Transplantation -Thrush

Question 1

What are the 4 types of tissue grafts?

Answer 1

1. Autograft – self tissue transferred from one site to another in the same individual (burns or blood vessels to replace blocked coronary arteries)
2. Isograft (syngeneic) – tissue transferred from genetically identical individuals (monozygotic twins)
3. Allograft – tissue transferred between genetically distinct individuals of the same species–> genetic differences can result in rejection
4. Xenograft – tissue transferred between different species–> only used temporarily

Question 2

What is first set rejection?

What is second set rejection?

Answer 2

1. First set rejection –due to a primary immune response. takes 1-2 weeks for immunological recognition and rejection
2. Second set rejection – memory response. if put same tissue on individual again, then see a quicker rejection (5-6 days)

Question 3

What plays a central role in graft rejection?

Answer 3

T cells. Both CD4+ and CD8+ play a role in graft rejection

without CD8 but with CD4, will see graft rejection in the same amount of time as the control setting.

However, with no CD4, it will take nearly double the time to get graft rejection

without CD4 AND CD8, it will take much much longer to get graft rejection

Question 4

What are the 2 phases of graft rejection?

Answer 4

1. sensitization phase: alloreactive activation of CD4 and CD8 cells
   - DCs of graft can serve as APC
   - host (recipient) DCs can move into tissue, endocytose donor antigens and be APCs presenting both major and minor antigens
2. effector stage: recruit and destruction of graft
   DTH - inflammatory
   CTL-mediated cytotoxicity
   alloantigen recognition on graft cells

cytokine production:
-IL-2 – T cell proliferation and CTL activation
-IFNgamam - DTH response, recruitment of Mf
increased MHC I and II expression (= more APC activity)
-TNF-beta – directly cytotoxic to graft cells
-ADCC – although Abs are usually not as important as T cells
-CD4+ ca als have cytotoxic effects

Question 5

What are the 3 major categories of rejection? What causes each and when would they occur?

Answer 5

1. acute rejection: 2-4 weeks. usually due to differences in the classical MHC genes
2. hyperacute rejection: within a few days usually due to pre-existing antibodies (ex: repeated blood transfusions or a previous graft)
3. chronic rejection: months to years. typically from differences in the minor histocompatibility antigens or non-MHC genes

Question 6

What are important determinants of graft survival?

Answer 6

1. Major MHC loci plays the biggest role
   class II MHC&raquo_space; class I MHC matches
   -don’t need as many matches in certain organs (liver and heart)
2. blood type differences
3. minor histocompatability loci

Question 7

What is graft versus host disease?

What can help prevent GvHD?

Answer 7

pathology related to the graft rejecting the host. Commonly seen when transplanting immune cells from the donor to the recipient. the recipient can be seen as foreign and react to it. ex: bone marrow transplant

partially removing donor T cells can help prevent GvHD and increase chances of survival

Question 8

What are some types of drugs used for immunosuppression?

Answer 8

1. mitotic inhibitors–> prevent T and B cell proliferation
2. corticosteroids–> anti-inflammatory
3. specific immunosuppression
   -fungal metabolites–> can prevent T cell activation
   -antibodies–> treat donor and/or graft tissue
   (anti-CD3 prevents complement activation, anti-CD25 suppresses activated T cells, anti-CD20 reduces B cell function and Ab production, CTLA4-Ig blocks co-stimulation/induces suppression)