Organ Transplantation
IRGAM HARIKA REDDY (48)
J CHARAN (49)
Contents
• Definition
• Systemic Causes
• Raynaud’s Phenomenon
• Embolism
• Atherosclerosis
• Buergers Disease
• Other Conditions
Introduction HISTORY
Definitions
● Allograft: an organ or tissue transplanted from one
individual to another
● Alloantigen: transplant antigen
● Alloantibody: transplant antibodies
● Xenograft: a graft performed between different species
● Orthotopic graft: a graft placed in its normal
anatomical site
● Heterotopic graft: a graft placed in a site different
from that where the organ is normally located
ORGAN PROCUREMENT
• Once brain death has been confirmed in cadaver donor, after giving inotropic
support drugs (T3 and argipressin) various organs are surgically removed carefully
with preservation of their vessels.
• Non-heart beating donors (NHBO)
• University of Wisconsin solution contains-potassium lactobionate; sodium
phosphate; magnesium sulphate; adenosine; allopurinol; glutathione; raffi-nose;
hydroxyethyl starch; insulin; dexamethasone; potassium; sodium; with 320
mosmol/1 osmolality and pH of 7.4.
• Living donor's organs are used commonly in kidney trans?plantation from
genetically related individuals.
GRAFT REJECTION
• Allografts provoke a powerful immune response that results in rapid graft rejection unless
immunosuppressive therapy is given.
• Allografts trigger a graft rejection response because of allelic differences at polymorphic genes that give
rise to histocompatibility antigens (transplant antigens) of which ABO blood group antigens and human
leukocyte antigens (HLAs) are the most important
HLA
• Allograft rejection (in blood group-compatible grafts) is directed
predominantly against HLA – a group of highly polymorphic cell-
surface molecules. HLA are strong transplant antigens by virtue of
their special physiological role as antigen recognition units for
display of antigens from foreign pathogens for recognition by T
lymphocytes.
Effector mechanisms of rejection
• The central role of the CD4 T cell in orchestrating the various effector mechanisms responsible
for allograft rejection. APC, antigen-presenting cell; DTH, delayed-type hypersensitivity; IFN-
γ, interferon-gamma; IL, interleukin; MΦ, macrophage; MHC, major histocompatibility
complex; NK, natural killer; Tc, T-cytotoxic cell; Tcp, T-cytotoxic precursor cell; TCR, T-cell
receptor
GRAFT REJECTION
• Host immune system rejects the transplanted organ,
recoginizing it as foreign body. lmmunosuppressive drugs are
used to suppress immune response to promote graft take up. In
humans, the MHC is called the human leucocyte antigen (HLA)
system and is located on the short arm of chromosome 6.
• The immune response to a transplanted organ consists of both
cellular (lymphocyte mediated) and humoral (antibody
mediated) mechanisms. The T cells (CD4, COB T cells) are
central in the rejection of grafts. The rejection reaction consists
of the sensi?tization stage and the effector stage.
Types of Graft
Rejection
Types of Rejections
1. Hyperacute rejection: The transplanted tissue is rejected within minutes to hours
because vascularization is rapidly destroyed. Hyperacute rejection is humorally
mediated as the recipient has pre-existing antibodies against the graft, which can
be induced by prior blood transfusions, multiple pregnancies, prior transplantation.
The kidney is most susceptible to hyperacute rejection; the liver is
relatively . resistant.
Types of Rejections
2. Acute rejection: It occurs within 6 months of transplantation.
Acute cellular rejection is mediated by recipient lymphocytes
against donor antigen.
Humoral rejection occurs due to presence of low level donor
specific antibodies or preformed antibodies.
Types of Rejections
3. Chronic rejection: Chronic rejection develops months to years after acute rejection
episodes have subsided. Chronic rejections are both antibody- and cell-mediated. The use
of immunosuppressive drugs and tissue-typing has increased the survival in the first year,
but chronic rejection is not prevented in most cases.
Chronic rejection appears as fibrosis and scarring in all transplanted organs.
Graft-versus-host disease
• Although the main immunological problem after transplantation
is graft rejection, the reciprocal problem of graft?versus-host
reaction is occasionally seen after certain types of organ
transplantation.
• Some donor organs (particularly liver and small bowel) contain
large numbers of lymphocytes, and these may react against
HLAs expressed by recipient tissues, leading to graft-versus-host
disease (GVHD).
• GVHD frequently involves the skin, causing a characteristic rash
on the palms and soles. It may also involve the liver (after small
bowel transplantation) and the gastrointestinal tract (after liver
transplantation).
• GVHD is a serious and sometimes fatal complication.
Treatment
• Assessment and monitoring : It is done by clinical examination; organ-specific assessment (urine output, urine
analysis, creati?nine estimation, US abdomen, graft kidney biopsy in kidney; liver function tests, liver biopsy);
blood parameter estimation.
• lmmunosuppression: Cyclosporine, tacrolimus, sirolimus, azathioprine, mycophenolate mofetil,
antilymphocytic globulin, basiliximab, daclizumab, steroids, monoclonal antibodies are used at different
regimes, combinations and doses. Complications are-infection; development of carcinoma, lymphoma;
hirsuitism, alopecia, hypertension, nephrotoxicity, neurotoxicity.
IMMUNOSUPPRESSIVE THERAPY
• Calcineurin inhibitors (ciclosporin and tacrolimus)
• Antiproliferative agents (azathioprine and mycophenolate)
• Steroids
• Antibody therapies(Monoclonal antibodies directed against the IL-2 receptor)
Complications
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