I - Suppressing The Immune Response Flashcards
do steroids have glucocorticoid or mineralocorticoid activity or both?
only glucocorticoid
how are steroids anti inflammatory
phospholipase a2 breaks down phospholipids to form arachidonic acid –> prostaglandins –> inflam
therefore, block phospholipase a2 –> anti inflammatory
what do steroids do to neutrophil count and what is the effect
increase neutrophils
reduced cell trafficking to site
4 effects steroids have on the adaptive immune system
lymphocytes sequestered therefore low WCC
block cytokine gene expression
block AB production
increase apoptosis of BTT cells
side effects of steroids
metabolic - DM, obesity, moon face, change in lipids, osteoporosis, hirsuitism, adrenal suppression
other - cataracts, glaucoma, peptic ulcer, pancreatitis, avascular necrosis
IMMUNE SUPPRESSION and infection
give 3 examples of anti proliferative agents
cyclophosphamide
azathioprine
mycophenolate
how do anti proliferative agents cause immune suppression
inhibit DNA synthesis of rapid turnover cells ie immune cells
SE of anti proliferative agents
BM suppression
infection
malignancy
teratogenicity
SE of cyclophosphamide
toxic to proliferating cells - hair loss, BM support, sterility
haemorrhagic cystitis
malignancy - bladder, blood, non melanoma skin
infection - PCP
SE of azothioprine
BM suppression - variable severity
hepatotoxicity
infection
which anti proliferative agent gives more infections as a SE
cyclophosphamide
mycophenolate SE
BM suppression
infection
which infections are most common with mycophenolate
HSV reactivation
JC virus causing progressive multifocal leucoencephalopathy
aim of plasma exchange
removal of pathogenic ABs
what happens in plasma exchange
pts own blood put through cell separator
removes Ig from plasma, then re infused
rebound AB production (however only temporary)
indications for plasma exchange
AB mediated disease ++severity
eg Goodpastures, MG, ABO incompatibility
which classes of drugs are used to inhibit cell signalling
calcineurin inhibitors
mTOR inhibitors
JAC inhibitors (Jakinibs)
PDE4i
how do calcineurin inhibitors suppress the immune system
T cell proliferation inhibitors
indications for calcineurin inhibitors
transplant
SLE
psoriatic arthritis
examples of calcineurin inhibitors
ciclosporin
tacrolimus
indication for mTOR inhibitors
transplant
examples of mTOR inhibitors
rapamycin
sirolimus
indications for jakinibs
RA
psoriatic arthritis
axial spondylrthritidies
how do jakinibs work
inhibits JAK-STAT signalling
inhibits production of inflammatory molecules and influences gene transcription
example of PDE4i
apremlias
indications for PDE4i
psoriatic arthritis
psoriasis
(not used commonly)
3 agents that bind to T cell surface antigens
rabbit anti thymocyte globulins
basiliximab / doclizumab
abatacept
what is rabbit anti thymocyte globulins used for
allograft rejection
how does rabbit anti thymocyte globulins work
reduced lymphocytes, modifies T cell activation
SE of rabbit anti thymocyte globulins
infusion reactions
leucopenia
infection
malignancy
how is rabbit anti thymocyte globulins given
daily IV infusion
what are basiliximab / doclizumab
CD25 AB
what are basiliximab / doclizumab used for
prophylaxis of allograft reaction
how do basiliximab / doclizumab work
blocks IL2 induced signalling and stops T cell proliferation
how are basiliximab / doclizumab given
IV pre and post transplant surgery
SE of basiliximab / doclizumab
infusion reaction
infection
malignancy risk long term
what is abatacept
CTLA4-Ig fusion protein
what is abatacept for
RA
how is abatacept given
IV 4x weekly or SC weekly
how does abatacept work
reduced co-stimulation of T cells via CD28
SE of abatacept
infusion reaction
infection - TB, HBV, HCV
malignancy
2 agents that bind to B cell surface antigens
rituximab
vedolizumab
what is rituximab
AB to CD20
what is rituximab used for
lymphoma
RA
SLE
how is rituximab given
2 x IV every 6-12 months
how does rituximab work
depletes mature B cells - leaves plasma cells
SE of rituximab
infusion reaction
infection - PML
exacerbates CVD
what is vedolizumab
alpha 4 beta 7 integrin AB
how does vedolizumab work
inhibits leucocyte migration
stops exavasation into tissues
what is vedolizumab used for
IBD
how is vedolizumab given
IV every 8 weeks
SE of vedolizumab
infusion reaction
hepatotoxicity
infection
malignancy
what are TNF alpha blockers used for
RA
psoriatic arthritis
IBD
FMF
ank spon
examples of TNF alpha blocker ABs
infliximab
adalimumab
certolizumab
golimumab
SE of TNF alpha blocker ABs
infusion reactions
infection - TB, HBV, HCV
Lupus like conditions
demyelination
cancer
example of TNF alpha antagonist
etanercept
what is etanercept used for
RA
ank spon
psoriatic arthritis
what are anti IL1 agents used for
FMF
gout
adult onset stills
what are anti IL6 agents used for
RA
GCA
large vessel vasculitis
what can anti IL23 agents be used for
ax spon
psoriatic arthritis
IBD
describe the inflammasome
pyrin / urate feed into the ASC –> procaspase 1 –> IL1 / NFKB / apoptosis
what are anti IL4/5/13 agents used for
asthma / eczema
what are anti rank and anti rank ligand agents used for
osteoporosis
4 main side effects of biological agents
infusion reactions
injection site reactions
infection
malignancy
how is infection risk for imm support managed
vaccination - not live attenuated
stop imm sup agents if ill
appropriate ABx
hand hygiene
avoid unwell contacts
4 potential viruses that can cause chronic infection in someone on imm supp
TB
hep B/C
HIV
JC virus
what can JC virus cause in someone imm sup
progressive multifocal leucoencephalopathy
what is progressive multifocal leucoencephalopathy
destroys oligodendrocytes - can be fatal
what cancers are imm sup people at risk of
lymphoma from EBV
non melanoma skin cancer - HPV
melanoma - unsure of risk
NOT solid tumours
