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MSc Immunology Tutorial

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MSc Immunology Tutorial 12: Revision

Dr Siobhan Darrington

Exam

  • Discuss answers for Section A and B of the ‘mock’ exam paper
  • ‘Mock’ exam: this is NOT the actual exam you will be given on 10th January. This is a mock where similar questions have been set to allow you to understand the style you should expect to be given in your exam
  • You may be asked questions on theories within the lecture material, but at Masters level you are expected to have read around the subject in the allocated study time. This means that you may be asked questions about diseases or concepts which have not been covered in depth in the lecture
  • Section A has various word limits, depending on marks allocated to question
  • The word limit for Section B is 1,000 words (+/-10%, i.e. lower = 900 or upper 1,100 words). Minus10% penalty if exceeded.
  • Both sections together are worth 100%.
    • Section A = 50 marks (50%)
    • Section B = 50 marks (50%)

Exam Strategy

  • Preparation is key!
•      Revise
  • Don’t rely on having access to online materials
  • Plan your day:
    • The exam will be available from 10.00 – 13.00 h on Tuesday 10th       January 2023
      • You will only be able to access the paper during these times
    • Make sure that you will have a quiet and comfortable place to work on the day. Do not to plan to do anything else
  • You must complete and submit your own work
  • Write in your own words
•      Penalties for plagiarism
  • You have completed the questionnaire on Academic Integrity as part of your Prep for research Project

Exam details

•       100 % of your final mark
  • Paper consist of:
    • Section A – 50 marks total
      • 5 questions (some may have more than one part, e.g. a, b, etc.)
        • Question 1 = 5 marks (50 words)
        • Question 2 = 5 marks (50 words)
        • Question 3 = 15 marks (150 words)
        • Question 4 = 20 marks (200 words)
        • Question 5 = 5 marks (50 words)
  • Section B – 50 marks total
    • Reference list at end of answer
    • Formatted in LBU Harvard style

Exam Strategy

  • Read all questions for both Section A and B carefully. Think about your understanding of the question and make sure that it is clear
    • Which questions (or parts) do you think you can complete without much effort? Do these first! The harder questions can then be completed
    • You could use the same strategy to answer a question where you know some, but not all of the answer (i.e. start with the parts you know)
    • Check the marking scheme. A five mark question will need five points, similarly ten points for a ten mark question, etc.
    • Section B: For each point, include a valid reference. Avoid using the same reference repeatedly
    • You can use some references provided in the module

Exam Strategy

•      Section A
  • Look at past case studies as a guide
•      Section B
  • Questions around one of the following topics:
    • CAR-T cells
    • Immunodeficiencies
    • Immune checkpoint inhibitors
    • Look at the plans we have discussed. Start to collect your references and prepare your reference list

Case studies from last week’s tutorial

Sam, a two-year-old child has failed to thrive. He has had allergic reactions at injection sites and showed a poor response to his childhood vaccinations. Blood tests are shown in Table 1:

 Reference RangePatient
White blood cell count6.0 – 14.0 x 109/L3.00 x 109/L
Neutrophils2.0 – 6.0 x 109/L2.50 x 109/L
Lymphocytes2.5 – 8.0 x 109/L0.60 x 109/L
Monocytes0.2 – 1.0 x 109/L0.30 x 109/L
Haemoglobin115 -140 g/dL90 g/dL
Platelet count150 – 400 x 109/L125 x 109/L
C-reactive Protein<10 mg/L14 mg/L
Erythrocyte Sedimentation Rate<15.0 mm/h20 mm/h
IgA0.40 – 2.0 mg/dL0.2 mg/dL
IgM39 – 240 mg/dL2.5 mg/dL
IgG4.9 – 16.1 mg/dL1.5 mg/dL

Sam, a two-year-old child has failed to thrive. He has had allergic reactions at injection sites and showed a poor response to his childhood vaccinations. Blood tests are shown in Table 1:

 Reference RangePatient
White blood cell count6.0 – 14.0 x 109/L3.00 x 109/L
Neutrophils2.0 – 6.0 x 109/L2.50 x 109/L
Lymphocytes2.5 – 8.0 x 109/L0.60 x 109/L
Monocytes0.2 – 1.0 x 109/L0.30 x 109/L
Haemoglobin115 -140 g/dL90 g/dL
Platelet count150 – 400 x 109/L125 x 109/L
C-reactive Protein<10 mg/L14 mg/L
Erythrocyte Sedimentation Rate<15.0 mm/h20 mm/h
IgA0.40 – 2.0 mg/dL0.2 mg/dL
IgM39 – 240 mg/dL2.5 mg/dL
IgG4.9 – 16.1 mg/dL1.5 mg/dL

2. A five year old child was admitted to hospital following repeated viral infections. She had recurrent respiratory infections since birth. Blood test results are shown in Table 2:

 Reference RangePatient
White blood cell count6.0 – 14.0 x 109/L3.00 x 109/L
NK cells2.0 – 6.0 x 109/L0.50 x 109/L
Lymphocytes2.5 – 8.0 x 109/L0.50 x 109/L
Haemoglobin115 -140 g/dL105 g/dL
Platelet count150 – 400 x 109/L135 x 109/L
C-reactive Protein<10 mg/L15 mg/L
Erythrocyte Sedimentation Rate<15.0 mm/h20 mm/h
IgA0.40 – 2.0 mg/dL0.1 mg/dL
IgM39 – 240 mg/dL0.8 mg/dL
IgG4.9 – 16.1 mg/dL0.1 mg/dL
  • A five year old child was admitted to hospital following repeated viral infections. She had recurrent respiratory infections since birth. Blood test results are shown in Table 2:
 Reference RangePatient
White blood cell count6.0 – 14.0 x 109/L3.00 x 109/L
NK cells2.0 – 6.0 x 109/L0.50 x 109/L
Lymphocytes2.5 – 8.0 x 109/L0.50 x 109/L
Haemoglobin115 -140 g/dL105 g/dL
Platelet count150 – 400 x 109/L135 x 109/L
C-reactive Protein<10 mg/L15 mg/L
Erythrocyte Sedimentation Rate<15.0 mm/h20 mm/h
IgA0.40 – 2.0 mg/dL0.1 mg/dL
IgM39 – 240 mg/dL0.8 mg/dL
IgG4.9 – 16.1 mg/dL0.1 mg/dL

Adenosine Deaminase (ADA) deficiency  •   Mutations in the ADA gene

Cells are unable to divide resulting in lymphopenia (T, B and NK cells most affected causing in impaired cell-mediated and antibody- mediated immunity)

ADA found in high amounts in thymus, lacking ADA impairs thymus function

Patients exhibit severe B-cell lymphopenia and hypogammaglobulinemia

Autosomal recessive

Section A: Case Study

 

Case Study

A 74-year-old female patient (Patient F) presented with illness following treatment and recovery from stomach cancer. The patient had positive Antinuclear antibodies (ANA), renal dysfunction and hypergammaglobulinemia, A year later, serositis and Antinuclear antibodies (ANA) were detected, anti-DNA antibody levels increased. The patient was diagnosed with SLE. The doctor concluded that the progression to SLE may have been a result of the patient’s previous medical history of stomach cancer.

Questions

  1. Examine and evaluate the patient history and data shown in Table 1

(15 marks)

  • Explain the immunological mechanism of Systemic Lupus Erythematosus (SLE)                                                                                        (10 marks).
  • Explain the link between the patient’s age and gender with SLE

(10 marks)

  • Do you agree with the doctor’s conclusion?                (5 marks)
  • Explain the rationale for treating the patient with Belimumab (your answer must include an immunological mechanism)

(10 marks)

Table 1:

TestPatient F levelsReference Range level
Red Blood Cell count3.7 x 1012/L3.8 – 5.8 x 1012/L
White Blood Cell count4.1 x 109/L4.0 – 11.0 x 109/L
Neutrophil count2.1 x 109/L2 – 7.5 x 109/L
Eosinophil count0.25 x 109/L0.04 – 0.5 x 109/L
Basophil count0 x 109/L0 – 0.1 x 109/L
Monocyte count0.6 x 109/L0.2 – 0.8 x 109/L
Lymphocyte count1.6 x 109/L1 – 4.5 x 109/L
Urea4.1 mmol/L2.5 – 7.8 mmol/L
Creatinine51 mmol/L49 – 90 mmol/L
Folate12.0mg/L5.4 – 24 mg/L
Vitamin B301 ng/L211 – 911 ng/L
AST30 IU/L< 40 IU/L
ALP61 IU/L30 – 130 IU/L
RF448 U/ml<14 U/ml

Highlight the key points!

A 74-year-old female patient (Patient F) presented with illness following treatment and recovery from stomach cancer. The patient had positive Antinuclear antibodies (ANA), renal dysfunction and hypergammaglobulinemia, A year later, serositis and Antinuclear antibodies (ANA) were detected, anti-DNA antibody levels increased. The patient was diagnosed with SLE. The doctor concluded that the progression to SLE may have been a result of the patient’s previous medical history of stomach cancer.

My list….

Think about what this information tells you

74-years old: could link to disease (stomach cancer & SLE (autoimmunity))

Female: link to autoimmunity

Had treatment for and recovered from stomach cancer: link to autoimmunity Positive Antinuclear antibodies (ANA): Suggestive of autoimmune disease (AID) Renal dysfunction: Common in SLE (immune system attacks kidneys) Hypergammaglobulinemia: Elevated IgG

One year later:            serositis Inflammation of serous membrane

Antinuclear antibodies (ANA): AID

anti-DNA antibody levels increased: Supports SLE diagnosis

Diagnosed with SLE

Progression to SLE may have been a result of the patient’s previous medical history of stomach cancer: linking cancer to SLE. Why?

TestPatient F levelsReference Range levelComment
Red Blood Cell count3.7 x 1012/L3.8 – 5.8 x 1012/LBelow RRL
White Blood Cell count4.1 x 109/L4.0 – 11.0 x 109/LLower end RRL
Neutrophil count2.1 x 109/L2 – 7.5 x 109/LLower end RRL
Eosinophil count0.25 x 109/L0.04 – 0.5 x 109/LMid RRL
Basophil count0 x 109/L0 – 0.1 x 109/LLower end RRL
Monocyte count0.6 x 109/L0.2 – 0.8 x 109/LMid RRL
Lymphocyte count1.6 x 109/L1 – 4.5 x 109/LLower end RRL
Urea4.1 mmol/L2.5 – 7.8 mmol/LMid RRL
Creatinine51 mmol/L49 – 90 mmol/LLower end RRL
Folate12.0mg/L5.4 – 24 mg/LMid RRL
Vitamin B301 ng/L211 – 911 ng/LLower end RRL
AST30 IU/L< 40 IU/LBelow RRL
ALP61 IU/L30 – 130 IU/LMid RRL
RF448 U/ml<14 U/mlAbove RRL
Now do the same thing with Table 1: 
TestPatient F levelsReference Range levelComment  
Red Blood Cell count3.7 x 1012/L3.8 – 5.8 x 1012/LBelow RRLCould link to SLE & autoantibodies 
White Blood Cell count4.1 x 109/L4.0 – 11.0 x 109/LLower end RRLDue to SLE, treatment, previous history 
Neutrophil count2.1 x 109/L2 – 7.5 x 109/LLower end RRLPossibly Neutropenia, common in SLE 
Lymphocyte count1.6 x 109/L1 – 4.5 x 109/LMid-range RRLNormal – surprising 
Creatinine51 mmol/L49 – 90 mmol/LLower end RRLNormal – surprising 
RF448 U/ml<14 U/mlExtremely highIndicative of auto-antibodies 

 

Questions

  1. Examine and evaluate the patient history and data shown in Table 1

(15 marks)

  • Explain the immunological mechanism of Systemic Lupus Erythematosus (SLE)                                                                                        (10 marks)
  • Explain the link between the patient’s age and gender with SLE

(10 marks)

  • Do you agree with the doctor’s conclusion?                (5 marks)
  • Explain the rationale for treating the patient with Belimumab (your answer must include an immunological mechanism)

(10 marks)

1.                                   Examine and evaluate the patient history and data shown in Table

1                                                                         (15 marks)

Table 1:

Cells:

Red Blood Cell count below reference range. Link to SLE and autoantibodies. At lower end of reference range: White Blood Cell count, neutrophils and basophils. Could be related to SLE also Cancer recovery, although patient has recovered. Mid-range: monocytes, lymphocytes (would expect levels to be affected, also ranges of CD4+/CD8+ cells)

Other components: Urea, creatinine (strange, should be elevated in SLE), folate, Vitamin B, AST, ALP all within range. RF highly upregulated suggestive of autoantibodies, link to SLE.

2.  Explain the immunological mechanism of Systemic Lupus Erythematosus (SLE)
  • Systemic lupus erythematosus (SLE, lupus) is an autoimmune disease (ref). Predominantly affects pre- menopausal women (ref). Strong genetic link HLA- DR2/3 MHC II (ref). Loss of self-tolerance (ref). Circulating self-reactive antibodies deposit in tissues, including skin, kidneys, and brain, and the ensuing inflammatory response leading to tissue damage (ref). MHC II present self-antigen to Th1 CD4+ cells resulting in B cells to produce IgG to self antigen
  • Explain the link between the patient’s age and gender with SLE                                                                     (10 marks)

Patient is 74 years old: Thymus involutes with age. Negative selection is impaired. Recognition to self-antigen is not robust (ref), production of autoantibodies. Change in T cell population (reduction in CD4+/CD8+ populations. Reduction in TCR repertoire).

Dysfunctional AIRE which would normally delete self-reactive T cells. Reduced BCR repertoire. Shift to myeloid lineage enhanced inflammatory response.

Gender: Governed by sex hormones. Higher CD4+ T cells. CD4/CD8 ratios. Higher Ab titres

4. Do you agree with the doctor’s conclusion?             (5 marks)

Will need a strong argument, either for or against, with evidence: Possible that this is the case given link to autoimmunity and cancer (ref). Could also be linked to treatment with Belimumab (ref).

5. Explain the rationale for treating the patient with Belimuab (your answer must include an immunological mechanism)

(10 marks)

Belimumab is a recombinant full humanised monoclonal antibody, therefore should be safe. Prescribed to SLE patients who are auto-antibody positive. Belimumab acts binds to soluble B-cell activating factor (BAFF), B- lymphocyte stimulator (BLyS). Elevated circulating BLyS levels common in SLE patients, correlating with increased disease activity and antidouble- stranded DNA (dsDNA) antibody levels, promoting B-cell function and survival. Belimumab binds to soluble BLyS preventing signalling via receptors on both normal and autoreactive B cells, resulting in apoptosis of these cells.

Could include a figure which is labelled, described and referemced.

Section B: Essay

Essay

  • CAR-T-cells
  • Checkpoint inhibitors
  • Primary immunodeficiencies
  • Question will be on one of these topics
  • You will not be asked on the topic directly
    • e.g, What do you know about….?
    • You should collect information and build your knowledge to apply to question
    • Collect references related to topic and build your formatted reference list

Critically evaluate the role of CAR T-cells in Transplantation

  • Introduce what they are
    • Chimeric Antigen Receptor which has been genetically engineered allowing targeting of T-cells to specific antigens
    • Basic structure (add a Figure which you explain in text)
    • Generations of CAR T-cells
  • Brief examples of application in Autoimmunity, Transplantation & Cancer
  • Specific details on Transplantation
  • Issues with use
  • Ways forwards
  • Conclusion

Critically evaluate the role of PD-1 immune checkpoint inhibitors in the treatment of Cancer

  • State what immune checkpoints are
  • Immune checkpoint inhibitor types
  • Mechanism (could add a figure which you explain)
  • Checkpoint inhibitors PD-1
  • Mechanism (could add a figure which you explain)
  • Cancers treated
  • Therapies with examples
  • Issues with treatments
  • Ways forward (could detail combination treatments)
  • Conclusion

Critically evaluate how Immunodeficiencies have enhanced the understanding of Immunology

•         Introduce ID’s

  • Examples of types

•         ID’s illustrate importance of immune system in protecting against infection

  • Examples could include ID’s with defects in T-cell/B-cell maturation and function, etc.
    • Innate immune defects
    • Prone to opportunistic/recurrent infection, allergies
    • Progressive
  • Conclusion

Good Luck &

Thank you

Any questions:

Please email me: s.darrington@leedsbeckett.ac.uk

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