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Exam 2 > Transplantation Lecture 5 > Flashcards

Transplantation Lecture 5 Flashcards

1
Q

Immune response against transplant

A

graft rejection shows specificity and memory: mediated by lyphocytes

genes that contribute the most to rejection of graphs: MHC and HLA

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2
Q

Immunologic responses

A

Responses to MHC ags on another cells

  1. One of the strongest immune responses known
  2. Mature T cells with some affinity for self MHC molecules survive selection in the thymus
  3. Will have high affinity for self MHC displaying foreign peptides
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3
Q

Immunologic reactions

A

Allogeneic MHC molecules containing peptides derived from allogeneic cells may look like self MHC molecules plus bound foreign peptides

represents immunologic cross reaction

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4
Q

autograft

A

from one part of the body to another (trunk to arm)

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5
Q

isograft

A

between genetically identical individuals (eg monozygotic twins, or within an inbred strain)

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6
Q

allograft

A

between different members of the same species

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7
Q

Xenograft

A

between members of different species

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8
Q

Induction of graft responses- Direct recognition

A

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

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9
Q

Induction of graft responses: Indirect recognition

A

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

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10
Q

Types of rejection

A

hyperacute
acute
chronic

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11
Q

hyperacute

A

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

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12
Q

microscopic (hyper acute)

A

Lots of polymorphonuclear neutrophils in: arteries, glomeruli, peritubular capillaries

neutrophils can indicate acuteness
lymphocytes may indicate something chronic

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13
Q

Minutes-hours of hyper acute rejection

A

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

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14
Q

Immuno assay

A

Use anti-antigen that binds to the immuno complexes in order to identify the amount of immune response.

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15
Q

acute rejection

A

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

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16
Q

acute cellular rejection

A

Extensive mononuclear infiltrate

Endothelitis: CD8 cells invade and damage vascular endothelium.

Tubules: can be infiltrated with lymphocytes. Called tubulointerstitial rejection and can cause necrosis.

17
Q

Acutue humoral rejection

A

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.

18
Q

Acute humoral rejection: proliferative vascular lesions

A

less servere

intima thickening

lumen filled with fibroblasts, myocytes macrophages.

Similar to arteriosclerotic disease

can result in infarction and renal cortical atrophy

19
Q

chronic rejection

A

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

20
Q

chronic rejection

A

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

21
Q

graph versus host disease

A

primarily in BM transplant

can occur after liver transplant due to large number of lymphs transplanted

blood transfusion, not irradiated, rare.

22
Q

Graft-veresus host disease

A

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

23
Q

Acute GVH

A

Major organs: immune system, skin, GI tract, liver

24
Q

Graft versus host disease 2

A
  1. Patient is immune incompetent due to pretransplant immunosuppression
  2. Bone marrow transplant contains mature and memory allogeneic donor T cells
  3. donor t cells circulate trough blood into 2nd lymphoid organs where they encounter allogeneic patient (host) antigen)
  4. effector donor t cells enter target tissue and cause tissue damage
25
Q

Skin

A

get generalized rash

can result in desquamation

biopsy shows prominent apoptosis occuring in the epidermis

26
Q

GVH

A

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

27
Q

GVH

A

Immune system: Patient immunosuppressed, much due to treatment. Increased susceptibility to infections. CMV important in these patient. CMY pneumonitis- can be fatal

28
Q

chronic GVH

A

Skin: similar to systemic sclerosis. INcreased fibrosis. Loss of appendages in dermis

liver: chronic cholestatic jaundice

gi tract: esophageal strictures

imune system: profound immunosuppression

29
Q

Minimizing graft rejection

A

ABO blood group typing

HLA typing to determine compatibility between donor graft and recipient of that graph

30
Q

HLA cross matching

A
  1. Hunders of patients are waiting for organs. Each is HLA typed and entered into a national registry.
  2. When kidneys becomes available, the donor is HLA typed
  3. Transplantation will not go ahead if the recipient has preformed antibodies against donor HLA
  4. Kidney is sent to an HLA matched potential recipient
32
Q

HLA cross matching

A
  1. Hunders of patients are waiting for organs. Each is HLA typed and entered into a national registry.
  2. When kidneys becomes available, the donor is HLA typed
  3. Transplantation will not go ahead if the recipient has preformed antibodies against donor HLA
  4. Kidney is sent to an HLA matched potential recipient
32
Q

Immunosuppression

A

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

Exam 2 (23 decks)

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