Transplant - Grayson

Question 1

Two major issues with Transplantation:

1. When a kidney is transplanted, the ___ T cells attack the transplant - TRANSPLANT REJECTION
2. When bone marrow is transplanted, the T cells in the __ attack the recipient’s tissue - GRAFT VERSUS HOST DISEASE

Question 2

Hyperacute rejection of organs is a type ___ HSR.

Give an example:

Answer 2

II

Healthy kidney is grafted into patient with a defective kidney. Bad thing is that there are pre-existing antibodies against the donor’s blood group antigens. What will happen now?

Host’s antibodies against the donor blood group antigens will bind vascular endothelium of graft, initiating an inflammatory response that will occludes blood vessels.

Question 3

Tranplant recognition is a type __ HSR.

When host’s T cells, recognize donor cell’s APC’s, this is called ___ recogniztion.

When host APC’s take up parts of the donor graft and present it to self T cells, that is called ____ recognition.

Answer 3

IV

When host’s T cells, recognize donor cell’s APC’s, this is called DIRECT allorecogniztion.

When host APC’s take up parts of the donor graft and present it to self T cells, that is called INDIRECT recognition.

Question 4

___ graft, aka ___ graft: between identical twins or inbred animals

Answer 4

Syngeneic aka autologous

Question 5

___ graft: between genetically distinct individuals

Answer 5

Allogeneic

Question 6

___ graft: between different species

Examples?

Answer 6

Xenogeneic

Use pig organs in humans

Question 7

Transplant rejection is an immunologic reaction that is characterized by immunologic ___ and ___.

Answer 7

Transplant rejection is an immunologic reaction that is characterized by immunologic memory and specificity

Question 8

Graft rejection is due to the recipient response against __ and __ antigens.

Answer 8

MHC and mHC

Question 9

Graft rejection is due to the recipient response against donor Major HC and minor HC. Foreign HLA are ___ antigens. ___ antigens are intracellular proteins that may exist in more than one form in the population.

Foreign HLA (MHC) and minor histocompatibility antigens are terms ___.

Answer 9

Graft rejection is due to the recipient response against donor Major HC and minor HC. Foreign HLA are Major histocompatibility antigens. minor HC antigens are intracellular proteins that may exist in more than one form in the population.

Foreign HLA (MHC) and minor histocompatibility antigens are terms ALLOANTIGENS.

Question 10

___ ARE ANTIGEN

Question 11

T/F: Differences in minor histocompatibility aingens can trigger graft rejections.

Answer 11

T

Question 12

How do we figure out/assess if a person is compatible to receive a donor’s kidney?

Answer 12

Do a MLR (mixed lymphocyte reaction).

What you are looking for are donor cells that do not undergo lots of proliferation after being exposed to recipient HLA.

Explanation below:

You take the recipients lymphocytes and irradiate them. Now what will happen if they try to divide? They will die because they have DNA damage. If I put donor cells on top of it, and if the donor cells recognize the HLA on recipient lymphocytes, then the donor cells will undergo a lot of proliferation. NOT A GOOD DONOR.

Question 13

When recipient T cells recognize donor HLA (the bun), this is called ___ allorecognition.

Answer 13

DIRECT

Question 14

Host (organ-recipient) dendritic cells process proteins from the transplanted graft, and trigger a T cell response.

Is this indirect or direct allorecognition?

Answer 14

Indirect

Question 15

The alloantibodies that cause chronic rejection of organ transplants are the result of stimulation by the __ pathway of allorecodtion.

Answer 15

The alloantibodies that cause chronic rejection of organ transplants are the result of stimulation by the INDIRECT pathway of allorecodtion.

Question 16

___ ___: Due to circulating antibodies against ABO or HLA antigens; occurs within 48 hours after transplant; Results in complement activation, thrombosis, neutrophil infiltration, necrosis and organ shutdown.

__ ___: Response to foreign HLA histocompatibility antigens; usually occurs in 7-10 days after transplant but may occur after 6-12 months; Mediated by cytotoxic T cells, macrophages and antibodies.

__ ___: Response to minor histocompatibility antigens; may occur up to several years following transplant; Mediated by macrophages and Th1 cells; Characterized by progressive vasculitis—may represent a form of chronic DTH or ischemia caused by damage to blood vessels.

Answer 16

1. Hyperacute rejection: Due to circulating antibodies against ABO or HLA antigens; occurs within 48 hours after transplant; Results in complement activation, thrombosis, neutrophil infiltration, necrosis and organ shutdown.
2. Acute rejection: Response to foreign HLA histocompatibility antigens; usually occurs in 7-10 days after transplant but may occur after 6-12 months; Mediated by cytotoxic T cells, macrophages and antibodies.
3. Chronic rejection: Response to minor histocompatibility antigens; may occur up to several years following transplant; Mediated by macrophages and Th1 cells; Characterized by progressive vasculitis—may represent a form of chronic DTH or ischemia caused by damage to blood vessels.

Question 17

Chronic rejection: Response to__ ___ antigens; may occur up to several years following transplant; Mediated by ____ and ___ cells; Characterized by progressive ____—may represent a form of chronic DTH or ischemia caused by damage to blood vessels.

Answer 17

Chronic rejection: Response to minor histocompatibility antigens; may occur up to several years following transplant; Mediated by macrophages and Th1 cells; Characterized by progressive vasculitis—may represent a form of chronic DTH or ischemia caused by damage to blood vessels.

Question 18

__ ___: Response to foreign HLA histocompatibility antigens; usually occurs in 7-10 days after transplant but may occur after 6-12 months; Mediated by cytotoxic T cells, macrophages and antibodies.

Answer 18

Acute rejection: Response to foreign HLA histocompatibility antigens; usually occurs in 7-10 days after transplant but may occur after 6-12 months; Mediated by cytotoxic T cells, macrophages and antibodies.

Question 19

Since acute rejection is primarily due to differences in ___ alleles between donor and recipient, ____ typing is used to obtain the best match between donor and recipient.

Answer 19

Since acute rejection is primarily due to differences in HLA alleles between donor and recipient, histocompatibility typing is used to obtain the best match between donor and recipient.

Question 20

Immunosuppressive therapy following transplantation:

1. _____: prevents the induction of cytokine synthesis in T cells by inhibiting the activation of the transcription factor, NF-AT (NFAT is required for production of __ and ___).
2. _____: inhibit the synthesis of HLA antigens, cytokines and adhesion molecules.
3. Anti-___ monoclonal antibodies: Deplete circulating T cells.
4. ____ and ___ mofetil: anti-metabolites that inhibit lymphocyte proliferation by interfering with the synthesis of nucleotide precursors for ___ ___.

Answer 20

Immunosuppressive therapy following transplantation:

1. Cyclosporin A: prevents the induction of cytokine synthesis in T cells by inhibiting the activation of the transcription factor, NF-AT. NFAT is required for production of IL-2 and CD25.
2. Corticosteroids: inhibit the synthesis of HLA antigens, cytokines and adhesion molecules.
3. Anti-CD3 monoclonal antibodies: Deplete circulating T cells (depletes rejection) In immunology, the CD3 (cluster of differentiation 3) T-cell co-receptor helps to activate the cytotoxic T-Cell
4. Azathioprine and mycophenolate mofetil: anti-metabolites that inhibit lymphocyte proliferation by interfering with the DNA sythesis.