Immunomodulation Flashcards
When is immune modulation indicated?
- Suppression of inappropriate immune responses
- Enhance immune response against neoplasia
- Limit the immune response in degenerative disease
Which hypersensitivity reaction is IgG mediated?
Type II
What is the action of anti-inflammatory medications?
Act to block some effector mechanisms of the innate immune system
What is the action of immunosuppressive medications?
Mainly act to reduce the function of the adaptive immune system
Reduce lymphocyte proliferation
What are the 3 main groups of immunosuppressive drugs used in a veterinary practice?
Drugs which inhibit:
- Cytokine gene expression
- IL-2 production
- DNA synthesis
What is used as the first line immunosuppressive treatment for many immune mediated diseases?
Glucocorticoids
Where are glucocorticoids metabolised and excreted?
Metabolised in the liver
Excreted by the kidneys
Describe the MOA of glucocorticoids?
- Bind to receptors in the cytoplasm
- Transit to nucleus and bind to DNA influencing transcription of a huge number of genes in many tissues
- Reduce degranulation
- Reduce pro-inflammatory cytokine production
- Reduce antigen presentation
The effect of glucocorticoids depends on..?
Dose and formulation
List some adverse effects of glucocorticoids
- Skin thinning
- Weight gain
- Muscle loss
- Polyphagia
- PU/PD
- GI bleeding
- Lethargy
What systemic effects are expected of glucocorticoids?
- Stimulate gluconeogenesis
- Suppress inflammation
- Alter fat, protein and carbohydrate metabolism
- Suppress HPA axis
Which cells produce IL-2?
CD4+ cells
IL-2 leads to stimulation of…?
- Activation of T-cells
- B-cell proliferation
- Activity of innate immune cells (macrophages, NK cells)
What occurs when IL-2 is inhibited?
- Reduced activity of all functions requiring helper T-cells (adaptive immunity)
- Cytokine suppression
Which 2 drugs are most commonly used to inhibit IL-2 production/action?
Ciclosporin
Tacrolimus
Which molecule is blocked by the drugs which inhibit IL-2 production?
Calcineurin
Name 2 drugs which inhibit DNA synthesis
Azathioprine Mycophenolate mofetil (MMF)
Which enzyme is targeted by drugs which inhibit DNA synthesis?
Purine
What are second line immunosuppressives used in conjunction with?
Steroids
What are immunosuppressives and steroids used in conjunction for?
- To increase the immunosuppressive effect
- To increase the rate at which steroids can be withdrawn
- To reduce dose and adverse effects of steroids
What is the action of imiquimod?
Applied to the skin and it stimulates the immune system
What is the action of a vaccine dependant on?
- Route of vaccine
- Type of vaccine
- Presence or absence of co-stimulatory molecule
