Transplant Immunity Flashcards
Autograft
Transfer self tissue from one body site to another same individual; Immune system does not respond because of same tissue eg skin graft bone, bone marrow transplant
Isograft
Tissue transfer between genetically identical individuals; no foreign MHC eg twins
Allografting and Xenografting
graft of tissue from one individual to a different individual of same species; foreign antigen
Graft transfer of tissue from one species to another; foreign antigen pig heart valves
ABO Blood groups
First routine employed type of transplant; each person has antibody to antigen they lack (in ABO system)
Mismatched blood transfusion: Intravascular coagulation, complement assisted lysis and hemolysis
life-threatening—> systemic shock and kidney failure—> blockage of kidney glomeruli
ABO blood groups
A B O and rhesus D antigen
O is absence of A and B antigen
Group O is universal donor
AB is universal recipients but only receives from AB
Forward and Reverse typing
Determines antigens on patients or donors blood; cells tested with Antisera reagents -A and -B
Determines antigens on patients or donors SERUM OR PLASMA; serum tested with A1 cells and B cells also known as BACK TYPING or SERUM CONFIRMATION
MHC and HLA typing
HLA part of MHC
Found on short arm of CHROMOSOME 6
MHC Class 1a (loci ABC)
MHC Class 1b (loci EFGH)
Genes of 1a and class II are polymorphic
MHC Class 1 and Class II HLA DR alleles are important for successful transplantation
Transplants must be matched for blood type antigens
Does MHC (HLA) matching prevent rejection
Reduces rejection
Due to its variability prob of finding HLA match in family is high
Used to be determined by antibodies against MHC (HLA typing)
use allele specific PCR and seq to test DNA
Greatest prob of a match sibling
Can cause too much polymorphism, too little time and few donors (we cant match most grafts)
Need immunosuppression
Assessing Compatibility Mixed leukocyte Reaction
Detect tissue incompatibility
Mix leukocytes from potential donor with irradiated leukocytes from potential recipient
If mismatched donor leukocytes will proliferate and lyse host cell
Mechanism of allogenic Transplant Rejection Direct Presentation: Direct Alloreactivity
Direct Presentation: Direct Alloreactivity
-Recognize an intact MHC molecule displayed by donor APC in the graft
-Basically self MHC molecule recognizes the structure of an intact allogenic MHC molecule
-Common in acute rejection
-Involves CD8 and CD4 T cells
Mechanism of allogenic Transplant Rejection Direct Presentation: INDirect Alloreactivity
Donor MHC is processed and presented by recipient APC
Donor MHC molecule is handled like any other foreign antigen
Chronic rejection
INVOLVES ONLY CD4 T cells
Antigen presentation by class II MHC molecules
Hyperacute Rejection
Time frame: Occurs few hrs to days after transplant (once anastomasis is complete)
Caused by antibody mediated and completed dependent graft destruction by coagulative necrosis
Preformed antibodies specific to alloantigens
Target is vascular endothelium thrombosis intravascular clothing
Happens even before patients
Kidney becomes cyanotic mottled and flaccid secreting few drops of urine
Hyperacute Rejection
Typically happens to recipients who has had multiple transfusions or pregnancies, prior grafts
Mediated by preexisting antibodies to vascular endothelium that activate complement; deposites on vessel wall, endo injury, neutrophil accumulation, necrosis
MHC Class I: normally expressed on endothelium
Class II: induced on endothelium as a result of inflammation, infection trauma, ABO antigens
Acute Rejections
5 days to 6 months
CD4 and CD8 T cells
Directed against donor MHC antigens
Infiltration of lymphocytes and macrophages. Both destruction of cells by CTL, phagocytosis, presentation of transplanted antigen to Th cells
Immunosuppressive therapy
Inflammation of tubules
The major role is the T cell
Acute Humoral Rejection and Chronic Rejection
Inflammation of glomeruli peritubular capillaries
Slow indolent takes months to years
Lymphoid proliferation and lymphoid follicles within transplanted organ
Arteriole thickening and intestitial fibrosis
