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Flashcards in immunotherapy Deck (17)
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1
Q

What is immunotherapy?

A

Harnessing the power of the immune system to fight disease

2
Q

What are common strategies for immunotherapy?

A

Generalised immunosuppresion

Tailored therapies for specific immune response

3
Q

What are the risks of generalised immunosuppresion?

A

High risk of opportunistic infection

4
Q

What is acute rejection to organ transplant?

A
  • Acute rejection in particular is associated with T cell responses that mediate immune cell infiltration into the graft and effect its rejection
5
Q

What ways can we stop graft cell rejection?

A

Methods for inhibiting T cell activation to treat graft rejection

  • Cyclosporins which inhibit calcineurin
6
Q

See image of passive vs active immunity:

A
7
Q

What are the three types of established immnosuppressive drugs?

A
  • Corticosteroids
  • Azathioprine
  • Cyclophosphamide
8
Q

Established immnosuppressive drugs

What is the role and mechanism of corticosteroids?

A
  • Affect both T and B cell function
  • Effect: cytokine networks, inflammation, T cell and monocyte function and transit of active cells
  • but side effects mean long term use is often not faesable
9
Q

Established immnosuppressive drugs

Explain the role and mechanism of Azathioprine?

A
  • purine analogue which inhibits DNA synthesis.
  • Inhibits T & Natural Killer cell functions.
  • Anti-inflammatory
  • Used in combo with steroids to reduce need for higher doses of steroid
10
Q

Established immnosuppressive drugs

Explain the role and mechanism of cyclophosphamide:

A
  • Alkylating agent which interferes with DNA synthesis.
  • Little anti-inflammatory activity and is therefore generally given in combination with steroid.
  • Useful for suppressing B cell activity and antibody production, particularly autoantibody production
11
Q

What are the main newer immunosuppressant drugs?

A
  • Cyclosporin and Tacrolimus
  • Sirolimus
  • Mycophenolic acid
12
Q

Newer immunosuppressant drugs

How does cyclosporin and tacrolimus work?

A
  • Fungal products.
  • Both are pro-drugs which require to bind to cytoplasmic receptors to become active.
  • Both involved in modulation and down-regulation of various genes, particularly transcription of interleukin-2 gene.
  • As a result major immune suppressive effects are on T cells (especially Th cells) and Natural Killer cells.
13
Q

There are alternatives to drug therapies: what are their aims?

A
  • destroy immunologically active cells, b) disrupt interaction of HLA molecule / antigen / T cell receptor, c) interfere with traffic or activity of inflammatory cells, d) interfere with or remove inflammatory or immune mediators
14
Q

Alternatives

Explain the use and mechanism of monoclonal antibodies:

A
  • Creation of a single cell clone line that can continously create specific antibodies
  • Can either be used in naive form (unconjugated) or linked (conjugated) to cytotoxic drugs, toxins or isotopes and have a more specific therapeutic approach
  • T cell receptors, CD3, CD4, CD52 (Campath), HLA molecules, adhesion molecules, cytokines & cytokine receptors can all be produced.
  • Difficulty is that most of them are cleaved from rat/mouse DNA so we have to humanise them to reduce adverse reaction and increase efficacy
15
Q

Alternative

Explain the use and mechanism of cytokine therapy:

A

Can involve:

  • Production of in vitro recombinant cytokines
  • or
  • Factors that will effect the body’s cytokines

Aim

  • Inhibit the activity of harmful cytokines and increase the activity of beneficial cytokines

Examples:

  • IL-1, IL-2, IFNalpha
16
Q

Alternative

Please explain the role and mechanism of plasmapheresis:

A
  • Frequently used in treatment of myasthenia gravis, Goodpastures syndrome and various forms of systemic vasculitis usually in combination with additional immunosuppressive measures such as steroid and cytotoxic drug therapy
  • Plasma is whisked off blood and replacement products put in
  • Very expensive
  • Time consuming
17
Q

When is immunoglobulin therapy indicated?

A
  • As replacement therapy in patients with primary or secondary antibody deficiency
  • As immune modulating therapy in certain inflammatory or autoimmune disorders. Examples of these are:
    • Kawasaki disease
    • Vasculitis
    • Myasthenia