The document provides an overview of organ transplantation, including:
- Definitions of different types of organ transplants such as allografts and xenografts.
- A historical background of major transplant milestones from the 1950s onward including the first successful kidney, liver, lung, and heart transplants.
- Details about transplant immunology, the immune response to foreign organs, and ways to suppress the immune system like with immunosuppressant drugs.
- The types of organ rejection such as hyperacute, acute, and chronic rejection.
- Considerations for organ donation, procurement, preservation, and transplantation.
- Complications after transplantation like infection and potential future directions.
Transplantation involves transferring organs, tissues or cells from one place to another. Key events in transplant history include Alexis Carrel's vascular anastomosis technique, Peter Medawar's discovery of organ rejection, and drugs like azathioprine that helped prevent rejection. Organ donation can involve deceased donors (after brain death or circulatory death) or living donors. Strict criteria must be met to declare brain death. After recovery, organs are preserved, transported on ice, and implanted in recipients. Immunosuppression helps prevent organ rejection. The Transplantation of Human Organs Act regulates organ donation and transplantation in India.
PRINCIPLES OF ORGAN TRANSPLANTATION 2003.pptOlofin Kayode
The document provides an overview of principles of transplant surgery. It defines different types of transplants including autotransplants, allotransplants, and xenotransplants. It discusses the history of transplantation, basic immunology including HLA antigens and allo-graft rejection. It also covers clinical immunosuppression with drugs like corticosteroids and cyclosporin. Organ procurement, specific organ transplants, and future trends are briefly mentioned.
This document provides an overview of transplant surgery, including:
1. It describes different types of transplants such as orthotopic, heterotopic, autotransplant, allotransplant, isotransplant, and xenotransplant.
2. It discusses graft rejection and the immune response, including hyperacute, acute, and chronic rejection.
3. It outlines the pretransplant evaluation process for transplant candidates and donors.
4. It provides details on renal transplantation techniques and evaluations of both living and deceased donors.
This document provides an overview of organ transplantation principles. It defines different types of transplants and discusses the history and key developments in the field. The basic immunology of transplantation is explained, including allograft rejection mechanisms and the roles of human leukocyte antigens and immunosuppressive drugs like corticosteroids and cyclosporin in preventing rejection. Tissue typing and matching donors to recipients is also covered.
This document provides an overview of organ transplantation, including definitions, categories of transplants, history, graft rejection, HLA matching, organ procurement, and donation after brain death and cardiac death. Key points include:
- Transplantation involves transferring an organ or tissue from one place to another. Allotransplants between individuals of the same species require immunosuppression.
- Major milestones include the first successful organ transplant in 1954 and development of immunosuppressive drugs in the 1960s.
- Graft rejection is mediated by the immune system recognizing transplanted organs as foreign. Acute rejection typically occurs in the first 6 months while chronic rejection develops later.
- HLA matching aims to reduce rejection by finding donors with similar
This document provides an overview of transplantation surgery principles. It defines key terms like transplantation, graft types, and alloantigens. It discusses indications for common organ transplants like kidney, liver, heart and lungs. It also covers the immunological basis for graft rejection, focusing on the role of the major histocompatibility complex and human leukocyte antigens in triggering rejection. Finally, it summarizes strategies for tissue matching between donors and recipients, principles of immunosuppressive therapy to prevent rejection, potential complications of transplantation, and methods for organ donation and preservation.
1. Transplantation immunology examines the immune response to transplanted tissues.
2. Major events include the first successful organ transplants in the 1950s-60s of kidneys, livers, hearts, and bone marrow.
3. Graft rejection is driven by an immune response to foreign histocompatibility antigens like MHC proteins, with T-cells playing a key role through cell-mediated responses. Immunosuppressive drugs help prevent rejection by inhibiting T-cell activation and proliferation.
Transplantation involves transferring organs, tissues or cells from one place to another. Key events in transplant history include Alexis Carrel's vascular anastomosis technique, Peter Medawar's discovery of organ rejection, and drugs like azathioprine that helped prevent rejection. Organ donation can involve deceased donors (after brain death or circulatory death) or living donors. Strict criteria must be met to declare brain death. After recovery, organs are preserved, transported on ice, and implanted in recipients. Immunosuppression helps prevent organ rejection. The Transplantation of Human Organs Act regulates organ donation and transplantation in India.
PRINCIPLES OF ORGAN TRANSPLANTATION 2003.pptOlofin Kayode
The document provides an overview of principles of transplant surgery. It defines different types of transplants including autotransplants, allotransplants, and xenotransplants. It discusses the history of transplantation, basic immunology including HLA antigens and allo-graft rejection. It also covers clinical immunosuppression with drugs like corticosteroids and cyclosporin. Organ procurement, specific organ transplants, and future trends are briefly mentioned.
This document provides an overview of transplant surgery, including:
1. It describes different types of transplants such as orthotopic, heterotopic, autotransplant, allotransplant, isotransplant, and xenotransplant.
2. It discusses graft rejection and the immune response, including hyperacute, acute, and chronic rejection.
3. It outlines the pretransplant evaluation process for transplant candidates and donors.
4. It provides details on renal transplantation techniques and evaluations of both living and deceased donors.
This document provides an overview of organ transplantation principles. It defines different types of transplants and discusses the history and key developments in the field. The basic immunology of transplantation is explained, including allograft rejection mechanisms and the roles of human leukocyte antigens and immunosuppressive drugs like corticosteroids and cyclosporin in preventing rejection. Tissue typing and matching donors to recipients is also covered.
This document provides an overview of organ transplantation, including definitions, categories of transplants, history, graft rejection, HLA matching, organ procurement, and donation after brain death and cardiac death. Key points include:
- Transplantation involves transferring an organ or tissue from one place to another. Allotransplants between individuals of the same species require immunosuppression.
- Major milestones include the first successful organ transplant in 1954 and development of immunosuppressive drugs in the 1960s.
- Graft rejection is mediated by the immune system recognizing transplanted organs as foreign. Acute rejection typically occurs in the first 6 months while chronic rejection develops later.
- HLA matching aims to reduce rejection by finding donors with similar
This document provides an overview of transplantation surgery principles. It defines key terms like transplantation, graft types, and alloantigens. It discusses indications for common organ transplants like kidney, liver, heart and lungs. It also covers the immunological basis for graft rejection, focusing on the role of the major histocompatibility complex and human leukocyte antigens in triggering rejection. Finally, it summarizes strategies for tissue matching between donors and recipients, principles of immunosuppressive therapy to prevent rejection, potential complications of transplantation, and methods for organ donation and preservation.
1. Transplantation immunology examines the immune response to transplanted tissues.
2. Major events include the first successful organ transplants in the 1950s-60s of kidneys, livers, hearts, and bone marrow.
3. Graft rejection is driven by an immune response to foreign histocompatibility antigens like MHC proteins, with T-cells playing a key role through cell-mediated responses. Immunosuppressive drugs help prevent rejection by inhibiting T-cell activation and proliferation.
Power point presentation about general principles of organ transplantation and pioneer surgons and investigators, Specific discussion about Heart, Heart lung and Lung transplantation is given
The document discusses transplantation and the immune response. It begins by defining transplantation as moving cells, tissues, or organs from one site to another, either within an individual or between donors and recipients. There are several types of transplantation - autografts within an individual, isografts between identical twins, allografts between non-identical individuals of the same species, and xenografts between different species. Rejection can be acute, occurring within 6 months, or chronic with repeated acute episodes ultimately causing transplant failure. Immunosuppressive drugs are used to reduce rejection by dampening the immune response.
This document discusses the history and science of transplant surgery. It outlines some of the earliest attempts at tissue transplantation throughout history. It then summarizes key developments like the first human kidney transplant performed by Yu Yu Voronoy in 1936. The document also discusses Peter Medawar's important research in the 1940s which showed that graft rejection is an immune response. Finally, it provides an overview of transplant types, graft rejection, immunosuppression, and challenges like chronic rejection.
Dr. Dharmendra Joshi presented on the principles of organ transplantation. Key points included: defining transplantation terms; organs that can be transplanted; immunology principles like graft rejection; pre-operative, intra-operative, and post-operative principles; ethical considerations; and future trends like newer immunosuppressive therapies. The goal of transplantation is to replace a failing organ with a functioning one from a donor to treat end-stage organ disease through improved surgical techniques and immunosuppression.
This document discusses pediatric kidney transplantation, including its history, indications, recipient and donor evaluation processes, surgical procedure, immunosuppression regimens, complications, and long-term management. Key points include: the first successful human kidney transplant was in 1950; recipients must not have active infection or malignancy; living donors are preferred when possible; tissue typing and crossmatching are important; immunosuppression involves induction agents, steroids, calcineurin inhibitors, and other drugs; and complications can include rejection, infection, graft failure, and malignancy. Long-term follow up is needed to monitor graft function and patient health.
Transplant immunology is the study of the immune response that occurs when tissue is transplanted from one individual to another. There are three main types of transplants - autografts within the same individual, allografts between genetically different members of the same species, and xenografts between different species. For allografts and xenografts, the recipient's immune system recognizes the donor tissue as foreign and mounts an attack, leading to graft rejection. Rejection can occur rapidly via hyperacute rejection or more slowly through acute or chronic rejection as the immune response destroys the transplant tissue over time. Immunosuppressive drugs are given to recipients to reduce rejection by suppressing the immune system.
Organ transplantation involves transferring a whole or partial organ from a donor to a recipient in need of replacement of a damaged or failing organ. Major transplantable organs include the liver, kidney, heart, lungs, pancreas and intestine. Transplant rejection is a major complication that occurs when the recipient's immune system attacks the donor organ. The main types of rejection are hyperacute, acute vascular, acute cellular and chronic rejection. Rejection is combatted using immunosuppressive drugs that inhibit lymphocyte proliferation and activation such as corticosteroids, calcineurin inhibitors, antiproliferatives and anti-T cell agents. With advances in immunosuppression and organ matching, transplantation has become an established treatment for end-stage organ
Principles of organ transplant and Renal transplantDr Navil Sharma
This document provides an overview of organ transplant principles. It defines different types of transplants and discusses transplant immunology, including graft rejection. The key principles covered are pre-operative (patient selection, counseling, informed consent), intra-operative (organ procurement and preservation), and post-operative (assessment, immunosuppression, follow up). Complications and ethical considerations are also mentioned. Overall, the document outlines the major concepts and steps involved in organ transplantation.
This document provides an overview of hematopoietic stem cell transplantation (HSCT). It defines hematopoietic stem cells and HSCT, and describes the types of transplants including autologous and allogenic. The key indications for each type are outlined. The process of HSCT is summarized, including donor selection, stem cell collection, cryopreservation, conditioning chemotherapy, stem cell infusion, and engraftment recovery. Post-transplant complications and supportive care measures are briefly discussed.
Transplantation refers to transferring cells, tissues or organs from one site to another. The first successful human kidney transplant occurred between identical twins in Boston in 1954. There are four main types of transplants - autograft, isograft, allograft, and xenograft - which differ based on the genetic similarity between the donor and recipient. Autografts have no immune response, while xenografts between different species have the most vigorous rejection response.
The document discusses the history and techniques of organ transplantation. It begins with ancient Chinese legends of organ swapping from 300 BC. Modern transplantation originated in the early 1900s with experiments in vascular suturing and blood transfusion. The first successful organ transplants were kidney transplants in the 1960s, followed by liver, lung, small bowel and other organs. The document outlines the immunological challenges of transplantation and methods used for organ retrieval, preservation, transplantation and immunosuppression to prevent rejection. It provides classifications and details various aspects of organ transplantation surgery and post-operative care.
This document provides an overview of transplantation immunology. It discusses the different types of transplants including autografts, allografts, xenografts, and ABO incompatible transplants. It describes how the immune system can reject transplants and the challenges of finding donor-recipient matches. Key concepts covered include acute rejection occurring within 6 months, chronic rejection developing over longer periods, and the use of immunosuppressive drugs to reduce rejection risks. HLA tissue typing aims to find immunologically compatible donors by matching proteins on white blood cells.
This document summarizes a seminar on organ transplantation presented by Dr. Soumen Kanjilal. It provides a brief history of organ transplantation, highlighting some key events and discoveries. It then discusses what organ transplantation is, the organs that can be transplanted, types of donors, how donor organs are evaluated and preserved, and techniques for transplantation of kidneys and livers. Potential complications of kidney and liver transplants are also outlined.
Transplantation involves transferring organs, tissues or cells from one part of the body to another or between individuals. Compatibility of immune molecules like HLA antigens, ABO blood groups, MIC antigens and KIR determines transplant success. Major histocompatibility complex (MHC) molecules control immune response and are targets in transplant rejection. Incompatibility can lead to hyperacute, acute cellular or chronic rejection as well as graft-versus-host disease. Immunosuppressive agents like corticosteroids, calcineurin inhibitors and monoclonal antibodies are used to suppress anti-graft immune responses.
Haematopoietic Stem Cell Mobilisation and ApheresisEBMT
The document provides an overview of autologous stem cell transplantation, including scientific background on blood cell formation and the bone marrow microenvironment. It describes the stem cell transplant process, including stem cell mobilization using agents like filgrastim and plerixafor, stem cell collection via apheresis, and patient evaluation and preparation for the collection procedure. The goal of the process is to collect enough CD34+ stem cells from the patient's peripheral blood to later be reinfused after high-dose chemotherapy or radiation to rescue the patient's bone marrow.
Renal transplantation involves transplanting a kidney from a living or deceased donor into a patient with end-stage renal disease. Kidney transplantation provides better outcomes than long-term dialysis, including longer survival, improved quality of life, and avoidance of dialysis. Evaluation of both recipients and donors is required to minimize risks of rejection and other complications. While transplantation has higher initial costs, it becomes cost-effective compared to lifelong dialysis within a few years.
Lecture 11 (blood gruoping, blood transfusion, organ transplantation)Ayub Abdi
The document discusses blood groups, blood transfusions, and organ transplants. It explains that blood is grouped into types based on the presence or absence of antigens (A, B, Rh). Compatible blood must be used in transfusions to avoid reactions. O blood can be donated universally while AB recipients can receive any type. Organ transplant rejection occurs unless immunosuppressive drugs prevent the immune system from attacking foreign tissues. Matching donors and recipients based on human leukocyte antigens reduces rejection risks.
This document discusses the pathology and management of malignant bowel obstruction. It defines malignant bowel obstruction as luminal narrowing of the small or large bowel due to metastatic cancer. The most common primary cancers causing MBO are colorectal, ovarian, stomach, and pancreatic cancers. The document outlines the classification, signs and symptoms, diagnostic tests including CT scan, and various treatment options for MBO, including surgical resection, endoscopic stenting, non-operative management with medications like octreotide to relieve symptoms, and palliative care since MBO represents terminal cancer. The primary goals of treatment are palliation to improve quality of life by relieving nausea, vomiting and pain.
- Malignant melanoma is a deadly form of skin cancer that has been increasing in incidence over the past 50 years.
- It typically presents as an asymmetric mole with irregular borders and varies in color.
- Risk factors include family history, numerous moles, sun exposure, and fair skin.
- Staging involves evaluating tumor thickness and spread. Treatment may include surgery, lymph node assessment, radiation, immunotherapy, and targeted drug therapy. Prognosis depends on stage, with thinner tumors having better survival rates.
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Power point presentation about general principles of organ transplantation and pioneer surgons and investigators, Specific discussion about Heart, Heart lung and Lung transplantation is given
The document discusses transplantation and the immune response. It begins by defining transplantation as moving cells, tissues, or organs from one site to another, either within an individual or between donors and recipients. There are several types of transplantation - autografts within an individual, isografts between identical twins, allografts between non-identical individuals of the same species, and xenografts between different species. Rejection can be acute, occurring within 6 months, or chronic with repeated acute episodes ultimately causing transplant failure. Immunosuppressive drugs are used to reduce rejection by dampening the immune response.
This document discusses the history and science of transplant surgery. It outlines some of the earliest attempts at tissue transplantation throughout history. It then summarizes key developments like the first human kidney transplant performed by Yu Yu Voronoy in 1936. The document also discusses Peter Medawar's important research in the 1940s which showed that graft rejection is an immune response. Finally, it provides an overview of transplant types, graft rejection, immunosuppression, and challenges like chronic rejection.
Dr. Dharmendra Joshi presented on the principles of organ transplantation. Key points included: defining transplantation terms; organs that can be transplanted; immunology principles like graft rejection; pre-operative, intra-operative, and post-operative principles; ethical considerations; and future trends like newer immunosuppressive therapies. The goal of transplantation is to replace a failing organ with a functioning one from a donor to treat end-stage organ disease through improved surgical techniques and immunosuppression.
This document discusses pediatric kidney transplantation, including its history, indications, recipient and donor evaluation processes, surgical procedure, immunosuppression regimens, complications, and long-term management. Key points include: the first successful human kidney transplant was in 1950; recipients must not have active infection or malignancy; living donors are preferred when possible; tissue typing and crossmatching are important; immunosuppression involves induction agents, steroids, calcineurin inhibitors, and other drugs; and complications can include rejection, infection, graft failure, and malignancy. Long-term follow up is needed to monitor graft function and patient health.
Transplant immunology is the study of the immune response that occurs when tissue is transplanted from one individual to another. There are three main types of transplants - autografts within the same individual, allografts between genetically different members of the same species, and xenografts between different species. For allografts and xenografts, the recipient's immune system recognizes the donor tissue as foreign and mounts an attack, leading to graft rejection. Rejection can occur rapidly via hyperacute rejection or more slowly through acute or chronic rejection as the immune response destroys the transplant tissue over time. Immunosuppressive drugs are given to recipients to reduce rejection by suppressing the immune system.
Organ transplantation involves transferring a whole or partial organ from a donor to a recipient in need of replacement of a damaged or failing organ. Major transplantable organs include the liver, kidney, heart, lungs, pancreas and intestine. Transplant rejection is a major complication that occurs when the recipient's immune system attacks the donor organ. The main types of rejection are hyperacute, acute vascular, acute cellular and chronic rejection. Rejection is combatted using immunosuppressive drugs that inhibit lymphocyte proliferation and activation such as corticosteroids, calcineurin inhibitors, antiproliferatives and anti-T cell agents. With advances in immunosuppression and organ matching, transplantation has become an established treatment for end-stage organ
Principles of organ transplant and Renal transplantDr Navil Sharma
This document provides an overview of organ transplant principles. It defines different types of transplants and discusses transplant immunology, including graft rejection. The key principles covered are pre-operative (patient selection, counseling, informed consent), intra-operative (organ procurement and preservation), and post-operative (assessment, immunosuppression, follow up). Complications and ethical considerations are also mentioned. Overall, the document outlines the major concepts and steps involved in organ transplantation.
This document provides an overview of hematopoietic stem cell transplantation (HSCT). It defines hematopoietic stem cells and HSCT, and describes the types of transplants including autologous and allogenic. The key indications for each type are outlined. The process of HSCT is summarized, including donor selection, stem cell collection, cryopreservation, conditioning chemotherapy, stem cell infusion, and engraftment recovery. Post-transplant complications and supportive care measures are briefly discussed.
Transplantation refers to transferring cells, tissues or organs from one site to another. The first successful human kidney transplant occurred between identical twins in Boston in 1954. There are four main types of transplants - autograft, isograft, allograft, and xenograft - which differ based on the genetic similarity between the donor and recipient. Autografts have no immune response, while xenografts between different species have the most vigorous rejection response.
The document discusses the history and techniques of organ transplantation. It begins with ancient Chinese legends of organ swapping from 300 BC. Modern transplantation originated in the early 1900s with experiments in vascular suturing and blood transfusion. The first successful organ transplants were kidney transplants in the 1960s, followed by liver, lung, small bowel and other organs. The document outlines the immunological challenges of transplantation and methods used for organ retrieval, preservation, transplantation and immunosuppression to prevent rejection. It provides classifications and details various aspects of organ transplantation surgery and post-operative care.
This document provides an overview of transplantation immunology. It discusses the different types of transplants including autografts, allografts, xenografts, and ABO incompatible transplants. It describes how the immune system can reject transplants and the challenges of finding donor-recipient matches. Key concepts covered include acute rejection occurring within 6 months, chronic rejection developing over longer periods, and the use of immunosuppressive drugs to reduce rejection risks. HLA tissue typing aims to find immunologically compatible donors by matching proteins on white blood cells.
This document summarizes a seminar on organ transplantation presented by Dr. Soumen Kanjilal. It provides a brief history of organ transplantation, highlighting some key events and discoveries. It then discusses what organ transplantation is, the organs that can be transplanted, types of donors, how donor organs are evaluated and preserved, and techniques for transplantation of kidneys and livers. Potential complications of kidney and liver transplants are also outlined.
Transplantation involves transferring organs, tissues or cells from one part of the body to another or between individuals. Compatibility of immune molecules like HLA antigens, ABO blood groups, MIC antigens and KIR determines transplant success. Major histocompatibility complex (MHC) molecules control immune response and are targets in transplant rejection. Incompatibility can lead to hyperacute, acute cellular or chronic rejection as well as graft-versus-host disease. Immunosuppressive agents like corticosteroids, calcineurin inhibitors and monoclonal antibodies are used to suppress anti-graft immune responses.
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The document provides an overview of autologous stem cell transplantation, including scientific background on blood cell formation and the bone marrow microenvironment. It describes the stem cell transplant process, including stem cell mobilization using agents like filgrastim and plerixafor, stem cell collection via apheresis, and patient evaluation and preparation for the collection procedure. The goal of the process is to collect enough CD34+ stem cells from the patient's peripheral blood to later be reinfused after high-dose chemotherapy or radiation to rescue the patient's bone marrow.
Renal transplantation involves transplanting a kidney from a living or deceased donor into a patient with end-stage renal disease. Kidney transplantation provides better outcomes than long-term dialysis, including longer survival, improved quality of life, and avoidance of dialysis. Evaluation of both recipients and donors is required to minimize risks of rejection and other complications. While transplantation has higher initial costs, it becomes cost-effective compared to lifelong dialysis within a few years.
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The document discusses blood groups, blood transfusions, and organ transplants. It explains that blood is grouped into types based on the presence or absence of antigens (A, B, Rh). Compatible blood must be used in transfusions to avoid reactions. O blood can be donated universally while AB recipients can receive any type. Organ transplant rejection occurs unless immunosuppressive drugs prevent the immune system from attacking foreign tissues. Matching donors and recipients based on human leukocyte antigens reduces rejection risks.
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2. Outline:
• Introduction
• Definition
• Epidemiology
• Historical background
• Transplant immunology
• Types of allograft rejection
• Perioperative considerations
• Pre op
• Intra op
• Post op
• Complications
• Future trends
• Conclusion
• Reference
3. Introduction:
Definitions:
• Transplantation: is the process of transferring an organ, tissue, or cell
from one place to another.
• Organ transplant: is a surgical procedure in which a failing organ is
replaced by a functioning one.
4. Introduction:
• Autograft the transfer of organ from one part to another in the same
individual
• Allograft from one individual to another of the same specie
• Isograft transfer of organ from one individual to his or her identical
twin
• Xenograft the transfer of organ from one individual to another of
different specie
• Orthotopic graft a graft placed in its normal anatomical position
• Heterotopic graft a graft placed at a site different from where the
organ is normally located.
5. Epidemiology:
• In 2017 alone, according to the United Network for Organ Sharing
(UNOS), about 115,000 patients in the United States were awaiting a
transplant, yet the number of transplants performed approached only
about 35,000.
• Advances in surgical technique and a better understanding of
immunology are the two main reasons that transplants have evolved.
• Lack of resources, cadaveric programs and technical facilities coupled
with late presentation continue to hamper transplant programs in
Africa
6. Historical background:
• 1954 – The first successful live donor human kidney transplant,
between identical twin brothers. The transplanted kidney functioned
for 8 years
• 1958 – The first kidney transplant in humans using
immunosuppression
• 1961 – The first successful kidney transplant between non-siblings
• 1962 – The first successful kidney transplanted from a deceased
donor occurred in Boston - the kidney functioned for 21 months. This
was the first use of the new immunosuppressive drug azathioprine
7. Historical background:
• 1963 – The first liver transplant by Thomas Starzl in Denver, Colorado.
• 1963 – The first lung transplant was performed by James Hardy in
Jackson, Mississippi.
• 1966 – The first pancreas transplant was performed by William Kelly
and Richard Lillehei in Minneapolis, Minnesota.
• 1967 – The first successful heart transplant was performed by
Christiaan Barnard in Cape Town, South Africa.
8. Transplant Immunology:
• Human leukocyte antigens (HLA): are a group of highly polymorphic
cell surface molecules that function as antigen recognition units that
display antigens for recognition by T- lymphocytes.
• HLA -A, -B, -C, -DR, -DP, and -DQ
• Class I antigens are present on all nucleated cells
• Class II antigens are expressed on antigen-presenting cells (APC) like
dendritic cells, macrophages and B lymphocytes.
• Major histocompatibility complex (MHC): genes that encode HLA.
• ABO compatibility
9. Transplant Immunology:
• The immune system recognizes graft from someone else as foreign
and triggers immune response
• Innate or acquired immune response
• Donor HLA class I and class II antigens recognize CD8 & CD4 T cells
respectively
• Activation of CD8 T cells cause target cell death via release of lytic
molecules like perforin and granzyme
10. Transplant Immunology:
• Expression of HLA class II by graft cells stimulate proliferation and
activation of CD4 T cells in response to IL-2.
• Activated CD4 T cells mediate direct target cell damage, release of
proinflammatory cytokines like Interferon 𝞬 (INF-𝞬) which recruit and
activate macrophages
• CD4 T cells also help in producing alloantibodies which bind to graft
antigen and induce target cell injury.
11.
12. Types of allograft rejection:
Hyperacute rejection:
• Immediate graft destruction due to ABO or preformed anti-HLA
antibodies
• Characterised by intravascular thrombosis and interstitial
haemorrhage
• Kidney transplants are particularly vulnerable to hyperacute graft
rejection, whereas heart and liver transplants are relatively resistant.
13. Types of allograft rejection:
Acute rejection:
• Usually occurs during first 6 months
• T-lymphocyte mediated but alloantibodies also play a role
• Characterised by mononuclear cell infiltration of the graft
• All types of organ allograft are susceptible to acute rejection (20-30%)
14. Types of allograft rejection:
Chronic rejection:
• Occurs after first 6 months
• Most common cause of graft failure
• Antibodies play an important role
• Non-immune factors contribute to pathogenesis
• Characterised by myointimal proliferation in graft arteries leading to
ischaemia and fibrosis
• Most important risk factor for chronic rejection after kidney
transplantation is acute rejection (with vascular inflammation) and
recurrent episodes of acute rejection.
15. Graft-versus-host-disease (GVHD):
• Occasionally seen after certain types of organ transplantation.
• Some donor organs contain large numbers of lymphocytes, and these
may react against HLAs expressed by recipient tissues, leading to
GVHD.
• Characteristic rash on the palms and soles.
18. Organ donation and procurement:
• Deceases donors: brain-stem-dead, donation after brain death (DBD) or donation
after circulatory death (DCD)
• Living donors
Brain death: irreversible cessation of function of the circulatory, respiratory and
entire brain, including medulla.
• Ruling out barbiturate coma, hypothermia, drug overdoses, intoxication
• Test for all the reflexes of cerebral function.
19. Organ donation and procurement:
Brain death protocol:
• 2 senior physicians independently & not associated with the teams needing the organs.
• Motor response to painful stimulation
• Pupillary response to light
• Corneal reflex testing
• Oculocephalogyric reflex (doll’s eye )
• Vestibuloocular (caloric) reflex
• Upper & Lower airway (pharyngeal & ETT suction) reflexes
• Gag reflex
• All the above × 2
• Apnea test: Stop ventilation until Pa CO2 = 60mmHg without respiration.
• EEG (in US, not Europe) should be flat.
• Cerebral angiography confirms surely.
20. Organ donation and procurement:
For DBD donors:
• Careful monitoring and management of fluid balance is essential.
• Vasopressin is often given to allow reduction or cessation of
catecholamine pressors.
• Donors are also usually given methylprednisolone to aid fluid and
metabolic management
• Triiodothyronine (T3) to help cardiovascular stability.
21. Organ donation and procurement:
DCD donors are grouped using the Maastricht classification
• Category 1: Dead on arrival
• Category 2: Unsuccessful resuscitation in hospital
• Category 3: Awaiting cardiac arrest after withdrawal of support
• Category 4: Cardiac arrest while brainstem-dead
• Warm ischaemic time for categories 1,2, and 5 is usually longer and
less predictable
22. Organ donation and procurement:
Living donors:
• Age 0 – 75yrs
• Willing & not financially induced or coerced.
• Satisfactory function of vital organs
• Serology
• Malignant disease
• ABO compatible
23. Organ donation and procurement :
• After removal, the organ is flushed with chilled organ preservation
solution e.g University of Wisconsin(UW), Euro-collins, Celsior,
Custodiol, citrate/Marshall solutions
• Cooled to 4-6o by isolated perfusion pre harvest or table lavage
• Warm ischaemic time
• Cold ischaemic time
• Storage time for organs vary
26. Immunosuppression:
• Aim is to maximize graft protection and minimize side effect.
• Act predominantly on T cells
• Need for immunosuppression is highest in the first 3 months
• Immunosuppressive protocols for different types of organ transplant
vary between centres, but almost all use a combination of
immunosuppressive agents acting at different points in the pathway
of lymphocyte activation.
27. Immunosuppressants:
• Induction
• Maintenance
• Rescue agents
Corticosteroids: e.g. prednisolone
• Used in combination with other agents
• Increase graft survival
• Anti inflammatory effects
• Side effects: Hypertension, dyslipidaemia, diabetes, osteoporosis,
avascular necrosis, cushingoid appearance
28. Immunosuppressants:
Calcineurin inhibitors: ciclosporin and tacrolimus
• Blocks the activity of calcineurin within the cytoplasm of the T cell.
• Calcineurin plays a critical role in facilitating the transcription of IL-2.
• Their immunosuppressive action, as well as their side effects, is
dependent on their blood concentration, and monitoring of whole-
blood drug levels
• Side effects: Nephrotoxicity, hypertension, dyslipidaemia.
29. Immunosuppressants:
Anti Proliferative Agents: Azathioprine and mycophenolic acid
preparations
• Part of maintenance therapy
• Inhibits purine metabolism
• Prevents proliferation of lymphocytes
• Side effects: leukopenia, thrombocytopenia, hepatotoxicity,
gastrointestinal symptoms
30. Immunosuppressants:
Antibody therapy:
• Monoclonal antibodies against IL-2 receptor on T lymphocytes (CD25)
• Anti-CD20 antibody - rituximab
• Others are alemtuzumab (anti-CD52 expressed on T cells and
dendritic cells )
• Polyclonal antibody - anti- thymocyte globulin (ATG)
• May be used to treat acute rejection episodes that fail to respond to
steroid therapy.
• Side effects: Infusion reaction, autoimmune disease and pulmonary
toxicity
31. Immunosuppressants:
Mammalian target of rapamycin (mTOR) inhibitors: sirolimus and
everolimus
• Interfere with intracellular signalling from the IL-2 receptor, arresting
T-cell division in the G1 phase
• Side effects: Thrombocytopenia, dyslipidaemia, pneumonitis,
impaired wound healing
32. Immunosuppressants:
T-cell co-stimulatory blockers: belatocept
• Binds to the co-stimulatory ligands CD80 and CD86 expressed on
antigen-presenting cells and prevents them from delivering the
costimulatory signals for full T-cell activation.
• May be associated with an increased risk of post-transplant
lymphoproliferative disease (PTLD).
34. Complications:
Infection: greatest risk in the first 6 months
• Viral: CMV , HSV, Herpes zoster
• Bacterial
• Fungal: Pneumocystis jiroveci
• Malignancy: especially skin cancers and PTLD
35. Future trends:
• Stem cell biology and tissue engineering:
• Totipotent stem cell- can give rise to whole organism
• Pluripotent stem cell can give rise to cells derived from three germ
layers
• Multipotent (organ specific) stem cell
36. Conclusion:
• Organ transplantation continues to play a vital role in the treatment
of many end stage organ diseases
• This has been made possible because of advances in immunology and
pharmacology.
• Advances in transplantation come with the ethical problems of organ
procurement and allocation
• In sub-Saharan Africa, transplant surgery is not widely practiced and
considered a difficult task
37. References:
• Bailey and Love’s “Short Practice of Surgery” 27th edition CRC press
Taylor and Francis group. 2013
• E.A Badoe et al, “Principles and Practice of surgery including
pathology in the tropics” 5th edition
• M.A.R Al-Fallouji; “Postgraduate Surgery the candidate guide”. 2nd
Edition. Rced Educational and Professional Pub. Ltd 1998
• Sabiston textbook of surgery. 18th edition.2007
• Schwartz’s Principle of Surgery. 11th edition. New York: McGraw
Hill;2019. 355-367p
• Principles involved in Organ transplant by Dr Bashir Yunus; 2015
Gradual increase in the organ shortage led to innovative surgical techniques. For example, deceased donor split liver transplants
took place at the Peter Bent Brigham Hospital in Boston, Massachusetts.
1959- First successful kidney transplant between fraternal twins
1960- First successful kidney transplant between non-twin siblings
A breakthrough was achieved in the early 1960s with the introduction of maintenance immunosuppression through a combination of corticosteroids and a less toxic derivative of 6-mercaptopurine, azathioprine.5,6
Vary due to different cell expression profiles
Class I: heavy chain and β2-microglobulin
Class II: α- and β-chain
They are clusters of genes on the short arm of chromosome 6 expressed on the cell surface as HLA
Naturally occurring anti-A or anti-B antibodies will likely cause hyperacute graft rejection however, there is no need to take account of rhesus antigen compatibility in organ transplantation.
Innate (mediated by WBC, null cells, NK cells, IFNs, Acute phase proteins)
Acquired (Specific)
Acquired:- cellular – T cells
Humoral – B cells
Important antibodies in graft rejection IgG, IgM, IgA
Allograft rejection manifests itself as functional failure of
the transplant and is confirmed by histological examination.
less susceptible to ischaemia than the kidney by virtue of its dual blood supply: 60% of the hepatic blood supply is derived from the portal vein and 40% from the hepatic artery.
Most episodes of acute cellular rejection can be reversed by additional immunosuppressive therapy. Acute antibody-mediated rejection is more difficult to treat effectively and may require plasmaphoresis or immunoadsorption.
the liver is more resistant than other organs to the destructive effects of chronic rejection.
there are organ-specific features of chronic graft rejection. These are:
● kidney: glomerular sclerosis and tubular atrophy;
● pancreas: acinar loss and islet destruction;
● heart: accelerated coronary artery disease (cardiac allograft
vasculopathy);
● liver: vanishing bile duct syndrome;
● lungs: obliterative bronchiolitis.
(particularly liver and small bowel)
Pt must meet the indication for transplant and must have a diagnosis with an end stage organ failure.
Hx: and Exam to look out for other co-morbidities, allergies, smoking, family hx. Serology: HIV, hepatitis,VDRL,CMV, septic work up for both donor and rescipient, ABO and tissue typing for HLA and lymphocytes crossmatching, FBC, Clothing profiles, ECG; , Jakob-Creutzfeldt’s Dx
Cancer within the last 5yrs
Initiation of preservation is in situ- for DCD donors
They all contain impairments to limit cell swelling, buffers to counter acidosis and electrolytes
UW solution:
Lactobionate- reduces cell swelling during storage
Glutathione
Adenosine
Allopurinol
Insulin
Hydroxethyl starch
cold storage times
Clinical –vital signs; fever, tarchychadia, hypertension, pain at site of transplant, pedal oedema (compession of external iliac vein), decrease urine volume- features of hyperacute rejection
O Investigations ;
U/Ecr
USS- increase in size, pelvicalyceal dilation
Biopsy; mononuclearinfiltrates,fibrinoid necrosis, interstitial
haemorrhage.
Others
Maintenance immunosuppression
DVT prophylaxis
Treatment of infection
Regular follow up
mainstay of most modern immunosuppressive protocols for organ transplantation.
Azathioprine is converted in the liver to its active metabolite, 6-mercaptopurine, which blocks purine metabolism
mycophenolic acid preparations (mycophenolate mofetil [MMF] and mycophenolic acid sodium [MPAS])
MMF is converted to its active metabolite MPA. It inhibits the enzyme inosine monophosphate dehydrogenase, which is the rate-limiting enzyme in the de novo pathway of purine nucleotide synthesis.
They potentiate the effects of the calceniurine inhibitors
intracellular kinase similar to CNI but mechanism of action differs…