L11: Transplantation Immunology

Question 1

Types of transplantation grafts

Answer 1

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

Question 2

Orthotic vs heterotopic transplant

Answer 2

• Orthotic = graft placed in its normal anatomic location

- Heterotopic = graft placed in anatomically different site

Question 3

What is meant by immunologically privileged site? What mechanisms confer privilege?

Answer 3

• 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

Question 4

What is sympathetic opthalmia?

Answer 4

• Following damaged to one eye by trauma, an autoimmune response to eye proteins develop and threatens undamaged eye

Question 5

True / False. Grafts derived from children will be rejected by either parent

Answer 5

• True

Question 6

What is the genetic basis of transplant rejection?

Answer 6

• Class I and II MHC proteins perceived as foreign d/t polymorphic expression and education of thymocytes (positive selection)

Question 7

Types of graft rejections following transplant. Note timeframe and mechanism that mediates this.

Answer 7

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

Question 8

Of the 3 types of graft rejections following transplantation, which can be treated?

Answer 8

• Acute rejection

Question 9

T cells require antigen and self MHC proteins in order to become activated. How to allografts activate T cells?

Answer 9

• 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.

Question 10

What is alloreactivity? Describe activation of T cells using this mechanism

Answer 10

• 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

Question 11

Strategies to prevent transplant rejection

Answer 11

1.) Select most compatible graft (class I and II MHC similarity)

2. ) Immunosuppresion:
   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)
   d. ) anti-IL-2R
   e. ) anti-TCR
   f. ) azathioprine, mycophenolate, rapamycin

3.) depletion of passenger leukocytes from graft can eliminate or delay graft rejection

Question 12

Function of corticosteroids in transplant rejection

Answer 12

• lyse immature thymocytes, block release of cytokines from macrophages and inhibit leukocyte migration

Question 13

Function of cyclosporine in transplant rejection

Answer 13

• 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

Question 14

Function of anti-lymphocyte globulin in transplant rejection

Answer 14

• anti-lymphocyte globulin (from horse serum): kills wanted and unwanted lymphocytes, but can reverse acute graft rejection (side effect = serum sickness)

Question 15

What is GVDH? Types? Treatment?

Answer 15

• 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

Question 16

True / False. Maternal-fetal interaction mimics alloreactivity and graft rejection (fetus is naturally occurring allograft).

Answer 16

• True

Question 17

What mechanisms prevent immune response against fetal antigens?

Answer 17

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

Question 18

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

1. asbestos.
2. certain viruses.
3. second-hand smoke.
4. UV or ionizing radiation

Answer 18

• 2. Certain viruses

Question 19

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

Answer 19

• 2. Depressed T cell immunity

Question 20

The _______ of an individual has the best chance of being a good match for a transplant.

1. child
2. father
3. mother
4. sibling

Answer 20

• 4. Sibling

Question 21

How can antibodies be stimulated that could participate in hyperacute rejection?

Answer 21

• Anti-ABO antibodies
• Blood transfusion
• Prior organ transplantation
• Pregnancy