ICL 11.0: Tranplantation Flashcards
what are the 4 types of grafts?
- autografts
- syngeneic grafts/isografts
- allografts/homofrafts
- xenografts/ heterografts
what are autografts?
from an individual to him/herself
what are syngeneic grafts?
grafts between identical twins
or grafts between animals of an inbred strains
what are allografts/homografts?
grafts between different individuals of the same species
or between two different inbred strains
what are xenografts/heterofrats?
grafts between indiviudals of different species
what are the main reasons for allograft failure?
- rejection
- surgical complications
- sepsis
- arterial thrombosis
- primary non-function
what is acute rejection?
aka first set rejection
skin or organ allografts are rejected by non-sensitized recipients in an acute fashion
acute rejection occurs between 7-30 days postgrafting in untreated recipients
but it can also occur later in immunosuppressed recipients! like up to 10 years later!
immunosuppression is sufficient to treat this!
what does a tissue biopsy of acute rejection show?
infiltration!
it’s like little black dots all over the tissue where the white should be
what is accelerated rejection?
aka second set rejection
30-40% of people have been exposed to alloantigens from previous transplants/blood transfusions/pregnancies and have become sensitized to those foreign antigens
they have acquired memory cells that mount a more aggressive response against the alloantigens during a second transplant from the same donor who has the same alloantigens that the person has been sensitized to!
recipients that had rejected first allograft can reject an allograft from the same donor significantly faster!
happens in 0-10 days after transplant
immunosuppression is NOT an effective treatment for this – you have to find a new donor to which the patient has not yet been sensitized
what is the mechanism of accelerated allograft rejection?
following transplantation memory T and B cells are activated inducing production of effector T and B cells
memory T and B cells are specifically recognizing the alloantigens from the first transplant and because of this they produce aggressive T and B cell responses that reject the graft faster
donor-specific antibodies bind to graft endothelial cells activating complement
what is hyper acute allograft rejection?
it’s mediated by preformed donor-specific antibodies
potential recipients are always tested for presence of anti-donor IgM and IgG antibodies
what is the mechanism of hyper acute allograft rejection?
recipients have preformed donor-reactive antibodies
immediately after reperfusion blood carrying antibodies enter the graft = 0-12 hours
antibodies react with donor endothelial cells initiating complement
the antibodies in the blood binding to the endothelial cells will block blood flow
after you open the body’s blood vessels to the graft, the graft should turn pink from the blood entering but in the case of hyper acute allograft rejection, the graft stays white because the blood flow is blocked
this is super rare these days though because we test the recipients blood for pre-formed antibodies against the donor’s cells
what is chronic allograft rejection?
progressive damage that over many years; 70-80% of all allografts are effected by the slow, progressive process of chronic rejection!
these are T cells and antibodies that are against the allograft
can induce thickening of the internal elastic lamina of blood vessels that is infiltrated by migrating smooth muscle cells, macrophages, granulocytes, and alloantigen-specific T cells
final overall effect = narrowing and obstruction of blood vessels!
eventually chronic rejection will kill the allograft….
what type of cell imitates allograft rejection?
T cells!!
if you get rid of T cells, there wouldn’t be any rejection – they are what start the process by recognizing alloantigens
what is direct antigen presentation?
there’s a host CD4+ T cell with a TCR
then there’s a donor APC with donor HLA
alloantigens like HLA are expressed on donor cells; every cell of an allograft has HLA and T cells can recognize the HLA directly
the T cells realize that there’s a difference between donor and recipient
this process happens during acute rejection and is called direct antigen presentation because the T cells directly recognize alloantigens
when does direct antigen presentation happen?
acute rejection
what is indirect antigen presentation?
there are classic host APC taking up alloantigens and processing them to make peptides and then these allopeptides are presented and recognized by CD4+ T cells of the host
this is just like a normal immune response
it mostly happens in chronic rejection
when does indirect antigen presentation happen?
chronic rejection
what are the characteristics of acute rejection?
- high density of donor-derived APCs
- high precursor frequency of T cells with direct specificity
- low precursor frequency of naïve donor- reactive T cells with indirect specificity
what are the characteristics of chronic rejection?
- direct pathway hyporesponsiveness
- lack of donor APCs
- low, persistent precursor frequency of indirectly-primed T cells
- indirect allo- reactivity with epitope spreading
what is graft-versus-hose immune response?
T cells of A strain are injected to C or A x B strain inducing anti-host immune response called graft-versus-host
immunocompetent T cells recognize foreign tissue inducing GVH
so like kidney tissue only has a few passenger cells that go with the transplant and are immune cells; you’re more likely to get a host vs. graft immune response
BM on the other hand has tons of T and b cells which are our immunocompetent cells
so if you transplant BM, the donor BM cells will recognize the host as a foreign tissue and attack it = GVHD!
what’s a comprehensive list of immunosuppressive drugs?
- azathioprine
- corticosteroids
- cyclosporine
- tacrolimus
- sirolimus
- mycophenolate mofetil
- anti-lymphocyte gamaglobulin
- anti-CD3 monoclonal Ab
- anti-CD25 (IL-2R) mAb
