Transplantation and the Immune System

Flashcards about Transplantation and the Immune System

Autograft

A graft from your own system; for example, transplanting skin from one area of your body to another.

Isograft

A graft between identical twins who share the same genetics.

Allograft

A graft between two individuals from the same species but with different genetics.

Xenograft

A graft from a donor organ from a different species, such as pig heart valves.

Organs for Transplantation

Heart, spine, kidney, liver, lungs, and pancreas.

Tissues for Transplantation

Bones, cartilage, corneas, heart valves, ligaments, skin, tendons, and veins.

Autologous Graft

Transplanting an organ in the same location.

Transplant Statistics (NHS Blood and Transplant)

Kidney: ~2,200; Liver: ~600; Heart: ~220; Lungs: ~130 (Year ending March 2024)

Organ Donation Law Change in the UK

Shifted from opt-in to opt-out, assuming willingness to donate unless specified otherwise.

Adaptive Immune System Response to Donated Organ

Recognizes the donated organ as foreign and induces inflammation, leading to rejection.

MHC

Major Histocompatibility Complex; also known as HLA (human leukocyte antigen) in humans.

Function of MHC

Presents peptides and is recognized by the adaptive immune system via T-cells, initiating an immune reaction.

MHC Diversity

High diversity ensures species resilience to pathogens but complicates donor matching.

MHC Class I

Presents endogenous, intracellular peptides to CD8 T-cells.

MHC Class II

Presents exogenous proteins taken up from the outside to CD4 helper T-cells.

T-Cell Receptor Recognition

Recognizes both the MHC and the peptide; restricted to recognizing HLA.

Ideal Tissue Transplantation Match

An exact match across all six major antigens (HLA A, B, C, DR, DQ, DP).

Impact of Mismatches

Mismatching of major histocompatibility complexes correlates with graft rejection.

Direct Recognition

T-cells recognizing MHC directly on donor tissue, regardless of the peptide presented.

Indirect Recognition

Recipient cells process donor material and present peptides, which T-cells recognize as foreign.

Direct Pathway T-Cell activation

T-cells recognize the foreign MHC molecule displayed by the donor antigen presenting cell, leading to their activation and proliferation.

Indirect Pathway T-Cell activation

Donor MHC is processed and presented by the recipient antigen presenting cell in MHC class II molecules, involving CD4 T-cells.

Kinetics of Graft Rejection

Hyperacute rejection, acute rejection, or chronic rejection.

Hyperacute Rejection

Occurs within minutes to hours, mediated by pre-formed antibodies and complement activation.

Acute Rejection

Begins after the first week and up to three months, mediated by T-cells and antibodies.

Chronic Rejection

Occurs within months to years, characterized by fibrosis and vascular abnormalities.

Tissue Typing

Checking the MHC and HLA genetic material in both donor and recipient.

Cross-matching

Looking for pre-existing antibodies in the recipient against HLA MHC molecules from the donor.

Blood Typing

Ensuring compatibility of blood types is essential for any graft.

Autograft

A graft from your own system; for example, transplanting skin from one area of your body to another.

Isograft

A graft between identical twins who share the same genetics.

Allograft

A graft between two individuals from the same species but with different genetics.

Xenograft

A graft from a donor organ from a different species, such as pig heart valves.

Organs for Transplantation

Heart, spine, kidney, liver, lungs, and pancreas.

Tissues for Transplantation

Bones, cartilage, corneas, heart valves, ligaments, skin, tendons, and veins.

Autologous Graft

Transplanting an organ in the same location.

Transplant Statistics (NHS Blood and Transplant)

Kidney: ~2,200; Liver: ~600; Heart: ~220; Lungs: ~130 (Year ending March 2024)

Organ Donation Law Change in the UK

Shifted from opt-in to opt-out, assuming willingness to donate unless specified otherwise.

Adaptive Immune System Response to Donated Organ

Recognizes the donated organ as foreign and induces inflammation, leading to rejection.

MHC

Major Histocompatibility Complex; also known as HLA (human leukocyte antigen) in humans.

Function of MHC

Presents peptides and is recognized by the adaptive immune system via T-cells, initiating an immune reaction.

MHC Diversity

High diversity ensures species resilience to pathogens but complicates donor matching.

MHC Class I

Presents endogenous, intracellular peptides to CD8 T-cells.

MHC Class II

Presents exogenous proteins taken up from the outside to CD4 helper T-cells.

T-Cell Receptor Recognition

Recognizes both the MHC and the peptide; restricted to recognizing HLA.

Ideal Tissue Transplantation Match

An exact match across all six major antigens (HLA A, B, C, DR, DQ, DP).

Impact of Mismatches

Mismatching of major histocompatibility complexes correlates with graft rejection.

Direct Recognition

T-cells recognizing MHC directly on donor tissue, regardless of the peptide presented.

Indirect Recognition

Recipient cells process donor material and present peptides, which T-cells recognize as foreign.

Direct Pathway T-Cell activation

T-cells recognize the foreign MHC molecule displayed by the donor antigen presenting cell, leading to their activation and proliferation.

Indirect Pathway T-Cell activation

Donor MHC is processed and presented by the recipient antigen presenting cell in MHC class II molecules, involving CD4 T-cells.

Kinetics of Graft Rejection

Hyperacute rejection, acute rejection, or chronic rejection.

Hyperacute Rejection

Occurs within minutes to hours, mediated by pre-formed antibodies and complement activation.

Acute Rejection

Begins after the first week and up to three months, mediated by T-cells and antibodies.

Chronic Rejection

Occurs within months to years, characterized by fibrosis and vascular abnormalities.

Tissue Typing

Checking the MHC and HLA genetic material in both donor and recipient.

Cross-matching

Looking for pre-existing antibodies in the recipient against HLA MHC molecules from the donor.

Blood Typing

Ensuring compatibility of blood types is essential for any graft.

Immunosuppression

Administering immunosuppressive drugs to suppress the recipient's immune system to prevent rejection of the transplanted organ.

Immunosuppressive medications

Includes calcineurin inhibitors, mTOR inhibitors, anti-proliferative agents, and steroids.

Calcineurin Inhibitors

Cyclosporine and tacrolimus; inhibit T-cell activation by disrupting calcineurin signaling.

mTOR Inhibitors

Sirolimus and everolimus; block T-cell proliferation by inhibiting mTOR kinase.

Anti-proliferative Agents

Azathioprine and mycophenolate mofetil; inhibit DNA synthesis, reducing proliferation of immune cells.

Steroids

Prednisone; reduce inflammation by suppressing the expression of pro-inflammatory cytokines.

Increased risk of infections, development of malignancies