L19 - Translplantation and HLA Flashcards
(24 cards)
define transplantation
transfer of living cells from one part of the body to another
when was the histocompatability complex locus disocvered and by who
1930s in mice
= Snell
when was the first full face transplant
2010
what barriers are there to succesfull transplantation
availability of organs/donors
donor organ treated as foreign and rejected by host immune system
HLAs are highly polymorphic –> lots of varinats of the same genes
who would be the ideal donor to avoid rejection
identical twin
= exact same HLA variants
for most people the best choice is a HLA identical sibling
= siblings can randomly receive the same HLA variants
each offspring can recieve ONE set of HLA from patenral and maternal = they may not receive the same sets in siblings as each person has 2 sets (mum has a choiuce between 2 and dada has a chouce between 2)
what is HLAmatching
assess how compatible 2 people are for transplantation by looking at there HLA
= too different = rejection is likely
is it common to find a HLA match in general population
No
= if no siblings availabale it is more likely to find suitable match in same ethnicity
= different ethnicities have more common/distribution of certain allelic variations of HLA genes
3 types of organ rejection
hyperacute:
rapid,minutes to hours –>
acute:
within 3 months
chronic:
months to years
describe what happenes in a hyperacute rejection to transplant
- ABO blood groups antigens are expressed on donor tissue HLA molecules
- detected and attacked by antibodys = classical complememt pathway
= pre-existing antibodies can also be present in blood ddue to previous interaction with foreign blood (pregnancy,transfusion or transplant)
= lead to rapid organ rejection
are there any treatments for hyperacute transplant rejection
no trearment to reverse once its happneed
= avoided by HLA typing, ABO-matching and cross matching
= cross matching determines whether recipient contaisn pre-existing antibodiues reactive against donor leukocytes
what is the end result of complement activation
MAC
= membrane attack complex
C5 to C9 –> inserts itself into membrane forming pore for lysis
what type of antigen are HLA
alloantigens
= vary between individuals and can trigger an immune response if transferred from one person to another
= due to genetic variations
cause of acute rejections
Alloreactive T-cells
= recognise the genetic/allelic differences between individuals in HLA molecules as foreign
what proportion of T cells are alloreactive to HLA
10%
= this is a very high proportion considering considering only 1 in a million T cells recognise a single peptide
name one way to help treat acute rejection due to HLA mismatch
immunosuppressive drugs to reduce T cell activation
what are the 3 pathways of activation of alloreactive T cells in acute rejections
direct:
donor dedndritic cell migrates to spleen/lymph node –> recognised by T cell causing activation
indirecet:
parts of donor cell membrane are endocytosed by host dendritic cell –> proscessed peptides are presented to T cells causing activation
semi-direct:
intact donor HLA are transferred and presented on host APCs –> causes stronger activation of T cells due to a forign HLA AND peptide being presented
describe the effects of semi-direct allogenic t cell activation
Sustains CD8+ cytotoxic T cell responses —> after donor APCs die out
= longer sustained and stronger response/rejection
define and explain what an alloantibody is - 2 types
Not naturally present unless you’ve been exposed to foreign human antigens
- Against Blood Group Antigens
If someone with blood type A receives type B blood, they may produce anti-B alloantibodies. - Against HLA Antigens
After an organ transplant (or pregnancy), the immune system may develop alloantibodies against HLA on donor cells → this can cause antibody-mediated rejection.
describe what happenes in Chronic organ rejection
- Repeated and ongoing low-level immune responses against donor antigens
- macrophages recruited to organ and produce cytokines and growth factors
= tissue remodelling and scarring (fibrosis)
- othjer immune cells activated and recruited –> alloantibodes formed
- increasing damage enables immune cells to enter tissue of the blood vessel wall and inflict MORE damaged
what percentage of kidney grafts are effective after a year
90%
= immunosuppressice dugs bloicking T cell activation
HOWEVER no chamnge in rate of chronic rejection = damage is still happening but takes a long tome to see
give 3 charecteristics of chronic graft rejection
- slow loss of function of the kidney
- macrophage infiltration and scarring
- alloantibodies produced allowing damage to enter blood vessel walls
describe how immunosuppresin drugs work
cyclsporin A inhibits production of IL-2
= inhibits T cell proliferation
what is the new ‘opt out system’
assumed since 2020 in England that you are willing to donate organs unless you ACTIVELY say so
what differs between the 3 blood groups - ABO
difference in carbohydares at end of chain
