Hyperacute

Timing

Hyperacute rejection occurs within minutes to hours of transplantation. It is usually

diagnosed by the surgeon in the operating room when the kidney becomes cyanotic
and mottled after Anastomosis of the donor and recipient blood vessels.

This form of transplant rejection is usually diagnosed by the surgeon in the

operating room when the kidney becomes cyanotic and mottled after Anastomosis
of the donor and recipient blood vessels. Perfusion through the transplanted organ
ceases immediately due to antibody and complement-mediated injury to the
vascular endothelium with formation of extensive thrombosis. This rapidly leads to
ischemic necrosis of the Glomeruli and renal cortex with little to no urine output.

Hyperacute rejection is an antibody-mediated reaction (type 2 HSR) caused by

preformed IgG antibodies within the recipient that are directed against donor
antigens. Origin of the circulating cytotoxic IgG is most commonly:

1. Previous failed graf

2. Blood transfusion
3. Pregnancy

Examples of such mismatch include:

1. Anti-ABO blood group antibodies

2. Anti-HLA antibodies

Hyperacute rejection occurs within minutes of transplantation. Preformed antibodies

against ABO or HLA are the cause. There is graft blood vessel spasm and diffuse
intravascular coagulation (DIC) with resultant ischemia. For this reason, Hyperacute
rejection is sometimes called white graft reaction. It is rare and is often
irreversible.

Outcome & Treatment

Graft must be removed immediately

Often irreversible event
Rare today
Due to cross matching
Usually due to HLA mismatch
Acute Rejection

overview

Acute Rejection is the result of both Humoral and Cell-mediated Immune Responses of the
host against donor tissues. Because the Adaptive Immune Response to donor tissues takes
time to develop and mature, the pathological consequences of Acute Rejection do not
become apparent for days or weeks following transplantation and can be slowed with
Immunosuppressive Drugs.

Acute transplant rejection occurs in 2 of every 5 heart transplanted and in the large majory of
cases occurs by the cell-mediated pathway. In rare cases, cardiac rejection is due to anti-
donor host antibodies, and cases of humoral rejection are diagnosed by direct
immunofluorescence.

The clue that indicates that the patient is experiencing acute rejection is the timeframe of
symptoms (e.g., two weeks post-transplant). Acute transplant rejection usually occurs 1 4
weeks after transplantation.

The histopathology most consistent with acute rejection is dense infiltrates of mononuclear
cells (primarily T-lymphocytes). Acute rejection of transplanted organ is mediated by host T-
lymphocytes sensitization against graft (foreign) MHC antigens. Acute rejection is usually
diagnosed before symptoms set in because of close surveillance of these patients, but
symptoms consistent with progressive rejection include: heart failure.
GVHD

There are 2 main types of rejection. The hosts immune system can attack the graft or
immune cells within the graft can attack the host. The 3 kinds of transplant rejection we
have covered so far are all host vs. graft. The last type of transplant reject we will
cover is Graft vs. Host.

Here donor T-Cells in the graft proliferate and attack the recipients tissue. This is
most commonly seen in Bone Marrow Transplants, because the donated tissue has a
large amount of immune cells. The immune cells from the graft spread through the body
and cause systemic symptoms that are not isolated to the transplanted organ.

Symptoms commonly include diarrhea, rash and jaundice. The timeframe for the onset
of Graft versus Host varies widely. Immunosuppressant are usually the treatment of
choice for Graft versus Host

GVHD is a condition that usually occurs after allogeneic bone marrow

transplantation. However, GVHD can also occur following transplantation of organs
rich in lymphocytes (e.g., liver) or transfusion of non-irradiated blood.

Patients affected with GVHD are generally severely immunodificient due to the
primary disease process or as a result of immunosuppressive medications. This
allows immunocompetent donor T cells from the graft to survive and migrate into
host tissues, where they recognize host MHC antigens as foreign and become
sensitized. On activation, donor CD4+ and CD8+ T cells participate in host cell
destruction.

Any organ may be a target of GVHD, but the skin, liver and GI tract are the most
frequently affected. Early signs of GVHD include:

1. Diffuse maculopapular rash that has a predilection for the palms and soles
and may desquamate in severe cases.

2. GI tract involvement: causes diarrhea, intestinal bleeding, and abdominal

pain. Liver damage may manifest as abnormal liver function tests. In this case,
the donated liver would not be significantly affected as the donor T cells
perceive the liver as self.
3.
 Common Clinical Scenarios

Bone Marrow Transplantation

Liver Transplantation: Livers are rich in lymphoid cells

Blood Transfusion: Only if transfused blood is not irradiated to kill donor T-cells

Because stringent antigenic matching is performed between host and donor, hyperacute rejection occurs rarely today.

Hyperacute Transplant Rejection

occurs almost immediately and is often evident while you are still in surgery. It is caused
by accidental ABO Blood type mismatching of the donor and recipient which almost
never happens anymore. This means the host has preformed antibodies against the
donated tissue. For example, a recipient with Type B blood would have pre-made
antibodies targeted at the carbohydrates on the blood of a Type A donor. The presence
of preformed antibodies is why the reaction takes places so quickly. This is an example of
Type II Hypersensitivity and results in thrombosis and occlusion of the graf vessel. The
transplanted organ must be removed immediately.

1. Vascular Fibrinoid necrosis

2. Neutrophil infiltration

Hyperacute = Vascular Fibrinoid necrosis & neutrophil infiltration of the

arterioles, Glomeruli, and peritubular capillaries are characteristics.
Hyperacute rejection occurs within minutes to hours after donor-recipient
vascular Anastomosis..

Timing Note

Hyperacut
Mints Hours Intraoperative
e

< 6 months
Acute Weeks Months
(usually in 1 month)

Chronic Months years > 6 months

GVHD Widely variable

Treatment Reversibility
Hyperacute Graf removal Irreversible

Acute Immunosuppressant Reversible

Chronic Graf removal Irreversible

GVHD Immunosuppressant Reversible

 Cellular
HSR Immune response
component

Hyperacute Type II Humoral only Neutrophils

Acute Type IV Humoral or cellular C8+ T cells

Chronic Type II & IV Humoral & cellular C4+ T cells

GVHD Type IV Cellular only T-cells (both)

Pre-existing recipient AB HLA & Blood Recipient against Donor

Hyperacute
against donor antigens group antigens antigen

Recipient cytotoxic T cells Recipient against Donor

Acute MHC
activated against donor MHC antigen

Recipient against Donor

Chronic MHC
antigen

Donor T-cells activated against

GVHD MHC Donor against recipient
host MHC

Scant inflammatory cells and interstitial fibrosis is most characteristic of chronic

rejection. Chronic rejection is a process mediated by host T-lymphocytes and B-
lymphocytes as well as antibodies.
 Hallmark

Hyperacut
Thrombosis Gross mottling & cyanosis
e

Acute Vasculitis Dense lymphocytic infiltrates

Scant inflammatory infiltrates

Arteriosclerosis
Chronic Intimal thickening & fibrosis
Interstitial fibrosis
of graft vessel

GVHD

Chronic transplant rejection:

Arteriosclerosis
Vascular wall thickening
Luminal narrowing

Interstitial fibrosis
Fibrosis of the transplant
 Parenchymal atrophy

Cellular infiltrates
Scant inflammatory cells
Vs. dense lymphocytic infiltrates in Acute rejection

Lungs Bronchiolitis Obliterans

Heart Accelerated Atherosclerosis

Kidney

Vanishing bile duct syndrome

Liver
(fibrotic non-functional bile ducts)