Lecture 15: Immunological Aspects of Renal System (Part 2)

Question 1

What is the difference between autografts, isografts, allografts and xenografts?

Answer 1

autografts: graft exchange within same individual
isograft: graft exchange within identical genetic constitutions (twins)
allograft: graft exchange witihin same species
xenograft: graft exchange between members of different species

Question 2

What must match to prevent graft rejection?

Answer 2

HLAs

Question 3

What factors affect successful transplantation?

Answer 3

condition of allograft
donor-host antigenic disparity
strength of host anti-donor response
immunosuppressive regimen

Question 4

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

Answer 4

longer will lead to graft damage > release DAMPS > activation of clotting cascade (fibrin, fibrinopeptides) & kinin cascade (bradykinin) > immune cell infiltration and incresed vascular permeability

*All leads to hyperacute allograft rejection

Question 5

is ABO compatibility necessary for kidney transplants?

Answer 5

Yes (w/o solid immunosuppression)

Question 6

With what type of transplants is ABO compatibility non important?

Answer 6

Non-vascularized tissue:

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

Question 7

Exercise: What type of blood can an A type recipient get?

Answer 7

O and A (no anti A antigens in these types)

Question 8

How do you perform the Microcytotoxicity Test for for Preformed Antibodies? When do you need to do this?

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

to see if there are pre-existing antigens in the recipient’s blood

Question 9

What are convenient sources of lymphocytes for HLA typing

Answer 9

Cadaver: spleen or lymph node

Peripheral blood

Question 10

How do you test for Class I HLA compatibility (Microtoxicity Test for Class I HLA)?

Answer 10

Take lymphocytes from recipient and donor
Take antisera with antibodies to certain HLA
Abs will bind Ags and activate complement and lyse the cells
If both types of cell are lysed = they both have that HLA = match

Question 11

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

Answer 11

Only donor cells will be lysed because it has that HLA. Recipient cell does not lyse since it does not have that HLA

Question 12

Why is class II HLA compatibility not too important?

Answer 12

Class II only present on antigen presenting cells

Question 13

What is mixed lymphocyte Response test for Class II HLA?

Answer 13

Mix recipient and donor cells (donor cells treated with 3H-thymidine so it does not proliferate)
If R cell proliferates = mismatch since it’s the first time the R cell has “met” that HLA because it’s not in the R’s cells

Question 14

What is a host versus graft disease?

How does immune memory relate to this type of rejection?

Answer 14

Recipient’s T cells attack new organ

more robust response if you get 2nd graft from the same donor

Question 15

What is the difference between direct and indirect allorecognition?

Answer 15

Direct: T cell recognize intact foreign HLA on graft cells
Indirect: T cell recognizes degraded HLA peptide on presenting MHC

Question 16

Cellular effectors of graft rejection

Humoral effectors of graft rejection

Answer 16

TH1 by releasing IL2, IFN-Y

TH2 by releasing IL4,5 and 10

Question 17

Describe hyperacute rejection.
Onset
Mechanism
Presentation
What type of hypersensitivity?

Answer 17

Onset: Immediate

Mechanism: Preformed antibodies in recipient immediately attacks donor tissue

Presentation: Normally in accidental ABO incompatibility

Type II

Question 18

Describe acute rejection.
Onset
Mechanism 
Presentation
What type of hypersensitivity?

Answer 18

Onset: Weeks to months

Mechanism: Donor DC cells activate recipient lymphocytes > cytotoxic T cells generation and induction of delayed type hypersensitivity reaction (Type IV)

Presentation: Inflammation and leukocyte infiltration of graft vessels

Type IV

Question 19

Describe chronic rejection
Onset
Mechanism
Presentation

Answer 19

Onset: Months to years

Mechanism: graft gets damaged (injury, ischemia, drugs) > body senses damage and induces macrophage and smooth muscle proliferation

Presentation: Intimal thickening and fibrosis of graft vessels

Question 20

What is a graft versus host disease?

Answer 20

Donor tissue rejects recipient

Question 21

How does graft versus host response occur?

Answer 21

Mostly occurs in immunocompromised patients

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

Question 22

What type of transplantation do graft versus host response normally occur?

Answer 22

Small bowel
Lung
Liver

Question 23

What is an acute graft versus host response?

symptoms?

Answer 23

Epithelial cell death in skin, liver, or GI

-rash, jaundice, diarrhea, GI hemorrhage

Question 24

What is an chronic graft versus host response?

symptoms?

Answer 24

Fibrosis and atrophy of affected organ

-dysfunction of affected organ, small airway obliteration

Question 25

What type of hypersensitivity is graft versus host response?

Answer 25

Type IV