Transplantation

Question 1

What are LRD/LURD?

Answer 1

Live related/unrelated donor

Question 2

What are the different graft types?

Answer 2

• Autograft- same person
• Isograft- genetically identical people
• Allograft- generically different people
• Xenograft- different species

Question 3

Which antigens are important for transplantation?

Answer 3

• HLA (MHC)
• ABO
• minor histocompatibility antigens, MICA/MICB, endothelial cell antigens

Question 4

What is alloimmune response?

Answer 4

Response to non self antigens of same species

Question 5

What are the mechanisms of allorecognition?

Answer 5

• Indirect pathway- recipient APCs recognise foreign antigens and present to T cells
• Direct pathway- passenger APC from donor organ recognise their own HLA and present fragments to recipient T cells
• Semi-direct pathway- recipient APC binds to donor HLA and presents it with antigen to T cells

Question 6

Outline ABO

Answer 6

• Present on most epithelial and endothelial cells
• Naturally occurring preformed Antibodies to non-O non-self antigens (haemagglutins)
• Can be temporarily removed- plasma replaced with donors, so able to transplant across ABO barrier
• A2 individuals express lower density of A antigen so can be successful donors to patients with anti-A
• Rhesus factor not important for solid organ transplants- not expressed on endothelium

Question 7

Outline MHC/HLA

Answer 7

• Chromosome 6
• Polygenic and polymorphic
• more than 200 genes
• codominantly expressed- HLA-heterozygous individuals express up to 6 class I isoforms and 6/8 class II
• Distribution of HLA antigens on population is not random- alleles are in LD
• Most important HLA genes for transplant are class I A, B and DR- others don’t present antigen to T cells
- 0,0,0 ideal for transplantation, 2,2,2 worst
- mismatches most important at DR

Question 8

What is pretransplant sensitisation?

Answer 8

Development of antibodies against donor HLA as result of prior exposure to foreign antigen such as transplant/pregnancy/transfusion

Question 9

What is pre transplant monitoring (screening)?

Answer 9

• Quantitate amount and anti-HLA specificity of pre-formed Antibodies
• expresses as PRA- panel reactive antibody
• % PRA from assay- HLA typed lymphocyte panel and c-FDA (fluorescence dye), +serum+complement-> anti-HLA antibodies present leads to cell lysis- loss of fluorescence
- PRA <10% means 98% chance not reacting against donor
• PRA now calculated from luminescent technique (flow cytometry)- patient serum incubated with beads carrying certain HLAs then add secondary antibodies specific to IgG- combination of dyes lets out specific signal
• PRA vs crossmatch- crossmatch is with single potential donor immediately prior to transplant

Question 10

Outline immunosuppression

Answer 10

• Induction

• corticosteroids- regulate gene expression, down regulate pro inflammatory cytokines
• polyclonal immunoglobulins/monoclonal Antibodies- anti-CD25 (IL-2 receptor)

• Maintenance

• calcineurin inhibitors- dephosphorylates NFAT which acts on IL-2
• mTOR inhibitors
• anti-metabolites- MPA Acts on nucleotide synthesis

Question 11

Outline rejection

Answer 11

• Cellular rejection- on recognition of foreign or allogenic MHC by recipient T cells, mediated by T cells TCMR
• Antibody-mediated rejection ABMR- donor specific antibodies binding to endothelium

Question 12

Outline graft versus host disease GVHD

Answer 12

Follows transplant of immunologically competent T cells or precursors into immunocompromised recipients
Recipient conditioning-> donor T cell activation-> effector phase

Question 13

What naturally occurring xenoreactive antibodies are there?

Answer 13

• Those directed against α-gal (non-primates)

* Complement activation and hyperacute rejection