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Immuno: Immune modulating therapies 1 Flashcards

1
Q

List some approaches to boosting the immune system.

A
  • Vaccination
  • Replacement of missing components (e.g. replacing immune cells)
  • Cytokine therapy
  • Blocking immune checkpoints
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2
Q

What happens when cells of the adaptive immune system engage with an antigen that it recognises?

A

Becomes activated - will proliferate and differentiate

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3
Q

What happens to T-cells when activated?

A

Proliferate and differentiate into effector cells (cytokine secreting, cytotoxic)

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4
Q

What are the two ways in which B cells can undergo clonal expansion once activated?

A
  • They can differentiate into T-cell independent IgM plasma cells
  • They can undergo a germinal centre reaction (T cell dependent) and become IgG/A/E memory and plasma cells
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5
Q

Which type of T cell undergoes a more pronounced proliferation following activation?

A

CD8 > CD4

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6
Q

List three types of antigen-presenting cell.

A
  • Dendritic cells
  • Macrophages
  • B lymphocytes
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7
Q

What are some important characteristics of memory cells?

A

Longevity
- Memory T cells persist for a long time in the absence of antigen due to low level continual proliferation in response to cytokines

Different pattern of cell surface proteins involved in chemotaxis cell adhesion
- Allows memory cells to rapidly access non-lymphoid tissues

Rapid, robust response to subsequent antigen exposure
- Memory cells are more easily activated than naive cells
- B cell memory involves that circulation of pre-formed high-affinity IgG antibodies

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8
Q

What are the aims of vaccines?

A
  • MEMORY – preformed antibodies, memory T cells, memory B cells, to provide long-lasting, protective immunity
  • No adverse reactions
  • Practical considerations – one shot, easy storage, inexpensive
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9
Q

Which cell surface receptor is used in the influenza vaccine?

A

Haemagglutinin (HA) - this is a receptor-binding and membrane fusion glycoprotein

ie. the reason influenza can infect cells

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10
Q

What are haemagglutination assays used for?
Describe how do they work.

A

Used to detect viral antibodies

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11
Q

How long does protection from the influenza vaccine last?

A

Starts 7 days after the vaccine and protection lasts for 6 months.

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12
Q

What agent is used in the BCG vaccine?

A

Attenuated strain of Mycobacterium bovis.

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13
Q

Describe the protection that is achieved by using the BCG.

A
  • Some protection against primary infection
  • Mainly protects against progression to active TB

NOTE : T cell response is important in protection against primary and progression to active TB

NOTE: protection lasts for 10-15 years

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14
Q

What is the Mantoux test?

A
  • A small amount of liquid tuberculin (PPD) is injected intradermally
  • The area of injection is examined 48-72 hours after the injection
  • A reaction would appear as a wheel around the injection site (this is suggestive of latent TB, active TB or previous BCG)
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15
Q

What is a live attenuated vaccine? List some examples.

A

The organism is alive but modified to limit its pathogenesis.

Examples: MMR, varicella zoster, typhoid, BCG, yellow fever, polio (Sabin), nasal influenza

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16
Q

List some advantages of live attenuated vaccines.

A
  • Raises broad immune response to multiple antigens – more likely to protect against different strains
  • Activates all phases of immune system. T cells, B cells – with local IgA, humoral IgG
  • May confer lifelong immunity, sometimes just after one dose
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17
Q

List some disadvantages of live attenuated vaccines

A

Possible reversion to virulence (recombination, mutation).
- Vaccine associated paralytic poliomyelitis (VAPP, ca. 1: 750,000 recipients)

Spread to contacts
- Spread to immunosuppressed patients

Storage problems

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18
Q

List some examples of inactivated vaccines

A
  • Inlfuenza (quadrivalent)
  • Cholera
  • Polio (Salk)
  • Hep A
  • Pertussis
  • Rabies
19
Q

List some examples of the following types of vaccine:

  1. Toxoids
  2. Component/Subunit
A
  1. Toxoids (inactivated toxins)
    • Diphtheria
    • Tetanus
  2. Component/Subunit
    • Hep B (HBsAg)
    • HPV (capsid)
    • Influenza (HA)
20
Q

What are the advantages of inactivated/component vaccines?

A
  • No risk of reversion to virulent form
  • Can be used with immunodeficient patients
  • Storage easier
  • Lower cost
21
Q

What are some disadvantages of inactivated/component vaccines?

A
  • Often do not follow normal route of infection (reduced local protection)
  • Some components have poor immunogenicity
  • May need multiple injections
  • May require modification to enhance immunogenicity e.g. conjugate to protein carrier, adjuvant
22
Q

Describe how conjugate vaccines work.

A

Polysaccharide and protein carrier
* Polysaccharides weakly immunogenic - induces a T-cell independent B cell response (transient)
* Addition of the protein carrier promoted T cell immunity which enhances B cell/antibody responses

23
Q

List some examples of conjugate vaccines.

A
  • Haemophilus influenzae type B
  • Meningococcus
  • Pneumococcus
24
Q

What are adjuvants and descibe how they work.

A

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
25
Q

List some examples of adjuvants.

A
  • Aluminium salts (MOST COMMON)
  • Lipids (monophosphoryl lipid A)
26
Q

How SARS-CoV mRNA vaccines work

A
  • 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
27
Q

What is another technique of SARS-CoV vaccination?

A

Adenovirus vector vaccines

28
Q

What are dendritic cell vaccines?

A
  • Used against cancer
  • Dendritic cells collected from patient and exposed to tumour antigens to try and boost the immune response against the cancer
29
Q

Give an example of a dentritic cell vaccine

A

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

30
Q

What is human normal immunoglobulin?

A
  • Immunoglobulin prepared from thousands of pooled donors
  • Covers wide range of unspecified antigens
  • Contains pre-formed IgG
  • Administered IV or SC
31
Q

What is the aim of cytokine therapy and give some examples

A

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

32
Q

What are two therapies which replace missing immune system components?

A
  • HSCT (SCID, CML)
  • Antibody replacement
33
Q

What are the main indications for haematopoietic stem cell transplantation?

A
  • Life-threatening immunodeficiency (SCID)
  • Haematological malignancy
  • Severe haematological disease (e.g. thalassaemia)
34
Q

What is antibody replacement?

A

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

35
Q

List some indications for antibody replacement

A
  • Primary antibody defect
    • X-linked agammaglobulinaemia
    • X-linked hyper IgM syndrome
    • Common variable immunodeficiency
  • Secondary antibody defect
    • CLL
    • Multiple myeloma
    • After bone marrow transplantation
36
Q

When might specific immunoglobulin be given?

A

Passive immunity as post-exposure prophylaxis for:
- Varicella Zoster
- Tetanus
- Hepatitis B
- Rabies

Derived from donors with high plasma IgG titres to specific pathogens

37
Q

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

A
  • Virus-specific T cells
  • Tumour infiltrating T cells (TIL)
  • T cell receptor T cells (TCR)
  • Chimeric antigen receptor T cells
38
Q

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

A

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

39
Q

Describe how tumour infiltration T cell therapy works

A

Same principle as virus-specific T cell therapy

40
Q

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

A

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
41
Q

Describe a use of CAR T cell therapy.

A

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

42
Q

What is ipilimumab and how does it work?

A
  • Ipilimumab is a monoclonal antibody that blocks CTLA4 (inhibitory T cell receptor)
  • Allows for greater T cell activation
  • It is used in advance melanoma
43
Q

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

A
  • 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
44
Q

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

A

Autoimmunity

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