Transplantation immunology

Question 1

What are the four types of grafts?

Answer 1

Autograft
Tissue transferred from one part of the body to another in the same individual

Isograft
Tissue transferred between genetically identical individuals

Allograft
Tissue transferred between genetically different members of the same species

Xenograft
Tissue transferred from one species to another species

Question 2

What is meant by histoincompatible and histocompatible?

Answer 2

Histocompatible
Tissues that share enough antigenic similarities, allowing transfer and acceptance of tissue without immunologic reactions (e.g., between twins or members of the same strain)

Histoincompatible
Tissues that share enough antigenic differences, inducing immunologic reactions which lead to graft rejection (e.g., an allograft without immune suppression is invaded by cellular infiltrate)

Question 3

Describe allograft rejections.

Answer 3

In a mouse study, a white mouse (B mouse) was given a graft from a grey mouse (A mouse).

After 14 days, the white mouse showed first-set rejection, exhibited by a necrotic scar.

A second graft was given to the same white mouse – the graft was rejected and a necrotic scar developed after 6 days. This second-set rejection occurred at a much faster rate due to the immunologic memory generated from the primary graft.

Another experiment was done where they gave splenic T cells from a primary graft to another mouse that is the same strain and has not received any grafts. The mouse showed second-set graft rejection due to the immunologic memory generated from the first mouse strain’s first graft.

Question 4

What are the roles of CD4+ and CD8+ T cells in graft rejection?

Answer 4

Studies have shown that CD4+ and CD8+ T cells contribute to graft rejection, especially when they are both present in the recipient – leading to a more pronounced graft rejection.

Animals treated with anti-CD4+ T cells showed prolong survival of a graft in the animals. Animals treated with both anti-CD4+ and anti-CD8+ T cells showed an even more dramatic and longer survival of the graft.

Question 5

Give examples of two immunosuppressive agents.

Answer 5

Cyclosporin A
- Inactivates the activity of IL-2, inhibiting the secretion of T(DTH) cells, CD8+ and CD4+ T cells, and B cells

CTLA-4lg

• Blocks costimulatory signals between CD28 and CD80/86 by binding to CD80/86
• CTLA-4 is coupled with an Ig heavy-chain that prevents its clearance from the bloodstream
• As a result, T cell mediated responses against a graft are inhibited, resulting in increased graft survival

Question 6

TH cell secretions

Answer 6

TH cells activate IL-2, IL-4, IL-5, and IL-6.

IL-2 stimulates T(DTH) cells, CD4+ and CD8+ CTLs, and B cells.

IL-4, IL-5 and IL-6 stimulate B cells.

Question 7

What is hyperacute reaction?

Answer 7

Very fast reaction based on pre-existing serum antibodies specific for unique antigens found on the graft

1. Pre-existing recipient antibodies bind to unique antigens found on the graft capillaries
2. This results in accumulation of neutrophils and complement deposition = Severe inflammation
3. Endothelial damage = Obstructs capillaries
4. Graft vascularisation is prevented

Question 8

What is a haplotype?

Answer 8

A set of closely linked genes that are inherited as a set (e.g., MHC genes)

Twins: 100% MHC haplotype
Parents and children: Recipient (child) is always mismatched due to MHC alleles inherited from the other parent (mum or dad)