Transplantation Immunopathology Lecture 15
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Questions and Answers

What is the primary target of the recipient's antibodies in Host-Versus-Graft Disease?

  • Graft interstitium
  • Graft stroma
  • Graft vasculature (correct)
  • Graft parenchyma

    • Which type of transplant rejection occurs immediately after transplantation?

  • Acute reaction
  • Delayed reaction
  • Hyperacute reaction (correct)
  • Chronic reaction

    • In which of the following transplants is Graft-Versus-Host Disease most likely to occur?

  • Bone marrow transplant (correct)
  • Kidney transplant
  • Heart transplant
  • Liver transplant

    • What is the main characteristic of Chronic Host-Versus-Graft Disease?

    <p>Dense fibrosis of the intimal layer of blood vessels</p> Signup and view all the answers

    What is the primary mechanism of Antibody-Mediated Diseases?

    <p>Opsonization and phagocytosis</p> Signup and view all the answers

    What is the primary cause of Autoimmune disorders?

    <p>Breakdown of immunologic tolerance to self-antigens</p> Signup and view all the answers

    Which of the following is a characteristic of Chronic Rejection?

    <p>Manifest by dense fibrosis of the intimal layer of blood vessels</p> Signup and view all the answers

    Which of the following is NOT a type of transplant rejection?

    <p>Delayed hypersensitivity reaction</p> Signup and view all the answers

    What is the primary reason for the development of transplantation immunopathology?

    <p>All of the above</p> Signup and view all the answers

    What type of transplantation occurs when the donor and recipient are identical twins?

    <p>Syngeneic</p> Signup and view all the answers

    What is the primary mechanism by which the host immune system recognizes and responds to allografts?

    <p>All of the above</p> Signup and view all the answers

    What type of immune response is triggered by the recognition of foreign MHC molecules by host CD4+ helper T cells?

    <p>Delayed type hypersensitivity (DTH) reaction</p> Signup and view all the answers

    What is the role of dendritic cells (DCs) in direct recognition of allografts?

    <p>They express high levels of MHC molecules and are the most likely APCs in direct recognition</p> Signup and view all the answers

    What is the function of CD8+ T cells in direct recognition of allografts?

    <p>They differentiate into cytotoxic T cells (TCLs) and kill cells in the graft</p> Signup and view all the answers

    What is the mechanism of indirect recognition of allografts?

    <p>Host CD4+ T cells recognize donor MHC molecules presented by host APCs</p> Signup and view all the answers

    What is the outcome of indirect recognition of allografts?

    <p>Production of antibodies against graft allo-antigens</p> Signup and view all the answers

    What is the outcome when circulating cells are coated with autoantibodies and complement proteins?

    <p>They become targets for phagocytosis by neutrophils and macrophages</p> Signup and view all the answers

    What is the result of antibodies binding to cellular or tissue antigens?

    <p>Activation of the complement system and recruitment of neutrophils and monocytes</p> Signup and view all the answers

    What is the effect of antibodies against acetylcholine receptors in myasthenia gravis?

    <p>Inhibition of neuromuscular transmission</p> Signup and view all the answers

    What is the outcome of antibodies stimulating thyroid epithelial cells in Graves' disease?

    <p>Hyperthyroidism</p> Signup and view all the answers

    What is the function of HLA antigens in the immune system?

    <p>Recognition of self-antigens</p> Signup and view all the answers

    What is the consequence of loss of immune tolerance?

    <p>Autoimmune diseases</p> Signup and view all the answers

    What is the process by which autoreactive T cells are eliminated in the thymus?

    <p>Clonal deletion</p> Signup and view all the answers

    Why do some autoreactive lymphocytes escape clonal deletion in the thymus?

    <p>Because some self-antigens may not be present in the thymus</p> Signup and view all the answers

    What is the mechanism of peripheral tolerance that involves the functional inactivation of lymphocytes?

    <p>Anergy</p> Signup and view all the answers

    Which of the following is NOT a mechanism of peripheral tolerance?

    <p>Antigen presentation by dendritic cells</p> Signup and view all the answers

    What is the term for the phenomenon where the body's response to a microbial antigen attacks self-tissues?

    <p>Molecular mimicry</p> Signup and view all the answers

    Which of the following is a genetic factor that contributes to the development of autoimmune diseases?

    <p>HLA locus</p> Signup and view all the answers

    What is the term for the deletion or inactivation of autoreactive T cells or B cells that escaped elimination in the central lymphoid organs?

    <p>Peripheral tolerance</p> Signup and view all the answers

    Which of the following is an example of an immune-privileged site?

    <p>Eye</p> Signup and view all the answers

    What is the mechanism of peripheral tolerance that involves the apoptosis of mature lymphocytes as a result of self-antigen recognition?

    <p>Activation-induced cell death</p> Signup and view all the answers

    Which of the following is a trigger for autoimmunity?

    <p>Viral infection</p> Signup and view all the answers

    What is the primary mechanism by which the provirus genome integrates into host cell DNA?

    <p>Through the action of viral integrase</p> Signup and view all the answers

    What is the primary mechanism of immune deficiency in HIV infection?

    <p>Loss of CD4+ T cells through various mechanisms</p> Signup and view all the answers

    What is the primary site of acute infection in HIV?

    <p>Mucosal T cells and DCs</p> Signup and view all the answers

    What is a common clinical feature of HIV infection?

    <p>Diarrhea</p> Signup and view all the answers

    What is a late complication of HIV infection?

    <p>Destruction of lymphoid tissue architecture</p> Signup and view all the answers

    What is a consequence of chronic HIV infection?

    <p>Progressive loss of CD4+ T cells</p> Signup and view all the answers

    Study Notes

    Transplantation Immunopathology

    • Solid organ and bone marrow transplants have become routine due to understanding of humoral and cellular immune response, development of immunosuppressive drugs, and understanding of MHC (Major Histocompatibility Complex) antigens.
    • MHC antigens are cell surface antigens that determine whether transplanted tissue is recognized as foreign or not.

    Types of Transplantation

    • Allogeneic: Donor and recipient are related or unrelated but share similar HLA types.
    • Syngeneic: Donor and recipient are identical twins.
    • Autologous: Donor and recipient are the same person.

    Immune Recognition of Allografts

    • Rejection of allografts is a response to MHC molecules, which are highly polymorphic.
    • There are two main mechanisms of host immune system recognition and response to MHC molecules on the graft:
      • Direct recognition: Host T cells directly recognize foreign MHC molecules on graft cells.
      • Indirect recognition: Host CD4+ T cells recognize donor MHC molecules after they are picked up, processed, and presented by host APCs.

    Host-Versus-Graft Disease (HVGD)

    • If the transplanted graft bears foreign MHC antigens, the recipient's immune system attacks the donor cells of the transplanted organ.
    • Rejection involves T cell-mediated and circulating antibody responses.
    • Three basic patterns of transplant rejection:
      • Hyperacute reaction: Occurs immediately after transplantation, often in kidney transplants.
      • Acute rejection: Usually occurs within the first few months after transplantation, evidenced by signs of organ failure.
      • Chronic HVGD: Occurs over a prolonged period, manifest by dense fibrosis of the intimal layer of blood vessels in the transplanted organ.

    Graft-Versus-Host Disease (GVHD)

    • GVHD occurs when the cellular immune system of the transplanted graft (donor T cells) recognizes and attacks the unrelated recipient HLA.
    • Occurs mainly in:
      • Bone marrow transplant.
      • Severely immunocompromised patients who have received blood products containing HLA-incompatible lymphocytes.
      • After transplantation of solid organs rich in lymphoid cells (e.g., the liver).

    Autoimmune Disorders

    • Caused by a breakdown in the ability of the immune system to differentiate between self and non-self antigens.
    • Normally, there is a high degree of immunologic tolerance to self-antigens, which prevents the immune system from destroying the host.
    • Autoimmune diseases can affect almost any cell or tissue in the body.
    • Some autoimmune disorders are tissue-specific, while others affect multiple organs and systems.

    Mechanisms of Antibody-Mediated Diseases

    • Opsonization and phagocytosis: Circulating cells coated with autoantibodies are targeted for phagocytosis by neutrophils and macrophages.
    • Inflammation: Antibodies bound to cellular or tissue antigens activate the complement system, recruiting neutrophils and monocytes, triggering inflammation in tissues.
    • Antibody-mediated cellular dysfunction:
      • Antibodies can impair or dysregulate cellular function without causing cell injury or inflammation (e.g., myasthenia gravis).
      • Antibodies can stimulate cell function inappropriately (e.g., Graves' disease).

    Immunologic Tolerance

    • The ability of the immune system to differentiate self from non-self antigens by the presence of HLA antigens.
    • Autoimmune diseases result from loss of immune tolerance.
    • Central tolerance: Elimination of autoreactive T cells in the thymus and B cells in the bone marrow.
    • Peripheral tolerance: Deletion or inactivation of autoreactive T cells or B cells that escaped elimination in the central lymphoid organs.
    • Several mechanisms in peripheral tissues that silence autoreactive T cells:
      • Anergy: Functional inactivation of lymphocytes.
      • Suppression of the response of T lymphocytes by regulatory T cells.
      • Activation-induced cell death: Apoptosis of mature lymphocytes as a result of self-antigen recognition.
      • Antigen sequestration: Some antigens are hidden from the immune system because they are located in immune-privileged sites.

    Mechanisms of Autoimmune Disease

    • Breakdown of self-tolerance and development of autoimmunity are related to the inheritance of various susceptibility genes and changes in tissues, often induced by infections or injury.
    • Genetic factors play an important role in the development of autoimmune diseases.
    • Role of infections and tissue injury:
      • Molecular mimicry: Viruses and other microbes share cross-reacting epitopes with self-antigens, leading to an immune response that attacks self-tissues.
      • Viral replication: Provirus genome integrates into host cell DNA, and viral gene expression is triggered by stimuli that activate infected cells.

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    Description

    This quiz covers the basics of transplantation immunopathology, including the transplantation of solid organs and bone marrow, humoral and cellular immune response, and the role of the major histocompatibility complex (MHC) antigens.

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