Immunology 5 Flashcards
Define rejection with regards to transplant
Damage done by the immune system to a transplanted organ
Define autologous transplant
Tissue returning to the same individual after a periods outside the body
Define syngeneic transplant/ isograft
Transplant between identical twins
Normally no problem with graft reflection
Define allogeneic transplant
Between genetically non identical members of the same species
Define cadaveric transplant
Use organs from dead donors
Define xenogeneic transplant
Takes place between different species and carriers the highest risk of rejection
Solid organ transplant criteria
Good evidence damage is irreversible
That alternative treatments are not applicable
Disease must not recur
How to minimise the rejection chances of transplant
Donor and recipient must be ABO compatible
Recipient must not have anti-donor human leukocyte antigen antibodies
Close as possible HLA match to recipient
Patient must take immunosuppressive treatment
What is a hyperacute rejection
Within hours Preformed antibodies binding to either ABO blood groups or HLA class I antigens on graft
Antibody binding triggers a type II hypersensitivity reaction and the graft is destroyed by vascular thrombosis
Type of hypersensitivity reaction of hyperacute rejection
Type 2
Type of hypersensitivity reaction of acute rejection
4
Describe acute rejection
Delayed
Takes place within days or weeks of transplant
Donor dendritic cells stimulate an allogeneic response in a local lymph node and T cells proliferate and migrate into donor kidney
HLA incompatibility is the main cause
What is a chronic rejection with regards to transplant
Takes months or years
An element of allogeneic reaction is often mediated by T cells, which can result in repeated acute rejection
May be caused by recurrence of pre-existing autoimmune disease
Describe immunosuppressive drugs
Prevent rejection until stopped
Also lack specificity of true tolerance and thus prevent immune response to infectious agents
Immunopathology of graft rejection
Afferent phase:
MHC molecules recognised by CD4+ T cells (allorecognition)
Effector phase:
CD4+ T cells recruit effector cells responsible for the tissue damage of rejection: macrophages, CD8+ T cells, NK cells and B lymphocytes
Tissue typing techniques
HLA typing
HLA cross matching
What is stem cell transplantation
Hematopoietic stem cells are used to restore myeloid and lymphoid cels
Describe the different types of stem cell transplantation
Autologous SCT
-marrow remove, frozen and reinfused, normally after chemotherapy
Allogenic SCT
- much riskier than solid organ donation
- due to Graft vs Host disease
When are allogenic SCT carried out
In:
Hematologic malignancy
Myeloid cell production is reduced
SCID
Sources of stem cells
Bone marrow,
Peripheral blood
Cord blood
What is conditioning
High dose chemotherapy
High dose radiotherapy
Destroy recipient’s stem cells and allow the engraftment of donor cells
What is Graft vs Host disease
Occurs when donor T cells respond to allogeneic recipient antigens
Mismatches in major or minor histocompatibility antigens
All patients given SCT are given immunosuppressive drugs to avoid
Acute GVHD occurs up to 4 weeks after SCT
-involves skin, gut, liver and lungs
Chronic GVHD occurs later
-affects skin and liver
Immunosuppressive drugs used
Corticosteroids,
T cell signalling blockade (cyclosporin (!!), tacrolimus)
IL-2 blockade (basiliximab and daclizumab (monoclonal antibodies against IL-2) and rapamycin)
Antiproliferatives (azathioprine, mycophenolate, mofetil, methotrexate) (inihibit DNA production preventing lymphocyte proliferation)
When are IL-2 blockade drugs used
Monoclonal antibodies against IL-2 receptor
-acute graft rejection
Rapamycin
-prevent graft rejection
Main side effect of antiproliferatives
Myelotoxicity
Bone marrow suppression
Xenotransplanation problems
Primates assemble different sugar side chains from other species
Antibodies against gal-α1,3-gal bind onto xenotransplanted organs, activate complement, and trigger hyperacute rejection.
Acute rejection may occur because pig proteins elicit T-cell responses.
Even pigs reared in microbe-free conditions are infected with endogenous retroviruses; these have never been known to infect humans, but there is a risk as pig viruses are more likely to infect recipients taking immunosuppressive drugs.
