Transplantation Lecture 5 Flashcards
Immune response against transplant
graft rejection shows specificity and memory: mediated by lyphocytes
genes that contribute the most to rejection of graphs: MHC and HLA
Immunologic responses
Responses to MHC ags on another cells
- One of the strongest immune responses known
- Mature T cells with some affinity for self MHC molecules survive selection in the thymus
- Will have high affinity for self MHC displaying foreign peptides
Immunologic reactions
Allogeneic MHC molecules containing peptides derived from allogeneic cells may look like self MHC molecules plus bound foreign peptides
represents immunologic cross reaction
autograft
from one part of the body to another (trunk to arm)
isograft
between genetically identical individuals (eg monozygotic twins, or within an inbred strain)
allograft
between different members of the same species
Xenograft
between members of different species
Induction of graft responses- Direct recognition
T cells may recognize allogeneic MHC molecules on the graft.
Displayed by donor dendritic cells in graft
may be processed and presented by host DC.
t cell become activated
Induction of graft responses: Indirect recognition
second pathway which is similar to recognition of any foreign antigen
if graft cells are ingest by recipient DC. Donor alloantigens are presented by self MHC molecules on recepient APCs
Types of rejection
hyperacute
acute
chronic
hyperacute
Occurs within minutes or hours after transplant; surgeon can see this occur.
Antigen antibody reaction
changes can be diffuse. Get thrombotic occlusion of capillaries. Fibrinoid occlusion of arterial walls. Kidney cortex get infarction with necrosis. Nonfunctioning kidney must be removed
microscopic (hyper acute)
Lots of polymorphonuclear neutrophils in: arteries, glomeruli, peritubular capillaries
neutrophils can indicate acuteness
lymphocytes may indicate something chronic
Minutes-hours of hyper acute rejection
target Ags on endothelium can also be non-blood group antigens and the alloantigen specific antibody is IgG
Complement activation, endothelial damage, inflammation and thrombosis
Immuno assay
Use anti-antigen that binds to the immuno complexes in order to identify the amount of immune response.
acute rejection
occurs in days after transplant or much later if patient stops immunosuppression (weeks to months)
both humoral and cellular mechanisms
can respond to increased immunosuppression
acute cellular rejection
Extensive mononuclear infiltrate
Endothelitis: CD8 cells invade and damage vascular endothelium.
Tubules: can be infiltrated with lymphocytes. Called tubulointerstitial rejection and can cause necrosis.
Acutue humoral rejection
Called rejection vasculitis
mediated by antidonor antibodies so get vasculitis
necrotizing vasculitis: necrosis of endothelial cells and polys (neutrophils) in vessel walls. Lead to thrombosis. Immuglobulin and complement in vessel wall.
Acute humoral rejection: proliferative vascular lesions
less servere
intima thickening
lumen filled with fibroblasts, myocytes macrophages.
Similar to arteriosclerotic disease
can result in infarction and renal cortical atrophy
chronic rejection
occurs months to years
see slow rise in creatinine
vessels- dense intimal fibrosis that occludes the vessel lumen
interstitial fibrosis
tubular atrophy with loss of renal parenchyma
glomerular changes: chronic transplant glomerulopathy - duplication of basement membrane
chronic rejection
occurs months to years
see slow rise in creatinine
vessels- dense intimal fibrosis that occludes the vessel lumen
interstitial fibrosis
tubular atrophy with loss of renal parenchyma
glomerular changes: chronic transplant glomerulopathy - duplication of basement membrane
graph versus host disease
primarily in BM transplant
can occur after liver transplant due to large number of lymphs transplanted
blood transfusion, not irradiated, rare.
Graft-veresus host disease
caused by the reaction of grafted T cells with alloantigens of the recipient
recipient is immunocompromised so recipient is unable to reject the allogeneic cells in the graft
develops when significant numbers of t cells are transplanted
often directed to minor histocompatibility antigens
acute and chronic forms of GVHD
target organs are skin, iver, and intestine
is the principal limitation in hematopoietic stem cell (bone marrow) transplantation
Acute GVH
Major organs: immune system, skin, GI tract, liver
Graft versus host disease 2
- Patient is immune incompetent due to pretransplant immunosuppression
- Bone marrow transplant contains mature and memory allogeneic donor T cells
- donor t cells circulate trough blood into 2nd lymphoid organs where they encounter allogeneic patient (host) antigen)
- effector donor t cells enter target tissue and cause tissue damage
Skin
get generalized rash
can result in desquamation
biopsy shows prominent apoptosis occuring in the epidermis
GVH
Liver: jaundice and destruction of small bile duct
GI tract: GI bleeding that occurs from mucosal ulceration
do not get abundant lymphocytic infiltrate
mediated by CD* T cells and cytokines
GVH
Immune system: Patient immunosuppressed, much due to treatment. Increased susceptibility to infections. CMV important in these patient. CMY pneumonitis- can be fatal
chronic GVH
Skin: similar to systemic sclerosis. INcreased fibrosis. Loss of appendages in dermis
liver: chronic cholestatic jaundice
gi tract: esophageal strictures
imune system: profound immunosuppression
Minimizing graft rejection
ABO blood group typing
HLA typing to determine compatibility between donor graft and recipient of that graph
HLA cross matching
- Hunders of patients are waiting for organs. Each is HLA typed and entered into a national registry.
- When kidneys becomes available, the donor is HLA typed
- Transplantation will not go ahead if the recipient has preformed antibodies against donor HLA
- Kidney is sent to an HLA matched potential recipient
HLA cross matching
- Hunders of patients are waiting for organs. Each is HLA typed and entered into a national registry.
- When kidneys becomes available, the donor is HLA typed
- Transplantation will not go ahead if the recipient has preformed antibodies against donor HLA
- Kidney is sent to an HLA matched potential recipient
Immunosuppression
Some current immunosuppressive agents are products of chance discover adn some are the result of deliberate design
common to all is the ability to directly or indirectly inhibit T cell responses
