Lecture 14: Immunological Aspects of Renal System (Part 2)

Question 1

What are autografts?

Answer 1

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

Question 2

What are isograts?

Answer 2

Grafts exchanged b/t different individuals of identical genetic constitutions (e.g. identical twins)

Question 3

What are allografts?

Answer 3

Grafts exchanged between nonidentical membrane of same species (e.g. human to human)

Question 4

What are xenografts?

Answer 4

Grafts exchanged between members of different species (e.g. pig to human)

• more susceptible to rapid attack
• can insert human genes to donor animals to increase chance of successful transplant

Question 5

Why should a transplant take place within 36 hours of the donor’s death?

Answer 5

Trauma to the donor tissues can have the higher potential to release DAMPs, leading to immediate tissue damage

• Clotting cascade: generates fibrin, which is a chemoattractant for immune cells
• Increases local vascular permeability for immune cells to accumulate
• Bradykinin: increase vasodilation and vascular permeability

*All leads to hyperacute allograft rejection

Question 6

is ABO compatibility necessary for kidney transplants?

Answer 6

Yes (w/o solid immunosuppression)

Question 7

With what transplants is ABO compatibility non important?

Answer 7

Non-vascularized tissue:

• corneal transplantation
• heart valve transplantation
• bone and tendon grafts

Question 8

How do you perform the Microcytotoxicity Test for for Preformed Antibodies?

Answer 8

1) Recipient serum with antibodies added to donor cells
2) Complement added after washing
3) Dye Added
4) If existing antibodies already existed, they are present

Question 9

Why is HLA matching important?

Answer 9

Prevents graft rejection

Question 10

What are convenient sources of lymphocytes for HLA typing

Answer 10

Cadaver: spleen or lymph node

Peripheral blood

Question 11

How do you test for Class I HLA compatibility?

Answer 11

1) In separate dishes, antibodies to a specific antigen are added to donor are recipient cells.
2) Complement is added after washing –> Macs form pores in cells
3) Dye is added
4) Accumulation of dye in both cells mean there is compatibility

Question 12

What happens if there is no compatibility when testing for Class I HLA compatibility?

Answer 12

Only donor cells will develop pores due to MAC complex and have dye accumulated in cells

Question 13

Why is class II HLA compatibility not too important?

Answer 13

Class II only present on antigen presenting cells

Question 14

What is mixed lymphocyte response?

Answer 14

1) Donor cells undergo radiation and do not proliferate.
2) These donor cells are mixed with recipient cells and 3H-thymidine.
3) If there is compatibility, proliferation of recipient cells does not occur.

Question 15

What is a host versus graft disease?

Answer 15

Recipient rejects donor tissue

• adaptive immune response: very strong
• High frequency of T cells
• immune memory plays role

Question 16

What is direct allorecognition?

Answer 16

Donor APC cells present to recipient T cells

-recipient recognizes unprocessed allogeneic MHC molecules on graft APCs

Question 17

What is indirect allorecognition?

Answer 17

Donor alloantigens recognized by recipient class II molecules after they are processed by recipient APC

Question 18

How does host versus graft response occur?

Answer 18

1) DAMPs activate endothelial cells
2) T cells eventually enter allograft
3) T cells release cytokines, activating greater immune response

Question 19

Humoral rejection of transplants utilize what effector mechanism?

Answer 19

Th2 cells

-releases cytokines IL-4, IL-5, IL-10

Question 20

Cellular rejection of transplants utilize what effector mechanism?

Answer 20

Th1 cells

-releases IL-1, IFN-γ

Question 21

Describe hyperacute rejection.

Answer 21

Onset: Immediate

Mechanism: Preformed antibodies in recipient immediately attacks donor tissue

Presentation: Normally in accidental ABO incompatibility

Question 22

What type of hypersensitivity are hyperacute rejections?

Answer 22

Type II

Question 23

Describe acute rejection.

Answer 23

Onset: Weeks to months

Mechanism: Donor DC cells migrate to lymph nodes, triggering immune response in recipient —> leads to T cell mediated process. Also activation of classical complement pathway.

Presentation: Inflammation and leukocyte infiltration of graft vessels

Question 24

Describe chronic rejection

Answer 24

Onset: Months to years

Mechanism: T-cell mediated process - foreign MHC similar to self MHC carrying antigen. Macrophages infiltrate tissue

Presentation: Intimal thickening and fibrosis of graft vessels

Question 25

What type of hypersensitivity are acute and chronic rejections?

Answer 25

Type IV

Question 26

What is a graft versus host disease?

Answer 26

Donor tissue rejects recipient

Question 27

How does graft versus host response occur?

Answer 27

Mostly occurs in immunocompromised patients

-donor cytotoxic T cells attack allo-antigens of host either by Fas-FasL or perforins

Question 28

Where do graft versus host response normally occur?

Answer 28

Small bowel
Lung
Liver

Question 29

What is an acute graft versus host response?

Answer 29

Epithelial cell death in skin, liver, or GI

• rash
• jaundice
• diarrhea
• GI hemorrhage

Question 30

What is an chronic graft versus host response?

Answer 30

Fibrosis and atrophy of affected organ

-dysfunction of affected organ

Question 31

What type of hypersensitivity is graft versus host response?

Answer 31

Type IV