Advanced Immunology 2 Flashcards
How many MHC HLA classes are there?
3
Which MHC HLA classes present foreign peptides?
1 and 2
What is MHC II HLA split into?
DP,DQ and DR
What is MHC I HLA split into?
A, B and C
What is inheritance of MHC alleles like?
Co-dominant, from surface of cells of a mother and father.
Autograft
Transplant from one part of the body to another
Isograft
Between genetically identical individuals (twins)
Allograft
Between different members of the same species
Xenograft
Between different members of different species
What do Allografts require?
Immunosuppressive therapy, even if well matched MHC I and II haplotype
What are concerns regarding Pig xenografts?
Transmission of retrovirus
What is first set rejection?
Individual has never seen those antigens before, never had a graft before
What is second set rejection?
When an individual has already seen these antigens before.
Process of Autograft acceptance?
- Autograft transplanted
Day 3-4 Blood vessels need to revascularise
Day 7-10 Healing, neutrophils examine
Day13-14 - resolution and acceptance
Process of first set rejection?
- Revascularisation
- Immune cells investigate skin, cellular infiltration.
- Leads to thrombosis and necrosis due to foreign antigens
Process of second set rejection?
- Graft occurs
- Cells infiltrate prior to revascularisation of the graph
- Swift thrombosis and necrosis occurs.
What is the difference in immune responses to first and second set rejection?
- Memory T cells present in Second set rejection
What is the importance of minor HLA antigens?
Can cause slow graft rejection, even in identical strains.
What are minor HLA antigens?
Short self peptides from the donor, which bind to the groove of donor Class I MHC molecules
How are alloantigens in grafted organs recognised?
Direct and indirect recognition
What is the process of direct recognition of alloantigens?
- Passenger DCs in the graft enter LN
- Present donor antigen to alloreactive T cells = allorecognition
- Effector T and B cells are activated, leave the LN and return to the graft
- Destruction of the Graft
What is the process of indirect recognition of alloantigens?
- Recipient DCs enter graft tissue
- They process foreign donor MHC and present it on MHC II, which migrates to the LN.
- Recipient APC provides signal 1 and costimulatory signal 2.
- Cytokines provide signal 3 to naive T cells.
5 Thelper cells become fully activated and now activate B and T cells. - Graft is destroyed
What is the ability of T cells being able to respond to foreign antigens on foreign MHC called?
Cross-reactivity
What are the two phases of acute graft rejection?
Induction and Effector
Which cells are involved in acute graft rejection?
B cells, CD8+, NK cells and polymorph leucocytes.
How are NK cells involved in acute graft rejection?
IFN-y produced by activated NK cells up regulates MHC I expression and induces MHC II expression.
Making recognition via T cells easier.
How are T helper cells stimulated in chronic rejection?
By DCs to release IL-2
What are required for CD8+ T cell activation?
IL-2 and IFN-y
What are involved in B cell activation to cause antibody release and ADCC?
IL-2,IL4 and IL5
What do Th cells produce to activate macrophages in chronic graft rejection?
Lymphotoxin and IFN-y cytokines
What do NK cells produce to upregulate MHC II expression on graft cells?
IFN-y
How are HLA types determined through the microcytotoxicity method?
- WBCs from potential donors and the recipient are added to separate wells.
- Antibodies for each HLA will bind to lymphocytes if they are present.
- Addition of complement that binds to the antibody will cause cells to become leaky.
- Dye addition allows uptake and cells with the HLA will become coloured under a microscope.
Which MHC has the biggest impact on graft survival?
MHC II, a single difference has the same effect as 3/4 MHC I mismatches.
What is used to detect anti-HLA antibodies in graft recipients?
Luminex Cross matching assay.
- Microbeads have fluorochromes of different intensities which detect pre-existing antibodies.
