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

Immuno: Immune modulating therapies 1 Flashcards

1
Q

List some approahces to boosting the immune system.

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

Describe the variety of antigen receptors found in the adaptive immune system.

A
  • Contains a wide variety of antigen receptors
  • Not entirely genetically encoded as genes are rearranged and recombined
  • This has the potential to generate autoreactive cells but these are removed
  • The adaptive immune system has exquisite specificity
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3
Q

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

A

Undergoes massive clonal expansion

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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 (with help from T helper cells) and become IgG 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 T cells?

A
  • Longevity - memory T cells persist for a long time in the absence of antigen due to low level 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 subsequenct antigen exposure (lower threshold for activation of naïve T cells)

NOTE: memory B cells have similar characteristics and are able to produce rapid and robust responses

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8
Q

What are the aims of vaccines?

A
  • Generate protective, long-lasting immunity
  • No adverse reactions
  • Single shot
  • Easy storage
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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

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10
Q

Describe how haemagglutinin inhibition assays work.

A
  • If you put normal red blood cells in a petri dish, they will clump at the bottom forming a red spot
  • If you add influenza virus, the HA makes red cells stick together and causes a diffuse coloration across the well
  • If you add the serum of someone who has a lot of antibodies against HA, it will inhibit the haemagglutination effects of HA so the red cells remain as a discrete red spot
  • The higher the dilution of serum at which the red cells remain as a little dot, the more antibodies are present in the serum

NOTE: sialic acid receptors on RBCs bind to HA leading to haemagglutination

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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

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 virus vaccine? List some examples.

A

The organism is alive but modified to limit its pathogenesis.

Examples: MMR, typhoid, BCG, yellow fever, polio (Sabin)

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16
Q

List some advantages and disadvantages of live attenuated virus vaccines.

A
  • Advantages: establishes infections, raised broad immune response against multiple antigens, activates all phases of the immune system, often confer life-long immunity after one dose
  • Disadvantages: storage problems, possible reversion to virulence, spread to contacts, cannot be used in immunocompromised patients
17
Q

List some examples of the following types of vaccine:

  1. Toxoids
  2. Component/Subunit
A
  1. Toxoids
    • Diphtheria
    • Tetanus
  2. Component/Subunit
    • Hep B (HBsAg)
    • HPV (capsid)
    • Influenza (HA)
18
Q

What are the advantages and disadvantages of inactivated/component vaccines?

A
  • Advantages - no mutation or reversion, can be used in immunodeficient patients, easier storage, lower cost
  • Disadvantages - often do not follow normal route of infection, poor immunogenicity, may need multiple injections, may require conjugates/adjuvants
19
Q

Describe how conjugate vaccines work.

A
  • Polysaccharide and protein carrier
  • Polysaccharide induces a T-cell independent B cell response (transient)
  • Addition of the protein carrier promoted T cell immunity which enhances B cell/antibody responses
20
Q

List some examples of conjugate vaccines.

A
  • Haemophilus influenzae type B
  • Meningococcus
  • Pneumococcus
21
Q

Describe how adjuvants work.

A
  • Increases the immune response without altering its specificity
  • They mimic the action of PAMPs on TLF and other PRRs
22
Q

List some examples of adjuvants.

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

NOTE: the mechanism of action of aluminium salts is not fully understood but it may allow antigens to be released slowly over time, may induce a mild inflammatory reaction or may activate Gr1 + IL4 + eosinophils

23
Q

List some example of experimental vaccine adjuvants.

A
  • ISCOMs - immune-stimulating complexes (enhances cell-mediated immunity)
  • CpG - cytosine-phosphate-guanosine motif that can bind via PRR to induce an immune response
  • DNA vaccines - plasmid containing a gene of choice (e.g. from a pathogen) is inserted into a muscle cell which will then express the antigen. This stimulates T cells responses (WARNING: this can lead to autoimmunity)
24
Q

What are dendritic cell vaccines?

A
  • Used against tumours
  • You collect some dendritic cells from the patient and load them with the antigen from the tumour to try and boost the immune response against tumour antigens
25
Q

What are the main indications for haematopoietic stem cell transplantation?

A
  • Life-threatening immunodeficiency (SCID)
  • Haematological malignancy
26
Q

What is human normal immunoglobulin?

A
  • Immunoglobulin prepared from thousands of pooled donors
  • Contains pre-formed IgG
  • Administered IV or SC
27
Q

List some indications for IVIG

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
28
Q

When might specific immunoglobulin be given?

A

Passive immunity as post-exposure prophylaxis (e.g. Hep B, tetanus, rabies, VZIG)

29
Q

List four types of T cell adaptive cell transfer.

A
  • Virus-specific T cells
  • Tumour infiltrating T cells (TIL)
  • T cell receptor T cells (TCR)
  • Chimeric antigen receptor T cells (CAR T Cell Therapy)
30
Q

Using an example, describe how virus-specific T cells are used.

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

31
Q

Describe how TCR and CAR T cell therapy works.

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)
  • In CAR therapy, the receptors are chimeric (containing both B and T cell components)
32
Q

Describe a use of CAR T cell therapy.

A
  • Used to target CD19 (present on B cells)
  • Receptors on the CAR cell have an immunoglobulin variable domain and is joined to a TCR
  • This means that it recognises CD19 through an immunoglobulin domain but signals through the TCR pathway

NOTE: this is used in ALL and NHL

33
Q

What is ipilimumab and how does it work?

A
  • CTLA4 and CD28 are both expressed by T cells and they recognise antigens (CD80 and CD86) on APCs
  • Signalling through CD28 results in a stimulatory response
  • Signalling through CTLA4 results in an inhibitory response
  • Ipilimumab is a monoclonal antibody that blocks CTLA4 thereby removing this inhibitory response
  • It is used in advance melanoma
34
Q

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

A
  • PD-1 and PD-2 ligands are present on APCs and interact via PD-1 receptors on T cells to cause an inhibitory response
  • They can also be expressed by some tumour cells
  • Pembrolizumab and nivolumab are antibodies that are specific to PD-1, thereby blocking this effect
  • This is also used in advanced melanoma
35
Q

List some examples of the therapeutic use of recombinant cytokines.

A
  • Interferon alpha - used as an adjunct in the treatment of Hep B, Hep C, Kaposi sarcoma, CML and multiple myeloma
  • Interferon beta - Behcet’s disease, relapsing MS
  • Interferon gamma - chronic granulomatous disease

YEAR 5: Immunopathology (12 decks)

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