Major Histocompatability Complex And Rransplantation Immunology Flashcards
Major Histocompatibility Complex (MHC)
Surface proteins on cells that are important for the distinction of self or foreign molecules
Primary immune cell for infections
T-cells
The NK cells will target those lacking MHC
Which cells have MHC on they’re surfaces?
Nucleated cells and antigen presenting cells
They present peptides bound to MHC
What is the major role of MHC?
To bind small antigenic peptides on the cell surfaces where they can be recognized by T cell receptors
MHC genes
Encode MHC proteins (leukocyte antigens) expressed on cell surfaces
Ex: Human LA, Bovine LA, Swine LA
Autograft
Transplant between organs within the same individual
Allograft
Transplant between individuals of the same species
Xenograft
Transplant between individuals of diff species
Isograft/syngraft
Transplant between clones or inbred strains
Ex: Between identical twins
Relationship between MHC and transplants
Host recognizes diff foreign MHC antigens on grafted tissues and ,mounts an immune response —> rejection
Graft tissue process for graft rejection
- Recipient blood flows through graft
- Entering T cells encounter MHC 1, 2 and peptides on graft (leading to activation)
- Antigen presenting cells encounter grafted cells, damaged cells, cytokines, etc (activation)
- If blood group different Abs encounter BVs and Ags (antigen-antibody reacton)
Host/ recipient process for graft rejection
- Grafts APCs migrate to draining LNs
- APCs encounter T cells reactive against graft
- APCs attacked
Blood types must match to prevent ______________
Hyperacute rejection
Hyperacute rejection
Happens in minutes to 48 hours
Happens when preexisting Abs react
Immediate thrombosis and vascular destruction
Accelerated rejection
Within a week
Cell mediated recognition of foreign MHC graft cells
Acute Rejection
Within weeks
Most celll-mediated
Chronic rejection
Within months
Both Abs and cells involved
How do you prevent allograpft rejection?
Match for compatibility
Dogs and cats reject renal allografts within 6-30 days if not treated with drugs to suppress rejection
What drugs prevent allograft rejection?
Azathioprine (prevent cell replication, DNA/RNA synthesis)
Cyclosporine (lymphocyte signaling and cytokine repsonse)
Prednisolone
Immunosuppression makes patients susceptible to infection like ___________
opportunistic pathogens
When are xenografts possible?
In biomedical research on immuno-deficient mice that lack T or B cells
Genetically engineered pigs
Pig and bovine heart valves
Graft-Versus-Host Disease (GVHD)
When the recipient patient has no immune reaction to destroy the grafted immune-potent cells and grafted cells destroy the host
When does GVHD occur?
When bone barrow replacement is given, grafted cells proliferate and occupy the host
How is sperm not rejected?
Seminal plasma is immunosuppressive
Prostatic fluid inhibits complement activation
Why SHOULD the fetus be rejected?
Fetus half non-self
Paternal MHC molecules are expressed and placenta lodges deep into uterus wall
Uterus perse not a privileged site
Mother-fetus may have different blood group Ags
Why is the fetus not rejected?
Lack of polymorphic MHC molecule expression
Non-polymeric MHCs silence NK cells
T-reg cells abundant
Abundant immunosuppressive molecules prevent lymphocyte activation
Some maternal abs coat and protect placenta
Close balance maintained
Privileged sites
Organs/ tissues where survival of foreign grafts may be prolonged or where immune responses are inhibited, suppressed or subverted
Which tissues/ organs are privileged sites?
Cornea/eye, testis, brain, pregnant uterus
How are there privileged sites?
Deficient lymphatic drainage
Physical barriers
Specialized epithelial or endothelial cell barriers
Locally operating immunosuppressive factors
Cross-matching
Step to check if there are pre-existing Abs in the donor product or in recipient serum/ plasma
Which species don’t require a cross match the FIRST time?
Dogs/ horses because they don’t naturally pre-exist (don’t do it the second time)
Major crossmatching
Test if the recipient already has Abs to the RBCs that will be transfused
Check RBC from donor against serum from recipient
Minor crossmatching
Test if the donor blood product/ serum has Abs against recipient RBCs
Check serum from donor against RBC from recipient