Immuno: Immune modulating therapies Pt.2

Question 1

List some examples of conjugate vaccines.

Answer 1

encapsulated bacteria

• Haemophilus influenzae type B
• Meningococcus
• Pneumococcus

Question 2

What are adjuvants and descibe how they work.

Answer 2

Adjuvants increase the immune response to a vaccine

• They mimic the action of PAMPs on TLR and other PRRs
• Increases the immune response without altering its specificity

Question 3

List some examples of adjuvants.

Answer 3

• Aluminium salts (MOST COMMON)
• Lipids (monophosphoryl lipid A)

Question 4

How SARS-CoV mRNA vaccines work

Answer 4

• Infect E-coli with DNA for spike protein
• Harvest DNA and transcribe to mRNA
• Complexed with lipids, injected into arm
• Once injected, mRNA enters human cells which is then translated
• Spike protein then expressed by cells to stimulate immune response

Question 5

What is another technique of SARS-CoV vaccination?

Answer 5

Adenovirus vector vaccines

Question 6

What are dendritic cell vaccines?

Answer 6

• Used against cancer
• Dendritic cells collected from patient and exposed to tumour antigens to try and boost the immune response against the cancer

Question 7

Give an example of a dentritic cell vaccine

Answer 7

Sipuleucel-T (Provenge)

• Used in prostate cancer
• Dendritic cells are harvested from patient and exposed to recombinant PAP-GMCSF (PAP is the tumour antigen, GMCSF stimulates the dendritic cell response)
• Dendritic cells reinfused back into patient to stimulate immune response

Question 8

What is human normal immunoglobulin?

Answer 8

• Immunoglobulin prepared from thousands of pooled donors
• Covers wide range of unspecified antigens
• Contains pre-formed IgG
• Administered IV or SC

Question 9

What is the aim of cytokine therapy and give some examples

Answer 9

Modifies immune response
Examples:

• IL-2 - stimulates T cells in renal cancer
• IFN-gamma - enhance macrophage function in CGD
• IFN-alpha - enhance antiviral response in hepatitis B and C

Question 10

What are two therapies which replace missing immune system components?

Answer 10

• Hematopoietic stem cell transplantation (SCID, CML)
• Antibody replacement

Question 11

What are the main indications for haematopoietic stem cell transplantation?

Answer 11

• Life-threatening immunodeficiency (SCID)
• Haematological malignancy
• Severe haematological disease (e.g. thalassaemia)

Question 12

What is antibody replacement?

Answer 12

Normal human immunoglobulin
Pooled from >1000 healthy donors
Contains preformed IgG to a wide range of unspecified organisms

Question 13

List some indications for antibody replacement

Answer 13

• Primary antibody defect
  
  • X-linked agammaglobulinaemia
  • X-linked hyper IgM syndrome
  • Common variable immunodeficiency
• Secondary antibody defect
  
  • CLL
  • Multiple myeloma
  • After bone marrow transplantation

Question 14

When might specific immunoglobulin be given?

Answer 14

Passive immunity as post-exposure prophylaxis for:

• Varicella Zoster
• Tetanus
• Hepatitis B
• Rabies

Derived from donors with high plasma IgG titres to specific pathogens

Question 15

List four types of T cell adoptive cell transfer (cellular immunotherapy)

Answer 15

• Virus-specific T cells
• Tumour infiltrating T cells (TIL)
• T cell receptor T cells (TCR)
• Chimeric antigen receptor T cells

Question 16

Using an disease example, describe how virus-specific T cells therapy works

Answer 16

Used for EBV in patients who are immunosuppressed to prevent the development of lymphoproliferative disease

• Blood is taken from the patient or from a donor
• Peripheral blood mononuclear cells are isolated and stimulated with EBV peptides
• This creates and expansion of EBV-specific T cells which are then reinfused into the patient

NOTE: tumour infiltration T cell therapy follows the same principle but uses tumour antigens

Question 17

Describe how tumour infiltration T cell therapy works

Answer 17

Same principle as virus-specific T cell therapy

Question 18

Describe how TCR and CAR T cell therapy works and how these 2 therapies differ

Answer 18

T cells are taken from the patient and vectors are used to insert gene fragents that encode receptors

• In TCR therapy, the gene will encode a specific TCR (e.g. against tumour antigen), but it requires tumour cells to express MHC to be activated
• In CAR therapy, the receptors are chimeric and can be activated by tumour antigens alone

Question 19

Describe a use of CAR T cell therapy.

Answer 19

Tisagenlecleucel - targets CD19 (present on B cells)
Used to treat ALL and NHL

Question 20

What is ipilimumab and how does it work?

Answer 20

• Ipilimumab is a monoclonal antibody that blocks CTLA4 (inhibitory T cell receptor)
• Allows for greater T cell activation
• It is used in advance melanoma

Question 21

Explain the use of antibodies against PD-1 in treating cancer.

Answer 21

• Pembrolizumab and nivolumab are monoclonal antibodies that block PD-1 (inhibitory T cell receptor)
• Prevents tumours expressing PD-L1 from inhibiting T cell response
• Used in advanced melanoma, NSCLC, metastatic renal cell carcinoma

Question 22

What is the main complication with targetting T cell inhibitory receptors?

Answer 22

Autoimmunity