10.2 Organ Grafts

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Questions and Answers

What is the initial mechanism that leads to hyperacute rejection?

Cytokines cause inflammation in the graft

Intimal smooth muscle cell proliferation occludes arteries

Cytotoxic T cells attack graft cells

Preexisting antibodies bind to donor endothelial antigens (correct)

Which of the following describes acute rejection?

It results from arterial occlusion due to smooth muscle proliferation.

It is characterized by immediate thrombotic occlusion of the graft.

It involves alloreactive T cells and inflammation from cytokines. (correct)

It occurs within minutes and is mediated by antibodies.

What characterizes chronic rejection of a graft?

Inflammation caused by helper T cells

Rapid onset of thrombotic occlusion

Destruction of graft parenchyma by antibodies

Proliferation of intimal smooth muscle cells leading to arterial occlusion (correct)

Which statement about the direct rejection pathway is true?

It leads to the destruction of graft cells by the host's lymphocytes. Signup and view all the answers

What is a key factor in the mechanism of acute graft rejection?

Host cytokines activating cytotoxic T lymphocytes (CTLs) Signup and view all the answers

Which type of rejection occurs within 48 hours after grafting?

Hyperacute rejection Signup and view all the answers

What is the primary mechanism through which T cells cause damage to the grafted tissue?

Inducing chemokines that attract more T cells Signup and view all the answers

What condition typically indicates acute rejection in a recipient?

Rapidly rising blood creatinine Signup and view all the answers

In what type of recipient does hyperacute rejection occur immediately?

Sensitized individuals Signup and view all the answers

Which organ is specifically noted to show signs of acute rejection during evaluation?

Kidney Signup and view all the answers

Which of the following is a sign of chronic rejection?

Small, hyperechoic kidney Signup and view all the answers

What common molecule triggers T cell responses during the allograft rejection process?

MHC molecules Signup and view all the answers

Which type of rejection does NOT typically occur rapidly after grafting?

Chronic rejection Signup and view all the answers

What type of graft occurs when tissue is moved to a different part of an animal's own body?

Autograft Signup and view all the answers

Which type of graft is most frequently associated with a strong immune response due to genetic differences?

Allograft Signup and view all the answers

What is the primary reason xenografts cause the strongest immune reaction?

Different species Signup and view all the answers

What characterizes the rejection mechanism of allografts?

Differing MHC antigens Signup and view all the answers

Which statement about grafts between genetically identical individuals is true?

They are never rejected Signup and view all the answers

Which of the following statements about genetic factors in graft rejection is correct?

Grafts between genetically identical individuals are always accepted Signup and view all the answers

What type of graft represents a transplant between two genetically identical individuals?

Isograft Signup and view all the answers

Which strategy is commonly employed to prevent graft rejection?

Immunosuppressive therapy Signup and view all the answers

What is the primary goal of immunosuppressive therapy in allograft transplantation?

To prevent rejection while minimizing infection risk Signup and view all the answers

Which type of drug is cyclosporine classified as?

Inhibitor of T cell signaling pathways Signup and view all the answers

What is the role of plasmapheresis in allograft rejection prevention?

To remove alloantibodies and alloreactive B cells Signup and view all the answers

Which of the following is an example of an anti-inflammatory drug used in allograft rejection prevention?

Prednisolone Signup and view all the answers

Acute Graft-Versus-Host Disease (GVHD) is primarily caused by which of the following?

Reaction of grafted mature T cells with host alloantigens Signup and view all the answers

In which scenario is GVHD most likely to occur?

In immunocompromised individuals post irradiation Signup and view all the answers

What role does ketoconazole play in the treatment of allograft rejection?

It suppresses cyclosporine metabolism and extends its half-life Signup and view all the answers

How soon can allografts in dogs be rejected without treatment?

Within 6-14 days Signup and view all the answers

What is the primary mediator responsible for hyperacute rejection of a graft?

Preexisting antibodies in the host circulation Signup and view all the answers

Which mechanism distinguishes acute rejection from chronic rejection?

Inflammation due to cytokines and alloreactive T cells Signup and view all the answers

What triggers the indirect pathway of graft rejection?

Host's lymphocytes encountering graft antigens Signup and view all the answers

Which description best matches the process of chronic rejection?

Gradual ischemic damage due to arterial occlusion Signup and view all the answers

Which type of cells are primarily involved in the mechanism of acute graft rejection?

Helper T cells and cytotoxic T cells Signup and view all the answers

What type of graft is characterized by being transplanted between genetically identical individuals?

Isograft Signup and view all the answers

Which type of graft typically triggers the strongest immune reaction?

Xenograft Signup and view all the answers

Which statement accurately describes the immune response to allografts?

They always provoke a strong immune response. Signup and view all the answers

What genetic principle explains why offspring do not reject grafts from either parent?

They share identical genetic makeup with one parent. Signup and view all the answers

What is the primary reason that grafts between genetically non-identical individuals are always rejected?

Differences in MHC and blood group antigens Signup and view all the answers

What mechanism is primarily involved in the destruction of allograft tissue?

Cell-mediated immunity Signup and view all the answers

Which type of graft is an example of tissue transplanted to a different part of an animal’s own body?

Autograft Signup and view all the answers

Which strategy is commonly used to prevent graft rejection?

Immunosuppressive therapy Signup and view all the answers

What triggers antibody formation in the allograft rejection process?

Blood group antigens Signup and view all the answers

Which event occurs during the acute rejection process?

Thrombosis of blood vessels in the graft Signup and view all the answers

How does the rejection timeline differ in sensitized individuals compared to unsensitized individuals?

Rejection occurs immediately in sensitized individuals Signup and view all the answers

Which symptom is commonly associated with acute rejection of a renal allograft?

Rapidly rising blood creatinine Signup and view all the answers

What typically signifies the beginning of the chronic rejection process?

Gradual rise in creatinine and urea levels Signup and view all the answers

What is the role of chemokines in the acute rejection process?

Attracting more T cells into the graft Signup and view all the answers

In the context of graft rejection, what are MHC molecules responsible for?

Triggering T cell responses Signup and view all the answers

What is a typical consequence of acute rejection in a renal allograft?

Hemorrhage and death of the grafted organ Signup and view all the answers

What is the primary aim of immunosuppressive therapy during allograft transplantation?

To achieve minimal immunosuppression to prevent rejection Signup and view all the answers

Which class of drugs is specifically used to block T cell costimulatory pathways?

Costimulatory blockade drugs Signup and view all the answers

How does ketoconazole contribute to the treatment of allograft rejection in cats?

It suppresses cyclosporine metabolism and prolongs its half-life Signup and view all the answers

What is a significant consequence of acute GVHD?

Biliary epithelial cell death Signup and view all the answers

What is the effect of azathioprine and mycophenolate mofetil in preventing allograft rejection?

They act as metabolic toxins to eliminate proliferating T cells Signup and view all the answers

What treatment can enhance allograft survival in dogs?

Treatment with rabbit antidog thymocyte serum Signup and view all the answers

In which situation does GVHD most commonly occur?

When immunosuppressed by total-body irradiation Signup and view all the answers

Which type of drug is commonly used to prevent allograft rejection in dogs?

Antimetabolites Signup and view all the answers

What primarily mediates hyperacute rejection?

Preexisting antibodies Signup and view all the answers

Which process is primarily responsible for acute rejection damage to the graft?

Cytotoxic T cell activity Signup and view all the answers

Why does chronic rejection lead to graft failure?

Due to arterial occlusion and ischemic damage Signup and view all the answers

What type of lymphocyte response is involved in the direct pathway of graft rejection?

Cytotoxic T cell response Signup and view all the answers

What characteristic defines acute cellular rejection compared to hyperacute rejection?

It involves alloreactive T cells Signup and view all the answers

What is one potential consequence of acute rejection affecting the grafted organ?

Progressive damage to endothelial cells Signup and view all the answers

What characterizes hyperacute rejection in allograft patients?

Immediate rejection within 48 hours Signup and view all the answers

Which factor is critical in the development of chronic rejection over time?

Gradual rise in creatinine and urea levels Signup and view all the answers

What role do MHC molecules play in the rejection process of allografts?

They trigger T cell responses against the graft Signup and view all the answers

Which clinical manifestation is indicative of acute rejection in a kidney transplant recipient?

Elevated creatinine levels Signup and view all the answers

What is one of the primary mechanisms causing thrombosis in the acute rejection process?

T cell-mediated damage to blood vessels Signup and view all the answers

In sensitized individuals, which response is expected upon receiving an allograft?

Immediate hyperacute rejection Signup and view all the answers

Which type of immune cells specifically mediate the rejection process of graft tissues?

Cytotoxic T cells Signup and view all the answers

Which type of graft is characterized by transplants between genetically different individuals of the same species?

Allograft Signup and view all the answers

What is the primary reason why xenografts elicit a stronger immune response than allografts?

They contain more foreign antigenic material. Signup and view all the answers

Which of the following statements regarding the immune response in graft rejection is true?

The immune system identifies and destroys foreign grafts. Signup and view all the answers

What is the main aim of immunosuppressive therapy in preventing allograft rejection?

Minimize immunosuppression to prevent rejection Signup and view all the answers

Which drug is an example of an inhibitor of T cell signaling pathways?

Cyclosporine Signup and view all the answers

What typically describes the outcome when grafts are transplanted between genetically identical individuals?

They are never rejected. Signup and view all the answers

What is the best description of an autograft?

Tissue moved within the same individual's body. Signup and view all the answers

Which strategy directly targets alloreactive B cells?

Plasmapheresis Signup and view all the answers

What type of immunosuppression strategy is azathioprine classified as?

Antimetabolite Signup and view all the answers

What condition typically allows for the development of Graft-Versus-Host Disease (GVHD)?

The host being immunocompromised Signup and view all the answers

In what time frame can allografts in dogs be rejected without treatment?

6-14 days Signup and view all the answers

In the context of graft rejection, what primarily causes the immune system to attack allografts?

Differences in MHC and blood group antigens. Signup and view all the answers

What role does ketoconazole play in the treatment of allograft rejection in cats?

It suppresses cyclosporine metabolism Signup and view all the answers

Which of the following is a common consequence of acute GVHD?

Epithelial cell death in specific organs Signup and view all the answers

Study Notes

Organ Graft Rejection

Organ grafts, like transplants, involve moving tissues or organs from one organism to another.
The immune system's role in rejection is to identify and destroy non-self ("abnormal") cells. This is a normal immune response.
Rejection is a reflection of the immune system's function in identifying and destroying foreign cells.
Organ rejection is a complex process involving various cell types and immune responses from both the recipient and donor.

Types of Organ Grafts

Autografts: Tissue moved within the same organism. This does not trigger an immune response. Examples include covering a burn with skin, or a segment of vein bypassing a blocked cardiac artery.
Isografts: Tissue moved between genetically identical individuals. These do not provoke an immune response.
Allografts: Tissue transplanted between genetically different members of the same species. This is the most frequent type of graft. Differences in MHC and blood group antigens trigger a strong immune response, leading to rejection. Renal allografting is now routine for dogs and cats. Bone marrow allografts are beneficial in some tumors
Xenografts: Tissue transplanted between animals of different species. This causes the strongest immune reaction, leading to most rapid rejection. Examples include transplanting a baboon heart to a human infant. Xenografts cause faster immune response due to extreme differences.

Genetics of Graft Rejection

Grafts between genetically identical individuals never get rejected.
Grafts between genetically non-identical individuals always get rejected.
Offspring of genetically different individuals will not reject grafts from either parent (though NK cells in the offspring can, often violated by bone marrow transplantation). Grafts from the offspring of two genetically different individuals will be rejected by either parent.

Allograft Rejection

Allografted organs are major sources of foreign molecules, including blood group antigens and MHC molecules (both class I and class II).
Rejection mechanisms are similar regardless of the tissue.
Antibodies and T cells are involved in the rejection process. Acute rejection progresses through various stages.

Acute Rejection Process

Grafted tissue becomes infiltrated with cytotoxic T cells, leading to progressive endothelial cell damage lining small blood vessels.
T cell-mediated damage attracts more T cells, triggering cellular destruction, blockage of blood vessels (thrombosis), hemorrhage, and ultimately graft death.
Repeated grafts from the same donor often trigger rapid rejection involving antibodies and complement. This is due to prior sensitization.

Clinical Renal Allograft Rejection

Rejection can happen at any time.
Types of rejection include hyperacute (within 48 hours), accelerated (up to 7 days), acute (after 7 days), and chronic (months after).
Rejection in unsensitized individuals happens after at least 10 days, but immediately in sensitized individuals (hyperacute). Renal allografting is now routine for dogs and cats. Bone marrow allografts are beneficial in some tumors

Manifestations of Acute Rejection

Recipient shows a rapidly rising blood creatinine level.
The kidney becomes enlarged and painful.
Signs of depression, anorexia, vomiting, proteinuria, and hematuria.
Ultrasound shows an enlarged, hypoechoic kidney.

Signs of Chronic Rejection

Gradually rising creatinine and urea levels.
Proteinuria.
Macroscopic hematuria.
A small, hyperechoic kidney.

Pathogenesis of Allograft Rejection

Allograft rejection targets dominant antigens on graft cells.
MHC molecules trigger T-cell responses.
Blood group antigens trigger antibody formation.

Two Stages of the Rejection Process

Direct pathway: Host lymphocytes directly encounter graft antigens.
Indirect pathway: Cytotoxic T cells and antibodies from the host enter and destroy graft cells.

Graft Rejection Pathways

Includes direct and indirect pathways for recognition.
Direct pathway: Direct recognition of donor MHC molecules on cells of the graft by the recipient's T cells.
Indirect pathway: Recipient's APCs process and present peptides from donor MHC to T cells.

Mechanism of Graft Destruction (Hyperacute Rejection)

Thrombotic occlusion of the graft vasculature, rapidly following anastomosis.
Antibodies in the host's circulation bind to donor endothelial antigens and initiate complement activation.

Acute Rejection

Injury is caused by multiple factors including inflammation caused by cytokines produced by T cells, CTL-mediated killing of graft cells, and the action of preexisting host antibodies which bind to donor antigens. These factors result in injury to the graft's parenchyma and blood vessels.

Chronic Rejection

Occlusion of arteries due to intimal smooth muscle cell proliferation and subsequent ischemic damage.

Prevention of Allograft Rejection

Minimal immunosuppression is the aim. Prevent rejection without making the receiver too susceptible to common infections.
General strategies involve inhibiting T cell signalling pathways (e.g., cyclosporin, FK506), using antimetabolites (e.g., azathioprine, mycophenolate), and targeting alloantibodies and alloreactive B cells (e.g., plasmapheresis or anti-CD20). Anti-inflammatory drugs (e.g. corticosteroids) are used to prevent rejection. In dogs, azathioprine, leflunomide, prednisolone, and cyclosporine are used; in cats prednisone and cyclosporine. Ketoconazole can complement and prolong cyclosporine half life.

Graft-Versus-Host Disease (GVHD)

Caused by mature T cells in the grafted bone marrow inoculum reacting against the host's alloantigens.
Occurs when the host is immunocompromised.
May follow total-body irradiation or cyclophosphamide treatment.

Acute GVHD

Epithelial cell death in the skin, liver (biliary epithelium), and gastrointestinal tract, resulting in clinical signs like rash, jaundice, diarrhea, and gastrointestinal hemorrhage.

Chronic GVHD

Characterized by fibrosis and atrophy of organs.
No acute cell death; is often a late-stage consequence.

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