Chapter 30 Transplantation Immunology Flashcards

1
Q

What is histocompatibility?

A

Whether a foreign donor cell is likely to be accepted and engrafted in a recipient, most often when sharing identical genes.

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2
Q

What does the Major Histocompatibility Complex (MHC) encompass?

A

The main set of genes that rule transplantation acceptance or rejection, referred to as MHC class I and MHC class II molecules.

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3
Q

What is an allograft?

A

Cells or tissue harvested from one individual and transplanted to another individual with a different haplotype.

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4
Q

What is a haplotype?

A

An individual’s set of alleles of histocompatibility loci.

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5
Q

What is the Equine Leukocyte Antigen (ELA)?

A

The haplotype of a horse’s MHC class I and MHC class II antigens, often determined by serology.

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6
Q

What are microsatellites?

A

Short repeating sequences of DNA used as molecular markers in small groups or large population studies and fingerprinting.

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7
Q

What is an autograft?

A

Cells or tissue harvested and transplanted within an individual.

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8
Q

What are minor histocompatibility antigens?

A

Peptides from other cellular proteins that differ between individuals and may cause slower graft rejection.

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9
Q

What are some examples of minor histocompatibility antigens?

A

H-Y proteins encoded on the Y chromosome, and proteins expressed on red blood cells that define blood groups.

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10
Q

What role do MHC class I molecules play in immune surveillance?

A

They present peptide segments from intracellular proteins to the T cell receptor on CD8+ T cells.

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11
Q

Where are MHC class I molecules expressed?

A

On most nucleated cells.

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12
Q

What happens if a nucleated cell lacks MHC class I expression?

A

It will be destroyed by natural killer (NK) cells.

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13
Q

What is the function of MHC class II molecules?

A

To present peptides derived from exogenous proteins to CD4+ T cells.

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14
Q

Where are MHC class II molecules expressed?

A

On antigen-presenting cells (APCs) such as dendritic cells, macrophages, B lymphocytes, and T lymphocytes in horses.

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15
Q

How was the genomic organization of equine MHC genes determined?

A

By creating a contig of large insert (bacterial artificial chromosome or BAC) clones spanning the equine leukocyte antigen ELA-A3 MHC.

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16
Q

How many distinct MHC class I genes were sequenced in the ELA-A3 haplotype?

A

Fifteen distinct MHC class I genes, including seven expressed in various tissues and eight designated as pseudogenes.

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17
Q

What technique was traditionally used to assess variation of horse MHC class I proteins?

A

Serologically by the lymphocyte microcytotoxicity assay.

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18
Q

How many distinct specificities or haplotypes can the lymphocyte microcytotoxicity assay discern?

A

Nineteen distinct specificities or haplotypes.

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19
Q

What are the limitations of the lymphocyte microcytotoxicity assay?

A

Limited specificities, limited amount of typing sera, and the possibility of polyclonal alloantisera.

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20
Q

What molecular alternatives to the lymphocyte microcytotoxicity assay have been explored?

A

PCR and sequencing, as well as DNA microarrays.

21
Q

What is immunosuppression in transplantation?

A

The use of immunosuppressive drugs administered to the recipient before and transiently after transplantation to promote graft acceptance.

22
Q

What drugs have been used for immunosuppression in horses?

A

Cyclophosphamide, cyclosporine A, and anti-lymphocyte antibodies.

23
Q

What is immunotolerance?

A

When the recipient is unresponsive to foreign donor antigens, avoiding inflammatory responses.

24
Q

What is chimerism?

A

The mosaic status of a recipient harboring engrafted donor cells.

25
Q

What is hyperacute graft rejection?

A

Occurs within minutes to hours if the recipient harbors pre-existing antibodies against antigens expressed on donor cells.

26
Q

What is acute graft rejection?

A

Occurs within days of transplantation or the cessation of immunosuppressive drugs, mediated by either direct or indirect allorecognition.

27
Q

What is chronic graft rejection?

A

Develops months or years after transplantation, with graft-specific T cells or antibodies generated against the graft.

28
Q

What is graft-versus-host disease?

A

Occurs when the donor’s mature T cells initiate an immune response against recipient antigens.

29
Q

What are current transplantation applications in horses?

A

Blood transfusions, skin grafts, corneal transplants, joint/cartilage/bone grafts, and stem cell transplantation.

30
Q

What is the significance of MHC matching in transplantation?

A

Matching MHC haplotypes between donor and recipient reduces the risk of graft rejection.

31
Q

What is neonatal isoerythrolysis?

A

Hemolytic anemia in neonatal foals resulting from fetal-maternal blood group incompatibility.

32
Q

What is the recommended donor for RBC transfusion in cases of neonatal isoerythrolysis?

A

The mare is the ideal donor, provided only her RBCs are transfused (washed RBCs).

33
Q

What are the success rates of corneal transplants in horses?

A

88% success rate in overall vision retention.

34
Q

What is the role of stem cell transplantation in horses?

A

Used for regenerative treatment of conditions such as soft palate defects and tendon lesions.

35
Q

What is the difference between mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs)?

A

MSCs can differentiate into osteoblasts, adipocytes, and chondroblasts, while HSCs can repopulate erythroid, myeloid, and lymphoid blood lineages.

36
Q

What are the immunomodulatory effects of MSCs?

A

They may exert immunomodulatory and anti-inflammatory effects via soluble factors and direct interactions with immune cells.

37
Q

What is the most common cause of hemolytic anemia in neonatal foals?

A

Neonatal isoerythrolysis.

38
Q

What are the types of grafts used in horses?

A

Allografts (between different individuals), autografts (within the same individual), and stem cell transplants.

39
Q

What are the complications of corneal transplants in horses?

A

Graft rejection, primarily mediated by CD4+ T lymphocytes.

40
Q

What are the benefits of using autologous MSC transplants?

A

They can repair defects and promote better healing in various tissues.

41
Q

What is the importance of MHC class II variability in transplantation?

A

High levels of variation in DRB, DQA, and DQB genes affect graft acceptance and immune responses.

42
Q

What is the method used to identify equine MHC haplotypes?

A

Serology, PCR, sequencing, and DNA microarrays.

43
Q

What are the challenges in developing transplantation techniques in horses?

A

Cost-prohibitive immunosuppressive drugs, lack of equine-specific reagents, and limited MHC typing assays.

44
Q

What is the function of MHC class I molecules?

A

To present intracellular protein peptides to CD8+ T cells for immune surveillance.

45
Q

What is the role of immunosuppressive drugs in transplantation?

A

To delay graft rejection, induce graft tolerance, and decrease graft-versus-host disease.

46
Q

What are the indications for blood transfusions in horses?

A

Severe blood loss, decreased erythrocyte production, immune-mediated hemolytic anemia, or neonatal isoerythrolysis.

47
Q

What is the primary purpose of cross-matching before blood transfusion?

A

To identify compatible blood donors and recipients to prevent hemolysis of donor cells.

48
Q

What are some examples of regenerative treatments using stem cells in horses?

A

Repair of soft palate defects, tendon lesions, and articular defects.