Transplantation

Question 1

Blood transfusion

Answer 1

Simplest transplanting clinical practice
Compatibility determined by:
-genetic diversity
-associated immunological response to non self

Question 2

What is the ABO SYSTEM

Answer 2

Determined by single gene encoding glycosylation enzyme
Modifies cell surface antigen H

Question 3

What are the alleles

Answer 3

Allele A MODIFIES H INTO A
Allele B TURNS H INTO B
ALLELE O encodes non functional enzyme- no modification

Question 4

What do humans produce against carb structures and because of what?

Answer 4

IgM antibodies
Due to cross reaction with bacterial antigens

Question 5

Why are blood transfusions not that good?

Answer 5

Not long lasting, acute treatment

Question 6

Why are organ and bone marrow transplants better?

What is a constant barrier?

Answer 6

More immunological complex
Last longer
Allows patient to live healthy long life

Rejection is a main barrier to long term transplant survival

Question 7

What is acute rejection?

Answer 7

Allografts start successful without immunosuppression but fail after 10-14 days

Question 8

What is chronic rejection?

Answer 8

Effective immunosuppression let’s allografts last longer for years but do degrade overtime

Question 9

What is hyper acute rejection

Answer 9

Xenografts rejected within hours

Question 10

What is an autograft

Answer 10

A graft of tissue from one body site to another in the same person

Cells are autologous or synergic like skin graft

Question 11

What is this? Transplant from an unrelated person of the same species sometimes called homograft

Answer 11

Allograft

Question 12

What is this? Transplant using the same tissue of a different species. Cells or tissue are xenogenic such as using animal organs in humans

Answer 12

Xenograft

Question 13

What features are these of-
animal is given a second allograft reject it even quicker

T cells from allografted mouse accelerate the rejection

Is mediated by MHC and T CELLS
Allograft isn’t rejected when put on naked mice

Answer 13

Acute rejection

Question 14

What is this? Antigens that differ between members of the same species and generate alloreactive response

Answer 14

Alloantigens

Question 15

I am the major source of alloantigens

Answer 15

MHC

Question 16

We are the most polymorphic proteins
We provide the greatest source of diversity between donor and recipient

Answer 16

MHC PROTEINS

Question 17

What improves when you minimise mismatch at the MHC

Answer 17

Allograft outcome

Question 18

What is this? Antigen presenting cells such as APC and DENDRITIC cells present in the grafted tissue:
- migrate out of the graft and into the recipient lymph nodes
- they engage with recipient T CELLS

Answer 18

Direct allorecognition

Question 19

What becomes quickly present when there is a higher MHC mismatch

Answer 19

Alloantigens

Question 20

It needs me to recognise allo- MHC or PEPTIDE to break MHC Restriction

Answer 20

TCR

Question 21

I allow host T CELL to attack graft what am I

Answer 21

Direct TCR allo MHC

Question 22

Donor DC present in graft eventually dies but rejection persists which is a second mechanism

If donor DC is depleted form graft rejection happens
What is this?

Answer 22

Direct allorecognition

Question 23

Allogenic cells or molecules process directly by recipient APC and present to recipient T CELLS

T cells can’t attack graft directly
T cells activate macrophage causing inflammation and tissue damage
Can induce anti graft antibody response (alloantibodies)

WHAT AM I?

Answer 23

Indirect allorecognition

Question 24

What is this process:
1. Fragments of donor cell with allo MHC
2. DYING OR DEAD DONOR CELL
3. recipient CD4+ T CELL WITH specificity against donor. Allo MHC derived peptide in context of self MHC

4. Recipient macrophage has ingested donor cell and is presenting allo MHC derived peptide on recipient MHC
5. T CELL IS activated by the macrophage and in return T cell provides signal like IFN- GAMMA
6. This activates the macrophage to go through respiratory burst and cytokines reproduction

ACTIVATED MACROPHAGE DAMAGE DONOR TISSUE

Answer 24

Indirect allorecognition

Question 25

Involves transfer of donor MHC to recipient APC

Answer 25

Semi direct allorecognition

Question 26

What is this: CD8 cells from direct recognition attack graft directly CD4 CELLS from direct recognition help B cells make anti graft antibodies against graft Antibodies bound graft lead to destruction via complement and ADCC macrophage and NK cells and further antigen presentation CD4 T CELLS from indirect recognition help macrophage become activated and damage tissue

Answer 26

Tissue damage

Question 27

T cells positively and negatively selected when they develop for those whose TCR bind to self MHC but don't react to self peptide as T cell learn self from non self T cells bind strongly to MHC that are eliminated But transplanted tissues gives new molecules to T cell post thymic that haven't been calibrated on foreign tissues

Answer 27

Why T cells are reactive to allo MHC

Question 28

Allo MHC. Peptide complex binds efficiently to some recipient TCRs triggers what

Answer 28

Triggers T cell activation

Question 29

What do I also need alongside TCR and allo MHC

Answer 29

Allo MHC PEPTIDE

Question 30

What is this transplantation called? Recipient immune system is remove to allow repopulation with donor derived HSC

Answer 30

Haematopoietic stem cell transplantation

Question 31

In haematological malignancies like leukemia and lymphoma Or genetic diseases like congenital immunodeficiency Bone marrow failure and high dose chemotherapy for solid tumours - patient has their endogenous HSC destroyed chemically or irradiation and the donor HSC is infused This means the recipient is allogenic to donor HSC and resultant donor derived immune system

Answer 31

Graft versus host disease- fatal so managed by immunosuppression Alloreaction benefits in graft versus leukemia

Question 32

Foetus and placenta genetically half mom and dad 50% foetal genes codes proteins foreign to dad includes MHC molecules Foetus is called hemi allograft

Answer 32

Common allograft

Question 33

What is this? Foetal maternal interface ( trophoblast) doesn't express MHC class 2 but low MHC class 1 and a special MHC CLASS 1 (HLAG INHIBIT NK CELLS) LIMITS. Allo MHC reactions Placenta has factors to suppress T cell effectors Promotes inhibitory regulatory T CELLS (Treg) Uterine tissue (maternal) has mechanisms to limit cell attraction via chemokiens

Answer 33

Foetal maternal tolerance

Question 34

Polymorphism in MHC can disrupt MHC-TCR interaction and peptide-TCR interaction due to constraints on the peptide Some MHC alleles are “better” at presenting certain peptides Diversity at MHC provides selective advantage, pathogens less likely to evade antigen presentation

Answer 34

MHC POLYMORPHISM