The different types of grafts

• Autograft: tissue transferred from one part of the body to another within the same individual• Isograft: tissue transferred between genetically identical individuals• Allograft: tissue transferred between genetically different individuals of the same species• Xenograft: tissue transferred between individuals of different species

Histocompatibility• Tissues that are antigenically similar said

to be histocompatible.• Such tissues do not induce an immunologic response that leads to tissue rejection.

Histoincompatibility• Tissues that display significant antigenic differences are

histoincompatible and induce immune responses that lead to tissue rejection.

What are the antigens that cause rejection?

• Red blood cell compatability.• MHC compatability

– In humans this complex is called the human leukocyte antigen (HLA) complex. – In mice it is called the H-2 complex.

Mechanism of graft rejection

There are two phases to cell mediated

graft rejection

• sensitization stage

• effector stage

Sensitization

• Both CD4+ and CD8+ cells recognize alloantigens on the surface of grafted cells and proliferate in response• There are two ways of presenting alloantigens on the transplant to the recipients T cells

– Direct allorecognition-mhc donor – Indirect allorecognition-peptida donor

Effector Stage

A variety of effector mechanisms participate in allograft rejectionThe most common are cell-mediated reactions involving Delay Type Hypersensitifity and CTL mediated cytotoxicity; less common mechanisms are antibody plus complement mediated lysis and ADCC

Clinical manifestation of graft rejection

• The time course of graft rejection varies depending on

– They type of tissue or organ grafted. – The immune response involved• Types of allograft rejection:Types of allograft rejection: - Hyperacute rejection- Hyperacute rejection - Acute rejection- Acute rejection - Chronic rejection- Chronic rejection

Rapid: occurs in minutes to daysRapid: occurs in minutes to days

Mediated by preformed antibodies and Mediated by preformed antibodies and complementcomplement

No treatmentNo treatment

PreventionPrevention

Hyperacute RejectionHyperacute Rejection

Most commonMost common

Occurs days to months post-transplantOccurs days to months post-transplant

Cell-mediated immune responseCell-mediated immune response

Treated by increasing the net-jaringan Treated by increasing the net-jaringan state of immunosuppressionstate of immunosuppression

Acute RejectionAcute Rejection

Progressive decline in allograft functionProgressive decline in allograft function

Presents differently in each organ Presents differently in each organ transplant typetransplant type

Occurs months to years post-transplantOccurs months to years post-transplant

Therapy: prevent vs. delay the Therapy: prevent vs. delay the inevitable?inevitable?

Chronic RejectionChronic Rejection

General immunosuppressive therapy

• Mitotic inhibitors

• Corticosteroids.

• Total lymphoid irradiation

• CyclosporinA, FK506, and rapamycin