Immunology SBAs Flashcards
A 10-year-old boy is seen by a paediatrician after suffering recurrent chest
infections. His mother reports purulent sputum production and cough for the
previous 2 years. Genetic testing reveals the child has a ΔF508 mutation on
chromosome 7. Which physical barrier to infection is most likely to be affected
by the child’s condition?
A Skin
B Gastric acid
C Mucociliary clearance
D Tears
E Gut flora
C Mucociliary clearance
Physical barriers to infection which form part of the innate immune
system provide initial protection against disease-causing organisms.
Impaired mucociliary clearance (C) may arise secondary to cystic fibrosis,
which is the most likely answer in this scenario. Cystic fibrosis is
an autosomal dominant disease which primarily affects the lungs but
also the pancreas, liver and gastrointestinal system. The most common
mutation is the ΔF508 mutation on chromosome 7, which codes for the
cystic fibrosis transmembrane conductance regulator (CFTR). Defective
sodium and chloride ion transport across epithelial cells leads to the formation
of viscous secretions. In the respiratory tract increased viscous
secretions produced by goblet cells cause damage to the cilia, as well as
diffuse lung injury, which can result in bronchiectasis.
A 62-year-old woman sees her GP for a regular check-up. On examination, she
has notable deformities of her hands, including swan-neck and Boutonniere
deformities of her fingers. Blood tests reveal a raised CRP. Which of the following
investigation results will most likely feature?
A Reduced AH50 and normal CH50
B Reduced C1 inhibitor
C Reduced C3 and C4
D Reduced C3 and normal C4
E High CH50
E High CH50
The complement system is composed of the classical, lectin and alternative
pathways. These individual pathways culminate in the formation of
the membrane attack complex (MAC), which traverses cell surface membranes
of pathogens, causing cell lysis. Components of the complement
system can be quantified in order to differentiate possible diagnoses.
CH50 (total complement activity) measures the level of factors of the
classical and final pathways (C1–C9). As complement factors are acute
phase proteins, a high CH50 (E) indicates acute or chronic inflammation.
Together with the raised CRP and clinical features, this patient is likely
to suffer from rheumatoid arthritis. Systemic lupus erythematosus (SLE)
is a systemic autoimmune disease characterized by antibody-
immune complex formation and deposition.
A 25-year-old woman, who has a history of allergy to nuts, is taken to accident
and emergency after eating a dessert containing peanuts. She has an evident
wheeze with an increased respiratory rate, swelling of her lips and itchy skin.
Which cell of the innate immune system is most likely to be responsible for her
symptoms?
A Natural-killer cells
B Dendritic cells
C Eosinophils
D Mast cells
E Neutrophils
D Mast cells
Mast cells (D) are involved in the inflammatory process that occurs in
allergy and anaphylaxis (the diagnosis in this case), but also provide
a protective function against pathogens. Mast cells are activated by
one of three mechanisms: direct injury (toxins or drugs), cross-linking
of IgE receptors or by activated complement proteins. Once activated,
mast cells release granules containing histamine and heparin. Histamine
causes vasodilatation leading to the characteristic features of inflammation
(oedema, warmth and redness of the skin). The ‘flare and wheal’
skin reaction is a feature of histamine release by mast cells. Mast cells
play a role in diseases such as asthma, eczema and allergic rhinitis.
A 35-year-old man develops diarrhoea with fever and malaise 24 hours after eating
a take-away meal. Stool cultures reveal the source of the infection is Salmonella
spp. Which antibody is responsible for protecting against gastrointestinal infections?
A IgA
B IgD
C IgG
D IgM
E IgE
A IgA
IgA (A) can exist as a monomer or a dimer (joined by a short peptide
known as the J chain). Its role is primarily related to the protection of
mucosal surfaces via salivary, respiratory, gastrointestinal and lacrimal
secretions. IgA is also present in breast milk, providing passive immunity
in neonates.
A 23-year-old man presents to his GP with recent onset diarrhoea, fatigue and
weight loss. The patient suggests that his symptoms are worsened after eating
bread or rice. Which human leukocyte antigen is most likely to be associated
with his disease process?
A HLA B27
B HLA DR2
C HLA DR3
D HLA DR4
E HLA DQ2
E HLA DQ2
HLA DQ2 (E) represents a risk factor for coeliac disease (HLA DQ8
is also a risk factor but to a lesser extent). The cell surface receptors
formed by HLA DQ2 bind with greater affinity to α-gliadin, a protein
present in wheat, barley and rye which is responsible for the pathogenesis
of coeliac disease. Therefore, receptors formed from HLA DQ2
are more likely to recruit T cells and initiate an autoimmune response
compared to other HLAs. HLA B27 (A) is associated with ankylosing
spondylitis. The association with HLA B27 suggests the involvement of
CD8+ T cells in the pathogenesis of ankylosing spondylitis. HLA DR2
(B) is associated with Goodpasture’s syndrome, an autoimmune disease
triggered by a type II hypersensitivity reaction. It is characterized by
glomerulonephritis and haemoptysis. HLA DR3 (C) is associated with
Graves’ disease, systemic lupus erythematosus (SLE) and myasthenia
gravis. HLA DR4 (D) is associated with type I diabetes mellitus and
rheumatoid arthritis; in these diseases, HLA DR4 recruits T cells with
subsequent production of islet cell antibodies.
A 3-year-old Afro-Caribbean boy is referred to a paediatrician after concerns
about his recurrent chest infections. The child’s hair slowly fell out and there is
evidence of depigmentation of his skin. Blood tests reveal hypocalcaemia and
high TSH levels. Which component of the immune tolerance system is likely to
be dysfunctional?
A Regulatory T cell
B TGF-β
C Autoimmune regulator
D Dendritic cells
E IL-10
C Autoimmune regulator
Central tolerance is the induction of tolerance to self, which is integrated
into T-cell development in the thymus, a major site for the maturation
of T cells. Within the thymus, T-cell receptors are exposed to
self major histocompatibility complexes (MHC). Those binding to these
MHCs with some affinity are positively selected, whereas those with no
affinity (unable to recognize MHC) are neglected and removed. T cells
binding with high affinity are removed by apoptosis, as these cells pose
an autoimmune risk. The autoimmune regulator (AIRE; C) is also present
within the thymus and presents T-cell receptors with a range of
organ-specific antigens. If T-cell receptors bind to such antigens, they
swiftly die via apoptosis. Autoimmune polyendocrine syndrome type 1
(APECED; associated with mild immune deficiency, dysfunctional parathyroid
gland/adrenal gland, hypothyroidism, gonadal failure, alopecia
and vitiligo) results from mutations in the AIRE gene. The child in this
scenario has features of APECED.
A 34-year-old man presents to his GP with fever, joint pain and a rash on his
trunk. On examination, a new murmur is auscultated. Blood investigations reveal
a raised anti-streptolysin O titre. What is the most likely mechanism for this
disease process?
A Defective immunoregulation
B Molecular mimicry
C T-cell bypass
D Release of hidden self antigens
E Cytokines
B Molecular mimicry
Molecular mimicry is the term used to describe the phenomenon
whereby pathogens produce antigens that are molecularly very similar
to self antigens.
The immune response to this pathogenic antigen generates
T cells and B cells which are both anti-pathogen and anti-self;
this process is known as immunological cross-reactivity. In the case of
post-streptococcal rheumatic fever, antibodies to M-proteins present on
the surface of group A streptococci cross-react with cardiac myosin; this
results in the inflammatory features of rheumatic fever (fever, raised
ESR/CRP, leukocytosis, carditis).
A 2-year-old girl is seen by an infectious disease paediatrician after suffering
recurrent infections since she was born. Her neutrophil count is normal. A nitroblue-
tetrazolium (NBT) test is performed, which remains colourless. What is the
diagnosis?
A Kostmann syndrome
B Cyclic neutropenia
C Leukocyte adhesion deficiency
D Chronic granulomatous disease
E Von Gierke’s disease
D Chronic granulomatous disease
Chronic granulomatous disease (CGD; D) 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 including Candida spp. and Aspergillus
spp. 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 NBT test distinguishes CGD from other phagocyte deficiencies. The
patient will have a normal neutrophil count as there is no defect in
neutrophil production. Treatment involves the use of prophylactic antibiotics
and interferon-gamma
A 29-year-old woman presents to her GP with recent onset joint pain and tiredness.
On examination she has a malar rash. Further blood tests reveal she is antinuclear
antibody and anti-double stranded DNA positive. Which component of
the complement system is she most likely to be deficient in?
A C3
B C4
C C6
D C9
E C1 inhibitor
B C4
This patient demonstrates symptoms, signs and diagnostic features consistent
with systemic lupus erythematosus (SLE) and is therefore most
likely to have a deficiency of the classical pathway such as C4 deficiency
(B). Other possible deficiencies in this pathway include C1q, C1r and
C1s and C2. The classical pathway is responsible for clearing immune
complexes and apoptotic cells; patients who have deficiencies in this
pathway therefore have a greater risk of developing immune complex
disease such as SLE.
A 4-year-old girl is seen by a paediatrician to investigate possible developmental
delay and learning difficulties. Initial blood tests reveal hypocalcaemia, reduced
CD4+ and CD8+ T-cell counts as well as deficiency in IgG and IgA. FISH analysis
reveals the child has a deletion of 22q11. What is the diagnosis?
A Di George’s syndrome
B Severe combined immunodeficiency
C Bare lymphocyte syndrome
D Wiskott–Aldrich syndrome
E Interferon-gamma receptor deficiency
A Di George’s syndrome
Di George’s syndrome (A) 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 reduced level 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
