Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
32 Cards in this Set
- Front
- Back
|
Types of transplants |
Autograft, allograft (non-identical member of same species) isograft (syngeneic – twin) xenograft – different species |
|
|
What type of transplant is used for skin?
Why is rejection not a major issue? |
autograft or allograft. Donor skin can re-grow so rejection less of an issue |
|
|
Reason for liver transplant? What is a major challenge? |
Biliary atresia (reduced bile flow), alcoholic cirrhosis
Revascularisation technically difficult |
|
|
Which is the most frequent most solid organ transplant? When is it used, what are the problems? |
Kidney End stage chronic renal failure. Can leave old kidney in place. Graft rejection. |
|
|
Pros of cornea transplant? Why? |
high survival rate (70% 5 year - Immune privilege so less chance of rejection. · Not vascularised so not rejected between unrelated people. |
|
|
Rejection - immune components involved |
APCs Helperand cytotoxicT cell activation Innateimmune cell activation Bcell activation Hyperacute rejection also involves preformedantibodies |
|
|
What is hyperacute rejection? |
within minutes of grafting. Pre-formed Abs against graft tissues, ABO mismatched grafts. Ab against donor Ags bind vascular endothelium of graft, inflammatory response, occludes blood vessels – haemorrhage. |
|
|
Explain the events in a hyperacute rejection with skin cells |
Langerhans’ cells migrate to local lymph node,activate effector cells – migrate to graft via blood and destroyed by effector cells. Accelerated rejection |
|
|
What is acute rejection? |
Within two weeks of graft. MHC mismatches. Depends on a T cell response. Skin grafted onto nude mice, which lack T cells, is not rejected. |
|
|
What is chronic graft rejection? |
months to years. May be result of minor genes presented by MHC I. Could be specific immune alloreactivity or non-immune injury, or both. |
|
|
What are the two types of T cell allorecognition?
|
Direct and Indirect |
|
|
Explain direct T cell allorecognition |
APCs from graft present to host effector T cells. APCs leave graft and migrate to secondary lymphoid tissues, inc. spleen and lymph nodes, via blood. Acute rejection Direct cytotoxic T-cell attack on graft cells – only made by T cells that recognise the graft MHC molecules directly |
|
|
How can direct T cell allorecognition be reduced? |
graft tissue is depleted of APCs by treatment with Abs or by prolonged incubation. |
|
|
Explain indirect T cell allorecognition |
APC from host present graft MHC II proteins to host T cells after processing.Peptides from foreign MHC molecules and minor histocompatibility antigens can be presented. Develop alloantibodies. |
|
|
What is Graft vs Host Disease? |
· Mature donor T cells of HSCs recognise the recipient as foreign (the graft is the immune system) – HSCT if mature lymphocytes, dendritic cells are transferred. |
|
|
How can Graft vs Host Disease be avoided? |
Use T cell depletion – can lead to relapse. Irradiate blood products to destroy immune-competent lymphocytes. |
|
|
When is GvHD severe? |
Mismatch of MHCI or II antigens.
|
|
|
What is Graft-vs-leukaemiaeffect:? |
allogeneic preparations of HSCs contain donor T cells that recognise minor histocompatibility antigens or tumour-specific antigens expressed by host leukemic cells. |
|
|
Treatment for Graft-vs-leukaemiaeffect:? Complications? |
remove alloreactive T cells in vitro. alternative, deplete recipients APCs |
|
|
In xenotransplantation, what is responsible for hyperacute rejections? |
· Expression of a protein a1-3gal sugar onto many cell surface proteins; epitope is recognised by large number of cells · Binding of XNAs (natural Ab – mainly IgM, someIgG and IgA) to donor endothelium, activates classical complement pathway –endothelial damage, inflammation, thrombosis and necrosis of transplant |
|
|
How can the rejection barrier be overcome? |
- Transgenic Pigs lacking lack the a1-3gal transferase enzyme - Pigs expressing human complement regulatory proteins - Interrupting complement |
|
|
how can complement be interrupted? |
· use of cobra venom factor, C1 inhibitor, anti-C5Abs. Expression of complement regulators – CD55, CD46 and CD59. Disad: toxicity of cobra venom factor and would deprive individual of functional complement system. |
|
|
What is Xenozoonosis? |
Infection transmission; rare |
|
|
Explain is Xenozoonosis |
· severely immunosuppressed recipient, humancomplement receptors (CD55, CD59) – expressed in transgenic pigs serve as virus receptors and protect viruses from complement attack |
|
|
What is a major of xenotransplantation? |
Porcine endogenous retrovirus(PERV) |
|
|
How is PERV transmitted? |
Vertically · Not usually infectious in host as accumulated many deletions and mutations · Dormant pig viruses – threaten an immunosuppressed transplant recipient if present in transplanted kidney. |
|
|
How can PERV be overcome? |
· Pig cells have been engineered to inactivate all62 PERVs in genome |
|
|
What are •Immunologicallyprivileged sites |
–Brain,eye, testis, uterus –Tissuegrafts into these sites do not produce an immune response |
|
|
What do immunologically privileged sites exclude entry ? Example Failure |
–naïvely mphocytes •Eg Blood-brain barrier •T cells specific for these sites are in immunological ignorance •Can break down to produce autoimmune disease |
|
|
What is the result of antigens which leaves these sites? |
•induce tolerance or non-destructive response |
|
|
What do Privileged sites produce? |
•Privileged sites also produce high levels of cytokines including TGF-b which produce Treg cells rather than an inflammator yresponse to the antigens •high levels of Fas ligand which will induce apoptosis in Fas bearing lymphocytes |
|
|
How can transplantation tolerance be induced? |
Tregs Prevent GVHD, allergy, hypersensitivity |
