A potentially lifesaving treatment for, endstage organ
failure cancersa autoimmune diseases immune deficiencies a variety of other
diseases
Transplantation
What will an allogenic response result in?
Graft rejection in solid organ and stem cell transplantation. Graft versus host
Transfer of living cells, tissues and organs from one part of the body to another or from one individual to another.
Graft or Translplant
What are the 3 class I antigens and what cells are they expressed on?
HLA - A
HLA - B
HLA - C
Expressed on most cells
What are the 3 class II antigens and what cells are they expressed on?
HLA - DR
HLA - DQ
HLA - DP
expressed on cells of lymphoid system
HLA are responsible for what two important roles?
development
function of the innate and adaptive immune systems
What is a cardinal feature of the genes encoding the HLA protein?
extensive degree of allelic polymorphism
The most polymorphic genetic system in humans.
HLA system
Although the HLA system has successfully enabled populations to survive infectious challanges what is the a downfall?
it severely restricts the ability to transplant foreign tissues or cells between any two individuals
What is a second set of transplantation antigens?
minor histocompatibility antigens (mHA)
Does MHC (HLA) matching prevent rejection?
It reduces rejection but there are still minor histocomtability antigens. (mHA)
How is MHC polymorphisms identified?
Formally, HLA typing and MLR
Now, DNA testing allele-specific PCR and sequencing
Finding a donor who shares the HLA antigens of the recipient, to minimize antigen disparities
Requires donor and recipient antigens to be identified
Matching
Testing the SERUM of the recipient for antibodies against the donor antigens
Cross-matching
Exposure to non-self HLA can cause ?
production of HLA-directed antibodies
Common causes of HLA-sensitization include?
Blood transfusions
Pregnancies
Previous transplants
Tissue patches implanted during cardiac surgery cause sensitization in....
Infants
The MHC class I–related chain A (MICA) encodes a cell surface protein that is involved in....
gamma/delta T cell responses
Name 6 cells that MIC proteins are expressed on:
endothelial cells
keratinocytes
Fibroblasts
epithelial cells
dendritic cells
monocytes
MIC proteins are not expressed on what cells?
T or B lymphocytes
MICA has been associated with what?
Rejection episodes
Decreased grapt survival
Carbohydrate structures expressed on many tissues and
organs
Including endothelium of organ transplants
ABO antigens
Are one of several types of cell surface molecules that
regulate the activity of natural killer (NK)
lymphocytes
Another polymorphic genetic system that impacts allogeneic transplantation
killer immunoglobulin-like receptor (KIR) system
Within the KIRs are:
activating inhibitory receptors that vary in number and type on any individual NK cell
The transfer of tissuefrom one area of the body to another of the same individual
Autograph
The transfer of cells or tissues between identical twins
syngeneic graft (isograft)
The transfer of cells or tissue between two individuals of the same species
Accounting for most transplantation
allograft
The transfer of tissue between two individuals of different species
xenograft
The recipient immune system recognizes foreign HLA
proteins via these two distinct mechanisms—
direct and indirect allorecognition
Direct or indirect allorecognition:
Recipient T cells bind and
Responddirectly to foreign (allo) HLA proteins on graft cells
Direct allorecognition
Direct or indirect allorecognition:
second pathway by which the immune system recognizes foreign HLA protein
The effector responses against transplanted allogeneic
tissue include:
direct cytotoxicity
delayed hypersensitivity reponses
antibody-mediated mechanisms
What are three types of transplant graft rejection?
Antibody mediated rejection (AMR)
Cellular rejection
Chronic rejection
Occurs within minutes to hours
Occurs after the vascular supply to the transplanted organ is established
Hyperacute rejection
Recipient–donor pairs must be ABO identical or
compatible for the prevention of incompatibility reaction?
ABO blood group incompatibility
Develops days to weeks after transplant
This is a cellular-type rejection but may also involve
antibodies
Acute cellular rejection
What are the predisposingfactors impact the development of chronic rejection?