ST.
XAVIER’S COLLEGE
KOLKATA
(AUTONOMOUS)
8th SEMESTER EXAMINATION
APRIL – MAY 2022
B.M.B.T.
Friday, May 20, 2022
MBTCR8201T 1:00 PM to 4.00 PM
3 hours
ADVANCED IMMUNOLOGY
Full Marks : 80
PLEASE READ THESE INSTRUCTIONS BEFORE YOU START WRITING:
1. Of the questions attempted, the answers to only the first required number of questions (as stipulated in
the question paper) will be evaluated. So please do not attempt extra questions.
2. Use fountain pen or ball-point pen of blue or black ink.
3. Write (not type) the answers legibly, in your own words as far as practicable, on A4 size sheets.
4. Save the pages of your answer sheets (hand-written document) to a single PDF file and name the
document accurately i.e. Roll No_Paper Code.PDF (example: 147_PH36141T).
5. Send the PDF file to the following email address (in REPLY mode) within 30 minutes of the
completion of the examination: mbtcr8201t2122@sxccal.edu
6. The scanned answer scripts should have enough clarity to enable evaluation.
7. On top of each page handwrite the following information: Name, Roll Number, Paper Code , Date,
and Page Number
8. No multiple submissions would be allowed.
The marks are given in brackets [ ] at the end of each question or part question.
The question paper consists of 7 pages.
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Of the questions attempted, the answers to only the first required number of
questions (as stipulated in the question paper) will be evaluated.
So, PLEASE DO NOT ATTEMPT EXTRA QUESTIONS.
MODULE A
(24 marks)
Answer ANY ONE question from Q1. - Q2.
1. [(1+3+1)+(1×3)+2+2+2=14]
(a) “Mrs. Saxena, a 26-year-old woman, was rushed to the Emergency Department of a local hospital,
complaining of difficulty in breathing and a pruritic rash. She had been in her usual state of health,
until the morning of admission. She first noticed the rash, and felt feverish over her entire body an
hour after sharing a peanut butter and jelly sandwich with her 3-year-old daughter. During the next
30 minutes, she experienced difficulty in breathing and felt "swollen," especially around her face.
Her vital signs were reported as follows: blood pressure 160/95 mm Hg, heart rate 95 beats/min,
respiratory rate 25 breaths/min and labored, and temperature 39.8 0C. On physical examination, her
face and neck were found to be edematous and swollen. A red maculopapular rash was prominent on
her cheeks and forehead. Also, the same rash was present on her abdomen. There were no lesions on
her mucous membranes or eyelids. Her heart sounds were normal. In all lung fields, bronchial,
wheezing breath sounds were audible, along with "barking" sounds on expiration.”
(i) Predict what type of hypersensitivity reaction has Mrs. Saxena developed?
(ii) Give a neat, labeled diagram to depict the general mechanism of this type of hypersensitivity
reaction.
(iii)What should be the initial treatment for her?
(b) For each of the following immunodeficiency disorders [(i)-(iii)], indicate (with reasons) which
treatment (1-3) would be appropriate:
Immunodeficiency
(i) CGD
(ii) IL-2R-deficient SCID
(iii)XLA
Treatment
1. Full bone marrow transplantation
2. Pooled human gamma globulin
3. Recombinant IFN-γ
(c) “Children born with SCID often manifest increased infections by encapsulated bacteria in the first
few weeks of life.” – Justify/criticize the statement.
(d) “Serum sickness can result when an individual is given a large dose of antiserum such as a mouse
antitoxin to snake venom.” – How could you make use of recent technological advancements to
produce an antitoxin that would not lead to serum sickness in patients who receive it?
(e) Discuss the role of ‘elastase’ in bacterial evasion of host immune defenses.
OR
2. [(1+3)+(1+2)+2+(1×3)+2=14]
(a) “Leprosy is a chronic infectious disease caused by Mycobacterium leprae. The ability of this
organism to cause disease is related to its ability to infect, persist in, and replicate within
macrophages. The ‘lepromin skin test’ is used to determine what type of leprosy a person has. In this
test, inactivated M. leprae organisms are injected just beneath the skin. At the site of injection, a
person with a positive test will develop an area of induration with erythema peaking around 48 hours
after the injection.”
(i) If this test measures a hypersensitivity reaction against the organism, what type of
hypersensitivity reaction is it intended to detect?
(ii) Give a neat, labeled diagram to depict the general mechanism of that type of hypersensitivity
reaction.
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(b) Why is cervical cancer a likely target for a vaccine that can prevent this cancer? Can this approach
being investigated for cervical cancer be applied to all types of cancer?
(c) “Clinicians monitor the level of skin-test reactivity in HIV-infected individuals.” – What change
might you expect to see in skin-test reactivity with progression to AIDS?
(d) Indicate which type(s) of hypersensitive reaction (I–IV) apply to each of the following attributes:
(i) Can be induced by Pneumocystis carinii.
(ii) Can be induced by local anesthetics.
(iii)Can be induced by foreign serum.
(e) Discuss the role of ‘coagulase’ in bacterial evasion of host immune defenses.
Answer ANY ONE question from Q3. & Q4. and ANY ONE question from Q5. & Q6.
3. [(1×2)+3=5]
(a) Justify, whether each of the following statements is true (T) or false (F):
(i) An adult suffering loss of the thymus due to accident or injury will experience a much less severe
T-cell deficiency as compared to patients with DiGeorge Syndrome.
(ii) Patients with advanced stages of AIDS always have detectable serum antibody to HIV.
(b) “Gene conversion in Neisseria gonorrhoeae tfp gene is detrimental to humans.” – Justify the
statement, giving a neat sketch in support of your answer.
OR
4. [(1×2)+3=5]
(a) Justify, whether each of the following statements is true (T) or false (F):
(i) All oncogenic viruses carry viral oncogenes.
(ii) XLA is a combined B-cell and T-cell immunodeficiency disease.
(b) “After an insect bite, a sensitive individual may have an immediate, localized Type I reaction at the
site. However, some 4–8 h later, a typical Arthus reaction may develop at the site, with pronounced
erythema and edema.” – Give only a neat, labeled diagram to illustrate the mechanism of a typical
Arthus reaction.
5. [(1×3)+2=5]
(a) In what way the following bacteria evade host immune responses?
(i) Mycobacterium tuberculosis
(ii) GAS
(iii)Listeria monocytogenes.
(b) “Both silencing and hyperactivity of cancer-associated genes may turn detrimental.” –
Justify/criticize the statement, with a suitable example of each event.
OR
6. [3+(1+1)=5]
(a) Graphically discuss HIV-1-associated CD4+ T cell dynamics in vivo.
(b) “In recent years, hypersensitivity to latex allergens in gloves has been increasing among health-care
workers. This is an example of ‘occupational hypersensitivity.’”
(i) Classify this hypersensitivity reaction, after Gell and Coombs.
(ii) Is this reaction systemic or localized? Why?
MODULE B
Section A
(24 Marks)
Answer ONE from Q1. - Q2. and ANY TWO from Q3. - Q.6.
7. [(2+2)+2+2+2+4=14]
(i) The following diagram represents the results of a flow cytometry experiment in which mouse spleen
cells were stained with antibodies directed against different components of the IL-2R. The number of
cells stained with fluorescein-conjugated anti-βγ IL-2R antibodies are shown along the x-axis of the
flow cytometry plot, and cells that stain with phycoerythrin labelled antibodies to the α subunit of the
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IL-2 receptor move along the Y-axis. The circle in the lower left quadrant represents cells that stain
with neither antibody. On this plot, draw, as circles, and label where you would expect to find the
populations representing unstimulated T cells and T cells after antigen activation, after treatment
with the two fluorescent labels described above. Give a brief justification.
(ii) Human red blood cells are not nucleated and do not express any MHC molecules. Why is this
property fortuitous for blood transfusions?
(iii)The B- and T-cell receptor proteins have remarkably short intracytoplasmic regions of just a few
amino acids. How can you reconcile this structural feature with the need to signal the presence of
bound antigen to the interior of the cell?
(iv)Cross presentation is allowed from the exogenous antigen processing pathway to the endogenous
pathway. Can you take an educative guess of the logic behind this?
(v) Which of the following are examples of mechanisms for the development of autoimmunity? For each
possibility, give an example.
a) Polyclonal B-cell activation
b) Tissue damage
c) Viral infection
d) Increased expression of TCR molecules
e) Increased expression of class II MHC molecules
OR
The cytokine IL-2 can activate all T cells to proliferation and differentiation. How does the immune
system ensure that only T cells that have been stimulated by antigen are susceptible to IL-2 signaling?
8. [(2.5+2.5)+(2+2)+(3+2)/5=14]
(i) You have fluorescein-labeled anti-CD4 and phycoerythrin-labeled anti-CD8. You use these
antibodies to stain thymocytes and lymph-node cells from mice. In the forms below, draw the FACS
plots that you would expect. Justify your drawing.
Thymus Lymph
Node
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(ii) You immunize an H-2k mouse with chicken ovalbumin (a protein against which the mouse will
generate an immune response) and isolate a CD4 + mature T cell specific for an ovalbumin peptide.
You clone the αβ TCR genes from this cell line and use them to prepare transgenic mice with the H-
2k or H-2d haplotype.
(a) Would thymocytes from a TCR transgenic mouse of the H-2k background have a proportion of
CD4+ thymocytes that is higher, lower, or the same as a wild-type mouse? Why?
(b) Would thymocytes from a TCR transgenic mouse of the H-2d background have a proportion of
CD4+ thymocytes that is higher, lower, or the same as a wild-type mouse? Why?
(iii)Experimental autoimmune encephalitis (EAE) has proved to be a useful animal model of
autoimmune disorders.
(a) Describe how this animal model is made.
(b) How has this animal model indicated a role for T cells in the development of autoimmunity?
OR
Starting with ligand-TCR interaction trace the signaling pathway that leads to activation of any of
these transcription factors – NFκB, NFAT or AP-1.
9. [3+2=5]
(i) As a graduate student, your adviser has handed you a T-cell clone that appears to be constitutively
(always) activated, although at a low level, even in the absence of antigenic stimulation, and he has
asked you to figure out why. Your bench mate suggests you start by checking out the sequence of its
lck gene. You agree that this is a good idea. What is your reasoning?
(ii) Knockout mice lacking class I MHC molecules fail to produce CD4 + mature thymocytes. True or
False. Justify.
10. [2+3=5]
(i) Measurement of the blood concentration of a particular cytokine reveals that it is rarely present
above 10-10 M, even under the conditions of an ongoing immune response. However, when you
measure the affinity of the cognate receptor, you discover that its dissociation constant is close to
10- 8 M, implying that the receptor occupancy must rarely exceed 1%. How do you account for this
discrepancy?
(ii) What known features of the TCR did Hedrick, Davis, and colleagues use in their quest to isolate the
TCR genes?
11. [3+2=5]
(i) You isolate naïve T cells from your own blood and want to polarize them to the TH1 lineage in vitro.
You can use any of the following reagents to do this. Which would you choose? Justify briefly.
Anti-TCR antibody, CTLA-4 Ig, IL-12, IL-4, anti-CD80 antibody, IL-17, IFNγ, anti-CD28 antibody
(ii) Indicate whether the statement is true or false. If you think a statement is false, explain why.
Antigen can only come into the lymph node if it is associated with an antigen-presenting cell.
12. [2+3=5]
(a) What are Treg cells?
(b) With the help of a rough diagram differentiate between the mechanisms of action of effector T cells
versus Treg cells.
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MODULE B
Section B
(32 Marks)
Answer Q13., ONE from Q14. – Q15. and ANY TWO from Q16. - Q.19.
13. [(1.5+1.5)+3+2+2=10]
(i) When the genome of a (-) sense ssRNA virus is purified and introduced into cells that are permissive
to the original intact virus, what will happen? If you did this same experiment with a (+) sense
ssRNA virus, what would happen? Briefly justify your answers.
(ii) You have genetically modified a human cell line so that it cannot produce any of the various toll-like
receptors (TLRs). Upon infection of this cell line with Virus A you find that the cells produce as
much type I interferon (IFN) as unmodified cells. Next when you infect the genetically modified
human cells with Virus B, no IFN is produced while the unmodified cells produce plenty of IFN.
How do you reconcile these results?
(iii)It is still not completely clear how much of the pathology of AIDS is caused directly by the virus and
how much is caused by the immune system. Justify this statement.
(iv) What happens to cascade regulation of herpesvirus gene expression when a cell is infected in the
presence of a potent inhibitor of protein synthesis?
14. [(1+1+1+1+1+2)+(1+4)=12]
(i) The first steps of reverse transcription are illustrated below:
(a) What is the olive-green molecule called? What is its function?
(b) Part of the (+) strand RNA is degraded in steps 2 and 3. What is the name of the enzyme
responsible for this activity?
(c) Where in the cell do the reactions illustrated take place?
(d) The kelly green molecule is the viral genome. Where was this produced and by what enzyme?
(e) What is illustrated in the last panel by the arrow pointing from the (-) DNA?
(f) Sketch rough diagrams of a minimum retroviral genome before and after reverse transcription.
(ii) All cells have mechanisms to protect themselves from double stranded RNA (dsRNA) viruses. What
is this innate mechanism of protection? Briefly explain how it works.
15. [2+4+3+3=12]
(i) Taking example of adenovirus, schematically explain how in a newly infected cell expression of the
viral genome gets 'kick-started'.
(ii) Herpesvirus has a complex mechanism of egression of progeny virions. Justify this statement with a
labelled diagram.
(iii)Why individuals once infected by Herpesvirus suffer from recurring infections?
(iv) Acyclovir, an acyclic nucleoside analog, was introduced nearly 50 years back as a therapeutic agent
against Herpesvirus infection and is still in use. What is the mechanism of action of acyclovir?
16. [3+2=5]
(i) Describe three mechanisms by which Type I interferons “interfere” with the production of new viral
particles. Flow chart will suffice.
(ii) To cause cancer, retroviruses must carry an oncogene into the cell. True or False? Justify.
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17. [5]
Viruses have evolved several mechanisms to evade recognition and elimination by the immune system.
With the help of a proper example show how viruses have developed strategies to shun both innate and
adaptive immune responses of the host.
18. [1+2+2=5]
(i) What one factor unifies all virus receptors?
(ii) Why viruses involve interaction with multiple receptors on the host cell surface?
(iii)What is a polyprotein? How does it become functional mature protein? Give an example of a virus
which does this.
19. [5]
Novel drugs against herpes simplex viruses are welcome and needed. Nowadays knowing the
mechanism of action of a drug is almost a prerequisite for clinical development. With the help of a flow
chart demonstrate a logical approach for assessing the mode of action of anti-HSV compounds.
OR
Several methodologies have been established for assessing binding, entry, and viral capsid transport to
the nucleus in HSV-infected cells. Just give one assessment technique for each of the stages mentioned
above.
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