Transplantation immunology (complete) Flashcards
When is transplant indicated (needed)
1, good evidence of irreversable organ damage
- alternative treatments not applicable or helpful
- when the organ is in the end-stage of organ failure
What is the main complication of transplantation
the grafted tissue/organ is recognized as foreign and attacked by the bodies immune system
(host vs. graft response)
what is host vs. graft response, and what does it lead to
the host’s immune system attacks the graft because it sees it as foreign. this leads to transplant/graft rejection
what causes host vs. graft response
- differences in major HLA
- high frequency of host T-cells recognizing the graft HLA
- indirect recognition
what is graft vs. host reaction
when donor lymphocytes attack the host
when do you see graft vs. host reaction
bone marrow transplants
what is the treatment/prevention of graft vs. host reaction
removal of all t-cells from the graft
what are the different types of grafts
autograft - from one part of the body to another
isograft - from one geneticallly identical person to another
allograft - from another unidentical person
xenograft - from a different species
Are all grafts rejected at the same rate? if not, what are the different rates?
no
hyperacute rejection
acute rejection
chronic rejection
what is hyper acute rejection
rejection occuring within minutes or hours, that is usually Ab mediated
what is acute rejection
rejection occuring in days or weeks, usually initiated by alloreactive T-cells
what is chronic rejection
happens over months or years
what are the methodes that are used to test for transplant compatibility
- ABO compatibility
- HLA matching (tissue typing)
- Tissue cross matching
what else can be used along with best compatability to prevent graft rejection
immunosupressive drugs (blocking T-cells, or both B and T-cells)
how critical is ABO blood type compatibility for transplants, and why
essential, because it isn’t only found on the blood, but on other tissues
how critical is RhD blood type compatibility for transplants and why
it is unimportant, because it is only on RBCs
what is tissue typing
testing to see how closely HLA’s between the donor and recipient match up (the closer the better)
what is tissue cross matching
determining whether a patient has Abs that will react specifically with donor WBCs
how is tissue cross matching done
the recipients serum is mixed with donor leukocytes. if there is a reaction (positive result) then the transplantation is contra-indicated
what are the possible consequences of using an immunosuppresive drug to prevent transplant rejection
they are at an increased risk for infections (especially opportunistic ones) and cancer
what are some examples of opportunistic infections
candida Epstein-Barr virus (EBV) cytomegalovirus (CMV) Listeria Mycobacterial
what are the 4 types of immunosuppressors that affect T-cell function
Calcineurin inhibitors
T-cell activation and proliferation inhibitors
Anti-T-cell immunoglobins
IL-2 receptor antagonists
how do calcineurin inhibitors affect T-cell function
it inhibits calcineurin enzymes and activation of NFAT
BLOCKS TRANSCRIPTION and PRODUCTION OF IL-2
what is the function of IL-2
it stimulates T-cells to grow and proliferate
what drugs are calcineurin inhibitors, and thus block transcription and production of IL-2
cyclosporine(sandimmune)
Tacrolimus/FK-506 (Prograf)
What is MTOR
mammalian target of rapamycin inhibitor
what does MTOR do to T-cell activation
it inhibits MTOR, it inhibits IL-2 driven proliferation of T-cells
what are examples of MTOR
sirolimus (rapamune)(rapamycin)
how do anti-Tcell immunoglobins block T-celll function
the antibodies bind to T-cells
what are examples of anti T-cell immunoglobins drugs
- antithymyocyte Globin (Atgam)
2. murononab, a-CD3 (OKT3)
what does Atgam (antithymyocyte Globin) do
binds to Tcells, Bcells, platelets, and other leukocytes
NON-SPECIFIC
what does murononab, a-CD3 (OKT3) do
binds to CD3, and depletes all T-cells via complement and opsonization/phagocytosis
which immunosuppresive drug is used to treat acute rejection
murononab, a-CD3 (OKT3)
what do IL-2 receptor antagonists do
bind the IL-2 receptor of activated T-cells so that IL-2 can’t. this stops T-cells from proliferating
what are two examples of IL-2 receptor antagonists
DAclizumab (zenapax)
Basilixumab (simulect)
What are the drugs that affect B and T cell development
antimetabolites and corticosteroids
how do antimetabolites affect B and T cells
they inhibit purine synthesis in lymphocytes which blocks proliferation
what are two antimetabolites that block proliferation of B and T cells
azathioprine (Imuran) mycophenolate mofetil (cellcept)
how do corticosteroids affect T and B cell function
they inhibit PLA2 which leads to decreased synthesis of prostaglandins and leukotrienes
low prostaglandins lead to decreased inflammation and T-cell function
low leukotrienes leads to decreased inflammation, chemotaxis and degranulation of PMNs, and CTL proliferation
what are two examples of corticosteroiids
prednisone (orasone, deltasone)
methypredinisone (methylpred, solumedrol)
what happens to the immune system as a whole on corticosteroids
the whole system is supressed
what is oral chronic GVHD (cGVHD)
pathology of the oral cavity due to graft vs. host disease
what are the oral manifestations of oral chronic GVHD
lichenoid changes
mucosal atrophy and ulcerations
taste disturbances
salivary gland hypofunction
what are candidal superinfections
yeast like infections
what is the treatment for patients with extensive cGVHD
immunosupressive drugs
what is the problem with frequent use of inmmunosupressive drugs
more likely to get infections
more likely to have malignancy
sometimes death
what are the first drugs used for cGVHD
cyclosporine and corticosteroids (prednisone)
when in cGVHD would you use tacrolimus instead of cyclosporine
if the disease is manifest in the liver
what does thalidomide do
anti-inflammatory (decrease TNF-a)
what does methotrexate do
anti-metabolite
what would be the benefit of using topical/local immunosupressants for those with cGVHD
it doesn’t supress the entire immune system, just the local immune system
what are the topical drugs for cGVHD
- topical corticosteroids
- topical cyclosporine
- local phototherapy
- topical azathioprine
- topical tacrolimus
