Transplant + Immunology Basics Flashcards
Transplantation is the process of…
Moving of living cells, tissues, or organs from a donor to a recipient - for the purpose of replacing recipient’s damaged or absent organ
The most common organs used for solid organ transplant include…
Kidneys, heart, liver, lungs
An autograft is…
A transplant “within the body” - self to self
An allograft is…
A transplant within 2 people of the same species
A xenograft is…
A transplant done within different species
Still experimental, heavy immune system barriers
Survival rates of transplants depends on…
The type of transplant done
ex: Kidney has much better survival rate than lung (lung requires more immunosuppression, exposed to external environment)
A notable factor about transplants and survival rates is that…
Organs cannot last forever
A workup for a transplant includes…
Evaluating patient for suitability for transplant - infection risk, ability to withstand surgery, etc.
If a patient is on the highly sensitized registry, this means that…
The patient is scanned whenever an organ becomes available to identify if the patient is a match
The purpose of immune system function is to…
Recognize + protect against infection by infection causing organisms
Recognition and destruction of cells with mutations
Cause cell injury + destruction to create inflammation and recruit furher immune system response
Recognition occurs via…
Proteins produced by ‘non-self’ organism - transplant organ
Signaling molecules created when inflammation is present
Components of the immune system involved in transplant include…
MHC/HLA
APC - B cells, macrophages, dendritic cells
T + B lymphocytes
Major histocompatibility complex
Human leukocyte antigens
The purpose of MHC/HLA is to…
Distinguish ‘self’ from ‘non-self’ - glycoproteins expressed on nucleated cells and binds peptides + presents them at cell surface for inspection by T-cells of the immune system
MHC and HLA are used interchageably, but HLA is most specific for human
Antigen presenting cells are involved in transplant by…
Displaying HLA to host T-cells, causing antigen specific T-cell activation
T lymphocytes are involved in transplant by…
CD4 - recognizing MHC class 2, stimulating B + T cells
CD8 - recognize MHC class 1, kill infected cells
B lymphocytes are involved in transplant by…
Responsibility for antibody formation against the antigen
Class 1 HLA are proteins…
Subtypes are…
Present on most nucleated cells + platelets - primary target for t-lymphocyte reactions
HLA-A, HLA-B, HLA-C
Class II HLA are proteins…
Subtypes are…
Present on selective immunoreactive cells (macrophages, monocytes, dendritic cells, etc.)
HLA-DR, HLA-DP, HLA-DQ
Class III HLA proteins are…
Part of complement system - do not play a specific role in graft rejection
HLA genes are ____ and are genetically inherited as a…
Polymorphic - haplotype (different phenotypes, shared between parents)
The T-cell 3 signal model is important to understand…
Drug mechanisms of action
“Signal 1” of the T-cell 3 signal model is…
Recognition
APC presents MHC class II antigen to T-helper cell through T-cell receptor complex
Activates calcineurin pathway to generate IL-2
“Signal 2” of the T-cell 3 signal model is…
Activation of T-cells
Occurs with interaction of co-stimulatory molecules on surface of APC’s and T cells
“Signal 3” of the T-cell 3 signal model is…
Cell proliferation
IL-2 is released and binds to IL-2 receptor on T-cell, activating cell proliferation
The end result of the T-cell 3 signal model is…
Activated, proliferating T-helper cell capable of recruiting other components of the immune system, causing rejection and eventually destruction of the graft
In general, the closer the HLA match between donor and recipient…
The better the outcome
B-cells may be involved with rejection via…
Production of anti-donor antibodies that bind to allografts
AKA humoral rejection
A PRA (pannel reactive antibody) test is when…
Blood sample from potential recipient is cross-matched from a panel of previously typed donors selected to represent as many HLA antigens as possible
A PRA represents…
The percentage of positive reactions among the total cell panel
Higher PRA = bad, more chances for rejection
A high PRA indicates ____, but it does not reflect ____.
Broad sensitization - does not reflect antibody strength or titer
A general measure
A lymphocyte cross-match is done to…
Directly test reactivity between patient’s serum + potential donor cells
Determines whether there are pre-formed antibodies to donor’s lymphocytes
A positive lymphocyte cross-match indicates…
Presence of cytotoxic IgG antibodies to the donor
Compatibility tests are done continuously while the recipient is waiting, because…
Antibody levels can fluctuate
Matching of blood type is critical, because…
Transplanting an organ with ABO incompatibility typically results in hyperacute rejection + destruction of the graft
To prevent the recipient’s immune system from rejecting the new organ…
Immunosuppressive regimens are needed - amount will vary depending on organ transplanted
Lung > Heart > Kidney > Liver
Drugs will work at different levels of the immune cascade
Hyperacute rejection is an…
Uncommon, immediate, immunological response (crossing blood types)
Acute cellular rejection may occur…
Usually mediated by??
At anytime - mediated by alloreactive T lymphocytes
Humoral rejection is an…
Antibody mediated process - associated with poorer prognosis
Chronic rejection refers to…
Slow, gradual decline in function - most common cause of late graft loss
No effective treatment
