Histocompatibility & Transplantation Immunology - 2

Question 1

what are histocompatability antigens?

Answer 1

• antigens responsible for rejection of graft from genetically different donor & recipient
• those encoded by MHC genes induce strong reactions

Question 2

donor’s MHC antigens can be directly targeted by…

Answer 2

recipient’s T cells and antibodies

Question 3

what kind of immune responses are caused by MHC incompatability b/w donor and recipient?

Answer 3

allogenic immune response

Question 4

what is performed before transplantation and why?

Answer 4

HLA typing is performed to ensure MHC compatability

Question 5

the closer the match between donor/recipient for MHC antigens the better the …

Answer 5

chance of organ survival

Question 6

why is matching the same class 2 antigens important for a successfull transplantation? ( name example of a class 2 antigen that’s most important for this)

Answer 6

leads to higher cellular expression + binding affinity for CD4+ cells —-> more potent humoral and cellular immune response ( HLA-DR )

Question 7

2 stages of T cell mediated rejection

Answer 7

1. sensitisation - recipient’s T cells proliferate in response to graft’s MHC antigens
2. effector stage - graft is immunologically destroyed

Question 8

role of CD4+ activation on T cell mediated rejection

Answer 8

• production of cytokines + chemotactic factors —-> activate + recruit macrophages, Nk cells —-> destruction of graft
• cytokines —-> B cell activation —-> Ab production
• cytokines —-> CD8+ proliferation —-> cytotoxicity

Question 9

role of CD8+ activation on T cell mediated rejection

Answer 9

direct cellular damage through degranulation of cytotoxic granules

Question 10

antibody-mediated rejection (2 ways)

Answer 10

1. immediately after transplant : recipient has pre-existing Ab to donor’s MHC (e.g. previous rejected transplant, previous blood transfusion)
2. later on; concurrently w T cell : B cells recognise MHC Ag on graft + makes Ab; when recipient has no previous exposure to donor’s MHC Ag

Question 11

antibody mediated rejection mediated through?

Answer 11

• activation of complement —-> graft cell lysis via Membrane Attack complex (MAC) formation
• activation of phagocytes —-> phagocytosis
• activation of NK cells —-> direct cell destruction through release of cytolytic molecules via Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC)

Question 12

name types of rejection

Answer 12

• hyper acute
• acute
• chronic

Question 13

hyper acute rejection
( when? involves immue response against? most common in? requires what? )

Answer 13

• occurs within a few hours after transplant
• involves immune response against blood vessels
• most commonly in highly vascularised organs (e.g. kidney)
• requires Ab already present in serum

Question 14

process behind hyper acute rejection

Answer 14

• Ab bind endothelial cells in blood vessels of the organs
• label the cells for attack by complement and NK cells
• phagocytosis by macrophages
• in the blood vessel, there are immune cells coming in, complement being fixated and inflammatory response taking place
• inflammation —> platelet activation —> blocking blood vessel —> lack of O2 supply to transplanted organ —> organ dies

Question 15

acute rejection

Answer 15

• takes a few days to occur
• involves triggering T cells through MHC proteins
• T cells recognise foreign MHC on transplanted organ —> become activated

Question 16

what is direct allo recognition?

Answer 16

when T cells recognise foreign MHC on transplanted organ, rather than the peptide it carries

Question 17

process behind acute rejection

Answer 17

• transplanted organ may be inflamed —-> activates own dendritic cells
• migrate to lymph nodes —> where they meet CD4+ cells + activate them
• activated CD4+ migrate towards transplanted organ —-> recognise MHC & bind to it —-> release cytokines & chemotactic facors —-> activation + recruitement of immune cells —-> destroy organ

Question 18

chronic rejection

Answer 18

• can take months to years
• gradual thickening of blood vessels —-> loss of blood supply to organ —-> ischaemia —-> cells die
• membrane fragments of dying cells containing MHC, taken up by recipient APC —-> chopped up + presented to CD4+ cells

Question 19

indirect allo-recognition

Answer 19

• antigen presentation activates B cells to make antibodies —-> inflammatory response
• directed mainly at MHC class 1 fragments of donor
• is indirect allo-recognition as response is against fragment of MHC protein, rather than whole molecule

Question 20

Graft Versus Host Disease

Answer 20

• systemic disorder that occurs when the graft’s immune cells recognize the host as foreign and attack the recipient’s body cells
• MHC matching most important
• until 1980 only identical twins were used because of risk of rejection
• largely T cell dependent

Question 21

what’s done to reduce risk of GHVD?

Answer 21

generally T cells are removed from the stem cell transplant to reduce risk

Question 22

symptoms/complications of GVHD
+ treatment

Answer 22

• blistering
• skin peeling
• stomach, intestinal, liver problems
• treatment - glucocorticoids