Immunomodulation 1&2 Flashcards
Cells involved in immune memory
pool of specific B and T cells
How do follicular T helper cells provide help to B cells for expansion and isotope swiching?
CD40L and cytokines
antibody order in immune response
IgM initial response
IgG than takes over
what criteria are important for generating a vaccine?
- Memory
- no adverse effects
- safe, easy to administer, one dose only if possible
Haemagglutiniation inhibition assay
wells with RBC only - dot where RBCs sink
wells with RBC plus virus - haemagglutination
wells with RBC and effective antibody - dot where RBCs sink because antibodies bind and neutralises to the HA -> no haaemaagglutiinataion
for influenza vaccination
Manatoux test - immune reaction
Type IV
(delayed response, have to read the results around 72h post injection)
Cytokine therapy -
used to be used
goal waas to induce interleukin 2 (two stimulate T cell response)
some of the TT-cells
Cytokine therapy - interlukin 2, where useful?
renal cell cancer
IFN-gamma cytokine therapy
add from lecture
can be used in chronic granulomatous disease
INF-alpha cytokine therapy
Replacing missing components of the immune system as immune modulating therapy
HSCT
Antibody replacement
noramal
How is human normal IgG made?
prepared form pools or >1000 people
….
human IgG when uussed.
primary and secondary antibody deficiencies
Specific Ig - when used?
PEP (Hep B)
Specific Ig - How made?
derived from plasma donors with high titres of IgG Abs to specific pathogens.
When do you use VZVIgG rather tthan
<20w pregnant
or
immunocompromised?
ACT - what is it?
ACT - when is it used?
TIL T-cell therapy
what does IL-2 do?
proliferation of T-cells
TCR and CAR-T cell therapy
Issue with checkpoint inhibitors
often develop autoimmune diseases (because of the T-cell activation)
Examples of what checkpoint inhibitors bind to?
PD1
PD2
CTLA4
Examples of checkpoint inhibitors
Which vaccines are live?
BCG
Polio (oral)
MMR
What do steroids block?
Phospholipase A2
Why are neutrophil counts high in poeple on high dose steroids?
interfere with trafficking and function in the innate immune system
….
effects of corticosteroids on lymphocyte function
lymphopenia (sequestration of lymphocytes ion lymphoid tissue)
Side effects of ssteroids
diabetes
central obesity
moon face
lipid abnormalities
osteoporosis
hirsutism
adrenal suppression
infection
cataracts
glaucoma
peptic ulcer
pancreatitis
Anti-proliferative immunosuppressaants - examples
cyclophosphamide (most toxic)
mycophenolate
azathioprine (caban be used in pregnancy)
Anti-proliferative immunosuppressaants - MoA
inhibitt DNA synthesis
Aside effects of cyclophosphamide
bone marrow depression
hair loss
sterility (men»_space;> women -> sperm storage)
haaemorrhagic cysts
malignancy (bladder cancer, haematological malignancies, non-melaonma skin cancer)
Infection (pneumocystsitis jiroveci)
Azathioprine SE
bone marrow suppression (1 in 300 individuals are extremely susceptible to this because of TPMT polymorphisms)
hepatotoxicity
Infection (less common)
Azathioprine SE
bone marrow suppression (1 in 300 individuals are extremely susceptible to this because of TPMT polymorphisms)
hepatotoxicity
Infection (less common)
What do you do before staarting azathioprine?
check TPMT for polymorphisms
if homozygous: don’t use
if heterozygous: use 50% dose
SE of mycophenolate mofetil
bone marrow suppression
herpes virus reactoncation
progressive multifocaal leukoencepaahlopathy (JC virus)
How does plasma exchange work?
remove patients blood, filter out antibodies and return blood without the anttibodies
temporary effects until the
useful in severe antibody mediated disease or antibody mediated transplant rejection
T2 hypersensitivity reaction
What immune reaction type does plasma exchange work for>
type 2 (AB mediated)
What diseases can plasma exchange help wth ?
Myasthenia gravis
Goodpaasture syndrome
Tacrolimus
calcineurin inhibitor
where is tacrolmus used?
transplant
AI-diseasse e.g.SLE, psoriatic arthritis
examples of calcineurin inhibitors
tacrolimus
Rapamycin
mTOR inhibitor
mTOR inhibitor examples
Sirolimus
Rapamycin
Jakinibs
JAK inhibitors
effective in RA, psoriatic arthritis, axial spondyloarthritis.
more SE than some of the monocolonals
oraal agent so some people prefer it to monoclonals
Why do some people prefer Jakinibs to monoclonal despite more SE?
because they are an oral agent
Why do some people prefer Jakinibs to monoclonal despite more SE?
because they are an oral agent
anti-thymocyte globulin - how is it made?
inject human thymocyte into rabbit ???
more
toxic effects of anti-thymocyte immunoglobulin
CD25 antibody
IL-2R alpha chain
blocks the effect of IL-2
given before and after transplant surgery for prophylaxis of rejection
Toxicity associated with IL-2Ralpha chain monoclonla
CTLA4-Ig fusion protein mAb - indications
RA (IV 4 weekly, sc weekly)
How does CTLA4-Ig work?
reduces co-stimulation of CD28 + T cells
Rituximab - what is lit against?
CD20 = B-cells
depletes mature B cells but keeps plasma cells
Indications for rituximab
lymphoma
RA
SLE
2 doses IV every 6-12 months (RA)
toxicities of rituximab
Infusion reactions
infection (PML)
exacerbation CV disease
NOT mlaignancy
Vedolizumab - alpha4beta7 integrin - indication and frequency
IBD
IV every 8w
How does Vedolkizumab work?
inhibits leukocyte migration?
Toxic effects of Vedolizumaab
TNF-alpha blocker examples
Infliximab
Adalimumab
Certoliizumab
Golimumab
Conditions where you can use TNF-alpha inhibitors
RA
psoriasis
psoriatic arthritis
IBD
FMF
ankylosing spondylitis
sc or IV
Toxicity of TNF-alpha inhibitors
infusion or injection site reactions
infection (TB, HBV, HCV) - screen for latent TB infection before you start
lupus like conditions
demyelination
malaignancy
Etanercept
TNF - alpha inhibitor
works differently?
IL-1 blocl
IL-6 / IL-6 R block
in RA, GCA, LV vasculitis
affects T-cells, B-cells, synoviocytes
IL-23 and IL-17 pathway
important in spondyloarthriitides and related conditions
Important pathway in spondyloarthtitides
IL-23 ->
TH17 differentiation ->
IL-17 anad IL-22
can block this pathway with Secukinumab (anti IL17) and guuselkumab (anti IL 23)
IL 4, 5 13 axis
asthma
eczema
Where was Rank Rank ligand useful?
osteoporosis
Immunosuppression - advice to give aaptients
2x risk of infection
wash hands / avoid contact
vaccination /avoid live vaccines…
,,,,
what vaccines are we particularly worried about in immunosuppressed patients?
chronic infections, particularly TB
-> CXR and elispot/quantiferon usually done before starting treatment
latent TB in someone you want to start immunosuppressive treatment in
generally, treat latent TB before starting immunosuppressive treatment
if the disease is very severe you may not want to wait
JCV
John Cunningham virus
common polyomaviru s….
what malignancies are we worried about in immunosuppressed individuals.
lymphoma (EBV) - 3-4x risk
non-melanoma skin cancer (HPV)
?melanoma
AI side effects of iimmunosuppression
SLE and lupus like syndromes
APS
vasculitis
interstitial lung disease
sarcoidosis
autoimmune hepatitis
…
when do you see lupus like syndromes?
in TNF alpha therapy
Psoriasis and psoriatic aarthritis - what type of autoimmunity
T-cell mediated autoimmunity
