transplant immunology Flashcards
3 types of transplantation :
- Haemopoietic Stem Cell (HSC) Transplantation
- Solid Organ Transplantation
- Tissue Transplantation
sources of donors:
* — : – autologous / autograft
* Another — : – allogeneic / allograft
* Another — : – Xenogeneic / xenograft
self
human
species
tissue transplantation Non-vascularised, non-haemopoietic tissue and are I mmunologically inert , these include:
- —- is not a significant issue
- exposure recipient to — antigens can results in —- impacting future transplantation
tissue which includes:
* Bone grafts
* Heart Valves
* Corneas (occas. need immunosuppression)
* Blood Vessels
rejection
non self HLA antigens
anti HLA antibodies
- Allogeneic Bone Marrow
- Autologous Bone Marrow
are all in —- transplantation
Stem cells purified from — - Autologous/Allogeneic stem cell transplantation
- Cord blood stem cells
HSC
blood
- Kidney
- Pancreas
- Liver
- Heart
- Lung
- Islet cell transplantation
- Small bowel / multivisceral transplants
- Vascularised composite grafts – face, hand
are in —- transplantation
solid organ
solid organ transplantation indications:
* Irreversible —
* Disease with low risk of —
* Recipient free of —
* Recipient free of —
* Recipient fit for — surgery
* Recipient — suitable
organ failure
reoccurrence
infection
malgincacy
major
psychologically
ethical issues includes
* Allocation of —-
* Living — programme
* Xenotransplantation – risk to — – transfer of —
scarce resources
donor
public health
animal pathgens
check slide 13
testing pre transplant
1-When recipient listed
* — group x 2
* — type x 2
* —- at listing & — monthly
2-When donor available, donor testing:
* — group
* —-
Run list of potential recipients. Allocation criteria
Crossmatch – final check of compatibility of donor &
recipient
blood
HLA
anti HLA antibodies
3
blood
HLA
3 key concepts:
1- — match
* Compare HLA type of donor and recipient
* — match HLA-A, B, Cw, DR, DQ, DP
* 000000 is the — match
2- — compatible
* Recipient has no — against the donor
* Can be well matched or not
3- —- Patient (HSP)
* Patient has antibodies to — percentage of the population
* — to find compatible donor
* Consider — risk transplants to improve access
HLA
6
antibody
no antibodies
Highly Sensitised Patient
high
difficult
high risk
HLA matching :
* Relevant to — and —
* Better matching — the immunological barrier
* Better —
* Less – (anti-HLA antibodies)
solid organ n HSCT
decreases
outcomes
sensitisation
check slide 20
classification of rejection:
* —- –> <24 hours
* —- — > <6 mths
* —- –> usually < 6 weeks if late ? Non-adherence
* —- —> years
hyper acute
acute cellular
acute antibody mediated
chronic rejection
mechanism of tissue damage:
1- Hyperacute (— hours ; should not happen with modern H & I)
Preformed —
Activates —
— inflammation
Endothelium becomes — – thrombosis
2- Acute antibody mediated (first — weeks; late – non-adherence)
Antibody develops – transplant (de novo / rebound)
— activation / inflammation
Change in — function
If untreated may get —
3- Cellular Rejection (first — )
Donor antigen presented to recipient —
T cell — damage
Injures the —
Common (10-20% renals)
4- Chronic Rejection ( — )
Role of antibodies now prominent
Multiple additional factors
— in response to injury
Ultimate cause of — of most grafts
<24
aitbody
complement
acute
prothrombiotic
6 weeks
post
complement
endothelial
thrombosis
first 6 months
T cells
cytotoxic
injures the graft
scarring
loss
preformed antibodies to graft:
* Can cause —
* Contraindication
(except for – transplants)
* — antibodies (ABO & other)
* —- antibodies
hyper acute rejection
liver
blood group
anti hla
-HLA antibodies sensitisation history :
* —
* —
* Previous —
-Transfusion of a potential transplant recipient should ALWAYS be made at — level
-Also make anti-HLA antibodies after
* — transplantation
* —
* Implanted — eg Left ventricular assist devices
transfusions
pregnancy
allograft
senior
tissue
infection
device
true or false in transplant outcomes
Improving over the years
Improvement mostly in early outcomes
Affected by donor & recipient factors
true
post reveal transplant - immunosupression:
* — depleting antibody ( aka — )
-Anti-CD-25
-Anti-thymocyte globulin (ATG)
* Tacrolimus – — inhibitor (Inhibit— action)
* Mycophenylate (Inhibit — )
* —
T cell
depletion
calcineurin
cytokine
proliferation
steroids
post transplant immunsupression :
All patients significantly immunosuppressed
* Increased risk of:
– —
– —
Need to carefully consider —
infection
malignancy
drug interaction
solid organ transplantion summary
* Main problem is —
– Modern testing prevents —
– Can — most cellular rejection, and >80% of antibody mediated rejection
Early outcomes have – significantly
Late attrition of grafts lremains a problem
rejection
hyperacute rejection
reverse
improved
in hemopiotic stem cell transplantation
1- what is transplanted ? :-
* Bone marrow
—- (from someone else)
— (patients own)
* Haemopoietic Stem cells
mobilised with—
Autologous
Allogeneic
* — blood
allogenic
autogous
growth factors
cord
HSCT indications:
* —- disease
– Leukaemia & lymphoma
– Solid organ tumours, Multiple myeloma
* —- diseases
– Immunodeficiency & Haematological
– Storage disorders
* — disease (rare; few units)
HSCT process:
* Bone marrow/stem cells — and —
* Often depleted of —
* Patients bone marrow ablated
“Conditioning”
* — given
* Patient — until white cells recover
HSCT complication includes :
malignant
genetic
autoimmune
collected n processed
mature T cells
infusion
isolated
complications are:
* Non-engraftment
* Infection
* GvHD (Graft versus Host Disease)
* Recurrence
* Toxicity of conditioning regimen
—- Can occur when viable T cells are given to immunodeficienct /
immunosuppressed recipient
also occurs by :
* —- transplantation
* — Tx – lungs & liver (very rarely)
* — n severely immunocompromised
GvHD (Graft versus Host Disease)
bone marrow
solid organ
post transfusion
graft vs host disease :
1- acute affects ( which is common ) :
2- chronic causes :
- skin —
- — syndrome
- —
- —
affects skin GIT liver bone marrow and prophylaxis ( (immunosuppression) may
be given ( im not sure if this is for both or only acute )
thickening
sicca
pneumonitis
immunodeficiency
transplant immunology summary:
* HSC recipient immune system replaced by—
* Main problem —
* Solid organ – main problem —
* Reduce problems in both situations- — and —
summary :
* Transplant outcomes improving
* Understanding of immunological mechanisms necessary
for rational treatment.
What we would like:
* More targeted immunosuppression
* Organ specific tolerance
donor immune system
graft vs host disease
rejection
matching n immunosuppression
