Transplantation Immunology Flashcards
______ are classified on the basis of the genetic relationship between the host and the donor.
Grafts
These are grafts exchanged from one part to another part of the same individual.
Autografts
These are grafts exchanged between different individuals of identical genetic constitutions (i.e., identical twins).
Isografts
These are grafts exchanged between nonidentical members of the same species.
Allografts (allogeneic)
These are grafts exchanged between members of different species.
Xenografts (xenogeneic)
Xenografts are particularly susceptible to rapid attack by naturally occurring ______ and complement. The insertion of human genes into the genomes of the donor animals (miniature swine) increases the chances of successful survival.
Abs
There are hundreds of allelic forms of ______ molecules. Each individual inherits only 10-12 alleles/person.
HLA
HLA Ags are co-dominantly expressed. The class-I HLA Ags (______ and ______) are particularly strong barriers to transplantation. The class-II HLA, the three most important for transplantation pairs, are _____, _____, and ______.
HLA-A; HLA-A
HLA-DR; HLA-DP; HLA-DQ
The _______ allorecognition pathway is primary response against graft. The T cell receptors on recipient T cells directly recognize the donor MHC molecules.
Direct
The _______ allorecognition pathway has recipient T cells recognize donor MHC molecules that have been processed by recipient APCs. The donor MHC molecules are presented as peptides in the context of recipient MHC class II molecules.
Indirect
The indirect pathway is important during _______ ______ (when the number of donor professional APCs is low to stimulate a direct immune response).
Chronic rejection
This type of graft rejection is caused by the pre-existing Abs binding to the endothelial cells lining the blood within minutes to hours.
Hyperacute
In ________ graft rejection, the recipient has pre-existing Abs that are reactive with the donor tissue. This may be caused by:
– ABO blood group incompatibility
– The recipient has been sensitized to the donor MHC by previous transplants, multiple blood transfusions, or pregnancy.
– Abs bind to endothelial cells which activates the classical pathway of complement activation
– Complement activation can lead to death of the endothelium.
Hyperacute
This type of graft rejection occurs in days to weeks and is initiated by alloreactive T cells. Donor DCs (also called passenger leukocytes) play an important role in triggering this type of rejection.
Acute
In acute graft rejection, after transplantation, donor ______ migrate to the lymph nodes draining the organ and stimulate a primary recipient response.
DCs
In acute graft rejection, once activated the T cells migrate to the organ and it leads to tissue damage. Both _____ and _____ T cells can cause graft rejection, and the indirect response can also contribute to acute rejection.
CD4+
CD8+
This type of graft rejection occurs in months to years following transplantation. It occurs due to the occlusion of blood vessels and subsequent ischemia of the organ.
Chronic
In chronic graft rejection, ________ infiltrate and smooth muscle cell proliferation is often seen.
Macrophages
In chronic graft rejection, the main pathogenic mechanism is the (DIRECT/INDIRECT) pathway. Abs can also be involved in chronic rejection (the deposition of complement in graft tissues).
Indirect
Non-immunologic factors in a chronic rejection may be:
– Ischemia-reperfusion damage
– Recurrence of the disease that caused failure of own kidney
– The effects of _________ drugs (i.e., cyclosporine A)
Nephrotoxic
T/F. Chronic rejection responds well to immunosuppressive therapy.
False. Chronic rejection does not respond to immunosuppressive therapy.
The key concepts that determine transplant outcome include:
1) The condition of the _______
2) Donor-host antigenic disparity
3) Strength of host anti-donor response
4) _________ regimen
Allograft
Immunosuppressive
Mechanical trauma and _______-_______ can cause injury to the graft tissues.
Ischemia-reperfusion
When transplanted, damaged graft tissues release ________ which trigger several biochemical cascades leading to immediate tissue damage. These early pro inflammatory responses, if uncontrolled, can result in allograft _______.
Mediators
Rejection
Damaged graft tissues release mediators that trigger several biochemical cascades leading to tissue damage, which includes:
– Clotting cascade generates ______ and ________.
Fibrin; Fibrinopeptides
Fibrinopeptides increase local vascular permeability and serve as ________ for neutrophils and macrophages.
Chemoattractant
Damaged graft tissues release mediators that trigger several biochemical cascades leading to tissue damage, which includes:
– The kinin cascade produces ________ that causes vasodilation, smooth muscle contraction, and increased vascular permeability.
Bradykinin
In the donor-recipient work-up, ______ blood group compatibility is first established. Very strong cell surface Ags are found on many other tissues.
ABO
In the donor-recipient work-up, tissue typing to identify ______ is then performed.
HLAs
In the donor-recipient work-up, cross-matching is used to test the recipient serum for preformed _____ against donor’s HLAs.
Abs
In the donor-recipient work-up, the mixed lymphocyte reaction may be used to determine if the donor cells stimulate _________ of the recipient’s lymphocytes.
Proliferation
This is the major blood group system.
ABO
ABO is a barrier to transplantation of solid ______.
Organ
Abs to A and B are in individuals w/o these antigens on their _______.
RBCs
ABO matching is not important for…
Corneal transplantation
Heart valve transplantation
Bone and tendon grafts
ABO incompatibility is not a contraindication to _____ ______ transplantation.
Stem cell
Blood group Ags are also expressed on other ______ (renal, endothelium).
Tissues
***Study the ABO tables (Slide 23-26)
Study for 5 minutes
The success of transplantation is dependent on matching of the _______ Ags. These Ags are encoded by the major histocompatibility complex, _______ and _______.
MHC MHC class I MHC class II
In humans, the MHC is termed the _______ complex.
HLA (Human leukocyte antigen)
HLA compatibility between donor and recipient is required due to the extreme _________ of HLA.
Polymorphism
The identification of HLA Ags until recently has been complement-dependent _______.
Serology
The convenient sources of lymphocytes for HLA typing are the ______ and ______ ______ (from cadaver).
Spleen
Lymph node
HLA antisera are mostly obtained from multiparous women or from planned immunization of volunteers. The antisera contain ______ to HLA Ags.
Abs
Abs bind to HLA Ag on the surface of ________.
Lymphocytes
The Ag-Ab complex formed activates the classical complement cascade and this will result in lymphocyte ______.
Lysis
Cross-matching is used to test the recipient serum for preformed Abs against donor’s HLAs. This is needed to prevent hyperactive Ab-dependent ________ of graft.
Rejection
The presence of preformed Abs reactive with various allogeneic HLA Ags can cause hyperactive graft rejection. Recipients are screened for the presence of such Abs by using a __________ test with complement-activated cell damage.
Microcytotoxicity
Recipient’s ______ is mixed with cells of a donor – if there is no cell damage, then a potential donor is identified.
Serum
In the microcytotoxicity test for preformed Abs, if there are no Abs in the recipient then the donor cells are not _______.
Stained
Class II ______ typing – mixed lymphocyte reaction (MLR) may be used to determine if the donor cells stimulate proliferation of the recipient’s lymphocytes.
HLA
In class II HLA typing, leukocytes from two unrelated individuals are _______. Lymphocytes from the donor are irradiated to stop their proliferation and called ________ cells.
Mixed
Stimulator
Stimulator cells are used for presentation of _________ Ags.
Class II MHC
Lymphocytes from the recipient are intact and called _______ cells. These cells will be activated by mismatched class II MHC and proliferate. Proliferation (the response) is measured by incorporation of _______ ______.
Responder
Tritiated thymidine
If class II MHC Ags are the same, proliferation (WILL/WILL NOT) occur.
Will not
When a kidney is transplanted the recipient’s T cells attack the transplant, this is called…
Host-versus-graft disease
When bone marrow is transplanted the T cells in the transplant attack the recipient’s tissues, this is called…
Graft-versus-host disease
In a host-versus-graft response, the host immune system attacks the donor tissue. It is an _______ immune response against a graft. The immune response against a graft is much more vigorous and strong than the response seen against a pathogen.
Adaptive
A more vigorous and strong immune response against grafts than pathogens is due to a higher frequency of _______ that recognize the graft as foreign.
T cells
Unimmunized individual has less than 1/100,000 T cells which respond upon exposure to a virus. About 1/100-1/1,000 T cells respond to allogeneic ______.
APCs
The immune memory of previous encounters with donor Ags is important:
– From animal experiments - if a second graft is performed from the same donor, it is rejected more (SLOWLY/RAPIDLY).
Rapidly
Up to 2 percent of the host T cells are capable of recognizing and responding to single foreign ______.
MHC
Non-immune injury of the graft (Danger Signals) activates endothelial cells, and T cells enter the allograft. Ag-specific T cells interact with ______ and become stimulated (activated). The inflammatory cytokine/chemokine field is created and causes further activation of _____, endothelium and leukocyte traffic.
APC
APC
Effector mechanisms of graft rejection:
- ________ rejection Th2 (IL-4, IL-5 and IL-10)
- ________ rejection Th1 (IL-2, IFN-y)
Humoral
Cellular
Graft-versus-host disease often occurs when transplants are small bowel, lung, or liver, which naturally contain a number of _______.
T cells
GVHD is caused by the reaction of grafted mature _______ in the tissue transplant with allo-Ags of the host. Reaction is directed against miHAs of the recipient (HLA Ags are usually matched).
T cells
GVHD occurs in the immunocompromised recipients because their immune system is unable to reject the _______ cells in the graft.
Allogeneic
For solid grafts, GVHD may be classified as:
– _______ GVHD - epithelial cell death in the skin, liver, and GI (clinically – rash, jaundice, diarrhea, and GI hemorrhage).
– _______ GVHD - fibrosis and atrophy of affected organ (clinically – may lead to complete dysfunction of the affected organ, or two of the same)
(May produce obliteration of small airways)
Acute
Chronic
After the initiation phase, donor APCs can activate donor ______ T cells by cross-presenting exogenously acquired Ags (through the uptake of apoptotic recipient or shed proteins) on MHC class I molecules.
CD8+
T/F. In this case, donor APCs could reprime donor CD8+ T cells previously activated by recipient APCs against the same antigens expressed by recipient APCs. Alternatively or in addition, donor APCs could activate naive donor CD8+ T cells against new, non-hematopoietic Ags (epitope spreading).
True
