Immunomodulators (year 2) Flashcards
what are the two ways to modulate the immune system?
immune suppression
enhance host immune response
what can be targeted to suppress immune response?
inflammatory response
allergic response
inappropriate immune response
when may we want to enhance the immune response?
infection
vaccination
against neoplasia
what are the 4 hypersensitivity reactions?
1 - IgE and MCT mediated
2 - IgG mediated
3 - immune complex
4 - cytotoxic T cell mediated
what do anti-inflammatory medications target?
block some effector mechanism of the innate immune system
what do immunosuppressive medications target?
reduce function of adaptive immune system by reducing lymphocyte proliferation or limit their effect
what are the three main groups of immunosuppressive drugs?
inhibit cytokine gene expression
inhibit IL2 production/action
inhibit DNA synthesis
what is the first line immunosuppressive treatment for many diseases?
glucocorticoids
where are glucocorticoids metabolised and excreted?
liver and excreted by kidney
are glucocorticoids protein bound?
yes
what is the mechanism of action of glucocorticoids?
bind to receptors in cytoplasm this transmits a signal to the DNA which then switches on/off genes
what are the functional outcomes of glucocorticoids?
stabilise mast cells to reduce degranulation
reduce pro-inflammatory cytokine production (IL2)
downregulate Fc receptor expression on macrophages
reduce antigen presentation
what are the three main glucocorticoids?
prednisolone
methylprednisolone
dexamethasone
what glucocorticoid is the longest acting and has the highest potency?
dexamethasone
what are the other effects of glucocorticoids?
stimulate gluconeogenesis
suppress inflammation
alter fat, protein and CHO metabolism
suppress HPA axis
what side effects do glucocorticoids cause?
PUPD lethargy GI bleeding hypercoagulability polyphagia weight gain muscle loss
what cells produce IL2?
Th (CD4) cells
what does IL2 stimulate?
clonal proliferation
activation of T cells
B cell proliferation
activity of innate immune system (NK, macrophages)
what are the two most common IL2 inhibitors?
ciclosporin
tacrolimus
how is ciclosporin administered?
topical, oral, parenteral
where is ciclosporin and tacrolimus metabolised and excreted?
liver and excreted in bile
what are the adverse effects f ciclosporin and tacrolimus?
transient vomiting
opportunistic infection
increase risk of neoplasia
what are the main DNA synthesis inhibitors?
azathioprine
mycophenolate mofetil (MMF)
leflunomide
what does azathioprine inhibit?
purine synthesis - stops DNA and RNA synthesis
what part of the immune response does azathioprine reduce?
Th1 mediated immunity
how is azathioprine administered?
orally
where is azathioprine metabolised to its active form?
liver
what species should azathioprine not be used in?
cats
what are the adverse effects of azathioprine?
hepatopathy
myelosuppression
GI signs
pancreatitis
what does mycophenolate mofetil inhibit?
an enzyme crucial to purine synthesis in lymphocytes
what response does mycophenolate mofetil reduce?
T cell differentiation
antibody response
dendritic cell maturation
where is mycophenolate mofetil metabolised and excreted?
hepatic metabolism then excreted renally
what are the adverse effects of mycophenolate mofetil?
diarrhoea
weight loss
what are the actions of human immunoglobulin?
binds T and B cells to prevent proliferation and activation
block immune function
what are the adverse effects of human immunoglobulin?
hypercoagulability
glomerulonephritis
transfusion reactions
