Intro To MHC & Transplantation Immunology Flashcards
MHC function
Help immune system differentiate between self and foreign particles
MHC 1 vs MHC 2
- 1: CD8
- 2: CD4
Leukocyte antigen types
- HLA: human
- BoLA: bovine
- SLA: swine
Heterozygous animals
- 2 MHC alleles @ each locus
- express 6 diff. antigen presenting molecules
Homozygous animals
- one MHC
- one allele coded for at each locus
Iso/syngrafts
Transplant between clones/twins
Reproductive allografts
Sperm, pregnancy
Primary immune cells that distinguish self from foreign
T cells
Steeper survival curve means
Lower survival & rejection
Whats involved in graft rejection
- T cells
- blood vessels (1st attacked)
- antigen presenting cells
- MHCs
Host/recipient graft rejection
- grafted APCs-> lymph nodes
- APCs (MHCII) encounter T cells reactive against graft
- APCs attacked
Grafted tissue rejection events
- recipient blood flows thru graft
- entering t cells encounter MHC I & II & peptides
- APCs encounter grafted cells, etc
- if blood group is different, antigen antibody rxn occurs
Hyperacute rejection
- minutes -> 48 hrs
- preexisting antibodies react
- immediate thrombosis & vascular destruction
accelerated rejection
- within a wk
- cell mediated recognition of foreign MHC on graft cells
Acute rejection
- weeks
- cell mediated (lymphocyosis)
Chronic rejection
- months
- antibodies and cells (fibrosis)
Prevention of allograft rejection
- match for compatibility
- dogs & cats reject renal allografts in 6-30 days if not given drugs
- azathioprine, cyclosporine, prednisolone, etc.
Azathioprine
- interferes w/ DNA/RNA synthesis
Cyclosporine
- interfere w/ lymphocyte signaling and cytokine response
Prednisolone
- wide range
- not very potent
- given w/ other drugs
Xenograft research usually conducted on
Immunodeficient mice that lack t and/or b cells
Issues w/ pig to human xenografts
- pre-existing pig antibodies
- both species have different complement regulation
- delayed attack by generated antibodies
- disease transmission
Pig & bovine heart valves
- transplanted since 60s
- Rx w/ gluteraldehyde to preserve and reduce immunogenicity
Graft vs host disease (GVHD)
- Recipient doesn’t have immune rxn to destroy grafted immune-potent cells
- grafted cells destroy host
- bone marrow replacement therapy is a cause
Why is sperm not rejected/ considered foreign
- seminal plasma is immunosuppressive & makes sperm non-immunogenic
- prostatic fluid inhibits complement activation
Why isnt fetus rejected
- lack of polymorphic MHC expression on trophoblast
- non-polymorphic MHCs silence NK cells
- Treg cells abundant in placenta
- immunosuppressant molecules prevent lymphocyte activation
- maternal antibodies against fetal MHCs can coat/protect placenta
-close balance maintained until end of gestation-> rejection rxns
Rejection rxns
Invasion of uterus by large # of immune cells
Immune privileged sites & transplantation
Organs or tissues where survival of foreign grafts can be prolonged or immune responses suppressed/inhibited/subverted
Cross matching
Checks if pre-existing antibodies in donor product or recipient serum/plasma are present
Dogs and horses ____ have naturally pre-existing antibodies, so first time transfusions can be run _______ cross match
Don’t; without
(Needs a cross match for 2nd transfusion)
Major crossmatch testing
Check RBC from donor against serum from recipient
Minor crossmatch testing
Check serum from donor against RBC from recipient
