MedEd Immuno 2 Flashcards
what is oral allergy syndrome
allergy sx limited to mouth
when does the allergy not happen in oral allergy syndrome
cooked !
allergens are heat labile
in oral allergy syndrome, why can you be allergic to things other than allergen
cross reactive IgE to foods eg pollen –> stone fruit
2 examples of mixed IgE and cell mediated type 1 reaction
atopic dermatitis
eosinophilic oesophagitis
example of non IgE mediated allergic disease
coeliac
(lymphocytic destruction)
Ix for allergy
skin prick test
IgE bloods
oral challenge
benefits of skin prick test
easy to do
cheap
high negative predictive value
cons of skin prick test
need to stop antihistamines before
poor positive predictive value
affected by severe derm diseases (eg rlly bad eczema)
risk of anaphylaxis
what is IgE blood test aka
RAST
benefits of IgE blood test
prediction of allergy RISK
when is IgE blood test good
if skin prick test not possible
what is gold standard allergy test
oral food challenge
cons of oral food challenge
high risk of anaphylaxis
time consuming
difficult in little kids to see if they get sx
close supervision
what is the prerequisite for type 2 reactions
breakdown in self selection
examples of type 2 reaction
goodpastures
pemphigus vulgaris
graves
myasthenia gravis
how is type 2 and type 3 different
type 3 is a soluble Ag, type 2 is on your cells
example of type 3 reaction
SLE
polyarteritis nodosa
what type of damage is done in type 3 reactions
fibrinoid necrosis
effects of cd4 response
reactive oxygen species generation
lysozymes
inflam
effects of cd8 response
apoptosis from
- perforin
- granzyme
4 examples of type 4 reactions
contact dermatitis
tuberculin skin test
T1DM
Hashimoto’s
important determinants of transplant rejection
HLA / MHC
ABO blood group
what chr is HLA encoded on
6
types of HLA 1
A B C
types of HLA 2
DR DQ DP
which cells have HLA 1 or 2
all have 1
APCs have 2
which groups are most important to match
DR > B > A
what is the chance your sibling is your perfect HLA match
1/4
3 pathways by which t cells recognise transplant –> rejection
direct - donor APC present’s donor MHC to recipient t cells
indirect - recipient APC present’s donor peptides to recipient’s t cells
semi direct - recipient APC presents parts of MHC to recipient t cells
in what scenarios are anti HLA ABs made
not naturally occurring
pre formed - transplant, transfusion, pregnancy
post-formed - graft damage
which ABs involved in B cell mediated rejection occur naturally
anti A / B (blood group)
where do the ABs bind to transplant to cause rejection
endothelium of BV of graft
mx of transplant rejection
screen for it
- ABs - before / during / after
- T cell - biopsy
definitive diagnosis of transplant rejection
biopsy - inflammation
name induction immunosuppressants (pre op)
anti thymosite globulin (ATG)
anti CD52
anti CD25
name baseline immunosuppressants
calcineurin inhibitor
azothioprine or MMF
steroids
tx of t cell rejection
methylprednisolone IV then oral
tx of b cell rejection
plasma exchange
IVIG
anti CD5 / 20 (stops B cells producing ABs)
autologous vs allogenic SCT
autologous = patients own stem cells
allogenic = HLA matched donor SCs
when is autologous vs allogenic SCT used
autologous = MM, lymphoma, solid tumours
allogenic = leukaemia, myelodysplasia
which type of SCT has higher relapse rate
autologous
which type of SCT is more tolerable
autologous
which type of SCT has GVHD risk
allogenic
is GVHD reversible
NO
what is GVHD
donor lymphocytes attack recipient’s tissues
- GI / skin / bone Sx
which type of SCT needs immunosuppression
allogenic
how can the immune system be boosted (4)
vaccination
replacement of missing components
cytokines
checkpoint inhibition
3 requirements of a vaccination
generates immunological memory
no adverse reactions
practical
how can vaccines be enhanced
adjuvants
- boost response without affecting specificity
- more persistent Ag or assisted activation
example of vaccine adjuvant
aluminium salts
what is a depot adjuvant of vaccines
more persistent Ag
what is a stimulant adjuvant of vaccines
assisted activation
examples of live attenuated vaccine
MMR
VZV
BCG
oral polio (Sabin)
typhoid
yellow fever
pros of live attenuated vaccines
lifelong immunity possible (no boosters)
multi strain protection
all phases of immune system activated
cons of live attenuated vaccines
reversion to virulence possible
risk if immunocompromised
complex storage - refrigeration etc
examples of inactivated vaccines
influenza
polio - salk
cholera
plague
hep A
rabies
pertussis
examples of component vaccines
hep B
HPV
influenza recombinant
examples of toxoid vaccines
diptheria
tetanus
pros of inactivated / component vaccines
no reversion to virulence
safe if immunocompromised
easier storage
cheap
cons of inactivated / component vaccines
poor immunogenicity
repeated boosters needed
do not follow natural infection route eg SC for flu
examples of conjugate vaccines
meningitis
influenza
strep pneumonia
tetanus
pros of conjugate vaccines
effective against encapsulated bacteria
good for kids
cons of conjugate vaccines
poor immunogenicity
repeated boosters
do not follow normal route of infection
examples of DNA / RNA vaccines
covid pfizer
covid AZ
pros of DNA / RNA vaccines
non infectious and non integrating
cons of DNA / RNA vaccines
possible autoimmunity response
need target that envokes a good immune response
what is a live attenuated vaccine
live pathogen modified to limit pathogenesis
what is an inactivated / component vaccine
inactivated = destroyed pathogen
component = isolated Ag protein
what is a conjugate vaccine
polysaccharide + Ag protein carrier
what are DNA / RNA vaccines
pathogen’s DNA/RNA delivered to host via viral vector / lipids
which vaccines are good against encapsulated bacteria
conjugate vaccines
which vaccines can’t immuncompromised people have
live attenuated
which vaccines are completely safe for immunocompromised people
inactivated / component
pneumonic for encapsulated bacteria (and for examples of conjugate vaccines)
NHS
n. meningitis
h. influenza
strep pneumonia
3 types of replacement of missing components for immune boosting
haematopoeitic stem cell transplant
ABs
T cell transfer
what type of ABs can be given to boost immune system
normal Ig
specific Ig
who gets normal Ig replacement
AB deficiencies eg alpha gamma globulinaemia, hyper IgM, CVID (all primary) or cancer / BMT (secondary)
when is specific Ig replacement done
post exposure eg hep B, rabies, VZV
3 examples of T cell transfer use
virus specific
tumour infiltrating
CART
when is IL2 replacement given
renal cancer
2 effects of IFN alpha replacement
antiviral
anti cancer
examples of antiviral IFN alpha replacement
Hep B / C
examples of anticancer IFN alpha replacement
kaposi’s sarcoma
hairy cell leukaemia
CML
melanoma
when can IFN g replacement be given
chronic granulomatous disease
- increase macrophage function
when can IFN b replacement be given
relapsing remitting MS
- this is reducing the immune system tho
what is the point of giving checkpoint inhibitors
anti cancer
- immunosuppressive signals upregulated by cancer - removing the immune brakes = boosted immune response
name 2 checkpoint inhibitors and their method of action
ipilimumab (CTLA4) - allows t cell activation
nivolumab (PD1) - prevents t cell death
2 examples of when checkpoint inhibitors can be used
advanced melanoma
metastatic renal cell carcinoma
how do steroids suppress the immune system
affect transcription
2 descriptors of the effect of steroids
widespread
not immediate
how do steroids affect prostaglandins
inhibit phospholipase a2 –> reduces prostaglandins –>
less inflammation
3 effects of steroids on phagocytes
reduced trafficking –> neutrophil count RISES
reduced phagocytosis
reduced enzyme release
4 effects of steroids on lymphocytes
lymphopenia
cytokine gene expression blocked
reduced AB production
pro-opportunistic
how do anti proliferative agents suppress the immune system
inhibit DNA synthesis
3 examples of anti proliferative agents
azothioprine
cyclophosphamide
mycophenolate mofetil
what type of cells do anti proliferative agents affect the most
cells with rapid turnover
2 types of cell signalling inhibitors used to dampen immune system
calcineurin inhibitors
mTOR inhibitors
how do calcineurin inhibitors dampen immune system
reduce IL2 expression –> reduce cell proliferation / function
2 examples of calcineurin inhibitors
tacrolimus
cyclosporine
what conditions are calcineurin inhibitors used in
transplant
psoriasis
SLE
how do mTOR inhibitors dampen immune system
inhibit t cell proliferation and function
2 examples of mTOR inhibitors
rapamycin
sirolimus
when are mTOR inhibitors used
transplant
2 drugs that target T cell surface Ags
basiliximab
abatacept
how does basiliximab dampen immune system
inhibits t cell proliferation
use of basiliximab
rejection prophylaxis
how does abatacept dampen immune system
fusion protein that blocks T cell activation
use of abatacept
RA
example of b cell surface Ag targeting agents
rituximab
how does rituximab dampen immune system
depletes mature b cells
use of rituximab
NHL
how does vedlizumab work
prevents leucocyte migration
use of vedlizumab
IBD
what does basiliximab bind to
cd25
what does abatacept bind to
cd80 / 86
what does rituximab bind to
cd20
what does vedlizumab bind to
alpha 4 beta 7 integrin
name 2 TNFa blockers and common indications for use
infliximab
adalimumab
RA / psoriatic arthritis
what can infliximab be used for
RA
ank spon
psoriasis / psoriatic arthritis
IBD
what does etanercept target and what is it used for
TNF alpha and beta
ank spon, JIA, RA, psoriatic arthritis
what does ustekinumab target and what is it used for
p40 subunit of IL12/23
psoriasis, psoriatic arthritis, crohns
what does secukinumab target and what is it used for
IL17A
psoriasis, psoriatic arthritis, ank spon
what does natalizumab target and what is it used for
a4b1 integrin
MS
what does denosumab target and what is it used for
RANK ligand
osteoporosis
what does toculizumab target and what is it used for
IL6R
RA, castleman’s disease
when is plasma exchange used and what is being removed
severe AB mediated disease
- goodpastures (anti GBM)
- MG (anti Ach R)
- humoural transplant rejection / ABO incompatability (anti HLA/AB)
limitation of plasma exchange & solution
rebound AB production
- prescribe anti proliferative (MFM)
generic SEs of immunosuppression
infection - atypicals and more severe
malignancy - EBV lymphoma, melanoma, non melanoma skin cancer
- AID
SE of steroids
metabolic - DM, dyslipidaemia, osteoporosis, adrenal suppression
peptic ulcers
avascular necrosis
cataracts, glaucoma
pancreatitis
important prescribing note with steroids & reason why
do not stop suddenly - adrenal suppression –> crisis **key one
SEs of cyclophosphamide
haemorrhagic cystitis **key one
bladder cancer
non melanoma skin cancer
infertility M>F
PCJ pneumonia
SEs of MMF
PML (JC virus reactivation) ** key one
herpes reactivation
SE of azothioprine
BM suppression **key one
SE of all cell surface Ag agents
infusion reactions
Se of rituximab
worsening CVD
PML
SE of abatacept
TB
Hep B/C
SE of vedlizumab
hepatotoxic
PML
SE of TNFa/b ABs
TB
Hep B/C
lupus like disease
demyelination
SE of toclizumab
dyslipidaemia
hepatotoxicity
SE of denosumab
avascular necrosis of jaw **key one
what test should you do prior to starting AZ
TPMT
how is HIV detected
ABs - serology
Ag = direct confirmation of viral particles
RNA / DNA = direct confirmation of viral genetic material
when will HIV ABs be positive
after seroconversion 15-45 days
in whom can’t you use AB test to detect HIV infection
neonates - passive transfer from mother
describe HIV lifecycle
binding to host cell
fusion with host cell membrane
reverse transcription
integration
replication
assembly
budding
which class of drugs inhibit HIV lifecycle at binding to host cell
CCR5 inhibitors
which class of drugs inhibit HIV lifecycle at fusion with host cell membrane
fusion inhibitors
which class of drugs inhibit HIV lifecycle at reverse transcription
NRTIs or NNRTIs
example of NRTI and use
tenofovir - PrEP
which class of drugs inhibit HIV lifecycle at integration
integrase inhibitors
which class of drugs inhibit HIV lifecycle at budding
protease inhibitors
when should HIV+ patients be given ART
immediately after Dx - no longer wait for low CD4 etc
what types of drugs would a newly Dx HIV+ patient be given
2 NRTIs and a protease inhibitor
