Transplantation Flashcards
What are the 3 stages of transplant rejection?
1) Recognition
2) Activation
3) Effector function
What is recognised following a transplantation?
HLA - A, B, DR = these are the most important
Minor HLA - other polymathic self peptides
ABO Blood Antigens
What are the two types of recognition that occur in transplantation?
1) Direct
2) Indirect
What is Direct Transplant Recognition?
Donor APC presenting antigen and/or MHC to recipient T-cells. Acute rejection mainly involves direct presentation
What is Indirect Transplant Recognition?
Recipient APC presenting donor antigen to recipient T-cells - i.e. the immune system working normally, as it would for an infection. Chronic rejection mainly involves indirect presentation
Hyperacute Transplant Rejection - Time frame?
Mins-Hrs
Hyperacute Transplant Rejection - Mechanism?
Preformed Ab which activates Complement
Hyperacute Transplant Rejection - Pathology?
Thrombosis and Necrosis
Hyperacute Transplant Rejection - Treatment?
Prevention - Crossmatching
Acute Cellular Transplant Rejection - Time frame?
Weeks-Months
Acute Cellular Transplant Rejection - Mechanism?
CD4 activating a Type IV reaction
Acute Cellular Transplant Rejection - Pathology?
Cellular Infiltrate
Acute Cellular Transplant Rejection - Treatment?
T-cell Immunosuppression
Acute Antibody Mediated Transplant Rejection - Time frame?
Weeks - Months
Acute Antibody Mediated Transplant Rejection - Mechanism?
B-cell activation - antibody attacks vessels
Acute Antibody Mediated Transplant Rejection - Pathology?
Vasculitis, C4d
Acute Antibody Mediated Transplant Rejection - Treatment?
Ab removal and B-cell Immunosuppression
Chronic Transplant Rejection - Time frame?
Months - Years
Chronic Transplant Rejection - Mechanism?
Immune and non-immune mechanism
Chronic Transplant Rejection - Pathology?
Fibrosis
Chronic Transplant Rejection - Treatment?
Minimise Organ Damage
Graft v Host Disease - Time frame?
Days - weeks
Graft v Host Disease - Mechanism?
Donor cells attack Host
Graft v Host Disease - Pathology?
Skin (rash), Gut (D+V, bloody stool) and liver (jaundice) involvement
Graft v Host Disease - Treatment?
Prevention/ Immunosuppression - corticosteroids
Immune Recognition
T cells recognise antigen with MHCs, B cells can recognise just antigen
APCs present antigen to T cells (dendritic cells, Macrophages, B cells)
Tissue Matching for Transplant
Important to reduce Antigen differences and therefore recognition and rejection
1) determine donor and recipient blood group and HLA type - PCR. Maximise similarity
2) Check recipients pre-formed Ab against ABO and HLA - via CDC (complement Dependent Cytotoxicity), FACS (flow cytometry) and Luminex (like solid phase FACS- can pick up abs to individual HLAs)
3) Cross Match- via CDC and FACS. test if serum from recipient is able to bind/kill donor lymphocytes - positive crossmatch is contraindicated for transplantation
4) after transplant check again for new antibodies vs the graft
Pre-transplant induction agents?
Suppress T cell responses e.g. anti CD52 Alemtuzumab or anti-CD25 Basiliximab
What can you use to treat repeat episodes of acute rejection?
Cellular - Steroids, IVIG
Ab-mediated - IVIG, plasma exchange, anti-c5
3 Other post transplantation complications?
1) Infections
2) Malignancy
- Viral associated (x100) Kaposi’s (HHV8) and Lymphoproliferative Diseases (EBV)
- Skin Cancer (x20)
- other - lung, colon (x2-3)
3) Atherosclerosis - Hypertension and hyperlipidaemia (x20)
