Lecture 11 Solid Organ Transplant

Autografts def

transplant from one part of the body to another in the same individual

What is an isograft (also called what)

(also called syngeneic graft) transplant between genetically identical individuals

What is a xenograft?

A transplant between different species, such as from animal to human.

What is an allograft?

A transplant between genetically different individuals of the same species.

What are alloantigens?

specific antigens on the donor organ that the recipient's immune system identifies as "foreign," triggering rejection

antibodies and T cell that react against the alloantigens are called

alloreactive

The principal alloantigens are

proteins of the MHC/HLA class

LMN blood typing system

When a graft is transplanted for the first time, it is referred to as a and may be rejected within

primary graft
rejected within 14 days

When another graft from the same donor is transplanted the second time or more times, then the graft is said to be a what and rejected when?

secondary graft

rejected within 5-6 days

Hyperacute rejection timing

within minutes to hours following the transplant

Hyperacute rejection involves antibodies such as ___ and bind to where

IgM antibodies
bind to the graft vascular endothelium immediately after transplant

For hyperacute rejection, the antibodies bind to antigen on the graft and activate what system resulting in what? (think of blood)
Results in what? (overall what happens to transplant?)

complement system and clotting system 

leading to necrosis and failure

Accelerated organ rejection involves what other cells?

A rejection caused by both antibodies and T cells that is difficult to treat .

Acute Rejection: timing and is mediated through what cells?

Occurs days to weeks post-transplant and is mediated through T cells and antibodies specific to alloantigens in the graft

Chronic Rejection: timing

occurs months to years post-transplant

Chronic Rejection is clinically seen as

narrowing of the graft blood vessels

inflammation + fibrosis of the transplant

Narrowing of the graft blood vessels happens during what rejection and is also called

graft arteriosclerosis

Which rejection is usually the target of immunosuppressive therapy that we covered?

chronic rejection

Rejection is caused by the immune system recognizing the graft as foreign. The specific antigens targeted are called

alloantigens

The principal alloantigens are proteins of the

major histocompatibility complex (MHC)

HLA

What is Tissue Typing?

Matching HLA antigens on leukocytes between the donor and recipient is a strategy used to prevent incompatibility-based rejection

Why use Tissue Typing? 

MHC/HLA are the principal alloantigens that must be matched between donor and recipient to minimize the risk of transplant rejection.

acute rejection example

CD8+ CTLs directly destroying graft cells or CD4+ T cells secreting cytokines to induce inflammation.

What is the Direct Pathway of Allorecognition

DONOR antigen presenting cells (APCs) migrate out of allograft tissue and present DONOR antigen through donor APC surface MHC-II molecules to the recipient’s CD4+ T cells (donor-recipient).

What is the indirect pathway of Allorecognition?

RECIPIENT’s APCs migrate into allograft (transplanted) tissue and phagocytize donor antigen.

These recipient APCs display DONOR antigen to recipient T cells (recipient-recipient). This is a more important long-term mechanism that may cause rejection to occur over months to years.

Three phase of immunosuppressive therapy

Induction, Maintenance, and anti-rejection phase