Immune modulating therapies Flashcards
what are the pros and cons of live attenuated vaccines
Pros = lifelong immunity (no boosters), activates all phases of the immune response, protects vs cross-reactive strains
Cons = danger to immunocomp + immunocomp contacts, revision to virulence, cold storage
MMR, Polio (sabin), influenza and varicella virus
live attenuated vaccines
Pertussis, Polio (salk), cholera vaccine
Inactivated vacc
tetanus, dipheria vaccine
toxoid inactivated vacc
Hep B, HPV vacc
subunit inactivated vacc
pros and cons of inactivated vacc
Pros = no reversion risk, safe for immunocomp, low cost, easy storage
Cons = low longevity, needs boosters, may req conjugation/adjuvants
what vaccine is used for encapsulated organisms (NHS bac)
conjugate - tetanus toxin + Ag form encapsulated org
req boosters
= poorly immunogenic polysaccharide (Ag) + immunogenic protein carrier (adjuvant)
most common adjuvant used in vaccines and their function
Aluminium hydroxide
-> increase immune response without decreasing specificity (prolong release of Ag)
what vacc type is provenge
dendritic cell vaccine - Ex-vivo dendritic cells pulsed with tumour Ag
Provenge = personal immunotherapy for prostate cancer
harvest sites for HCST
bone marrow, periph blood, umbilical cord
what HCST is used for MM and lymphoma
Auto
what HCST is used for leukemia
Allo
indications for IVIG
CVID, Hyper IgM, MM, CLL, post HCST
how is IVIG produced
large donor pool that is screened then filtered+ treated for microorg
how is specific Ig produced
prod by single donor with high titres of IgG to specific pathogens
indications for specific Ig
post-exposure prophylaxis for Hep B, rabies, VZV in preg/immunosuppression, tetanus
indications for viral specific T cell therapy
for severe, persistent viral inf in immunocomp
indications for tumour infiltrating T cell therapy
immunotherapy for metastatic cancer
what are the indications for CAR-T cell therapy
ALL and NHL
how does CART-T cell therapy work
leukapherisis -> T cells engineered to express chimeric Rs that bind to CD19 on B cells -> binding triggeres cytotoxic killling of B cells
what does CTLA4-CD80 binding stimulate and where are these Rs expressed
inhib T cell activation
CTLA4 = T cell
CD80 = APCs
what does PD1-PD1L binding stimulate and where are these Rs expressed
Inhib T cell activation
PD1 = T cells
PD1L = APCs
what does CD28-CD80 binding stimulate and where are these Rs expressed
stimulate T cell activation
CD28 = T cells
CD80 = APCs
what ligands can Tumour cells express to evade T cells activation
CD80 and PD1
function and use of ipilimumab
= CDLA4 inhib
used vs advanced melanoma
complication = autoimmunity
function and use of pembrolizumab/nivolimumab
PD1 inhibitor
vs advanced melanoma / metastatic renalCC
function and use of IL2
stim T cell response
used vs RCC
function and use of IFNa
= antiviral
vs HepB/C, hairy cell leukemia, kaposi sarcoma, MM, CML
function and use of IFNb
immunomodulator
used vs Behcet’s lymphoma, relapsing MS
function and use of IFNg
enhances macrophage function
used vs CGD
what are antiproliferative agents used to treat
used vs cells with high turnover rates (vs canceers and for immunosupp)
what is azathioprine converted to and what is it used to treat
conv to 6mp in liver -> inhib de novo purine synth
used to prev graft rejection
what is mycophenolate converted to and what is it used to treat
conv to mycophenolic acid -> inhib de novo guanine synht
used to preg graft rejection
function and use of cyclophosphamide
alkylates guanine base -> inhib DNA synth
function and use of mehtotrexate
dihydrofolate reductase inhibitor -> inhib DNA synth
adverse effects of Azathioprine
BM suppression, infection, malig
TPMT polymorph -> toxic accum -> hepatotox
adverse effects of mycophenolate
BM suppression, infection, malig
-> progressive multifocal leukoencephalopathy + HSV reactivation
adverse effects of cyclophosphamide
BM suppression, infection, malig
haemorrhagic cystitis + non-melanoma skin cancer
adverse effects of methotrexate
BM suppression, infection, malig
pulmonary fibrosis, pneumonitis, folate def
class and method of action of tacrolimus and cyclosporine
calcineurin inhib - block c stim IL2 expression
adverse effects of calcineurin inhib
gingival hyperplasia
class and method of action of sacrolimus
mTOR inhib - Block IL2 expression -> clonal expression of T cells
class and method of action of tofacitinib
JAK inhibitor - inhib JAK-STAT signalling -> dec pro inflam gene transcription
method of action of PDE4 inhibitors
dec cAMP -> dec cytokine prod
function and use of Rabbit ATG
= cell surface antigen inhib
-> dec lymphocytes, dec T cell activation
used vs acute allograft rej
function and use or basiliximab
= cell surface antigen inhib
blocks IL2
used vs acute allograft rej
function and use of abatacept
= cell surface antigen inhib
stim CTLA4-Ig -> dec T cell activ
used vs rheumatoid arth
function and use of rituximab
= cell surface antigen inhib
anti-CD20 - targets mature b cells
used vs B cell lymphoma
function and use of natalizumab
= cell surface antigen inhib
anti a4 integrin -> dec T cell migration
used vs MS
function and use of vadolizumab
= cell surface antigen inhib
anti a4b7 integrin -> dec cell migration to gut
used vs IBD
function and use iflixumab
anti TNFa abs (cytokine inhib)
used vs rheumatoid arth, psoriasis, ank spond, IBD
function and use anti IL12/23 cytokine inhib
inhib differentiation to Th1 and Th17 -> dec IL12%IL23
used vs psoriasis
function and use denusomab
anti RANKL
dec bone resorbtion - used vs osteoporosis
side efect of denusomab use
avascular necrosis of jaw
function and use of anti IL-6R
dec neutrophil/macrophage/T/B cell activation
used vs rheumatoid arth
difference between plasmapheresis and plasma exchange
blood passed through cell seperator
plasmapheresis - plasma Tx to remove Ig and reinfused
plasma exchange - plasma discarded and replaced with coloid (albumin)
indications for plasmapheresis
goodpastures, myaesthenic crisis, graft rejection
