Transplantation immunology (complete) Flashcards by Brock rose

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

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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)

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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

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what causes host vs. graft response

differences in major HLA
high frequency of host T-cells recognizing the graft HLA
indirect recognition

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what is graft vs. host reaction

when donor lymphocytes attack the host

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when do you see graft vs. host reaction

bone marrow transplants

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what is the treatment/prevention of graft vs. host reaction

removal of all t-cells from the graft

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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

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Are all grafts rejected at the same rate? if not, what are the different rates?

no
hyperacute rejection
acute rejection
chronic rejection

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what is hyper acute rejection

rejection occuring within minutes or hours, that is usually Ab mediated

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what is acute rejection

rejection occuring in days or weeks, usually initiated by alloreactive T-cells

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what is chronic rejection

happens over months or years

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what are the methodes that are used to test for transplant compatibility

ABO compatibility
HLA matching (tissue typing)
Tissue cross matching

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what else can be used along with best compatability to prevent graft rejection

immunosupressive drugs (blocking T-cells, or both B and T-cells)

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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

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how critical is RhD blood type compatibility for transplants and why

it is unimportant, because it is only on RBCs

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what is tissue typing

testing to see how closely HLA’s between the donor and recipient match up (the closer the better)

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what is tissue cross matching

determining whether a patient has Abs that will react specifically with donor WBCs

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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

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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

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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

1. 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

1. topical corticosteroids 2. topical cyclosporine 3. local phototherapy 4. topical azathioprine 5. topical tacrolimus