transplantation

Question 1

what are the most transplanted organs

Answer 1

kidney, liver, heart, lungs

Question 2

how is successful organ transplantation achieved?

Answer 2

best possible match of donor & recipient blood type and MHC (MHC at every locus- every MHC I and II loci)
- immune suppressive drugs
. not specific in the way vaccines work
. broadly inhibit immune response rather than just the response against the transplant

Question 3

what is alloantigen

Answer 3

(alloreaction)- immune responses directed against MHC that is different than self

Question 4

what are the 3 major types of transplantation

Answer 4

1- blood transfusion (match blood type)
2- solid organ (MHC also)
3- bone marrow (MHC also)

Question 5

transplant rejection vs. graft-versus-host disease

Answer 5

transplant rejection (solid organ, like kidney)- its the recipients T cells attacking the donor organ
- hyperacute, acute, chronic

graft-vs-host-disease- when bone marrow is transplanted, the T cells in the transplant attack the recipients tissues

Question 6

genetics of graft rejection (alleles example)

Answer 6

• if the MHC alleles match in donor & recipient – syngeneic graft not rejected
• if you add graft with B allele on every MHC locus to A allele recipient — fully allogeneic graft rejected
• allele B donor to hybrid recipient with both alleles A + B — graft not rejected
• hybrid donor A + B to allele A recipient — graft rejected because expression of B alleles

Question 7

mis-matches of MHC can result in either ___ or ___ allorecognition

Answer 7

direct
indirect

Question 8

describe direct allorecognition

Answer 8

the donor DC’s (APC) that express allo MHC can be recognized by recipient T cells (CD4 or CD8), responding to intact MHC as foreign
- rxn is MHC-driven (peptide not so important)

Question 9

describe indirect allorecognition

Answer 9

donor APC dying, engulfed by recipient DC, processed and presented into peptides and presented by recipient MHC and recognized by recipient T cells (peptide derived from MHC is recognized as foreign)

Question 10

Who can Rh+ donors donate to?

Answer 10

only Rh+ recipients
- RH- donors only to Rh- recipients

Question 11

name 3 types of rejection responses to solid organs

Answer 11

1- hyperacute
2- acute
3- chronic

Question 12

describe hyperacute rejection

Answer 12

extremely rapid response, pre-existing antibodies against HLA or ABO bind vascular endothelium, start inflammatory response, and occlude blood vessels, results in rapid death of graft

• complement activation, endothelial damage, inflammation and thrombosis
• irreversible process; prevented by determining if recipient serum contains antibodies that will recognize donor cells
• blood type A has antibodies against B, blood type AB has no antibodies, blood type O has antibodies against A and B
• anti-HLA antibodies can arise from pregnancy, blood transfusion, or previous transplants

Question 13

describe acute rejection

Answer 13

effector T cells responding to MHC differences between donor and recipient
- takes days to develop
- through direct pathway of allorecognition
- allo antigens (CD4/CD8 T cells) capable of recognizing allo MHC –> T cells destroy graft

• can be prevented by Mixed Lymphocyte Reaction- take donor APC and recipient T cells and mix in culture
  . if rnx if positive –> T cell proliferation and cytotoxicity, death of donor APC’s

Question 14

describe chronic rejection

Answer 14

• months or years after transplantation
• damage mediated by antibodies, T cells, and macrophages
• indirect pathway of allorecognition
• vessel walls of graft become thickened over years because of antibodies generated by MHC, T cells reacting to peptide antigens from donor MHC presented to recipient MHC –> leads to scarring and damage of walls
• alloantibodies specific for allo MHC also important part of chronic response

Question 15

what is the most common rejection response of solid organs transplants

Answer 15

chronic rejection

Question 16

acute response is more ___ -driven
chronic response is more ___-driven

Answer 16

CD8
CD4

Question 17

describe minor histocompatibility antigens

Answer 17

even when a full MHC match is achieved, chronic rejection can still be mediated in response to differences in minor histocompatibility antigens

• one ex is H-Y antigens- derived from proteins on Y chromosome, only males have the Y- issues can arise when donate to woman
• other polymorphic proteins other than HLA I and II can also function as minor histocompatibility antigens

Question 18

polymorphic self proteins that differ in ___ sequences between individuals give rise to ___ between donor and recipient

Answer 18

amino acid
minor histocompatibility antigens

Question 19

describe the 4 immunosuppressive drugs and their mechanisms

Answer 19

1- cyclosporin
2- tacrolimus
- act at level of eliminating calcium flux that occurs downstream of T cell receptor stimulation —> this cuts off the further steps of T cell activation

3- methotrexate
4- cyclophosphamide
- very potent immunosuppressive drug, occurs later on in process, inhibits DNA replication and cell cycle

Question 20

describe bone marrow transplantation

Answer 20

• used to treat wide variety of diseases from immune deficiency to cancer
• involves replacement of immune system
• myeloablative therapy- destroys recipient bone marrow, combo of irradiation and chemo
• to avoid potential graft-vs-host disease, autologous bone marrow transplants may be an option
• to avoid GVHD, remove mature T cells from bone marrow before transplant

Question 21

graft-vs-host disease is due to ___

Answer 21

donor T cells that attack the recipient’s tissues
- site of attack most often is skin, intestines, and liver

Question 22

compatibility (survival) vs GVHD is determined by…

Answer 22

how closely matched donor and recipient are