20. Transplantation Immunology Flashcards
What is an isologous (isograft) transplant?
Between genetically identical individuals (twins)
What is a homologous (allograft)?
Shit from other individuals same species
What is heterologous (xenograft)
Different species
What are the two aspects of compatibility?
Physical = size (heart from child to adult etc)
Genetic
What are the laws of transplantation immunology?
A - A = graft accepted
A - B = Graft rejected
B - AB = graft accepted
AB - B = Grat rejected
What is allograft rejection caused by?
Adaptive immune response
What is the process of the immune response?
1) Latent period
2) Memory
3) Specificity
4) Passive transfer by lymphocytes
5) Production of antibodies
What are histocompatibility antigens?
Antigens that give rise to the immune response results in rejection of a tissue allograft
What is MHC?
Major histocompatability complex
What is the MHC called in humans?
HLA - Human leukocyte antigen
What are Minor histocompatability Antigens?
mH - non MHC encoded
- Mostly single nucelotide polymorphisms
ABO
Sex chromosomes
What is MHC called in mice?
H-2 complex
Where is HLA genes located?
Short arm of chromosome 6
4 mill base pairs in length
What do HLA genes code for?
30% of 150 expressed genes Involved in immun response - Complement - Antigen processing - Cytokines
What are most famous members of HLA classes?
Class 1- HLA-A, B & C
- All nucleated cells
- Density varies from tissue to tissue
Class 2 - HLLA - DP, DQ & DR
- Antigen presenting cells
- B lymphocytes
- Activated T lymphocytes
Do HLA have many alleles at each locus?
Yes
What are the two ways in which allogenic HLA molecules are presented for T cell recognition?
Direct
- Recognition of intact foreign HLA molecules, presented by donor APC lelz
- Acute
- Can be controlled by immunosupression
Indirect
- Recognition of processed donor HLA molecules presented by recipient APC
- Chronic rejection
- No immunosupression
How the feck can a recipient T cell recognise a donor APC MHC?
Similar structure of HLA molecules
Can direct recognition be supressed?
Yes with immunosuppresion
Can direct recognition T cells invoke memory cells immediately if donor protein/HLA looks similar?
Yes
How does indirect alloantigen recognition work?
Allo-HLA molecule phagocytosed
Migrate to lymph
Presented on class 2
NOTE: HLA molecules are very different in structure
Why are allo-responses so vigourous?
Often anti-virus secondary response that cross=react with allo-HLA molecule
- Mistakes it
- Already has memory cells ready to pwn
(Direct)
What is hyperacute rejection?
Minutes, antibodies IgG
What is accelerated?
2-5 days, CMI + Ab
What is acute rejection?
7 - 21 days, CMI + Ab
What is chronic rejection?
> 3 months CMI + Ab
What happens in hyperacute rejection?
Binding to endothelium activates complement and clotting cascades
Graft fills with deoxygenated blood
Blood clots
How does hyperacute rejection arise?
Antibodies as results of previous alloantigens
- Blood transfusions
- Previous transplantation
- Multiple pregnancies
How does accelerated rejection occur?
Low titres of alloractive antibodies alrady present, (similar to hyperacute), thus rejection develops slowly
Involves cellular immune response
How is acute rejection mediated?
T lymphocytes
Direct pathway
Humoral
Antibodies
Blood vessel walls
Factors = clotting of graft etc
What is chronic rejection?
Allo-reactive T cells secrete IFNy and TNFa
Activate endothelial cells, SM and macros
Secretes growth factors + chemos
Acitvate smooth muscle cells
Blood flow to graft blocked
Parenchyma replaced by fibrous tissue
What are pathological characteristics of chronic rejection?
Lung = thickened small airways Liver = fibrotic and non functioal bile ducts
what is immunosupression?
Dampening down immunesystem
Avoid or delay rejection
How do immunosupression drugs work./
INhibit/Kill T cells - calcineurin inhibs
Metabolic toxins that kill proliferating T cells - MMF
Antibodies that react with T cell surface antigens OKT3
Drugs that block co-stimulatory pathways (CTLA-4)
Anti-inflammatory drugs
What are some complications of immunosupression?
Vulnerable to infections
Malignancies (due ot virus like CMV) - counter with Ganciclovir
Development of lymphoproliferative disorders - B cell derived non-hodgkins lymphomas - BEV
How can you reduce allograft immunogenicity?
Minimize alloantigenic differences
ABO matching
HLA compatability
Screen for presence of pre-formed antibodies - Cross matching
What HLA has strongest effect
HLA-DR
