L9 - Transplantation Flashcards
what are the types of transplantation?
1)Autograft
–Graft originates from the patient him/herself
–Split-skin graft or full-thickness skin graft for skin transplantation
–Saphenous vein graft for vascular bypass surgery
Bone graft from the iliac crest for bone reconstruction
2)Isograft
Graft originates from a genetically identical person (identical twin)
Various organ transplantations (e.g., kidney, liver, or cornea)
3)Allograft
–Graft originates from a genetically different person
4)Xenograft
–Graft originates from different species (e.g., pig)
–Porcine or bovine heart valves
examples of tissue transplantation…
Non-vascularized, non-hematopoietic tissue
Immunologically inert
• Bone grafts
• Heart valves
• Corneas (occasionally need immunosuppression)
• Blood vessels
what is the HSCT?
The transplantation of hematopoietic stem cells, which arise from peripheral blood, bone marrow transplant, or umbilical cord blood. There are two types of stem cell transplantation: autologous (removal of the patient’s own hematopoietic stem cells) and allogenous (transfer of hematopoietic stem cells from a sibling or donor).
–Also cord blood stem cells
what are the indications of autologous HSCT?
- -To allow the administration of higher doses of antineoplastic therapy than would otherwise be possible for certain non-hematological malignancies (e.g., germ cell tumors, soft tissue sarcoma)
- -Multiple myeloma
- -Lymphoma
- -High-dose chemotherapy would destroy the bone marrow and therefore cannot be used to treat neoplastic disease without subsequent bone marrow transplantation.
what are the indications of allogenous HSCT?
- -To replace abnormal but non-malignant cells of the lymphohematopoietic system with hematopoietic cells from a normal donor
- -Severe combined immunodeficiency
- -Aplastic anemia
- -Thalassemia
- -Leukemia (e.g., acute lymphoblastic leukemia)
what solid organs can be transplanted?
- Kidney
- Pancreas
- Liver
- Heart
- Lung
- Islet cell transplantation
- Small bowel
- Vascularized composite grafts
what are the indications of solid organ transplantation?
- Irreversible organ failure
- Disease with low risk of recurrence
- Recipient free of infection
- Recipient free of malignancy
- Recipient fit for major surgery
- Recipient psychologically suitable
what are the CI’s for organ donation?
- -Malignancy that is non-curable or metastatic
- -Sepsis in the donor
- -Transmissible spongiform encephalopathies (prion diseases such as Creutzfeldt-Jakob disease)
- -Cardiac arrest occurring before brain death (This comprises patients who suffer a sudden, unexpected cardiac arrest; the subsequent decline in bloodflow is associated with a high risk for thrombosis and ischemia of organs. This category should not be confused with deceased donors after cardiac death (DCD), who receive heparin before circulation ceases to prevent thrombosis.)
does
–Low-grade, localized tumors without evidence of metastasis at the time of death
–History of malignancy with a disease-free duration > 5 years
–Hepatitis B or C infection
–HIV infection
–Hypertension, diabetes, and/or elderly patients
are CIs for organ donation?
no
HIV infection was previously an absolute contraindication for organ donation and legally prohibited individuals from becoming organ donors in the US, but the HIV Organ Policy Equity (HOPE) Act implemented in November 2015 allows the transplantation of organs from HIV-positive donors into HIV-positive recipients at certain institutions.
what are the ethical issues in organ transplantation?
- Allocation of scarce resources
* Living donor programme
what is the allorecognition?
- -Definition: recognition of a foreign antigen as a non-self antigen by a host
- -Clinical importance: Activation of a particular T-cell by a foreign HLA peptide results in clonal proliferation of that type of T lymphocyte, a process that is mediated by IL-2 → acute rejection
what is the HLA matching?
• Relevant to solid organ and HSCT
• Better matching decreases the immunological barrier
• Better outcomes
• Less sensitisation (anti-HLA antibodies)
–MHC matching at the HLA-DR, HLA-A, and HLA-B loci
–The major histocompatibility complex (MHC) of both donor and recipient should correspond as much as possible in order to minimize the risk of transplant rejection. The matching of HLA-C, HLA-DP, and HLA-DQ is preferred but is not always required.
important concepts of transplant immunology
–MHC: a gene cluster on chromosome 6 that codes for human leukocyte antigen (HLA) molecules.
–HLA: proteins present on the surface of all cells that display antigenic peptides as a normal physiological function so that they can be recognized by T-lymphocytes as either self or non-self antigens.
Types of MHC
–MHC I cluster, which codes for class I HLA molecules, consists of three loci: HLA-A, HLA-B, and HLA-C.
–MHC II cluster, which codes for class II HLA molecules, also consists of three loci: HLA-DR, HLA-DP, and HLA-DQ.
classification of graft rejection?
- Hyperacute: <24 hours
- Acute cellular: common <6 mths
- Acute antibody-mediated: usually < 6 weeks
- Chronic rejection:
what is the mechanism of tissue damage in graft rejection?
• Hyper-acute &acute antibody-mediated Antibody & complement Acute inflammation & thrombosis • Cellular Rejection T cell cytotoxic damage • Chronic Rejection Role of antibodies now prominent Scarring in response to injury
what is the pathophysiology of hyperacute graft rejection?
- -Preformed cytotoxic antibodies against class I HLA molecules or blood group antigens are present → activation of complement system and adhesion to granulocytes → thrombosis of vessels → graft ischemia
- -Preformed antibodies against HLA antigens occur as result of a exposure to foreign HLA haplotypes during pregnancy, transfusion, or a previously failed transplantation. Preformed antibodies against blood group antigens are usually the result of ABO incompatibility.
