There is a terminology that is used in transplantation
that refers to first set or second set rejection.
Essentially, this is a specific term used in transplantation
to denote a primary or a secondary adaptive immune response.
In the example shown, you can see a strain A mouse that is
being used as a donor for a skin graft onto a strain B mouse.
After three to seven days, this graft
will still be present on the recipient.
There will be no evidence at that point
of time of immunological rejection.
However, that does not mean that this
graft isn’t being recognized as foreign.
Because if we leave the recipient mouse for a few days longer,
we will see that around about day 7-14, the graft is rejected.
And this is referred to
as first set rejection.
Looking now in the center of the diagram, again a
strain A donor mouse and a strain B recipient mouse.
However, if the recipient, the strain B mouse is sensitized
by previous graft from a strain A donor, then we see
a much more rapid rejection; what in transplantation
terminology is referred to as the second set rejection.
This is because immunological
memory has been generated.
And a much faster and stronger secondary
immune response is being generated.
Looking at the right side of the diagram now, we again
have a strain A donor mouse and a strain B recipient mouse.
But the recipient strain B is
injected with lymphocytes from another
strain B animal that has previously rejected a strain A graft.
In other words we are transferring
memory lymphocytes into this mouse.
Therefore when transplanted, there will be a second set
rejection, the faster stronger secondary type immune response.
Looking at the time course of rejection in patients receiving a
transplant, we can identify four different phases of rejection.
Hyperacute rejection which occurs in minutes, is due to the
pre-existence of anti-donor
antibodies and complement activation.
This is incredibly rare to see
these days because cross-matching
between the donor and the recipient and checking for the
presence of antibodies against the donor cells means that
this is not a situation that one would normally come across.
Accelerated acute rejection occurs one to five days following
transplantation, and is due to pre-existing anti-donor T-cells.
Again, this is very rarely seen these days because of
the procedures that are done to minimize this happening.
Acute rejection occurs within weeks, and
is due to the activation of naïve T-cells.
Most commonly seen is chronic rejection, which
occurs months or years following the transplant.
And there are a variety of
mechanisms that cause this.
It’s often rather unclear exactly what
is involved in this rejection process.
But it can involve antibodies, it can involve
immune complexes, can involve T-cells.
Or it may simply be a
recurrence of the disease.
If somebody needed a heart transplant
because of something metabolic going
wrong in their body, that’s not changed
by having a new heart put into them.
And that process that caused them to need a transplant in the
first place may reoccur, affecting the transplanted organ.
In front of you, you can see the number of transplants
performed in the United States of America in 2015.
Of course blood transfusion is the most common type of
transplant where cross-matching needs to be carried out.
Skin transplantation is very often an
autologous transplant, where skin is taken from
one area of the body and transferred to another
area of the body in the same individual.
For example, in a patient with burns.
Corneal transplants are unusual, in
that there is no need to cross-match.
Even though the cornea is coming from a different
individual, the cornea generally is not vascularised.
So immune system cells can’t
actually mediate a rejection process.
Hematopoietic stem cells can be isolated from bone
marrow, from peripheral blood or from cord blood.
And again, very often these transplants
are autologous transplants.
For example, in patients with leukemias that
are being treated with radiation and cytotoxic
drugs, you need to replenish their immune system
cells that are damaged by those treatments.
And then you can read down the rest of this and this gives you
some idea of the most common types of transplant that occur.
This is a graph just to give you an indication of the number
of individuals in the USA with functioning organ grafts.
And as you can see, transplantation is now almost
a routine procedure for many types of transplants.
And many people are living
successfully with transplants.
And the numbers are
increasing year on year.
However graft rejection
remains a continuing problem.
Here you can see a number of different
types of transplant, and that over
the time course of a number of years,
the graft survival rate decreases.