Immunology - Immune-modulating therapies 1 & 2 Flashcards
By what mechanism can B cells provide immunological memory?
High affinity IgG remains circulating in blood
What is the best predictor of immunity to influenza following a vaccine?
IgG against haemaglutinnin (moreso than CD8 T cells) detected using a Haemagluttinin (HA) assay
Why is adjuvant used in some vaccines?
increase the immune response without altering its specificity:
What does PEP for HIV contain?
Specific immunoglobulin for HIV
What monoclonal antibody can be used in melanoma treatment? Its specific for what antibody?
Ipilimumab (anti-CTL-A4)
This blocks an immune checkpoint by binding to CTLA4, forces CD80 and CD86 to go through stimulatory CD28 pathway –> enhanced T cell response
In what disease can IFN gamma be given therapeutically?
Chronic granulomatous disease
In what disease can IL2 be given therapeutically?
Renal cell carcinoma
IL-2 expands NK and T cell responses via the IL-2 surface receptor
In what 2 diseases can IFN alpha be given therapeutically?
CML
Multiple myeloma
How do steroids inhibit the immune response?
Inhibit phospholipase A2 which is a key enzyme in prostaglandin formation, reducing inflammation
Also decrease phagocyte trafficking (hence there is a transient increase in neutrophil count)
Recall 3 examples of anti-proliferative agents
Cyclophosphamide
Azothioprine
Mycophenalate
What is the mechanism of action of cyclophosphamide?
alkylating agent
Alkylation of guanine –> inhibition of DNA synthesis
affects B cells > T
What is the mechanism of action of azothioprine?
purine analogue
coverts purine to 6 mercaptopurine (6-MP
inhibits de novo purine synthesis and acts as an antiproliferative
affects T cells > B
What must always be checked before prescribing azothioprine?
TPMT activity
Thiopurine methyltransferase
How can plasmapheresis be used to treat autoimmune diseases? What should you give in conjunction
emoves problematic antibody
Need to give alongside an antiproliferative agent such as cyclophosphamide to prevent rebound antibody production
How do calcineurin inhibitors work?
blocks IL2 production
Give 2 examples of a calcineurin inhibitor? What cells do they inhibit
inhibit t lymphocytes
Cyclosporine
tacrolimus
Give 2 diseases in which JAK2 (janus kinase) inhibitors can be useful?
Rheumatoid and psoriatic arthritis
By what mechanism do PDE4 (phosphodiesterase) inhibitors work, and in what disease are they useful?
increased cAMP
activates PKA (protein kinase A)
leads to decrease in cytokine production
Recall 2 immune-modulating therapies that are useful in the prophylaxis of allograft rejection
Anti-thymocyte globulin (rabbit)
Anti-CD25 (Basiliximab)
Wha type of antibody is rituximab?
Anti-CD20
What monoclonal antibody can be used in IBD treatment?
Vedolizumab
Anti - alpha4beta7 integrin
What is infliximab?
Anti-TNF alpha
What monoclonal therapy can be used in osteoporosis?
anti-RANK/RANK-ligand = Denosumab
What is the mechanism of action of tofacitinib
JAK inhibition
What is the mechanism of action of apremilast?
Anti-PDE4
What is the mechanism of action of basilixumab?
Anti-CD25 (alpha chain of interleukin 2)
What is the mechanism of action of Abatacept?
CTLA4 Ig
opposite of ipilimumab
it turns off T cells reducing autoimmunity hence why used in RA
What is the mechanism of action of rituximab?
Anti-CD20
What is the mechanism of action of natalizumab?
Anti-alpha4 integrin
What is the mechanism of action of tocilizumab?
Anti-IL6-Receptor
What is the mechanism of action of muromonab
Mouse monoclonal against CD3
What is the mechanism of action of alemtuzumab?
Anti-CD52
What is the mechanism of action of adalizumab?
Anti-TNF alpha
What is the mechanism of action of certolizumab?
Anti-TNF alpha
What is the mechanism of action of golimumab?
anti-TNF alpha
What is the mechanism of action of etanercept?
TNFa antagonist
What is the mechanism of action of ustekinumab?
Anti-IL12/23
What is the mechanism of action of sekukinumab? Treats what 2 conditions
Anti-IL17a
psoriasis/psoritatic arthritis
ankylosing spondy
What condition can be treated with apremilast?
Psoriasis
What conditions can be treated with natalizumab?
MS
Crohn’s
What conditions can be treated with abatacept?
Rheumatoid arthritis
give 2 live attenuated vaccines
BCG
MMR
give 4 inactivated vaccines
influenza
pertussis
polio
hep A
what’s the mechanism of mycophenelate
anti metabolite
blocks guanosine nucleotide synthesis, prevents DNA replication
prevent T cell proliferation > B cell
give an example of a JAK2 inhibitor
ruxolotinib
give an example of a PDE4 inhibitor
apremilast
give 3 classes of drug that inhibit cell signalling
calcineurin inhibitors
JAK inhibitors
PDE4 inhibitors
give 4 anti TNFa drugs
infliximab
adalimumab
certolizumab
golinmumab
anti IL-12 and IL-23 can be used for what 2 conditions
psoriasis/psortiatic arthritis
crohns
guselkumab is used to treat what?
psoriasis
guselkumab is anti IL…
IL 23
What infection should be ruled out before commencing inflximab for cronhs
TB via mantoux test
if mantou +ve then an interferon gamma release assay (IGRA)
if ve = latent TB mist treat before immune modulating therapy
whats a recombinant vaccine? give 2 examples
accine contains proteins found on the surface of the viruses in addition to an adjuvant. Examples include Hep B and HPV.
what a conjugate vaccine? what are they used against? give 3 examples
For encapsulated bacteria.
Consist of bacterial polysaccharides conjugated to an immunogenic toxin (diphtheria toxin).
Used for Haemophilus influenzae, meningococcus and pneumococcus.
What antigen is injected intradermally as part of the mantoux screening test for tuberculosis?
Tuberculin Purified Protein Derivative
how is the mantoux test interpreted
The size of the induration (not erythema) is measured after 48-72 hours.
>5mm is positive in HIV or immunosuppressed patients or people at very high risk of TB (such as living with someone with active TB)
>10mm is positive in IVDU, medium risk populations such as healthcare workers or children <4 years old
>15mm is positive in low risk populations.
give a complication of the use of natalizumab, mycophenelate & rituiximab
Progressive Multifocal Leukoencephalopathy caused by the
john cuNNINGHAM vIRUS
What mouse monoclonal antibody targets CD3 on the surface of T cells?
Muromonab
what antibody targets cd 25? whats its use
basiliximab
allograft rejection
what is tocfatinib and its use
JAK inhibitor used in rheum arthritis
what monoclonal antobody targerts CD52. whats the effect
alemtuzumab
depletion of all lymphocyte subsets
state 4 anti TNFa drugs
Infliximab/Adalimumab/Certolizumab/Golimumab
directly bind to TNFa
give the se’s of prednisolone, cyclophosphamide and tacrolimus
pred - osteoporosis
cyclo - infertility
tacro - nephrotixicity