IS Lecture -- TRANSPLANTATION

• Transplantation


  Transfer of tissue or organ from one individual to another
• Transfusion


  Transfer of blood from one individual to another
• Antibodies are responsible for transfusion reactions
• Rejection of transplanted tissue is mediated predominantly by sensitized T cells
• Types of graft


  • Autologous (Autograft)
  • Syngeneic (Syngraft, Isograft)
  • Allogeneic (Allograft, Homograft)
  • Xenogeneic (Heterologous graft, Heterograft)
• Autograft


  A graft or transplant from one area to another on the same individual, recognised as autologous (self) with no immune response induced
• Isograft / Syngraft


  Graft or transplantation of cells, tissue or organ from 1 person to another who is syngeneic (genetically identical) to the donor, with no immune response
• Allograft


  Graft or transplant from one individual to another with a different genetic make-up, within the same species, recognised as foreign and immunologically rejected
• Xenograft


  Graft between a donor and a recipient from different species, recognised as foreign and immune response will destroy or reject graft
• Clinical phases of rejection

  • Hyperacute (Mins to hrs)
  • Accelerated (After several days)
  • Acute (10-30 days)
  • Chronic (Months to years)
• Hyperacute rejection


  Preexisting antibodies to donor HLA antigens activate complement, causing swelling and interstitial hemorrhage in the transplanted tissue, with no therapy for successful prevention or termination
• Acute rejection


  Seen in recipient who has not previously been sensitized to transplant, common type of rejection experienced by individuals for whom transplanted tissue is a mismatch
• Chronic rejection


  Caused by both antibody and cell mediated immunity, occurs months after transplanted tissue has assumed its normal function
• Laboratory tests


  • ABO Blood typing
  • Tissue typing (HLA Matching)
  • Screening for Presence of Preformed Antibodies to allogeneic HLA
  • Crossmatching
• Graft-vs-Host Disease (GVHD)


  Occur when immunocompetent tissue (fresh whole blood, thymus, or bone marrow) is transplanted into an immunocompromised host, where T cells from the transplant recognize the host MHC molecules as nonself and attack the host
• Situations leading to GVHD

  • Allograft in a recipient in whom specific immunological tolerance has been induced
  • Present with clinically retardation of growth, diarrhea, hepatosplenomegaly, lymphoid atrophy, anemia, terminating fatally
  • Syndrome: Runt disease
• Classification of transplant


  • Based on Nature of Organs (Kidney, Liver, Heart, BM, Skin)
  • Based on Anatomical Site (Orthotropic, Heterotypic)
• Tumor


  Abnormal cell mass resulting from excessive cell growth & division
• Types of tumors


  • Benign: Slowly growing, well differentiated & organized, usually capsulated
  • Malignant: Disorganized masses, rarely encapsulated, easily spread (invasiveness)
• Cancer


  Multigene disease which arises as a result of mutational and epigenetic changes coupled with activation of complex signaling networks
• 3 main classes of genes involved in cancer

  • Proto-oncogenes (involved in cell division & growth)
  • Tumor Suppressor Genes (regulate growth and development)
  • DNA Repair Genes
• Tumor marker


  Substance produced by a tumor or by the host in response to a tumor which is used to differentiate a tumor from normal tissue or to detect the presence of a tumor based on measurements in blood or secretions
• Ideal characteristics of a tumor marker

  • Highly specific
  • Highly sensitive
  • Specific to a particular organ
  • Correlate with the prognosis
  • Have a reliable prediction value
• Historical background of tumor immunology

  • 1846: Bence-Jones Protein
  • 1940: Acid Phosphatase
  • 1960: Immunoassay
  • 1963: Alpha-fetoprotein (AFP)
  • 1965: Carcinoembryogenic Antigen
  • 1970: Oncogenes
  • 1975: Monoclonal Antibody
  • 1980: CA 125, PSA, Carbohydrate Antigen, Tumor Suppressor Genes
  • 2001: Microarrays, Mass Spectrometry, Neural Networks, Multiparametric Analysis
• Enzymes as tumor markers

  • Alcohol Dehydrogenase & Aldolase (Liver Cancer)
  • Alkaline Phosphatase (Bone, Liver, Leukemia)
  • Prostatic Acid Phosphatase (Prostate)
  • Neuron Specific Enolase (Small Cell Lung Cancer, Neuroblastoma, Melanoma)
  • Lactate Dehydrogenase (Lymphoma, Leukemia)
• Hormones as tumor markers

  • ACTH (Cushing's Syndrome, Lung Cancer)
  • ADH (Lung, Adrenal Cortex, Pancreatic)
  • Bombesin (Lung)
  • Calcitonin (Medullary Ca Thyroid)
  • Vasoactive Intestinal Peptide (Pheochromocytoma, Neuroblastoma)
  • Human Chorionic Gonadotropin (Choriocarcinoma, Embryonal)
• Prostate Specific Antigen (PSA)


  A single chain glycoprotein specific for prostatic tissue, used to screen for prostate cancer
• Oncofetal / Carcinofetal antigens

  • AFP (Hepatocellular, Germ Cell Tumor)
  • Carcinofetal Ferritin (Liver)
  • CEA (Colorectal, Gastrointestinal, Lung, Breast, Pancreatic)
  • Squamous Cell Antigen (Cervical, Lung, Skin, Head, & Neck)
  • Tennessee Antigen (Colon, Gastrointestinal, Bladder)
  • Cytokeratin (Breast, Colorectal, Ovarian, Bladder)
• Proteins as tumor markers

  • Beta 2 Macroglobulin (Multiple Myeloma, CML, Waldenstrom's Macroglobulinemia)
  • C-Peptide (Insulinoma)
  • Ferritin (Liver, Lung, Breast, Leukemia)
  • Immunoglobulins (Multiple Myeloma, Lymphoma)
  • Melanoma Associated Antigen (Melanoma)
  • Des-Gamma-Carboxy Prothrombin (Hepatocellular)
  • Soluble Mesothelin Related Peptides (Mesothelioma, Ovarian)
• Carbohydrates or mucins as tumor markers

  • CA-125 (Ovarian, Endometrial)
  • CA-15-3 (Breast, Ovarian)
  • CA-549 (Breast, Ovarian)
  • CA-27.29 (Breast)
  • MCA (Breast, Ovarian)
  • DU-PAN-2 (Pancreatic)
• Blood group antigen related markers

  • CA 72-4 (Ovarian, Pancreatic, Stomach)
  • CA 19-9 (Pancreatic, Gastrointestinal, Hepatic)
  • CA 19-5 (Pancreatic, Gastrointestinal, Ovarian)
  • CA 50 (Pancreatic, Gastrointestinal, Colon)
  • CA 242 (Pancreatic, Gastrointestinal)
• Oncogenes


  Derived from proto-oncogenes that may be activated by dominant mutations, insertions, deletions, translocations, or inversions, leading to cell division and proliferation
• Breast cancer oncogenes

  • Her-2/neu (ERBB2)
  • Oncogene c-erbB-2 gene
  • BRCA I gene on chromosome 17q
• Viral biomarkers

  • Hepatocellular cancer: HBV (& HCV)
  • ----- > Markers: analysis of viral DNA/proteins/antibodies; HBsAG, HBeAG, anti-HBV core antigen, anti-HBeAG, anti-HBsAG
  • Cervical cancer: Human Papillomavirus (HPV)
• gene for familial breast-ovarian cancer syndrome

  BRCA I gene on chromosome 17q