Histocompatibility & Transplantation Immunology - 2 Flashcards
what are histocompatability antigens?
- antigens responsible for rejection of graft from genetically different donor & recipient
- those encoded by MHC genes induce strong reactions
donor’s MHC antigens can be directly targeted by…
recipient’s T cells and antibodies
what kind of immune responses are caused by MHC incompatability b/w donor and recipient?
allogenic immune response
what is performed before transplantation and why?
HLA typing is performed to ensure MHC compatability
the closer the match between donor/recipient for MHC antigens the better the …
chance of organ survival
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)
leads to higher cellular expression + binding affinity for CD4+ cells —-> more potent humoral and cellular immune response ( HLA-DR )
2 stages of T cell mediated rejection
- sensitisation - recipient’s T cells proliferate in response to graft’s MHC antigens
- effector stage - graft is immunologically destroyed
role of CD4+ activation on T cell mediated rejection
- production of cytokines + chemotactic factors —-> activate + recruit macrophages, Nk cells —-> destruction of graft
- cytokines —-> B cell activation —-> Ab production
- cytokines —-> CD8+ proliferation —-> cytotoxicity
role of CD8+ activation on T cell mediated rejection
direct cellular damage through degranulation of cytotoxic granules
antibody-mediated rejection (2 ways)
- immediately after transplant : recipient has pre-existing Ab to donor’s MHC (e.g. previous rejected transplant, previous blood transfusion)
- 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
antibody mediated rejection mediated through?
- 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)
name types of rejection
- hyper acute
- acute
- chronic
hyper acute rejection
( when? involves immue response against? most common in? requires what? )
- 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
process behind hyper acute rejection
- 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
acute rejection
- takes a few days to occur
- involves triggering T cells through MHC proteins
- T cells recognise foreign MHC on transplanted organ —> become activated
what is direct allo recognition?
when T cells recognise foreign MHC on transplanted organ, rather than the peptide it carries
process behind acute rejection
- 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
chronic rejection
- 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
indirect allo-recognition
- 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
Graft Versus Host Disease
- 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
what’s done to reduce risk of GHVD?
generally T cells are removed from the stem cell transplant to reduce risk
symptoms/complications of GVHD
+ treatment
- blistering
- skin peeling
- stomach, intestinal, liver problems
- treatment - glucocorticoids
