Immunology exam 3 - transplantation immunology

all done

how many people in NL have chronic kidney disease

1.7 million

how many patients in NL on dialysis

6500

What does this graph mean?

getting a kidney transplant reduces you life expectation but being on dialysis does so even more

peritoneal dialysis explanation

catheter in tummy which does fluid exchange

What does the image show?

What antibodies you have depending on blood type- what donors are compatible with what recipients

What is the most favorable blood type to be theoretically to get donations? what is it in practice though?

AB- no antibodies against A or B, best in practice is A because the donor pool is larger

What antibodies do you have if you are blood type O?

Anti-A and Anti-B antibodies

what antibodies do you have if you’re blood type A

anti-B antibodies

what transplant is most likely to be successful

between twins! because they have identical antibodies

incompatibility meaning in transplants

when transplant is rejected

what did they discover that joining white blood cells does?

leads to agglutination- reaction against each other

when does agglutination happen especially, why?

people who had received multiple blood transfusions, women who had been pregnant before - both have had most exposure to other peoples blood

what gene is important for tolerance?

HLA

what parts of the HLA gene are especially important in transplants and tested for?

HLA-A, B (both for MHC-I), DR (for MHC-II, most important!)

what determines where someone is on the postmortal waiting list?

screening of the recipient, waiting points per day of dialysism average waiting time differs by blood type but between 1.5 and 4 yrs

average lifespan of live kidney transplant?

15 years

crossmatching- basic info

developed to avoid hyperacute rejection, result of donor-specific antibodies (DSA), add patient serum to donor leukocytes (from spleen normally), diff methods available- if Ab kill the cells present- positive cross match- should not do transplant

what is the organ being very big after transplant a sign of?

huge immune response or lymphoma

standard transplantation treatment (4) & functions

corticosteroids - prednisolone, supress all immune cells, effective but toxic in the long run, increases circulating leukocytes (by preventing adhesion and movement to tissue)
Calcineurin inhibitor - CNI, tacrolimus, enzyme, neurological side effects
Antimetabolite - MMF, suppress T and B cells, interference in cell cycle
Anti-CD25 - binds to IL-2 receptor, inhibits activated T cells

drawback of antimetabolites

cause reduced immune response to vaccinations- many on it died in COVID and couldnt get effectively vaccinated

when is anti-CD25 given?

twice, once directly before transplant, once a few days after

mechanism of action of CNI

nuclear factor of activated T cells (NFAT), broadly distributed in the body, regulates T cell activity
CNI inhibits NFAT to be dephosphorylated

how many mismatches would you ideally have

0-0-0 (0 mismatches on each of HLA 1, B and DR)

what is the total HLA mismatch if you have a mismatch of 2-2-2

total 6

when should a kidney start working after live transplant

immediately- if not often something is wrong

what do you do if kidney is not working properly

kidney biopsy- CT scan and ultrasound do not show enough

two types of graft rejection

humoral (b cell, antibody) and cellular (T cells)

if 7 days after transplant there are many Ab against the graft what does it mean?

that Ab were present in body before transplant already

explain steps of transplant rejection

kidney graft with DCs, DCs migrate to the spleen where they activate effector T-cells, effector T cells migrate to graft via blood, graft destroyed by effector T cells

treatment for transplant rejection (3)

more immune suppresion drugs- high dose methylprednisolone (IV), plasmapheresis, anti-thymocyte globulins (ATG)

plasmatheresis explanation, how often, drawback

plasma exchange, 7x in 10 days, take plasma out with an IV, leads to a temporary decline in IgG and a susceptability for infections

ATG explain

very toxic, infusion of horse or rabbit-derived antibodies against human T cells, can only do this treatment once in a life (if you try again you would die from the immune exposure)

label Ab in plasma row

anti-B, anti-A, none, both anti-A and anti-B

label Ab in RBC

A antigen, B antigen, A and B antigen, none

Immunoadsorption description (4 points)

use of binding columns to bind Ab, only usable to filter specific Ab such as anti-A or anti-B., good option for ABOi transplantation, very expensive

(this is kidney function in mL/min, should be 120-150 in healthy person) what is the big drop caused by?

infection

procedure for ABO incompatible transplant (7 drugs/procedures)

start with rituximab 30 days before infection, then 2 weeks before start on tacrolimus/MMF/prednisone and continue lifelong, then just before do IVIG, then right after and 4 days after basiliximab, then biopt 10 days after

what do you do if there is chronic antibody mediated rejection?

no effective treatment

what does this show?

targets for the immunosuppresive drugs used in organ transplants

label 1-4 (2 is two diff ones)

belatacept, anti-CD3 & mAB, basiliximab, alemtuzumab

label 5-8

rATG, cyclosporin, tacrolimus, sirolimus

label 9-13 (one thats impact the cell cycle)

methotrexate, mycophenolate, cyclophosphamide, azathioprine

which immunosuppresive drugs target signal 1, signal 2, signal 3

signal 1: anti-CD3, mAB
signal 2: belatacept
signal 3: basiliximab

which immunosuppresive drugs target DNA replication (4)

methotrexate, mycophenolate, cyclophosphamide, azathioprine

which immunosuppresive drugs target: conversion Ca into calcineurin (2), mTOR into cyclin, CD52, immunodepletion

conversion Ca into calcineurin: cyclosporin, tacrolimus
mTOR into cyclin: sirolimus
CD52: alemtuzumab
immunodepletion: rATG

what two things do you have to match to do a kidney transplant?

both blood group and HLA (A, B and DR)

what happens with chronic Ab mediated rejection

Immune complex is deposited in the blood vessel walls of the transplanted kidney recruit inflammatory cells, enables immune affecters to enter the tissue of the blood vessel wall to inflict increasing damage

most important drug for transplants

tacrolimus- starting trials using just it long term

take home messages of lecture (6)

kidney transplants are still necessary, blood group matching, immunosuppressive treatment, rejection can be acute or chronic, complications