Lecture 21

Question 1

What body part is considered an immunologically privileged site?

Answer 1

Cornea

Question 2

Define autografts

Answer 2

Grafts exchanged from one part to another part of the same individual

Question 3

Define isografts

Answer 3

Grafts exchanged between different individuals of identical genetic constitutions (identical twins)

Question 4

Define allografts (allogeneic)

Answer 4

Grafts exchanged between nonidentical members of the same species

Question 5

Define xenografts (xenogeneic)

Answer 5

Graft exchanged between members of different species; these are particularly susceptible to rapid attack by naturally occurring Abs and complement; insertion of human genes into the genomes of the donor animals increases the chances of successful survival

Question 6

What are the class 1 HLA Ags?

Answer 6

HLA-A/HLA-B; strong barriers to transplantation

Question 7

What are the class 2 HLA Ags?

Answer 7

HLA-DR, HLA-DP, HLA-DQ; these are the 3 most important for transplantation pairs

Question 8

What is the difference between direct and indirect allorecognition of grafts?

Answer 8

Direct: T cell recognizes unprocessed allogeneic MHC molecule on graft APCs; primary response against graft

Indirect: T cell recognizes processed peptide of allogeneic MHC molecule bound to self MHC molecule on host MHC; important during direct chronic rejection (when the # of donor professional APCs is low to stimulate a direct immune response)

Question 9

Describe the different types of rejections (hyperacute, accelerated, acute, chronic)

Answer 9

Hyperacute: takes minutes to hours; preformed antidonor Abs and complement; may be caused by ABO blood group incompatibility

Accelerated: takes days; reactivation of sensitized T cells

Acute: takes days to weeks; primary activation of T cell; both CD4+ and CD8+ T cells can cause rejection

Chronic: takes months to years; both immunologic and nonimmunologic factors; occurs due to the occlusion of blood vessels and subsequent ischemia of the organ

Question 10

What are the 4 variables that determine the outcome of a transplant?

Answer 10

1. Condition of the allograft
2. Donor-host antigenic disparity
3. Strength of host anti-donor response
4. Immunosuppressive regimen

Question 11

What transplants are ABO blood matching not important?

Answer 11

Corneal transplant, heart valve transplant, bone and tendon grafts

Question 12

What is needed to prevent hyperactive Ab-dependent rejection of a graft?

Answer 12

Cross matching to test the recipient serum for preformed Abs against donor’s HLAs

Question 13

What test is performed to test for preformed Abs to donor HLAs?

Answer 13

Microcytotoxicity

Question 14

What test is used for class 2 HLA typing to determine if the donor cells stimulate proliferation of the recipient’s lymphocytes?

Answer 14

Mixed lymphocyte reaction (MLR)

Question 15

What are immunosuppressive drugs used for?

Answer 15

Prevention or treatment of rejection after transplantation after transplantation

Question 16

What are the primary goals of immunosuppression?

Answer 16

1) To effectively control immune responses against graft Ags

2) To minimize drugs’ side effects and toxicities

Question 17

T/F: Patients on immunosuppressive drugs are more prone to opportunistic infections and have raised incidence of malignancy

Answer 17

True

Question 18

What is the mechanism of action for steroids?

Answer 18

Anti-inflammatory, inhibition of T cell proliferation, transcriptional inhibition of pro-inflammatory genes, induction of lymphocyte apoptosis; used clinically for transplant rejection

Question 19

What is the mechanism of action for Cyclosporin A?

Answer 19

Inhibits IL-2 gene transcription, inhibits calcium-dependent pathway of T cell activation; forms a complex in cells (CsA-cyclophilin-calmodulin-calcineurin) that inhibits the translocation of NFATc into the nucleus; inhibits transcription of IL-2,3,4,5, interferon-gamma, TNF-alpha, and GM-CSF; used for induction and maintenance immunoprophylaxis as a basis component of most immunosuppressive protocols in all types of organ transplants

Question 20

What is the mechanism of action forAnti-CD3 monoclonal antibody (OKT3)?

Answer 20

T cell activation, opsonization, and depletion; blocks the function of the CD3 molecule in the membrane of human T cells; used clinically for induction therapy and treatment of acute or steroid-resistant rejection; effective in prophylaxis and treatment of allograft rejection in all types of solid organ transplants

Question 21

What is the mechanism of action for Tacrolimus?

Answer 21

Inhibits IL-2 gene transcription, inhibits the calcium-dependent pathway of T cell activation, forms a complex similar to CsA that inhibits the translocation of NFATc to the nucleus, and inhibits transcription of IL-2,3,4,5, IFN-gamma, TNF-alpha, GM-CSF; used in all types of organ transplants for induction and maintenance immunoprophylaxis and treatment of acute rejection

Question 22

What is the mechanism of action for Anti-CD25 monoclonal antibodies (IL-2R-alpha chain)?

Answer 22

Inhibits IL-2 function

Question 23

What is the mechanism of action for Sirolimus?

Answer 23

Inhibits cytokine-mediated signal