Chapter 30 Transplantation Immunology Flashcards
What is histocompatibility?
Whether a foreign donor cell is likely to be accepted and engrafted in a recipient, most often when sharing identical genes.
What does the Major Histocompatibility Complex (MHC) encompass?
The main set of genes that rule transplantation acceptance or rejection, referred to as MHC class I and MHC class II molecules.
What is an allograft?
Cells or tissue harvested from one individual and transplanted to another individual with a different haplotype.
What is a haplotype?
An individual’s set of alleles of histocompatibility loci.
What is the Equine Leukocyte Antigen (ELA)?
The haplotype of a horse’s MHC class I and MHC class II antigens, often determined by serology.
What are microsatellites?
Short repeating sequences of DNA used as molecular markers in small groups or large population studies and fingerprinting.
What is an autograft?
Cells or tissue harvested and transplanted within an individual.
What are minor histocompatibility antigens?
Peptides from other cellular proteins that differ between individuals and may cause slower graft rejection.
What are some examples of minor histocompatibility antigens?
H-Y proteins encoded on the Y chromosome, and proteins expressed on red blood cells that define blood groups.
What role do MHC class I molecules play in immune surveillance?
They present peptide segments from intracellular proteins to the T cell receptor on CD8+ T cells.
Where are MHC class I molecules expressed?
On most nucleated cells.
What happens if a nucleated cell lacks MHC class I expression?
It will be destroyed by natural killer (NK) cells.
What is the function of MHC class II molecules?
To present peptides derived from exogenous proteins to CD4+ T cells.
Where are MHC class II molecules expressed?
On antigen-presenting cells (APCs) such as dendritic cells, macrophages, B lymphocytes, and T lymphocytes in horses.
How was the genomic organization of equine MHC genes determined?
By creating a contig of large insert (bacterial artificial chromosome or BAC) clones spanning the equine leukocyte antigen ELA-A3 MHC.
How many distinct MHC class I genes were sequenced in the ELA-A3 haplotype?
Fifteen distinct MHC class I genes, including seven expressed in various tissues and eight designated as pseudogenes.
What technique was traditionally used to assess variation of horse MHC class I proteins?
Serologically by the lymphocyte microcytotoxicity assay.
How many distinct specificities or haplotypes can the lymphocyte microcytotoxicity assay discern?
Nineteen distinct specificities or haplotypes.
What are the limitations of the lymphocyte microcytotoxicity assay?
Limited specificities, limited amount of typing sera, and the possibility of polyclonal alloantisera.
What molecular alternatives to the lymphocyte microcytotoxicity assay have been explored?
PCR and sequencing, as well as DNA microarrays.
What is immunosuppression in transplantation?
The use of immunosuppressive drugs administered to the recipient before and transiently after transplantation to promote graft acceptance.
What drugs have been used for immunosuppression in horses?
Cyclophosphamide, cyclosporine A, and anti-lymphocyte antibodies.
What is immunotolerance?
When the recipient is unresponsive to foreign donor antigens, avoiding inflammatory responses.
What is chimerism?
The mosaic status of a recipient harboring engrafted donor cells.
What is hyperacute graft rejection?
Occurs within minutes to hours if the recipient harbors pre-existing antibodies against antigens expressed on donor cells.
What is acute graft rejection?
Occurs within days of transplantation or the cessation of immunosuppressive drugs, mediated by either direct or indirect allorecognition.
What is chronic graft rejection?
Develops months or years after transplantation, with graft-specific T cells or antibodies generated against the graft.
What is graft-versus-host disease?
Occurs when the donor’s mature T cells initiate an immune response against recipient antigens.
What are current transplantation applications in horses?
Blood transfusions, skin grafts, corneal transplants, joint/cartilage/bone grafts, and stem cell transplantation.
What is the significance of MHC matching in transplantation?
Matching MHC haplotypes between donor and recipient reduces the risk of graft rejection.
What is neonatal isoerythrolysis?
Hemolytic anemia in neonatal foals resulting from fetal-maternal blood group incompatibility.
What is the recommended donor for RBC transfusion in cases of neonatal isoerythrolysis?
The mare is the ideal donor, provided only her RBCs are transfused (washed RBCs).
What are the success rates of corneal transplants in horses?
88% success rate in overall vision retention.
What is the role of stem cell transplantation in horses?
Used for regenerative treatment of conditions such as soft palate defects and tendon lesions.
What is the difference between mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs)?
MSCs can differentiate into osteoblasts, adipocytes, and chondroblasts, while HSCs can repopulate erythroid, myeloid, and lymphoid blood lineages.
What are the immunomodulatory effects of MSCs?
They may exert immunomodulatory and anti-inflammatory effects via soluble factors and direct interactions with immune cells.
What is the most common cause of hemolytic anemia in neonatal foals?
Neonatal isoerythrolysis.
What are the types of grafts used in horses?
Allografts (between different individuals), autografts (within the same individual), and stem cell transplants.
What are the complications of corneal transplants in horses?
Graft rejection, primarily mediated by CD4+ T lymphocytes.
What are the benefits of using autologous MSC transplants?
They can repair defects and promote better healing in various tissues.
What is the importance of MHC class II variability in transplantation?
High levels of variation in DRB, DQA, and DQB genes affect graft acceptance and immune responses.
What is the method used to identify equine MHC haplotypes?
Serology, PCR, sequencing, and DNA microarrays.
What are the challenges in developing transplantation techniques in horses?
Cost-prohibitive immunosuppressive drugs, lack of equine-specific reagents, and limited MHC typing assays.
What is the function of MHC class I molecules?
To present intracellular protein peptides to CD8+ T cells for immune surveillance.
What is the role of immunosuppressive drugs in transplantation?
To delay graft rejection, induce graft tolerance, and decrease graft-versus-host disease.
What are the indications for blood transfusions in horses?
Severe blood loss, decreased erythrocyte production, immune-mediated hemolytic anemia, or neonatal isoerythrolysis.
What is the primary purpose of cross-matching before blood transfusion?
To identify compatible blood donors and recipients to prevent hemolysis of donor cells.
What are some examples of regenerative treatments using stem cells in horses?
Repair of soft palate defects, tendon lesions, and articular defects.
