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YEAR 5: Immunopathology PM > Immuno: Immune modulating therapies 1 > Flashcards

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.
V-BOY

Examples:

  • MMR,
  • Varicella zoster,
  • BCG,
  • Oral polio (Sabin)
  • Yellow fever,
  • nasal influenza, typhoid,
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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 (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

encapsulated bacteria

  • 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
List some examples of adjuvants.
* Aluminium salts (MOST COMMON) * Lipids (monophosphoryl lipid A)
26
How SARS-CoV mRNA vaccines work
* 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
What is another technique of SARS-CoV vaccination?
Adenovirus vector vaccines
28
What are dendritic cell vaccines?
* Used against cancer * Dendritic cells collected from patient and exposed to tumour antigens to try and boost the immune response against the cancer
29
Give an example of a dentritic cell vaccine
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
What is human normal immunoglobulin?
* Immunoglobulin prepared from thousands of pooled donors * Covers wide range of unspecified antigens * Contains pre-formed IgG * Administered IV or SC
31
What is the aim of cytokine therapy and give some examples
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
What are two therapies which replace missing immune system components?
- Hematopoietic stem cell transplantation (SCID, CML) - Antibody replacement
33
What are the main indications for haematopoietic stem cell transplantation?
* Life-threatening immunodeficiency (SCID) * Haematological malignancy * Severe haematological disease (e.g. thalassaemia)
34
What is antibody replacement?
Normal human immunoglobulin Pooled from >1000 healthy donors Contains preformed IgG to a wide range of unspecified organisms
35
List some indications for antibody replacement
* 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
When might specific immunoglobulin be given?
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
List four types of T cell adoptive cell transfer (cellular immunotherapy)
* Virus-specific T cells * Tumour infiltrating T cells (TIL) * T cell receptor T cells (TCR) * Chimeric antigen receptor T cells
38
Using an disease example, describe how virus-specific T cells therapy works
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
Describe how tumour infiltration T cell therapy works
Same principle as virus-specific T cell therapy
40
Describe how TCR and CAR T cell therapy works and how these 2 therapies differ
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
Describe a use of CAR T cell therapy.
**Tisagenlecleucel** - targets CD19 (present on B cells) Used to treat ALL and NHL
42
What is ipilimumab and how does it work?
* 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
Explain the use of antibodies against PD-1 in treating cancer.
* **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
What is the main complication with targetting T cell inhibitory receptors?
Autoimmunity

YEAR 5: Immunopathology PM (12 decks)

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