Tumor immunology Flashcards
H antigens
Histocompatibility determinants
Major = MHC = HLA (humans)
- acts as prevalent antigen itself, not just presenter
Minor - many more (ex H-Y)
- need immunosuppression even if perfect HLA match
Types of grafts
Autograft = same person (vessels, skin) Syngeneic = identical twin or inbred animal (perfect match) Allograft = same species - works with close alloantigen match and immunosuppression Xenograft = different species, always rejected
Transplant immune responses
Direct recognition - T cell -> foreign MHC (peptide doesn’t matter)
Indirect - APC ingests and presents MHC from surface of graft cell (foreign MHC = peptide)
Requires lymph flow - cornea, brain protected
CD4»_space; CD8 -> MHC Class II is most important to match
Hyperacute rejection
Preexisting circulating antibodies -> minutes/hours
Usually ABO due to cross-reactivity
Should not happen clinically!
Acute rejection
Cell mediated response -> fail within weeks-months
Cytotoxic T, monocytes, macrophages
Adaptive response -> specific to graft, shows memory response
Prevent with HLA match and immunosuppression
Chronic rejection
Months-years Mechanisms unclear Innate immune (macrophages, T, IgA?) -> artherosclerosis -> loss of function
Major problem for transplant (can suppress adaptive AND innate)
Donor screening
Must be ABO match (hyperacute)
HLA - want to minimize new H antigens that are on graft
- MHC class II more important than class I
- old methods - cytotoxicity
- new method - sequence HLA alleles
Bone marrow transplantation
Used as last resort for blood/marrow cancers
Destroy immune system -> introduce graft
Graft vs host disease - graft immune cells attack all tissues in body
25% mortality in first 100 days!
Immunosuppression
Glucocorticoids - broad (T, monocytes, IL12, IFN-g)
Antibiotics - interfere with lymphocyte dev’t
Block mitosis (cytotoxic)
Irradiation - can target subpopulations
Antibodies, globulins - target or disable lymphocytes
