Flashcards in L11: Transplantation Immunology Deck (21):
Types of transplantation grafts
1.) Autologous graft – individual to same individual
2.) Syngeneic graft – bw two genetically identical individuals (identical twins)
3.) Allogeneic graft – bw two genetically dissimilar individuals (from same species
4.) Xenogeneic graft – bw members of two different species
Orthotic vs heterotopic transplant
- Orthotic = graft placed in its normal anatomic location
- Heterotopic = graft placed in anatomically different site
What is meant by immunologically privileged site? What mechanisms confer privilege?
- Locations where allogenic transplants can be placed without risk of rejection – ant chamber of eye, cornea, testes, brain
1.) ECF bathing tissue doesn’t leave through conventional lymph
2.) TGF-beta (inhibitory) produced
3.) Fas-ligand reacts with Fas on lymphocytes to induce apoptosis
What is sympathetic opthalmia?
- Following damaged to one eye by trauma, an autoimmune response to eye proteins develop and threatens undamaged eye
True / False. Grafts derived from children will be rejected by either parent
What is the genetic basis of transplant rejection?
- Class I and II MHC proteins perceived as foreign d/t polymorphic expression and education of thymocytes (positive selection)
Types of graft rejections following transplant. Note timeframe and mechanism that mediates this.
1.) Hyperacute rejection: minutes (incl on OR table), mediated by pre-existing antibodies (eg. Anti-ABO blood group)
2.) Acute rejection: within 1 month, two types: 1.) acute humoral rejection (ab and complement-mediate lysis of graft tissue leading to necrosis of blood vessel walls) and 2.) acute cellular rejection (cell-mediated lysis of graft tissue by CTLs, NK cells and macrophages)
3.) Chronic rejection: months to years after transplant, may involve ab-mediated injury or type IV hypersensitivity, characterized by fibrosis and deposition of collagen resulting in vascular occlusion
Of the 3 types of graft rejections following transplantation, which can be treated?
- Acute rejection
T cells require antigen and self MHC proteins in order to become activated. How to allografts activate T cells?
- One option could be that recipient APCs present foreign peptides in conjunction with self class II MHC to activate T-helper cells.
- Answer = alloreactivity = foreign MHC proteins are recognized d/t polymorphic AAs on MHC that mimich conformation of both self MHC and foreign peptide.
What is alloreactivity? Describe activation of T cells using this mechanism
- Recognition of foreign MHC proteins by TCR d/t polymorphic AAs on MHC mimic conformation of self MHC loaded with foreign peptide
1.) Donor and recipient DCs present alloantigens, which stimulates CD4+ T cells to become activated
2.) CD4+ cells provide IFN-gamma and IL-2 to alloreactive CD8+ T cells to produce CTLs that lyse graft cells, alloreactive B cells produce anti-graft antibodies
Strategies to prevent transplant rejection
1.) Select most compatible graft (class I and II MHC similarity)
a.) corticosteroids: lyse immature thymocytes, block release of cytokines from macrophages and inhibit leukocyte migration
b.) cyclosporine: inhibits IL-2 and IFN-gamma expression preventing activation of cell-mediated immunity
c.) anti-lymphocyte globulin (from horse serum): kills wanted and unwanted lymphocytes, but can reverse acute graft rejection (side effect = serum sickness)
f.) azathioprine, mycophenolate, rapamycin
3.) depletion of passenger leukocytes from graft can eliminate or delay graft rejection
Function of corticosteroids in transplant rejection
- lyse immature thymocytes, block release of cytokines from macrophages and inhibit leukocyte migration
Function of cyclosporine in transplant rejection
- inhibits IL-2 and IFN-gamma expression preventing activation of cell-mediated immunity
- allows for maintenance of memory response, just knocks off primary immune response
Function of anti-lymphocyte globulin in transplant rejection
- anti-lymphocyte globulin (from horse serum): kills wanted and unwanted lymphocytes, but can reverse acute graft rejection (side effect = serum sickness)
What is GVDH? Types? Treatment?
- Graft-versus-host disease
- Disease following bone marrow donation
- 1.) acute = epithelial cell necrosis of skin, liver and GI – can be fatal if severe
- 2.) chronic = fibrosis in organs causing dysfunction – fatal if severely affects critical organs
- Treatment: anti-CD3 mab
True / False. Maternal-fetal interaction mimics alloreactivity and graft rejection (fetus is naturally occurring allograft).
What mechanisms prevent immune response against fetal antigens?
1.) trophoblasts don’t express paternal MHC proteins
2.) HLA-G keeps NK cells from becoming activated by trophoblast cells that express no MHC proteins
3.) Trophoblasts secrete inhibitory cytokines (eg. TGF-beta)
4.) Tryptophan broken down at MF interface, meaning T lymphocytes react poorly to antigen
Studies have shown that immunosuppressed transplant patients have a higher risk of malignancy. However, this patient population doesn’t develop all type of cancers. The types they are more susceptible to developing are those tumors induced by exposure to
4. UV or ionizing radiation
- 2. Certain viruses
Why are immunosuppressed transplant patients more susceptible to developing virus-induced cancers?
1.Deficient neutrophil function
2.Depressed T cell immunity
3.Inhibited macrophage phagocytosis
4.Poor dendritic cell activity
- 2. Depressed T cell immunity
The _______ of an individual has the best chance of being a good match for a transplant.
- 4. Sibling