Transplant

Question 1

Characteristics of hyperacute graft rejection in solid organ transplant

Answer 1

• Occurs within minutes of transplantation
• Pathophysiology:
  1. Mediated by pre-formed anti-donor antibodies in the recipient which are specific for and bind to donor antigens expressed on graft endothelial cells (eg donor HLA molecules/AB blood group antigens)
  2. Results in damaged endothelium → thrombosis → ischaemic necrosis of graft

Question 2

Immune responses involved in hyperacute graft rejection in solid organ transplant

Answer 2

Antibody binding results in:

• Complement dependent cytotoxicity → recruitment of inflammatory cells
• Opsonisation → phagocyte activation
• Antibody dependent cellular cytotoxicity → NK cell activation

Question 3

Characteristics of acute graft rejection in solid organ transplant

Answer 3

• Occurs days/weeks after transplantation
• Mediated by recipient allogenic CD8+ T cells → kill transplanted allogenic graft cells as they are recognised as foreign

Question 4

Complement system activation and function

Answer 4

They are activated by pathogens, leading to a cascade of reactions:
More leukocytes are attracted to site of infection → stimulating inflammation
Complement components mark pathogens → facilitating phagocytosis
Complement cascade leads to formation of membrane attack complex (MAC) which produces pores to kill gram negative bacteria

Question 5

Immune responses involved in acute graft rejection in solid organ transplant

Answer 5

Direct allorecognition

1. Recipient T cells recognise allogenic HLA-peptide complexes displayed by donor APCs
2. The donor APCs are capable of being mature APCs due to graft tissue damage which releases DAMPs that cause maturation of donor-derived APCs

Question 6

Host vs graft rejection causes - T cell response

Answer 6

Occurs when HSCT are transplanted into a recipient with some residual functional immunity (T cells that can reject donor HSCs), which can lead to marrow failure (no functioning marrow - donor/recipient)

Question 7

Host vs graft rejection causes -Antibody response - Donor specific antibodies

Answer 7

Donor specific antibodies - Pre-formed antibodies in the recipient specific for donor antigens, mainly anti-HLA antibodies
- Triggers complement-dependent cytotoxicity, opsonisation, ADCC against donor cells, including HSCs
Can also lead to graft rejection

Question 8

Host vs graft rejection summarised

Answer 8

1. Recipient Tc reject (attacking) HSC from donor
2. Donor specific ANTIBODIES in recipient triggers: complement-dependent cytotoxicity, opsonisation, ADCC against donor cells, including HSCs
3. ABO incompatibility

Question 9

Graft vs host disease (GvHD) causes

Answer 9

○ Administration of immunocompetent cells
○ Histo-incompatibility between donor and recipient
○ Inability of the recipient to destroy or inactivate the transfused cells

Question 10

MOA of NK cells

Answer 10

Cytotoxic - granules in their cytoplasm contain proteins such as perforin and proteases (granzymes) that will trigger apoptosis or cell lysis in an abnormal cell

• Exert their function in early phase of infection and help to contain the infection while CD8 T cells clear the infection
• Activity is increased by type I interferons and macrophage/dendritic cell derived cytokines such as TNF α and IL-12