Transplantation Flashcards
(57 cards)
What is an allograft?
The transplant of an organ, tissue, or cells from one individual to another individual of the same species who is not an identical twin.
What can you transplant?
Solid organs (kidney, liver, heart, lung, pancreas)
Small bowel
Free cells (bone marrow stem cells, pancreas islets)
Temporary: blood, skin (burns)
Privileged sites: cornea
Framework: bone, cartilage, tendons, nerves
Composite: hands, face
Where do organs come from?
Live donor
Deceased donor
What are the most common transplants?
Kidney Pancreas Cardiothoracic Liver Intestinal
How do improve transplant outcomes?
Improved surgical technique
Improved pre- and post-transplant patient management and monitoring
Better understanding of transplant immunology
(Immunosuppression, graft rejection)
What are the 3 phases of graft rejection?
Phase 1: recognition of foreign antigens
Phase 2: activation of antigen-specific lymphocytes
Phase 3: effector phase of graft rejection
What are the important immunological considerations in transplant?
Foreign object!
Mostly ABO and HLA (Chr6MHC)
Other: Minor histocompatibility genes
What are the two major components to rejection?
T cell-mediated rejection
Antibody-mediated rejection (B cells)
What is HLA?
Discovered after first failed attempts at human transplantation
Cell surface proteins
Presentation of foreign antigens on HLA molecules to T cells is central to T cell activation
How are HLA variable?
HLA Class I (A,B,C)– expressed on all cells
HLA Class II (DR, DQ, DP) – expressed on antigen-presenting cells but also can be upregulated on other cells under stress
Highly polymorphic – hundreds of alleles for each locus (for example: A1, A2, A3 – A372 and rising…)
How are HLA antigens connected to infections and neoplasia?
To maximise diversity in defense against infections, each individual has a variety of HLA proteins
Each individual’s HLA proteins are derived from a large pool of population varieties
What is the relevance of HLA in transplantation?
The variability in HLA molecules in the population provides a source for immunisation against the transplanted organ
What may help improve transplant outcomes regarding HLA?
Minimising HLA differences between donor and recipient improves transplant outcome
What is T cell mediated rejection?
T cells require presentation of the foreign HLA antigens by a professional antigen presenting cell (APC), in the context of HLA, to initiate activation of alloreactive T-cells
What do T cells do?
Proliferate Produce cytokines Provide help to activate CD8+ cells Provide help for antibody production Recruit phagocytic cells
What is graft infiltration?
Graft infiltration by alloreactive CD4+ cells
What is the role of Cytotoxic T cells?
Release of toxins to kill target Granzyme B Punch holes in target cells Perforin Apoptotic cell death Fas -Ligand
What do macrophages do?
Phagocytosis
Release of proteolytic enzymes
Production of cytokines
Production of oxygen radicals and nitrogen radicals
What is the histology of acute cellular rejection?
Interstitial inflammation and tubulitis
What are the phases of antibody mediated rejection?
Phase 1 – exposure to foreign antigen
Phase 2 - proliferation and maturation of B cells with antibody production
Phase 3 – effector phase; antibodies bind to graft endothelium (capillaries of glomerulus and around tubules, arterial)
What are the naturally occurring antibodies?
Anti-A or anti-B antibodies are naturally occurring
Other Anti bodies may be wither naturally or non naturally occurring
anti-HLA antibodies are not naturally occurring
Pre-formed – previous exposure to epitopes (previous transplantation, pregnancy, transfusion)
Post-formed - arise after transplantation
How do cells come to the graft?
Endothelial cell activation and inflammatory cell recruitment and injury
What are the ABO groups?
A and B glycoproteins on red blood cells but also endothelial lining of blood vessels in transplanted organ
Naturally occurring anti-A and anti-B antibodies
What is rejection?
T-cell mediated, antibody-mediated or combined
Both cause graft dysfunction (e.g. raised creatinine, raised LFT)
Graft biopsy: management and outcome are different
