Page 1 of 13 pages IMMUNOLOGY (IMM100S) NOVEMBER 2019

INSTRUCTIONS:

There are 2 3 parts to this paper: Part Section A, and PartSection B and Section C

PART SECTION A: ANSWER ALL THE QUESTION 1 (Compulsory)-4

PART SECTION B: ANSWER 3 OUT OF 56 QUESTIONS (I.E EITHER 3 from the

QUESTION 5 OR QUESTION 62, 3, 4, 5 OR 6)
SECTION A (compulsory)
QUESTION SECTION
1: C ANSWER 1 OUT OF THE 3 LONG QUESTIONS
Select the one-lettered answer that fits best in each question. You need only write down the letter of the
correct answer.

1.1 Antigen–antibody complexes are phagocytosed more effectively in the presence of

which complement component?

(a) C3a and C5a

(b) C3b3
(c) C56789 complex
(d) MBL
(e) Properdin (1)

1.2 NK cells express a killer immunoglobulin-like receptor, which recognizes:

(a) MHC class I molecules

(b) MHC class II molecules
(c) Cell adhesion molecules
(d) Glycophospholipid molecules
(e) CD40 molecules (1)

1.3 Which of the following is not true about antibody structure?

(a) Antibodies have multiple antigen binding sites.

(b) Antibodies are built from equal numbers of heavy and light peptide chains.
(c) Antibodies are secreted and function away from the cell. They are not attached
to the cell membrane.
(d) The class of antibody molecule is determined solely by its heavy chain/
(e) Not all antibodies have a J chain in their structure.
Page 2 of 13 pages IMMUNOLOGY (IMM100S) NOVEMBER 2019

1.4 Which of the following is not a feature of a secondary immune response to an antigen,
when compared to the first response to the same antigen?

(a) The antibody is generated faster.

(b) More antibody is produced.
(c) The antibody produced has a greater affinity for the antigen.
(d) Antibody is generated without T-cell help.
(e) More memory cells remain after the secondary immune response. (1)

1.5 In agglutination reactions, the antigen is a …….

(a) Whole cell

(b) Soluble molecule
(c) Bacterium
(d) Protein
(e) Virus
(1)

1.6 Which group of dendritic cells has the appearance of a lymphocyte prior to its (i.e
dendritic cell) activation?

(a) Langerhans cell

(b) Cortical epithelial cells
(c) Interdigitating medullary cells
(d) Plasmacytoid cell
(e) Monocyte (1)

1.7 All of the following statements regarding monoclonal antibodies are correct except:

(a) Monoclonal antibodies are the products produced from a hybridoma cell
formed by the fusion of a myeloma cell and plasma cell using
polyethyleneglycol (PEG).
(b) Recombinant monoclonal antibodies are better in that no hybridoma cells are
involved and therefore there is no risk of cells dying out.
(c) Monoclonal antibodies can be labelled by attaching molecules such as
enzymes, biotin, fluorescent dyes and radiolabels.
(d) In monoclonal antibody production, the plasma cells are obtained from the
spleen of an animal that has been immunised with the antigen against which
one wishes to produce antibodies.
(e) In monoclonal antibody production, one fuses myeloma cells and plasma cells
in a culture plate and hybridoma cells are obtained. All of the hybridoma cells
in this culture plate will secrete antibodies, all of which will recognise the same
epitope. (1)
Page 3 of 13 pages IMMUNOLOGY (IMM100S) NOVEMBER 2019

1.8 Which of the following steps is not involved in the activation of T cells?

(a) Foreign peptide needs to be bound to the correct MHC molecule to provide a
signal.
(b) The double-positive T cell converts to a single positive T cell.
(c) CD40 on the B cell must bind to the CD40L on the T cell.
(d) Both the - dimer and CD3 molecules are required for signal transduction.
(e) ICAM-1 on APC needs to interact with LFA-1 (1)

1.9 In a mouse model of a human disease, the RAG genes are deleted. Which of the
following is the expected immune response in this mouse?

(a) There is a cell-mediated response but no humoral response.

(b) Tc will recognise antigen presented to it by macrophages.
(c) There will only be an innate immune response.
(d) Plasma cells will only produce IgM antibody.
(e) Th2 cells will activate B cells. (1)

1.10 Without the interaction between CD40 on B cells and CD40L on T cells, B cells are
unable to undergo ……..

(a) Class switching.

(b) Development from the pro-B cell.
(c) Immunoglobulin gene rearrangement.
(d) Formation of an antigen-specific receptor.
(e) The production of cytokines required for the activation of T cells. (1)

1.11 A five-year-old child falls and scratches herself and within a few days has an enlarged
lymph node in the area draining the abrasion. The cells in the lymph node are reacting
to the foreign stimulus that entered the skin and that was transported to the lymph
node by which of the following?

(a) Complement receptors

(b) Dendritic cells
(c) Immunoglobulins
(d) T lymphocytes
(e) Toll-like receptors (1)
Page 4 of 13 pages IMMUNOLOGY (IMM100S) NOVEMBER 2019

1.12 A researcher decides to work on a method to prevent graft rejection by reducing the
expression of MHC class I molecules on the foreign cells (i.e. transplanted organ). This
strategy, however, would leave the transplanted cells more susceptible to which of
the following?

(a) Killing by NK cells.

(b) Attack by antibodies.
(c) Recognition by Thelper cells.
(d) Increased production of complement proteins.
(e) The increased production of TNF which would damage the transplanted
tissue. (1)

1.13 A man acquired a helminth infection after he swam in a parasite –infested river in East
Africa. Which subgroup of T cells would develop in response to the presence of the
helminth?

(a) Th0
(b) Th1
(c) Th2
(d) Th17
(e) Treg (1)

1.14 A patient presents with a bacterial infection characterised by fever. The fever is due
to which of the following?

(a) Bacterial infection of the hypothalamus.

(b) Increased bacterial reproduction.
(c) Antibody responses to bacteria.
(d) Cytokine production by phagocytes.
(e) Opsonisation of the bacteria with complement proteins. (1)

1.15 Which of the following statements about epitopes is false?

(a) An epitope may be shared by two different antigens.

(b) A protein molecule usually contains multiple epitopes.
(c) B cells can only bind to processed antigen epitopes.
(d) Epitopes may be linear or assembled?
(e) Some epitopes are more immunogenic than others. (1)
Page 5 of 13 pages IMMUNOLOGY (IMM100S) NOVEMBER 2019

1.16 Antibody affinity for antigen depends on

(a) The complementary shape and charge of each antibody V region for its antigen
epitope.
(b) Whether the antibody is in the serum or on the cell surface.
(c) The number of Fab regions in each antibody molecule.
(d) Whether the light chains are kappa or lamda.
(e) The antibody isotype. (1)

1.17 Which of the following changes to a serum IgM antibody molecule would definitely
decrease its avidity?

(a) Replace the VH and VL framework regions with those from a different antibody.
(b) Increase non-covalent antigen-antibody interactions in the hypervariable
region.
(c) Replace the Fc portion of the  (mu) chains with the Fc portion of alpha chains.
(d) Use limited enzyme digestion to make Fab fragments.
(e) Remove the secretory component. (1)

1.18 The T cell receptor most closely resembles

(a) A Class I MHC molecule.

(b) A Class II MHC molecule.
(c) A Fab region of an antibody.
(d) A Fc region of an antibody.
(e) A light chain of an antibody (1)

1.19 T cells are MHC-restricted in their ability to respond to antigen because

(a) All antigen must be processed and presented to activate lymphocytes.

(b) During an infection, all cells in the body present antigen on MHC Class I.
(c) MHC binds antigen more specifically than TCR does.
(d) TCR must recognize both antigen and MHC molecules.
(e) The T cells should not respond to antigen on allogeneic cells. (1)

1.20 When IgE on mast cell FceR is cross-linked by, antigen, the mast cell responds by

(a) Stimulating macrophage and neutrophil phagocytosis of the coated antigen.

(b) Secreting histamine and allergic mediators.
(c) Presenting the antigen to Th cells.
(d) Secreting IgE.
(e) Apoptosis. (1)
[20]
Page 6 of 13 pages IMMUNOLOGY (IMM100S) NOVEMBER 2019

SECTION B: Answer only 3 out of the 5 questions

QUESTION 2:
A 25 year old woman presented with a 4 week history of increasing bloody diarrhoea, abdominal pain and
weight loss. She reported smoking a pack of cigarettes per day. The physical examination revealed that
she had a temperature of 37.8°C and tenderness over the right iliac fossa. Endoscopy of her colon showed
the mucosa to be red, with mucopus, blood and granulomatous lesions. Laboratory investigations
presented the following results:

PATIENT’S
TEST REFERENCE RANGE
RESULT
HAEMATOLOGY

White cell count 0.9 g/ℓ 5.8 – 10 g/ℓ

Haemoglobin 10.8 g/dℓ 12.5 – 15.5 g/ dℓ

CLINICAL CHEMISTRY

Total serum proteins 54 g/ℓ 62 - 82 g/ℓ

C-reactive protein 67 mg/ℓ < 1 mg/ ℓ

Serum albumin 29 g/ℓ 35 – 50 g/ℓ

ANCA (antibodies to neutrophil

Negative Negative
cytoplasmic antigens)
MICROBIOLOGY
Faeces - microscopy No ova observed
Faeces - culture Negative for Culture
Faeces -Clostridium toxin
HISTOLOGY
The rectal biopsy taken at sigmoidoscopy showed a small area of ulceration of the surface
epithelium with considerable mucopus. Many crypt abscesses were present. The lamina
propria contained a heavy infiltrate of lymphocytes, plasma cells and macrophages.
Several non-caseating granulomas were present in the muscular layer. A small bowel
barium examination showed extensive areas of fissuring ulceration interspersed with
areas of apparently normal mucosa – skip lesions.
Page 7 of 13 pages IMMUNOLOGY (IMM100S) NOVEMBER 2019

The following Clinical chemistry tests were also conducted and results were all normal: Urea and
electrolytes, serum vitamin B12, folate, iron, ferritin and iron-binding capacity were normal.
The patients were diagnosed with one of the main types of Inflammatory Bowel Disease, namely Crohn’s
disease, a disease in which the lining of the gastrointestinal tract is inflamed.
The patient was initially treated successfully with steroids and antibiotics but three months later her
condition started deteriorating again. The doctor changed the steroid prescription but then the patient
developed spondyloarthropathy of the left hip, both knees and her left wrist. Spondyloarthropathy is a
group of rheumatic inflammatory diseases that cause arthritis and affect joints and the spine. Once again
the doctor changed the treatment as the steroids had limited success. She was given an intravenous
infusion of monoclonal antibodies to Tumour Necrosis Factor -α (TNF-α) and her condition improved.

2.1 Explain what C-reactive protein (CRP) is. (2)

2.2 What is the significance of a raised CRP result? (1)

2.3 The development of Crohn’s disease is thought to arise due to defects in the
regulation of the immune response to commensals. One of the reasons is thought to
be defects in components of the innate immune response. Describe the role of mucin
in innate immunity. (5)

2.4 Which is the predominant antibody that is produced in the humoral immune
response? (1)

2.5 Sketch and label a molecule of the antibody named in 2.4 (½ mark per label). (10)

2.6 Plasma cells switched from producing IgM to the class of antibody named in 2.4. Explain
what at the mucosal surfaces induces the class switching to this particular antibody
named in 2.4. (6)
Page 8 of 13 pages IMMUNOLOGY (IMM100S) NOVEMBER 2019

2.7 Crohn’s disease is an example of a delayed type hypersensitivity while rheumatoid

arthritis has traditionally been classified as a Type III hypersensitivity but in both cases
cytokines contribute to the source of tissue damage. Compare these 2 types of
hypersensitivities with respect to the following characteristics:
• Innate immunity mediators
• Adaptive immunity mediators
• Beneficial effects of the immune response
• Pathological effects of the immune response. (10)

2.8 The cytokines that cause damage in Crohn’s Disease are produced by Th1 and Th17 cells.
What is the traditional role of Th17 cells at the mucosal surface? (3)

2.9 Spondyloarthropathy is linked to the presence of the HLA-B27 gene.

2.9.1 What does the HLA- B27 gene code for? (1)

2.9.2 Sketch and label a molecule of HLA-B27 (½ mark per label). (6)
[45]

QUESTION 3:

21-year-old JDee presented to the doctor complaining of fever, sore throat, tender cervical
lymphadenopathy, painful mouth ulcers, severe flank pain and myalgia of his leg muscles. He had been
experiencing these symptoms for a week. His history indicated that prior to the age of 8 he had
experienced similar symptoms but this stopped after his tonsillectomy. Treatment was prescribed but
these symptoms occurred for another week before abating. Similar episodes continued to occur every
two to three weeks lasting about 2 weeks at a time. About six months later he consulted a specialist during
one of these episodes and blood was taken for analysis. His leucocyte count was raised, as well as the
erythrocyte sedimentation rate, C-reactive protein and the complement proteins C3 and C4. Tests for
antinuclear antibodies and rheumatoid factor were negative and serum immunoglobulin levels were
normal. However his serum TNF levels were greatly elevated. All his symptoms were compatible with
tumour necrosis factor receptor- associated periodic syndrome. Genetic analysis confirmed this as a
mutation was found in the gene that coded for the 55 kDa tumour necrosis factor (TNF) receptor
(TNFRSF1A). This is just one of many mutations which have been found in the gene for the TNF receptor.
gene. In this instance it affects the ability of the extracellular domain of the receptor of being cleaved
and released into the extracellular environment
Page 9 of 13 pages IMMUNOLOGY (IMM100S) NOVEMBER 2019

3.1 Describe the general activity that normally takes place within the cytoplasm when a
molecule such as TNF binds to its receptor on the surface of a cell. (5)

3.2 When a ligand binds to the TNFR, one of two pathways can be activated. Describe
briefly the outcomes of each of the two pathways. In your answer explain which
genes or transcription factors that are activated. (4)

3.3 The production of cytokines has to be tightly regulated in the body else it will result in
the damage of tissues. This is particularly true in the case of TNF. Control can be
regulated with the aid of the extracellular part of the TNF Type 1 receptors which can
be cleaved by an enzyme and released into the extracellular environment where it
binds TNF and inhibits it. Using this piece of information and that of the genetic
analysis provided in the scenario, suggest a reason why there was so much serum TNF
present in Emil’s body. (2)

3.4 TNF is central to the immune response. State how TNF exhibits the following
properties of cytokines: Pleiotropism, synergism, autocrine, paracrine and endocrine.
In your answer explain what each of these terms mean. (10)

3.5 Excessive production of TNF can be damaging. Discuss this statement. (3)

3.6 C-reactive protein (CRP) is raised in JDee’s serum. In addition to being a marker of
infections/inflammation, it can also act as an opsonin. How does it achieve this and
what is the purpose of opsonisation? (2)

3.7 The production of TNF along with other chemical mediators activates inflammation.
Describe the process of inflammation. In your answer include the names of cell
adhesion molecules involved in inflammation. (11)

3.8 Most of the cells that enter the infected site are neutrophils. Describe the contents of
the neutrophil granules. You do not need to include functions. (8)
[45]
Page 10 of 13 pages IMMUNOLOGY (IMM100S) NOVEMBER 2019

QUESTION 4:
Two year old Emil was admitted to hospital with a persistent cough, severe shortness of breath and chest
pain. A radiological examination revealed lesions in both his lungs. The differential count was 80%
neutrophils, 14% lymphocytes and 5% monocytes; Culture of the aspirated lesions produced Aspergillus
fumigatus, a highly pathogenic fungus. He spent another two months recovering in hospital during which
time he developed nosocomial infections with Pseudomonas aeruginosa and Enterococcus faecalis. His
serum immunoglobulin levels were analysed to establish whether his humoral immunity was functioning;
his IgG level was slightly raised but the IgM and IgA levels were normal. The next step was to determine
the microbicidal activity of the phagocytes. The nitroblue tetrazolium test was conducted and the
phagocytes were found to be unable to produce reactive oxygen species such as superoxide anions after
the formation of the phagolysosome. Emil was diagnosed with chronic granulomatous disease. Individuals
with this disease have a defective gene for the NADPH oxidase enzyme.

4.1 What role does NADPH oxidase play in the immune response? (2)

4.2 If the differential count was normal, suggest a reason why Emil kept on contracting
the infections. (1)

4.3 Phagocytes must first bind pathogens before they are able to kill them. There are
different classes of pathogen recognition receptors. Tabulate any two classes of
pathogen recognition receptors. For each class, give an example of the molecule,
where they are found and the PAMP to which the pathogen recognition receptor
binds. ((½ mark per answer: 8 x ½ = 4)) (4)

4.4 Describe the activities that take place within phagosomes in the presence of functional
NADPH oxidases, resulting in the destruction of pathogens. (10)

4.5 Macrophages play an important role in the immune system. Discuss the functions of
macrophages and for each function give examples of the molecules on their surface
that are implicated in their functions. (15)

4.6 Complement proteins can function in the innate immunity.

4.6.1 Name the complement pathway that is activated by a pathogen recognition
receptor found in the class of C-type lectins. (1)
Page 11 of 13 pages IMMUNOLOGY (IMM100S) NOVEMBER 2019

4.6.2 Use a diagram to explain the how the C5 convertase is formed in the Mannose-
binding lectin pathway. Indicate which molecules act as opsonins. (12)
[45]

QUESTION 5:

Martin was diagnosed with common variable immunodeficiency at the age of 24 years. He was treated
initially with intramuscular gammaglobulin injections and then changed to intravenous gammaglobulin at
3-weekly intervals. He experienced adverse reactions to each infusion due to his high levels of antibodies
to trace amounts of IgA in the gammaglobulin preparation. Eventually, he was transferred to a preparation
with an extremely low IgA content that was well tolerated and he was maintained in excellent health for
several years. However, 14 years after his initial diagnosis, the doctor monitoring his immunodeficiency
noted that his liver function tests were abnormal. Further tests revealed that he was positive for Hepatitis
C virus. The aetiology of his Hepatitis C infection was traced back to a batch of intravenous gammaglobulin
that was infected with the virus. He was treated with thrice-weekly subcutaneous injections of IFN-α for
6 months.

5.1 What type of adaptive immunity is provided by intravenous gammaglobulin? (1)

5.2 Why was it necessary for Martin to receive gammaglobulins every three weeks i.e why
was a once-off regimen not sufficient to provide him with life-long immunity. (1)

5.3 What was the purpose of treating Martin with IFN-α (i.e what is the function of this
cytokine in this example?). In your answer explain in detail how this cytokine works to
achieve its function. (5)

5.4 Describe how intracellular viruses will be processed and presented by MHC molecules
to the T cells. (11)

5.5 Virally-infected cells can be detected by both cytotoxic T cells and Natural Killer cells.
5.5.1 Describe how one would identify and differentiate between activated cytotoxic
T cells and Natural Killer cells in a blood sample? (2)
Page 12 of 13 pages IMMUNOLOGY (IMM100S) NOVEMBER 2019

5.5.2 Compare the functions of these 2 cells. In your answer include an explanation
of how these cells detect infected cells, how they are activated and kill the
infected cells. (15)

5.6 Describe how effector Tc migrate from the bloodstream to the infected tissue. (10)
[45]

QUESTION 6:
Three –week old Reggie was admitted to hospital with a rash all over his body, diarrhoea, dry cough and
purulent conjunctivitis (infection of the eye). An examination of his bone marrow revealed an
abundance of eosinophil precursors. Large numbers of eosinophils, lymphocytes and macrophages were
observed in the dermal layer of a skin biopsy. Ricardo’s condition worsened as he developed infections
with Staphylococcus aureus and Candida albicans. Further investigation of his lymphocytes by flow
cytometry revealed that there were less than 1% B lymphocytes and there were very few T lymphocytes.
These T lymphocytes reacted poorly when exposed to phytohaemagglutinin. Very few of the T
lymphocytes expressed T cell receptors and the diversity of these TCR were very limited. In other words,
they were the products of only a few T lymphocytes that had proliferated (i.e. few clones). Missense
mutations were found to have occurred in the RAG genes upon sequencing of these genes. Reggie was
diagnosed with Omenn syndrome, a form of Severe Combined Immunodeficiency

6.1 What is the significance of the missense mutation in the RAG genes to the number of
lymphocytes in Reggie? (1)

6.2 Describe with aid of a sketch how the alpha (α) chain of a TCR would have been
constructed from the germline DNA with V67 and J3 gene segments and expressed on
the surface of the T lymphocyte had the RAG genes been fully functional. (9)

6.3 Describe the different stages that characterise the development of B lymphocytes. (35)
[45]
Page 13 of 13 pages IMMUNOLOGY (IMM100S) NOVEMBER 2019

SECTION C: Answer only 1 out of the 3 questions

QUESTION 7:

In an essay format compare IgM and IgA with regards to their structures, functions, quantity in the body
and sites of action.
[25]

QUESTION 8:

Describe the structure of the thymus and for each region of the thymus describe, in detail, the events that
would normally take place in that part of the thymus.
[25]

QUESTION 9:
T lymphocytes are central to the adaptive immune response. α-T lymphocytes can be subdivided into
groups. Each group has a different role to play in the immune system. Discuss the different groups of α-
T lymphocytes. In your answer refer to the function, the cytokines that they produce, the cytokines that
affect their development and the markers by means of which we are able to characterise them.
[25]

SUBTOTAL SECTION C: 25 MARKS

SECTION A + SECTION B + SECTION C

20 + (3 X 45) + (1 X 25)
TOTAL MARKS: 180

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