IMMUNO: Transplantation Flashcards
What are the first and second most transplanted organs?
- 1st most common transplanted organs = KIDNEYS (average ½ life of a kidney is 12 years)
- 2nd most common = LIVER
What proportion of the world population has kidney disease?
5%, 7% or 11%?
11%
5years on what are the chances of survival of a patient on CKD starting dialysis?
35, 55 or 85%?
35% chance of 5 year survival
What are the phases of T cell immune response to transplanted grafts?
- Phase 1: recognition of foreign antigens
- Phase 2: activation of antigen-specific lymphocytes
- Phase 3: effector phase of graft rejection
What are the most relevant protein variations in clinical transplantation? Which one is the most important?
- ABO blood group
- HLA (on chromosome 6 by MHC; n.b. HLA can mean the proteins OR the genes) - MOST IMPORTANT
- Other minor histocompatibility genes
What are the two major forms/components of rejection?
- T cell-mediated rejection
- Antibody-mediated rejection
What is the difference between HLA class I and II?
MHC (chromosome 6)
-
HLA Class I (A, B and C) – expressed on ALL cells
- Thought to be the most immunogenic
- HLA Class II (DR, DQ, DP) – expressed on APCs (also be upregulated on other cells under stress)
Features:
- polymorphic with hundreds of alleles for each locus
- high degree of variability lining the peptide-binding groove = allows us to present a wide variety of antigens i
- number of mismatches is a major determinant of the risk of rejection
![](https://s3.amazonaws.com/brainscape-prod/system/cm/385/833/645/a_image_thumb.png?1637147564)
Which HLA are most important to match in transplantation?
DR>B>A
What happens in phase II of T cell mediated immune activation to transplantation?
- To activated alloreactive T cells, T cellls require:
- Presentation of foreign HLA antigens in MHC by APCs (both DONOR and HOST APC cells are involved)
- Co-stimulatory signals
- This occurs in lymph nodes and causes the effector phase of rejection –> inflammation caused leads to graft dysfunction (i.e. raised Cr).
- Biopsy can be done to diagnose.
What does 1,0,0 mean in terms of HLA matching?
1 mistmatch at HLA-A
0 mismatches at HLA-B
2 mismatches in HLA-DR
Maximum is 2 mismatches in each = 6
How are mismatches counted? Try below.
![](https://s3.amazonaws.com/brainscape-prod/system/cm/385/833/649/q_image_thumb.png?1637147934)
This would be written as 1,1,0.
![](https://s3.amazonaws.com/brainscape-prod/system/cm/385/833/649/a_image_thumb.png?1637147915)
What happens in the phase 2 of T cell mediated immune reaction to a transplant?
![](https://s3.amazonaws.com/brainscape-prod/system/cm/385/833/657/q_image_thumb.png?1637148272)
Action of activated T cells e.g.
- Proliferation
- Production of cytokines (IL2 is important)
- Providing help to CD8+ cells
- Providing help for antibody production
- Recruitment of phagocytic cells
What technique is used for HLA tissue typing?
PCR
Where does phase 2 vs phase 3 of immune T cell-mediated reaction to transplantation happen?
Phase 2 - lymph nodes
Phase 3 - within graft
How do cytotoxic T cells and macrophages affect the transplanted organ?
Cytotoxic T cells:
- Granzyme B (toxin)
- Perforin (punch holes)
- Fas-ligand (apoptosis)
Macrophages:
- Phagocytosis
- Proteolytic enzymes
- Cytokine release
- O2 and N2 radicals
What is shown?
![](https://s3.amazonaws.com/brainscape-prod/system/cm/385/833/661/q_image_thumb.png?1637148592)
T cell mediated tubulitis.
- Lymphocytic interstitial infiltration
- Ruptured tubular basement membrane
- Tubulitis (inflammatory cells within the tubular epithelium)
- Macrophages, recruited by the T cells
NB: Immunohistotyping can be used to mark which type of cells e.g. T cells, are present.
![](https://s3.amazonaws.com/brainscape-prod/system/cm/385/833/661/a_image_thumb.png?1637148573)