Organ Transplantation and Immunology Overview

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Questions and Answers

What is the main cause of allograft rejection?

An adaptive immune response. (correct)

Infection at the transplant site.

Insufficient organ preservation.

Incompatibility of blood types.

Which statement about transplanting organs between genetically identical individuals is correct?

It requires no immunosuppression.

It leads to a higher chance of rejection.

It results in immediate necrosis.

It is unlikely to cause rejection. (correct)

What typically happens when skin from unrelated donors is transplanted into burn patients?

There is a strong likelihood of graft-versus-host disease.

It leads to chronic inflammation in the recipient.

It is usually accepted without issues.

The transplant often results in necrosis within 1 to 2 weeks. (correct)

Which genetic scenario leads to the acceptance of grafts from either parent in animals?

Mating between genetically different inbred strains. Signup and view all the answers

What underlies the fundamental issue of organ transplant supply and demand?

The imbalance between organ supply and demand. Signup and view all the answers

Which of the following statements about graft rejection is incorrect?

Non-identical grafts have a high acceptance rate. Signup and view all the answers

The inflammatory reaction responsible for the failure of skin grafting is known as what?

Rejection. Signup and view all the answers

What type of individuals predominantly face the issue of organ rejection in transplantation?

Genetically nonidentical individuals. Signup and view all the answers

What is the phenomenon observed when HSCs from either parent are rejected by an (A × B) F1 recipient?

Natural killer (NK) cell violation Signup and view all the answers

What role do MHC molecules play in the immune response?

They display peptide antigens for T cell recognition. Signup and view all the answers

Which process specifically eliminates developing lymphocytes that strongly bind to self-antigens?

Negative selection Signup and view all the answers

How many class I MHC genes are present in humans, and what are they called?

Three: HLA-A, HLA-B, and HLA-C Signup and view all the answers

What is the primary outcome of failure to be positively selected by self MHC molecules?

Induction of apoptosis in T cells Signup and view all the answers

Which of the following accurately describes the structure of class II MHC molecules?

Heterodimer of α and β polypeptides Signup and view all the answers

What is referred to as the set of MHC alleles present on each chromosome?

MHC haplotype Signup and view all the answers

How do allogeneic MHC molecules of a graft get recognized by recipient T cells?

Through both direct and indirect recognition Signup and view all the answers

What is the primary action of corticosteroids in relation to anti-inflammatory genes?

They enhance the expression of anti-inflammatory genes. Signup and view all the answers

How do corticosteroids suppress inflammatory genes?

By blocking I-κB degradation. Signup and view all the answers

What role do coactivators such as CBP and pCAF play in corticosteroid action?

They enhance histone acetylation, leading to gene activation. Signup and view all the answers

What is the consequence of cyclosporine introduction in cardiac allograft patients?

Increase in five-year survival rates. Signup and view all the answers

Which protein's activation is primarily associated with inflammatory stimuli like IL-1β?

Nuclear factor (NF)-κB Signup and view all the answers

What is the molecular mechanism by which corticosteroids activate anti-inflammatory gene expression?

Binding of corticosteroids to glucocorticoid response elements in the nucleus. Signup and view all the answers

What characterizes hyperacute rejection in grafts?

Thrombotic occlusion of graft vasculature due to preexisting antibodies Signup and view all the answers

Which of the following genes is NOT induced by corticosteroids?

Tumor necrosis factor (TNF)-α Signup and view all the answers

Which process primarily mediates acute cellular rejection?

CTL-mediated killing of graft cells Signup and view all the answers

What effect does the transient coactivation by histone acetyltransferases have on gene expression?

It activates gene expression. Signup and view all the answers

What triggers the damage seen in acute antibody-mediated rejection?

Binding of alloantibodies to endothelial antigens Signup and view all the answers

Which of the following statements about chronic rejection is true?

It is characterized by the proliferation of intimal smooth muscle cells causing arterial occlusion. Signup and view all the answers

How do alloantibodies contribute to graft destruction during acute antibody-mediated rejection?

By binding to endothelial cells and triggering complement activation Signup and view all the answers

What is the main histological feature indicative of chronic rejection in vascularized grafts?

Arterial occlusion due to intimal smooth muscle cell proliferation Signup and view all the answers

Which type of rejection mechanism is primarily involved in the binding of graft alloantigens by host dendritic cells?

Indirect pathway of antigen presentation Signup and view all the answers

What contributes to the endothelial cell injury in acute antibody-mediated rejection?

Complement activation leading to cell lysis Signup and view all the answers

What occurs as the arterial lesions of graft arteriosclerosis progress?

Compromise of blood flow to the graft parenchyma. Signup and view all the answers

How does MHC matching influence renal allograft survival from deceased donors?

It significantly increases graft survival rates. Signup and view all the answers

What is the primary role of IL-2 in the immune response?

Acting as a growth factor for T lymphocytes. Signup and view all the answers

What is a key feature of the immune synapse?

It acts as a stable contact point for T cell and APC interactions. Signup and view all the answers

Which of the following correctly describes IL-2's function regarding regulatory T cells?

IL-2 promotes the survival and functionality of regulatory T cells. Signup and view all the answers

What signifies the turnover of signaling molecules within the immune synapse?

The termination of T cell activation. Signup and view all the answers

Which statement best summarizes the impact of HLA matching on live donor grafts?

HLA matching has a minimal impact on graft survival from live donors. Signup and view all the answers

What is the role of costimulatory receptors in the immune synapse?

They stabilize the interaction between T cell and APC. Signup and view all the answers

Study Notes

Organ Transplant Numbers

The number of organ transplants increased significantly between 1988 and 2018.
The most common organs transplanted are kidneys followed by livers.

Allogeneic Organ Transplantation

There's a growing imbalance between organ supply and demand, resulting in an expanding transplant waiting list.
Rejection of transplanted organs is a significant problem.
Skin grafts from unrelated donors are generally unsuccessful.

Genetics of Graft Rejection

Transplants between genetically identical individuals (identical twins or inbred strains of animals) are not rejected.
Transplants between genetically nonidentical individuals are almost always rejected.
Offspring of two different inbred strains will not reject grafts from either parent.

T Cell Signaling

T cells are crucial for immune responses.
They recognize antigens through the T cell receptor (TCR).
TCR stimulation triggers a cascade of intracellular signaling pathways, leading to T cell activation.

Mechanisms of Immunosuppressive Drugs

Immunosuppressive drugs are used to prevent rejection of transplanted organs.
These drugs target various steps in the immune response, such as inhibiting T cell activation and cytokine production.

Immunosuppressive Drug Influence on Graft Survival

Cyclosporine, introduced in 1983, significantly improved 5-year survival rates for cardiac transplant recipients.

Corticosteroids and Gene Expression

Corticosteroids are anti-inflammatory drugs.
They bind to glucocorticoid receptors, leading to changes in gene expression.
Corticosteroids activate anti-inflammatory genes, which code for proteins that suppress inflammation.
Corticosteroids also suppress expression of pro-inflammatory genes.

T Lymphocyte Maturation in the Thymus

Lymphocytes undergo maturation in the thymus.
Negative selection eliminates lymphocytes that bind strongly to self-antigens.

MHC Genes

MHC molecules play a crucial role in antigen presentation to T cells.
Different individuals have different MHC alleles, which leads to variations in antigen presentation.
Each individual inherits MHC alleles from both parents, maximizing the range of peptides presented.

Map of Human MHC Genes

Human MHC genes are located on chromosome 6.
There are three class I MHC genes (HLA-A, HLA-B, HLA-C).
There are three class II HLA gene loci (HLA-DP, HLA-DQ, HLA-DR).

Direct and Indirect Alloantigen Recognition

Recipient T cells can recognize donor MHC molecules through two pathways: Direct and Indirect.
In direct recognition, recipient T cells directly recognize donor MHC molecules on graft cells.
In indirect recognition, recipient antigen-presenting cells (APCs) engulf donor antigens, process them, and present them to T cells.

Hyperacute Rejection

Hyperacute rejection is a rapid and severe form of rejection.
It happens within minutes to hours of transplantation.
It is caused by pre-existing antibodies in the recipient that bind to donor endothelial antigens.
This leads to thrombosis of the graft vasculature.

Acute Cellular Rejection

Acute cellular rejection is mediated by T cells.
It involves CTL-mediated killing of graft cells and inflammation triggered by cytokines.

Acute Antibody-Mediated Rejection

Alloantibodies bind to donor MHC molecules on vascular endothelial cells.
This triggers complement activation, neutrophil recruitment, and thrombus formation.
Alloantibodies can also engage Fc receptors on NK cells, leading to cell killing.

Chronic Rejection

Chronic rejection is a long-term process.
It is characterized by vascular lesions that lead to graft failure.
The main lesion is arterial occlusion due to intimal smooth muscle cell proliferation.
Chronic rejection is likely mediated by alloreactive T cells and the secretion of inflammatory cytokines.

Influence of MHC Matching on Graft Survival

Matching MHC alleles between donor and recipient improves graft survival.
Matching is particularly important for kidney transplants from deceased donors.
Live donor transplants are less affected by MHC matching.

Biologic Actions of IL-2

IL-2 is a cytokine that stimulates T cell proliferation and survival.
It acts as an autocrine growth factor for T cells.
IL-2 also promotes the survival of regulatory T cells, which control immune responses.

The Immune Synapse

The immune synapse is a specialized interface between a T cell and an antigen-presenting cell.
It facilitates TCR signaling, delivery of secretory granules, and turnover of signaling molecules.
The immune synapse helps to ensure specific and efficient T cell activation.

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Description

This quiz covers key concepts related to organ transplantation, including statistics on transplants, the challenges of graft rejection, and the genetic factors involved in transplant success. It also highlights the role of T cells in the immune response. Test your knowledge on these vital topics in transplantation science.