Transplantation and Immunosuppressive Drugs

Question 1

Describe and explain the nature of the main types of transplantation of the immune system

Answer 1

1) Hematopoietic Stem Cell Transplantation (HSCT):

• Infusion of hematopoietic stem cells, usually from peripheral blood but can also be derived from bone marrow or umbilical cord blood, into a recipient with defective or depleted bone marrow
• Commonly used to treat cancers of the blood, such as leukaemia or lymphoma
• Autologous HSCT: The patient’s own HSCs are harvested, after a course of treatment that destroys both the cancer and the patient’s bone marrow, and then reinfused back into the patient. This allows high-dose chemotherapy to be used, more effective against the cancer
• Allogeneic HSCT: HSCs are harvested from a donor and. then infused into the patient. In this case, the donor’s immune cells can also attack any remaining cancer cells in a process called graft-versus-tumour (GVT) effect

2) Bone Marrow Transplantation (BMT):

• A specific type of HSCT where the stem cells are derived from the bone marrow, the process is similar and are often used interchangeably

3) Orang Transplantation:

• Transplantation of whole organs, such as the kidney, heart, liver or lung from a donor to a recipient
• Autograft: When tissue is transplanted from one location to another within the same person, such as a skin graft, tissue is elf so no immunological rejection
• Allograft: between two genetically non-identical members of the same species, immune-mediated rejection
• Xenograft: One species to another, significant immunological barriers
• The major challenge in transplantation is avoiding graft-versus-host disease (GVHD) in HSCT and rejection in organ transplantation, countered by immunosuppressive drugs and careful donor-recipient matching
• Allogeneic HSCT must carefully balance GVT to GVHD

Question 2

Describe and explain how MHC mismatching results in the activation of anti-transplant immune responses by the host/recipient

Answer 2

Immune system distinguishes self from non-self through the Major Histocompatibility Complex (MHC) system

MHC molecules are expressed on the surface of nearly all nucleated cells and present protein fragments, including those derived from pathogens or abnormal cells, to T cells

Graft rejection occurs through both direct and indirect pathways:

1) Direct allorecognition:

• Recipient’s immune system is directly interacting with and recognising the foreign MHC molecules on the graft’s cells

2) Indirect allorecognition:

• Presentation of donor peptides by recipient’s own MHC molecules
• Mainly involves CD4+ T helper cells

3) Semi-direct allorecognition:

• Transfer of donor MHC molecules to recipient dendritic cells, which then present these molecules to recipient T cells
• This pathway may involve both CD4+ and CD8+ T cells.

Once allorecognition occurs, these T cells become activated and proliferate, generating an immune response against the graft leading to acute transplant rejection

Question 3

Describe the types of immunosuppressive drugs for each phase of immune suppression along with their immunological targets