Transplantation of Tissues and Organs

Question 1

3 basic mechanisms of graft rejection

Answer 1

Hyperacute
Acute
Chronic

Question 2

Hyperacute Graft Rejection

slide 26

Answer 2

• occurs when there is pre-existing antibodies to donor graft antigens (usually from a previous blood transfusion, pregnancy, or other transplant)
• rejection occurs within minutes to hours

Question 3

Paths to Transplant Rejection

Answer 3

1) Direct allorecognition (3 D’s)
- Donor APCs (passenger Dendritic cells) directly migrate to recipient lymph nodes and stimulate alloreactive recipient T cells
- Acute rejection
- Depletion of graft APC prior to transplantation will slow rejection
2) Indirect allorecognition
- recipient APCs process and present donor allogenic proteins to recipient T cells

Question 4

Acute Rejection

slide 28

Answer 4

• HLA alloreactive T cells attack the graft (specific for HLA differences)
• Th and CD8+ T cells can be involved, depending upon the alloreactive HLA (MHC I vs II)
• Takes time to develop and can be managed with immunosuppressive drugs

Question 5

Chronic Rejection

Answer 5

• can occur years after transplant
• rxns against vasculature of graft thickens vessel walls and reducing lumina
  
  • blood supply of graft is compromised
• correlated with antibodies specific for HLA class I antigens
• grafts are infiltrated with CD40+ B cells and CD40L+ Th cells

Question 6

Histocompatibility genetics in humans

• which chromosome?
• where are different HLAs located?
• matching
• > renal tranplants
• > corneal transplants

Answer 6

• HLA loci on chr 6
• HLA-A, HLA-B, and HLA-C found on all nucleated cells
• HLA-D found on B cells, macrophages, epidermal cells, and sperm
• HLA proteins are co-dominantly expressed (ie each allele in pair is expressed)
• Identical twins would be identical, while siblings would have a 1 in 4 chance of possessing identical pairs of haplotypes
• complete haplotype matching is ideal, but matching of MHC I or II may be more important with different tissues
  
  • > MHC II important with renal transplants
  • > corneal transplants do not require HLA matching

Question 7

Matching Blood Group Antigens

• groups
• where are antigens found?
• why is pre-sensitization not req’d?
• antibodies against what?

Answer 7

• Blood groups are A,B, AB, and O -important in transplants
  
  • carbohydrate antigens found on red blood cells
    
    • antigens also found on other cells, including vascular endothelium
• Natural antibodies -pre-sensitization not req’d
  
  • due to presence of gut microflora expressing cross reactive carbohydrate capsules
• *can have antibodies against A or B or both
• **Rh antigens are on RBCs and important in blood transfusions and pregnancy

Question 8

Graft vs Host Disease

slide 32

Answer 8

a) bone marrow cells react against host
b) HLA matching critical
- minor histocompatibility antigens may also be a potential target
c) Immunocompetent donor lymphocytes reject recipient tissues
- transferred T cells recognize recipient MHC Ags (and minor histocompatibility Ags) as foreign
- recipient is immunocompromised and cannot reject the graft
d) Splenomegaly, hepatomegaly, enlarged lymph nodes, diarrhea, anemia, and weight loss
- inflammation and destruction of tissues
- most of the inflammatory cells recruited are the hot’s, recruited by cytokines released from donor lymphocytes