Transplantation and Tumor Immunology

• What is transplantation used to treat?

  End stage organ failure and cancers
• Why is compatibility important before transplantation?

  To prevent organ rejection
• What immune factors are considered before transplantation?

  • HLA system
  • Minor histocompatibility antigens (mHAs)
  • MHC Class I-Related Chain A (MICA) Antigens
  • ABO Blood Group Antigens
  • Killer Immunoglobulin-like receptors (KIRs)
• What is the largest immunologic barrier to organ transplantation?

  The HLA system
• What role does the HLA system play in the immune response?

  It initiates adaptive immune responses
• Where are HLA proteins found?

  On the surface of nucleated cells
• Why is HLA classification necessary?

  To avoid organ rejection
• How are HLA genes inherited?

  As haplotypes from parents
• What is the chance of siblings being HLA identical?

  25% chance
• What are the types of grafts in transplantation?

  1. Autograft: Self-tissue transfer
  2. Isograft: Tissue transfer between identical individuals
  3. Allograft: Tissue transfer between different individuals
  4. Xenograft: Tissue transfer between different species
• What is direct allorecognition?

  When T-cytotoxic cells bind to foreign HLA
• What do cytotoxic T-cells release to destroy foreign antigens?

  Perforins and granzymes
• What is indirect allorecognition?

  APCs present foreign antigens to T-cells
• What is graft acceptance?

  Revascularization and healing of the graft
• What are the two types of graft rejection?

  1. First-set rejection: Occurs 10-14 days after transplantation
  2. Second-set rejection: Occurs within 6 days of re-encounter
• What is hyperacute rejection?

  Rejection within 24 hours due to pre-existing antibodies
• What causes acute rejection?

  Begins in the first few weeks after transplantation
• What characterizes chronic rejection?

  Occurs months to years after transplantation
• What is graft-versus-host disease (GVHD)?

  Lymphoid cells in the graft attack the host
• When does acute GVHD occur?

  During the first 100 days post-infusion
• What is chronic GVHD?

  Occurs beyond 100 days post-transplant
• What are the types of immunosuppressive agents?

  1. Corticosteroids
  2. Antimetabolites
  3. Calcineurin inhibitors
  4. Monoclonal antibodies
  5. Polyclonal antibodies
• What is the role of corticosteroids in transplantation?

  Used for immunosuppression maintenance
• What is the first antimetabolite used?

  Azathioprine
• What do calcineurin inhibitors do?

  Block signal transduction in T lymphocytes
• What is the function of rapamycin?

  Inhibits T-cell proliferation
• What do monoclonal antibodies target?

  CD25 (IL-2 receptor)
• What is thymoglobulin?

  An antithymocyte antibody prepared in rabbits
• What tests are included in donor testing and tissue typing?

  • ABO/Rh
  • CMV
  • RPR and FTA
  • HbsAg
  • EBV
  • Anti-HIV 1 and 2
  • HBcAg
  • HTLV I&II
  • Parvovirus B19
  • HCV
• What is neoplasia?

  Uncontrolled growth of normal cells
• What are the classifications of tumors?

  1. Benign: Not invasive, not immortal
  2. Malignant: Immortal, invasive, cancer
• What is a carcinoma?

  Tumors from endodermal or ectodermal tissue
• What are leukemia and lymphoma?

  Malignant tumors of hematopoietic cells
• What is a sarcoma?

  Derived from mesodermal connective tissues
• What is metastasis?

  Spread of cancer cells to new sites
• What are proto-oncogenes?

  Genes regulating normal cell division
• What are oncogenes?

  Mutant forms of proto-oncogenes
• What are tumor markers?

  Glycoproteins elevated in certain cancers
• What are the categories of tumor-specific and tumor-associated antigens?

  1. Tumor-specific antigens (TSAs)
  2. Tumor-associated antigens (TAAs)

  • Shared TSAs
  • Differentiation antigens
  • Overexpressed antigens
• What are some human viruses associated with cancer?

  • Epstein-Barr virus (EBV)
  • Hepatitis B virus (HBV)
  • Hepatitis C virus (HCV)