CH15: Transplantation

Tissue Rejection

• Transplant can be treated as a foreign antigen

• adaptive immune response damages and kills transplant

• T cells attack the transplant

Graft-versus-host disease (GVHD)

• Graft attacks the host

• Bone marrow is transplanted: T-cells in transplant attack the recipient tissue

• donor tissue becomes a source of mature T cells, that can attack the host tissues as foreign antigens.

• MHC=HLA

Transplantation antigens

the major histocompatibility antigens (also known as the HLA system in humans)

Xenografts (for xenotransplantation)

transplants of organs between different species

Red blood cells express HLA antigens (T/F)

False

ABO blood type and the Rhesus factor

• the main transplantation antigens on erythrocytes

• Rh factor gene produces protein Antigen D

• There are 32 recognized antigens on human RBCs, from different genes

Alloantigens

antigens that vary between individuals of the same species

Immunogenetics

the study of alloantigens

Autograft

• A graft of tissue within the same body

• ex, in burn patient, skin may be transplanted

Isograft (or syngeneic) graft

A transplant made between genetically identical individuals

Allograft (or allogeneic transplant)

• transplant made between two genetically different individuals

• Blood transfusions are the most common transplant procedure

ABO antigens can also be expressed on endothelial cells which line the interior of blood vessels (Solid organ transplant) (T/F)

True

Hyperacute rejection (Solid organ Transplants)

Type III hypersensitivity rxn’s involving the formation of immune complexes of proteins, including complement, can form within minutes cause this

In order to avoid hyperacute rejections, tissue compatibility is

assessed using a -

-Cross-match test

Cross-match test

• Blood serum from a potential recipient is mixed with white blood cells from the potential donor.

• Usually B and T lymphocytes are isolated to assess

  the reactivity to MHC I vs. MHC II molecules.

Pregnancy is a normal state that provides opportunities for the

production of anti-HLA antibodies (T/F)

True

The maternal immune system

• can generate antibodies against HLA antigens acquired from the father, present in the fetus

• Blood transfusions (HLAs from platelets and leukocytes) and organ transplants also generate more potential positively reacting anti-HLA antibodies.

Solid organs that can donate

heart, lungs, kidneys, livers, pancreas, intestine, and thymus

Tissues to donate

bones, tendons, cornea, skin, heart valves, nerves and veins.

Ischemia

• Inadequate blood flow

• causes damage to transplants due to immune complex blockages

Panel reactive antibody (PRA)

• Recipient sera is tested for reactivity to HLA allotypes.

• The recipient sera is tested against a panel of potential

donor antigens.

• A higher score indicates an increased risk of tissue rejection.

• Individuals who receive ‘serial transplants’ (who have

had a previous transplant) are at an increased risk for

rejection.

• (as are multiparous mothers and recipients of multiple

blood transfusions)

direct pathway of allorecognition

• interaction of recipient T cells interacting with donor

  dendritic cells.

Acute Rejection

Macrophages are activated by the effector T cells (TH1), and they destroy the transplant tissue- which take days to develop

Mixed lymphocyte assay

• another test for potential tissue rejection

• The potential donor tissues are irradiated to

  prevent their mitosis.

• Potential recipient cells are measured for their reactivity with donor tissues by an increase in cell

  number or cytotoxic effects.

Individuals who inherit too many HLA antigens can actually

decrease-

- their overall T cell population because of selection

processes during T cell maturation.

12-13 HLA molecules are expressed in an individual

Chronic rejection

• a process that can occur years after

  transplantation

• mainly a problem at the level of circulation, as HLA antigens attack and cause inflammation

direct allorecogniton

• Dendritic cells from the donor are a primary problem with transplant rejections, so in this-

• the APC donor dendritic cells are recognize directly by host T cells

Indirect allorecognition

• due to the removal of donor dendritic cells by recipient dendritic cells.

• The host than acts as a normal APC and presents donor antigens to host T cells.

Indirect pathway of allorecognition

stimulates B cells (via T cells) and causes alloantibodies to be

produced against the donor antigens.

Tissue compatibility correlates with the decrease in chronic rejection (T/F)

True