immunotherapy Flashcards
(17 cards)
What is immunotherapy?
Harnessing the power of the immune system to fight disease
What are common strategies for immunotherapy?
Generalised immunosuppresion
Tailored therapies for specific immune response
What are the risks of generalised immunosuppresion?
High risk of opportunistic infection
What is acute rejection to organ transplant?
- Acute rejection in particular is associated with T cell responses that mediate immune cell infiltration into the graft and effect its rejection
What ways can we stop graft cell rejection?
Methods for inhibiting T cell activation to treat graft rejection
- Cyclosporins which inhibit calcineurin
See image of passive vs active immunity:
What are the three types of established immnosuppressive drugs?
- Corticosteroids
- Azathioprine
- Cyclophosphamide
Established immnosuppressive drugs
What is the role and mechanism of corticosteroids?
- 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
Established immnosuppressive drugs
Explain the role and mechanism of Azathioprine?
- 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
Established immnosuppressive drugs
Explain the role and mechanism of cyclophosphamide:
- 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
What are the main newer immunosuppressant drugs?
- Cyclosporin and Tacrolimus
- Sirolimus
- Mycophenolic acid
Newer immunosuppressant drugs
How does cyclosporin and tacrolimus work?
- 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.
There are alternatives to drug therapies: what are their aims?
- 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
Alternatives
Explain the use and mechanism of monoclonal antibodies:
- 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
Alternative
Explain the use and mechanism of cytokine therapy:
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
Alternative
Please explain the role and mechanism of plasmapheresis:
- 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
When is immunoglobulin therapy indicated?
- 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
