anti-LKM-1).
A Anti-smooth muscle B p-ANCA C Anti-Jo1 D Anti-cyclic citrullinated protein E Anti-centromere F Anti-double stranded DNA G Anti-parietal cell H Anti-thyroid stimulating hormone I Anti-topoisomerase
A 42-year-old woman presents to the rheumatologist with weakness in her
proximal muscles and describes how she is finding it difficult to climb stairs.
On examination, a rash is observed surrounding both eyes. A high resolution CT
scan reveals a pulmonary fibrosis picture.
C Anti-Jo1
Anti-Jo1 (C) antibody is present in patients with dermatomyositis.
Dermatomyositis is characterized by autoimmune inflammation of muscle
fibres and skin. Clinical features include a heliotrope rash around
the eyes, Gottron’s papules on the dorsum of finger joints as well as weakness
of the proximal limb muscles which causes difficulty in
climbing stairs and rising from a chair. Dermatomyositis is commonly
associated with SLE and scleroderma. The presence of anti-Jo1 in dermatomyositis
typically suggests interstitial pulmonary involvement.
Blood tests reveal an increased ESR and raised creatine kinase level.
A Anti-smooth muscle B p-ANCA C Anti-Jo1 D Anti-cyclic citrullinated protein E Anti-centromere F Anti-double stranded DNA G Anti-parietal cell H Anti-thyroid stimulating hormone I Anti-topoisomerase
A 43-year-old man is referred to the rheumatologist after experiencing paleness
in his fingers, especially when exposed to cold weather. The patient also complains
of recent onset difficulty in swallowing solid food.
E Anti-centromere
Anti-centromere (E) antibody is associated with limited systemic scleroderma
(CREST syndrome). CREST syndrome is characterized by calcinosis,
Reynaud’s syndrome, oesophageal dysmotility, sclerodactyly and telangiectasia.
The pathophysiology is defined by endothelial injury and chronic
fibrosis (orchestrated by PDGF and TGF-β). Blood investigations will reveal
a raised ESR, anaemia and hypergammaglobulinaemia. Anti-centromere
antibodies detected in the presence of primary biliary cirrhosis indicate
portal hypertension.
A Anti-smooth muscle B p-ANCA C Anti-Jo1 D Anti-cyclic citrullinated protein E Anti-centromere F Anti-double stranded DNA G Anti-parietal cell H Anti-thyroid stimulating hormone I Anti-topoisomerase
A 42-year-old woman presents to the rheumatologist with joint pain and stiffness.
On examination, the patient appears to have a tight mouth and fine end
inspiratory crackles on auscultation of the lungs. The woman also has a widespread
itchy rash on her body.
I Anti-topoisomerase
Anti-topoisomerase (I) antibody is characteristic of diffuse systemic
scleroderma. Diffuse systemic scleroderma shares some features of limited
systemic scleroderma, however, it is more aggressive in its course,
affecting large areas of the skin as well as involving the kidneys, heart
and lungs. The pathogenesis of diffuse systemic scleroderma is similar
to that of limited systemic scleroderma. The presence of anti-topoisomerase
antibodies in diffuse systemic sclerosis is associated with
pulmonary
interstitial fibrosis.
