L: 21 Transplantation 1 and 2 Flashcards
Autograft
grafts exchanged from one part to another of the same individual
isograft
grafts exchanged between different individuals of identical genetics (identical twins)
Allografts
Grafts exchanged between nonidentical members of same species
Xenografts
grafts exchanged between members of different species
Problems with Xenografts
particularly susceptible to rapid attack by natural occurring Abs and complement. Increased chance of success if human genes are inserted into genome
Explain Direct Allorecognition
T cell recognizes unprocessed allogenic MHC molecules on graft APCs
Explain Indirect Allorecognition
T cell recognizes processed peptide of allogenic MHC molecule bound to self MHC molecule on host APC
In the direct pathway the T cell receptor on recipient T cells directly recognize?
The donor MHC molecules
In the indirect response the recipient T cell recognize donor MHC molecules that have been processed by?
Recipient APCs
What pathway is most important during chronic rejection
Indirect Pathway
Phases of Host vs. Graft
Hyperacute- immediate
Acute- week-months
Chronic- months-years
*In all cases the host has immune response to graft
**Most important thing to remember is onset time frame.
Graft vs. host
Onset varies
Donor cells proliferate and attack the recipient tissue T cells in graft
Hyperacute graft rejection
Caused by pre-existing ABs that are reactive to donor tissue AND HAPPENS WITHIN MINUTES. Abs bind to endothelial cells which activate Classical pathway of complement activation—-leads to cell death
(ABO blood group incompatibility)
ABs b
Acute graft rejection
Occurs in days to weeks and is initiated by alloreactive T cells. Donor DC’s migrate to the lymph nodes draining the organ and stimulate a primary recipient response
Chronic Graft Rejection
Occurs in months to years occurs d/t occlusion of blood vessels and subsequent ischemia of the organs.
MAIN PATHOGENIC MECHANISM is the indirect pathway.
**Chronic rejection does not respond to immunosuppressive therapy
Non-immunologic factors in chronic graft rejection
- Ischemia-reperfusion
- Recurrence of disease
- Effects of nephrotoxic drugs
What 4 variable determine transplant outcome
- Condition of the allograft
- Donor-host antigenic disparity
- Strength of host anti-donor response
- Immunosuppressive regimen
During the Donor - Recipient work-up what is established first?
ABO blood group compatibility
ABO is a barrier to transplantation of what?
Solid organs
- *Not a barrier to corneal, heart valve, and bone/tendon graft transplantations
- *ABO incompatibility is not important to stem cel, transplant
Group A Abs and Ags
ABs- anti-B
Ag- A
Group B Abs and Ags
ABs- anti A
Ag - B
Group AB Abs and Ags
Abs - None
Ags - A/B
Group O Abs and Ags
Abs Anti- A/B
Ags - none
What is the universal donor and recipient?
Universal donor- O
Universal recipient- AB
The success of transplantation is dependent on matching of what Ags?
MCH Ags Which are encoded by MHC class I and class II
HLA compatibility between donor and recipient is required due to?
Extreme polymorphism of HLA
In humans, the MCH is termed?
Human leukocyte antigen complex (HLA complex)
Where is HLA antisera mostly obtained
Multiparous women or planned immunization of volunteers
What is cross-matching used for?
used to test the recipient serum for preformed Abs against donor HLAss
Why is cross-matching needed?
To prevent hyperactive Ab-dependent rejection of graft
What test is used to screen for preformed Abs?
Microcytotoxicity test
Recipient’s serum is mixed with donors, if no cell damage, then potential donor identified. No stain=no antibodies
What test may be used for class II HLA typing?
Mixed lymphocyte reaction (MLR). If class II antigens the same, no proliferation will occur. Used to determine if donor cells stimulate proliferation of recipients lymphocytes**Ags need to be the same for transplantation*Stained=same
What is Host vs Graft response?
Host Immune system attacks the donor tissue
What type of immune response occurs with Host vs Graft
Adaptive immune response
Rxn is much more vigorous and strong vs rxn seen against pathogen
Effector mechanism of graft rejection- Humoral
Th2 (IL-4, IL-5, and IL-10)
Effector mechanism of graft rejection-Cellular
Th2 (IL-2, IFN-gamma)
Graft-Versus-Host Disease
occurs when transplants are small bowel, lung, or liver because of natural higher number of T cells
***Occurs in immunocompromised recipients
A new era of transplantation and immunosuppression opened up with the discovery of what drug?
Cyclosporine A (CsA)
Steroid mechanism
Anti-inflammatory
Cyclosporin A mechanism
Inhibits IL-2 gene transcription
Anti-CD3 monoclonal antibody mechanism (OKT 3)
T-cell activation, opsonization and depletion
Tacrolimus mechanism
Inhibits IL-2 gene transcription
Anti-CD25 monoclonal antibodies (IL-2R alpha chain) Sirolimus
Inhibits IL-2 function Inhibits cytokine-mediated signal
What tests are done prior to transplant
- ABO blood grouping
- Tissue typing (identify HLAs)
- Cross-matching (check for pre-formed antibodies)
- Mixed lymphocyte reaction (check to see if donor stimulates recipient lymphocytes)
What does the Ag-Ab complex activate?
Classical complement cascade which results in lymphocyte lysis
