HI28 - Organ & Tissue Transplantation

"Define histocompatibility."

"Compatibility of tissue types between donor and recipient that allows transplanted tissue to coexist without provoking excessive immune responses."

"Define liquid transplant."

"Transplantation of cells or tissues in fluid form, including blood transfusions and hematopoietic stem cell transplants."

"Define solid organ transplant."

"Transplantation of an intact organ such as kidney, liver, heart, or lung."

"Define hematopoietic stem cell transplant."

"Transplantation of bone marrow, peripheral blood stem cells, or umbilical cord blood to reconstitute the immune and blood-forming systems."

"What is the most commonly transplanted tissue?"

"Red blood cells (blood transfusion)."

"What organs were most commonly transplanted in 2024?"

"Kidney (27,759), liver (11,458), heart (4,572), lung (3,340)."

"How often is someone added to the transplant waiting list?"

"Every 8 minutes."

"How many people die each day waiting for an organ?"

"17 people."

"What is an autograft?"

"A transplant where the donor and recipient are the same individual."

"Give an example of an autograft."

"Skin graft from one part of body to another; autologous stem cell transplant."

"What is an isograft?"

"Transplant between genetically identical individuals (monozygotic twins)."

"What is an allograft?"

"Transplant between individuals of the same species but different genetic backgrounds."

"What is a xenograft?"

"Transplant from a donor of a different species (ex: pig to human)."

"What are the important antigens for blood transfusion compatibility?"

"ABO and Rh antigen systems."

"What are the important antigens for organ and HSCT compatibility?"

"HLA (MHC) Class I and Class II molecules, plus ABO."

"Name the 6 main HLA markers."

"HLA-A, HLA-B, HLA-C (Class I), HLA-DR, HLA-DP, HLA-DQ (Class II)."

"What determines whether tissue is histocompatible?"

"Similarity between donor and recipient HLA molecules."

"What percentage of two siblings are HLA-identical?"

"25% chance."

"What percentage of two siblings are haploidentical?"

"50% chance."

"What percentage of siblings share no HLA haplotypes?"

"25%."

"Define rejection."

"Immune attack by recipient leukocytes against donor graft tissue."

"Define graft-versus-host disease (GVHD)."

"Immune attack by donor T cells against recipient tissues following HSCT."

"Which transplants most commonly cause GVHD?"

"Bone marrow and peripheral blood stem cell transplants."

"Why do erythrocytes not express MHC I or II?"

"They lack nuclei (no MHC I) and do not act as antigen-presenting cells (no MHC II)."

"What antigens do erythrocytes express?"

"ABO antigens and RhD antigen."

"What hypersensitivity type occurs in mismatched blood transfusion?"

"Type II hypersensitivity."

"What determines whether host serum will react with donor RBCs?"

"Cross-matching."

"What percentage of people are Rh+ or Rh-?"

"85% Rh+ and 15% Rh-."

"What are the U.S. ABO blood type frequencies?"

"O = 44%, A = 42%, B = 10%, AB = 4%."

"What antigen structure do all ABO blood groups share?"

"The O antigen (H antigen)."

"What antigen modifications define A and B groups?"

"Enzymatic addition of sugars to the O antigen."

"What blood type recognizes A and O as self?"

"Type A."

"What blood type recognizes B and O as self?"

"Type B."

What blood type recognizes A, B, and O as self?

Type AB.

"What blood type recognizes only O as self?"

"Type O."

"How soon does a Type II transfusion reaction occur after ABO mismatch?"

"Immediately, often during transfusion (minutes)."

"Why do individuals have antibodies to ABO antigens they do not express?"

Due to exposure to cross-reactive antigens on commensal bacteria that are similar to ABO antigens.

"What occurs during an acute hemolytic transfusion reaction?"

"Complement activation, hemolysis, cytokine release, fever, chills, shock, renal failure, death."

"How many ABO donor-recipient combinations exist?"

"16 total combinations."

"How many ABO combinations are compatible?"

"9 compatible."

"Which blood type is the universal donor?"

"Type O (O negative)."

"Which blood type is the universal recipient?"

"Type AB (AB positive)."

"Why are RhD antibodies usually absent before exposure?"

"RhD response requires prior sensitization."

"What can occur if an Rh- woman carries an Rh+ fetus?"

"Hemolytic disease of the newborn (erythroblastosis fetalis)."

"How is transfusion-associated GVHD prevented?"

"Irradiation of blood to inactivate donor T cells."

"Why does irradiated blood still function normally?"

"RBCs do not divide, so irradiation does not harm them."

"Why are leukocyte-reduced blood products used in immunocompromised patients?"

"To reduce the risk of alloimmunization and febrile reactions."

"What is the success rate of corneal transplant?"

"Varies; rejection up to 30% in full-thickness grafts."

"What is corneal graft failure?"

"Non-immune-mediated failure due to edema, trauma, or poor tissue storage."

"What immune cells exist in corneal tissue?"

"Low levels of dendritic cells and Langerhans cells."

"Where may antigen presentation occur in corneal graft rejection?"

"Uvea, conjunctiva-associated lymphoid tissue, draining lymph nodes."

"What cells mediate corneal graft rejection?"

"CD4+ T cells and recruited effector cells."

"What are the three major forms of transplant rejection?"

"Hyperacute, acute, and chronic rejection."

"What causes hyperacute rejection?"

"ABO mismatch causing Type II hypersensitivity against donor endothelial cells."

"How fast does hyperacute rejection occur?"

"Minutes; before the patient leaves the operating room."

"What immune components drive hyperacute rejection?"

"Preexisting IgG alloantibodies and complement activation."

"How is hyperacute rejection prevented?"

"Pre-screening for anti-ABO antibodies and crossmatching."

"Can ABO-incompatible kidney transplants be performed?"

"Yes, using plasmapheresis and antibody depletion/desensitization."

"What causes acute rejection?"

"Direct allorecognition of donor MHC by recipient T cells (Type IV hypersensitivity)."

"When does acute rejection occur?"

"1 week to 3 months after transplant."

"What cells mediate acute rejection?"

"CD4+ T cells (macrophage activation) and CD8+ T cells (cytotoxicity)."

"Where does direct allorecognition occur?"

"Recipient spleen (due to disrupted lymphatic drainage)."

"What triggers donor dendritic cell activation?"

"Inflammation in the graft from ischemia, trauma, or prior inflammation."

"What is indirect allorecognition?"

"Recipient DCs present donor MHC peptides on self-MHC to T cells."

"What type of rejection does indirect allorecognition cause?"

"Chronic rejection."

"What cells drive chronic rejection?"

"CD4+ T cells and donor-specific antibodies."

"What is the timeframe for chronic rejection?"

"Months to years."

"What hypersensitivity types are involved in chronic rejection?"

"Type III (immune complexes) and Type IV (T-cell mediated)."

"What occurs in chronic rejection pathologically?"

"Vascular thickening, occlusion, ischemia, and graft necrosis."

"What percentage of kidney and heart grafts fail within 10 years due to chronic rejection?"

"Over 50%."

"Why do living donor organs have better outcomes?"

"Reduced ischemia, less inflammation, fewer damaged tissues."

"What is myeloablative therapy?"

"Destruction of the patient's immune system to prepare for HSCT."

"What does HSCT replace?"

"All immune cells and blood cell precursors."

"What causes GVHD?"

"Donor T cells attacking recipient tissue due to lack of negative selection in recipient."

"What tissues are most affected in acute GVHD?"

"Skin, liver, and gastrointestinal tract."

"When does acute GVHD appear?"

"10-28 days post-transplant."

"What skin symptoms occur in acute GVHD?"

"Erythematous rash beginning on palms/face → trunk → desquamation."

"What oral symptom is common in GVHD?"

"Mucositis."

"When does chronic GVHD typically appear?"

"Within the first 3 years post-transplant."

"What is the 5-year mortality rate of chronic GVHD?"

"Approximately 70%."

"What organs can chronic GVHD affect?"

"Skin, mouth, eyes, GI tract, liver, lungs, joints, genitourinary tract."

"Why do bone grafts rarely require immunosuppression?"

"Mineralized matrix lacks viable donor immune cells; becomes a scaffold for recipient cell repopulation."

"Name the 4 types of immunosuppressive drugs used in transplantation."

"Corticosteroids, cytotoxic drugs, T-cell activation inhibitors, antibody-based therapeutics."

"What is the mechanism of corticosteroids?"

"Bind intracellular receptors, inhibit NFκB, reduce inflammatory gene transcription."

"Name common corticosteroids used in transplant management."

"Hydrocortisone, prednisone, dexamethasone."

"What are side effects of corticosteroids?"

"Fluid retention, weight gain, diabetes, adrenal suppression, high infection risk."

"When are corticosteroids used?"

"Before transplantation and during rejection episodes."

"What is the mechanism of cytotoxic drugs?"

"Kill dividing cells by disrupting nucleotide synthesis; prevent T cell clonal expansion."

"Name examples of cytotoxic drugs."

"Azathioprine, Mycophenolic acid, Methotrexate, Cyclophosphamide."

"What normal tissues do cytotoxic drugs affect?"

"Intestinal epithelium, skin, bone marrow."

"What dental complications occur with cytotoxic drugs?"

"Stomatitis and opportunistic infections."

"What drugs block NFAT signaling?"

"Cyclosporin and Tacrolimus."

"What dental side effect is associated with cyclosporine?"

"Gingival hyperplasia."

"What side effects are shared by cyclosporine and tacrolimus?"

"Poor wound healing, ulcers, nephrotoxicity, viral reactivation (herpesviruses)."

"What drug blocks IL-2 signaling via mTOR inhibition?"

"Rapamycin (Sirolimus)."

"What are the side effects of rapamycin?"

"Impaired wound healing, thrombocytopenia, diabetes-like syndrome."

"What do antibody-based immunosuppressive drugs do?"

"Deplete, block, or inhibit T cells."

"What major infections can be reactivated due to immunosuppression?"

"CMV, EBV, HSV, VZV, hepatitis B/C, tuberculosis, Kaposi's sarcoma virus."

"What is a major concern for transplant patients regarding vaccinations?"

"Reduced vaccine efficacy."

"What ocular complication is associated with chronic corticosteroid and calcineurin inhibitor use?"

"Posterior subcapsular cataracts."