Lec 5 - transplantation Flashcards
Define auto/ iso/ allo and xenografting.
Illustrate major antigenic differences between donor and recipient in humans.
Define the concept of privileged sites.
Illustrate complications of transplantation.
Describe measures taken to prevent graft rejection.
Describe mechanisms of graft rejection.
Illustrate the classification of graft rejection involved in hyperacute, acute and chronic rejection.
Define and explain Graft Versus Host Disease.
Illustrate the current clinical spectrum of transplantation.
Illustrate, broadly, measures for treatment of graft rejection.
Define auto/ iso/ allo and xenografting
AUTOGRAFT - transfer of tissue between different sites within the same organism (e.g. skin graft)
ISOGRAFT - transfer between genetically identical individuals, ie. identical twins, also known as syngeneic
ALLOGRAFT - transfer between genetically non-identical members of the same species
XENOGRAFT - transfer between species (HIGHEST RISK OF REJECTION; RARELY USED)
What is an autologous transplant
Refers to tissue returning to the same individual after a period outside the body, usually in a frozen state
What is a syngeneic transplant
Refers to transplant between identical twins; there is usually no problem with graft rejection
AKA ISOGRAFT!
Allogeneic transplant aka
Allograft
An example of autograft
Skin graft
When talking about recipient receiving organ from a stranger, what kind of transplant is that (commonest type)
Allograft
Examples of transplantable organs
Kidney, heart, lung, skin, bone, pancreas/ islets of Langerhans, small bowel, bone marrow, cornea, uterus
Main problem with all solid organ transplants is the risk for
REJECTION
Measures taken to prevent graft rejection (4)
Donor and recipient must be ABO compatible.
Recipient must not have anti-donor human leukocyte antigen (HLA) antibodies
Donor should be selected with as close as possible HLA match to the recipient
Patient must take immunosuppressants (before + after)
2 major antigens which donor and recipient must share in order for a graft to survive (2)
- ABO blood group antigens
2. Major Histocompatability Antigens (HLA)
Minor histocompatability antigens are less well defined and mismatch does not tend to be a major clinical problem. However, in what rare cases of may they be responsible for major rejection problems?
When donor and recipient are well matched for ABO and HLA antigens but rejection still occurs
Complications of transplantation.
1) Graft rejection
2) Graft versus host disease (GVHD)
3) Infection (as a result of immunosuppressive therapy or of transfer of infectious agent in graft)
4) Neoplasia (lymphoma, skin tumours)
5) Drug side effects
6) Recurrence of original disease
Graft rejection is usually caused by
Histocompatibility differences between donor and recipient
ABO blood group mismatch is rare
4 types of graft rejection
Hyperacute
Accelerated
Acute
Chronic
Describe hyperacute graft rejection
- how long after op
- mechanism
- triggers which type hypersensitivity
- common or rare
Minutes to hours
Pre-formed host antibody
against donor HLA or ABO antigens –> triggers type 2 hypersensitivity reaction and destroys graft by vascular thrombosis
RARE - as good cross matching prevents this
Describe acute graft rejection
- how long after op
- mechanism
- triggers which type hypersensitivity
1-3 weeks
Donor dendritic cells stimulate an allogeneic response in a local lymph node and T cells proliferate and migrate to the donor graft –> type 4 hypersensitivity reaction
Describe acute graft rejection
- how long after op
- mechanism
- triggers which type hypersensitivity
1-3 weeks
Donor dendritic cells stimulate an allogeneic response in a local lymph node and T cells proliferate and migrate to the donor graft –> type 4 hypersensitivity reaction
Immunopathology of graft rejection
- afferent phase
- effector phase
Afferent phase
-donor MHC molecules within the graft are recognised by the recipient’s CD4+ T cells (allorecognition)
Effector phase
-CD4+ T cells recruit effector cells responsible for the tissue damage of rejection, e.g. macrophages, CD8+ T cells, NK cells and B lymphocytes
Is autologous or allogenic SCT safer?
Is allogenic SCT or allogenic solid organ transplant safer?
Autologous SCT obviously as it’s their own cells
Allogenic SCT MUCH RISKIER than solid organ transplant, even with good cross matching
Name a disease principally associated with allogenic SCT but can also occur with organ or tissue grafts
Grast versus host disease (GVHD)
Sources of stem cells
Bone marrow
Peripheral blood
Umbilical cord blood
What is Grast versus host disease (GVHD)
- mechanism
- causes
When donor T cells respond to allogeneic recipient antigens
Causes
- presence of functioning immunocompetent donor T cells in the graft
- defective immunity (especially T cell immunity) in graft recipient
- HLA differences between donor & recipient
Grast versus host disease (GVHD) affects what organs
Skin, gut, liver, and lungs
Treatment of graft rejection = IMMUNOSUPPRESSANTS
Name some
Corticosteroids
T-cell signalling blockers, e.g. cyclosporine (block cytokine production)
IL-2 blockers
- monoclonal antibodies against IL-2, e.g. basiliximab
- rapamycin
Antiproliferatives
-inhibit DNA production
Cyclosporine, a T-cell signalling blockers, specifically blockers the production of which cytokine which is key for T cell proliferation and effector function
IL-2
