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Questions and Answers
What is the service key for Specialist Student Self-scheduling?
What is the service key for Specialist Student Self-scheduling?
What is the coupon code to be entered when making appointments starting August 1st?
What is the coupon code to be entered when making appointments starting August 1st?
Which of the following services is NOT listed under Telemedicine?
Which of the following services is NOT listed under Telemedicine?
Which number should be called for student acute care visits?
Which number should be called for student acute care visits?
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What type of counseling is offered 24/7 for immediate support?
What type of counseling is offered 24/7 for immediate support?
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What is the primary immune response involved in chronic rejection after organ transplantation?
What is the primary immune response involved in chronic rejection after organ transplantation?
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What is the estimated timeline for chronic rejection to occur post-transplant?
What is the estimated timeline for chronic rejection to occur post-transplant?
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What strategy is recommended to minimize acute rejection in transplant patients?
What strategy is recommended to minimize acute rejection in transplant patients?
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What is one potential consequence of not managing acute rejection effectively?
What is one potential consequence of not managing acute rejection effectively?
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In the context of immunosuppressive therapies, which phase is similar for both acute and chronic rejection?
In the context of immunosuppressive therapies, which phase is similar for both acute and chronic rejection?
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How can partial T cell depletion benefit transplant recipients?
How can partial T cell depletion benefit transplant recipients?
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What role do growth factors play in chronic rejection?
What role do growth factors play in chronic rejection?
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What factor is critical in determining the long-term outcomes of organ transplants?
What factor is critical in determining the long-term outcomes of organ transplants?
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Which of the following is a critical mental health resource mentioned for students in crisis?
Which of the following is a critical mental health resource mentioned for students in crisis?
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What is the purpose of academic support services mentioned in the content?
What is the purpose of academic support services mentioned in the content?
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What type of graft occurs between two genetically identical individuals?
What type of graft occurs between two genetically identical individuals?
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Which type of graft is subjected to the strongest immune response due to genetic differences?
Which type of graft is subjected to the strongest immune response due to genetic differences?
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What primarily mediates graft rejection in the adaptive immune system?
What primarily mediates graft rejection in the adaptive immune system?
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Which of the following is responsible for rapid and strong allograft rejection reactions?
Which of the following is responsible for rapid and strong allograft rejection reactions?
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What is the likely effect of mismatched MHC during transplantation?
What is the likely effect of mismatched MHC during transplantation?
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How do alloreactive T cells recognize allogeneic MHC molecules?
How do alloreactive T cells recognize allogeneic MHC molecules?
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What information does ABO typing provide in the context of organ transplantation?
What information does ABO typing provide in the context of organ transplantation?
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What is the main purpose of crossmatching in organ transplantation?
What is the main purpose of crossmatching in organ transplantation?
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Which form of graft rejection occurs immediately after transplantation?
Which form of graft rejection occurs immediately after transplantation?
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What is the difference between general immunosuppressive therapy and specific suppression of T cells?
What is the difference between general immunosuppressive therapy and specific suppression of T cells?
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What type of rejection occurs within minutes to hours due to pre-existing antibodies?
What type of rejection occurs within minutes to hours due to pre-existing antibodies?
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What role do alloreactive CTLs play in graft rejection?
What role do alloreactive CTLs play in graft rejection?
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In chronic rejection, which of the following processes contributes to graft dysfunction?
In chronic rejection, which of the following processes contributes to graft dysfunction?
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What is the primary mechanism leading to acute antibody-mediated rejection?
What is the primary mechanism leading to acute antibody-mediated rejection?
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Which of the following therapies is used for long-term prevention of graft rejection?
Which of the following therapies is used for long-term prevention of graft rejection?
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Which immunosuppressive agent directly inhibits IL-2 synthesis?
Which immunosuppressive agent directly inhibits IL-2 synthesis?
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What characterizes Graft vs Host Disease (GvHD)?
What characterizes Graft vs Host Disease (GvHD)?
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What is a common trigger for hyperacute rejection?
What is a common trigger for hyperacute rejection?
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Which immune response mechanism is primarily involved in chronic rejection?
Which immune response mechanism is primarily involved in chronic rejection?
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What kind of graft is least likely to elicit an immune response?
What kind of graft is least likely to elicit an immune response?
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What is the major immune cell type involved in acute cellular rejection?
What is the major immune cell type involved in acute cellular rejection?
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Which type of transplant involves a high likelihood of immune response due to species difference?
Which type of transplant involves a high likelihood of immune response due to species difference?
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What is the mechanism of tissue injury during acute rejection?
What is the mechanism of tissue injury during acute rejection?
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What effect do corticosteroids have in immunosuppressive therapy?
What effect do corticosteroids have in immunosuppressive therapy?
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Study Notes
Transplantation
- Transplanting cells, tissues, or organs (graft) from one individual (donor) to another (recipient)
- Individuals have different molecular structures in their cells and tissues due to genetic variation
- Grafts may stimulate an immune response (rejection) due to antigenic differences
- Adaptive immune system mediates graft rejection
Terminology
- Autologous graft (autograft) - Transplant from one individual to the same individual
- Syngeneic graft (isograft) - Transplant between two genetically identical individuals
- Allogeneic graft (allograft) - Transplant between two genetically different individuals of the same species
- Xenogeneic graft (xenograft) - Transplant between individuals of different species
- Immune response varies with the type of graft (autograft isograft < allograft < xenograft)
Transplantation
- Most transplants in the present day are allografts
- Alloantigens are foreign antigens on the surface of transplanted cells/tissues (mostly protein antigens encoded by polymorphic genes)
-
Alloreactive lymphocytes and antibodies react against alloantigens
- Alloreactive T cells (also called alloantigen-specific)
- Alloreactive B cells
- Alloreactive immunoglobulins
- The presence of alloreactive T and B cells poses a major limitation to transplantations
Histocompatibility Antigens
- Major histocompatibility antigens (MHC molecules) are responsible for strong immune responses, mainly due to mismatches in MHC alleles
- Minor histocompatibility antigens are various molecules that induce weaker or slower rejection reactions
Histocompatibility: MHC
- Histocompatibility type refers to the set of MHC glycoproteins in an individual
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Haplotype refers to the set of MHC alleles on each chromosome; each individual has two haplotypes
- Identical twins are haploidentical (100% HLA-matched)
- MHC molecules are crucial for T cell activation, leading to strong, rapid rejection events
- Focus on MHC molecules as alloantigens
- Inheritance pattern of the six most important MHC alleles for organ transplantation (HLA-A, HLA-B, & HLA-DR)
- 25% chance of two siblings sharing one haplotype (haploidentical)
- Parents are only 50% HLA-matched with their children, assuming parents have different haplotypes
Recognition of Allogeneic MHC
- Recipient T cells recognize allogeneic MHC molecules of the graft in two ways:
-
Direct recognition: Donor dendritic cells (DCs) present various peptides in MHCs to activate recipient T cells
- Cytotoxic T lymphocytes (CTL) kill graft cells
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Indirect recognition: Recipient DCs phagocytose graft cells and present peptides derived from donor MHC molecules in Class II MHC, activating helper T cells
- Antibody-mediated inflammation and injury
-
Direct recognition: Donor dendritic cells (DCs) present various peptides in MHCs to activate recipient T cells
Direct Recognition of Allogeneic MHC
- An allogeneic MHC molecule (on donor cells) with a self peptide can mimic the shape of a self MHC molecule (on recipient cells) containing a foreign peptide
- Allografts can elicit strong immune responses
Host vs Graft Rejection
-
Hyperacute rejection occurs within minutes to hours after blood vessels are joined (anastomosed) to the graft.
- Pre-existing antibodies in the recipient attack alloantigens (ABO blood group antigens or MHC molecules) on graft endothelial cells - Antibodies arise from previous exposure to alloantigens (e.g., blood transfusions, previous transplantations)
- Complement activation attracts neutrophils (PMNs)
- PMNs release lytic enzymes, damaging the endothelium and activating clotting mechanisms:
- Thrombi formation
- No blood flow to graft
- Hyperacute rejections are prevented by ABO blood typing and crossmatching tests
Host vs Graft Rejection
-
Acute rejection can occur as early as 7-10 days after transplantation, but typically occurs within the first 2 months
- T cells play a critical role (acute cellular rejection)
- T cells respond to alloantigens on endothelial and parenchymal cells:
- CD4 T cell-mediated inflammation
- CD8 T cell lysis of graft cells
- T cells respond to alloantigens on endothelial and parenchymal cells:
-
Acute antibody-mediated rejection can also occur due to alloantibodies:
- Alloantibodies bind to alloantigens on vascular endothelial cells:
- Complement activation
- Endothelial cell injury and intravascular thrombosis
- Alloantibodies bind to alloantigens on vascular endothelial cells:
- T cells play a critical role (acute cellular rejection)
Preventing Acute Rejection
- HLA typing (tissue typing) and crossmatching tests are performed to minimize acute rejection events:
- Fewer HLA mismatches increase the chance of graft survival
- Patients receive life-long immunosuppressive therapy
Host vs Graft Rejection
-
Chronic rejection occurs over months to years after transplantation and involves loss of graft function:
- Increased fibrosis due to chronic inflammation:
- TH1 cell cytokines stimulate matrix synthesis
- Smooth muscle cell proliferation in the vascular intima:
- Activated T cells in the graft induce macrophages to secrete cytokines and smooth muscle growth factors
- Increased fibrosis due to chronic inflammation:
Graft vs Host Disease (GvHD)
- T cells from the graft become activated against recipient tissues
- Complication of hematopoietic stem cell (HSC) transplants, though may occur with other tissues containing numerous T cells
- Donor T cells recognize alloantigens on recipient cells and attack host tissues
- GvHD can be acute or chronic: often impacts the skin, liver, and GI tract
Immunosuppressive Therapy
- Immunosuppressive drugs are classified as induction therapies and maintenance therapies:
- Induction therapies: Intense, early post-operative immune suppression
- Maintenance therapies: Long-term therapies to prevent rejection events
General Immunosuppressive Therapy
- Corticosteroids: Inhibit inflammation, reduce IL-1 and IL-2 production, and suppress MHC expression on antigen-presenting cells (APCs)
-
Mitotic inhibitors: Inhibit the biosynthesis of nucleic acids:
- Azathioprine (Aza)
- Mycophenolate mofetil (MMF)
T Cell Specific Immunosuppressive Therapy
- Some specific T cell immunosuppressive agents:
- Tacrolimus: Inhibits IL-2 synthesis
- Basiliximab: Anti-CD25 antibody blocks IL-2 binding to IL-2 receptor
- Sirolimus: Inhibits IL-2 receptor signaling (mTOR inhibitor)
Summary
-
Graft Type:
- Autograft: Self to self (skin grafts) - No immune response
- Isograft: Between identical twins (any tissues) - Minimal immune response
- Allograft: Human to human (not identical) (any tissues) - Immune response
- Xenograft: Between species (baboon to human heart transplant) - Strong immune response
-
MHC alleles trigger strong graft rejection, while minor histocompatibility antigens also contribute
- Direct presentation: Donor APCs present donor antigens to recipient T cells
- Indirect presentation: Recipient APCs present donor antigen (peptides of donor MHC) to recipient T cells
Summary
-
Rejection:
- Hyperacute: Pre-existing antibodies activate complement and antibody-dependent cell-mediated cytotoxicity (ADCC) - Minutes to hours after transplantation. Prevent with ABO blood typing and pre-existing antibody screening. No therapy.
- Acute: B/T cell activation - Earliest: 7-10 days, generally within 2-3 months. Prevent with ABO blood typing, MHC matching, general and specific immunotherapy. Induction and maintenance phases of therapy.
- Chronic: Th1-mediated inflammation, growth factors - Months to years following transplantation. MHC matching and partial T cell depletion can help. Therapy similar to acute and chronic.
Summary: Immunosuppressive Therapies
- See slides 19-21 for more details.
- Focus on the ones covered in class
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Description
This quiz covers the fundamental concepts of transplantation, including the types of grafts and immune responses involved in graft rejection. It explores autologous, syngeneic, allogeneic, and xenogeneic grafts, along with the significance of alloantigens. Test your knowledge on the mechanisms that influence the success of transplants.
