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Transcript
Nehal Draz
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1- Autograft: from one area to another, same
inbividual, NO IR
2- Syngraft (Isograft; Syngeneic): genetically
identical individuals, NO IR, Histocompatible
3- Allograft (commonest) two genetically
dissimilar individuals, same species,
Histoincompatible & rejection
4- Xenograft: donor & recipient from different
species Histoincompatible & rejection
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
Living graft: from a
living donor,e.g. liver
segment, kidney, BM
Cadaveric graft: from
a recently dead
individual,e.g. heart,
cornea, liver, kidney
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Bone marrow is the most immunogenic
Liver is the least immunogenic depending
on:
1- Lack of suitable APCs
In some tissues

2- Different expression of
HLA molecules
Privileged sites: e.g.cornea No significant
IR
Lack of lymphatic drainage
HLA
MHC
Refers to genes encoding
HLA proteins
MHC molecules
Refers to the protein HLA
Allelic polymorphism:
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The MHC genes represents the most
polymorhic genetic system
Multiple different allels of the same
gene exist in the human population
Different allels of the same gene can
give Ags with slightly distinct
sequences
e.g. A gene has 151 allels

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1- control IR by
MHC restriction
2- targets of IR
resulting in
cytotoxity in graft
rejection
3- Certain MHC
allels are associated
with some diseases
e.g. multiple
sclerosis &DR2

Recipient Tcells can recognize donor allo
Ags in the graft by 2 different ways:

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Recipient Tcells recognize donor;s Ags on
donor's MHC molecules on the graft APCs
Donor APCs leave the graft & migrate to
the regional lymph nodes
There they activate recipient’s Tcells
The activated Tcells are carried back to
the graft which they attack directly

Uptake of donor MHC molecules by the
recipient own APCs and presentation to
self Tcells on self MHC molecules
CD8
Tcells
- The generated alloreactive CTLS
attack graft cells bearing MHC I and
destroy them by direct cytotoxicity
CD4
Tcells
Secrete cytokines enhancing graft
damage:
- IL-2: stimulate CTLs
- IFNγ: increase allogenic MHC class I
&II on graft cells
- IL4, 5, 6 stimulate Ab production by
Bcells
C
M
I
HUMORAL
IgG or IgM
Foreign GRAFT
cell
MQ
NK
1- Opsonization destruction
3- ADCC
2- Complement mediated lysis
effector phase. cont

1- Hyperacute rejection

2- acute rejection

3- Chronic rejection

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Within minutes
Circulating preformed anti
ABO or anti-HLA
antibodies
Activation of compl. and
clotting pathways
No treatment
Prevention: proper
matching


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Within days or weeks
Treatment:
immunosuppression
Prevention: proper
matching
Destroy graft cells
TC
CD4 Lymphokines activating
Infl.& MQ
Endothelial injury
YYYY
Delayed type hypersensitivity
Alloantigen in
Vessel wall



After months or
years
No treatment
Prevention: proper
matching
CYTOKINES
Proliferation of smooth
Muscle cells
Gradual lumen narrowing
ischemia,
Interstial fibrosis
Loss of function
Histocompatibility testing
Recipient preparation
Post-operative immunosuppressive therapy
1- ABO typing
2- HLA testing: determination of HLA phenotype
for donor & recipient which can be done by:
a) microlymphocytotoxicity test
b) HLA molecular typing: PCR
c) white cell cross matching: mixed
lymphocytotoxicity test
3- detection of preformed Abs against donor cells
in the serum of the recipient
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Complete history taking & full clinical
examination
Treatment of hypertension if present
Treatment of infections if present
Prophylactic antibiotics
Pre-transplantation immunosuppressive
therapy

The drugs used to suppress the immune
system can be divided into 3 categories:
Powerful anti-inflammatory drugs (corticosteroid)
prednisone
Cytotoxic drugs
-Azathioprine
-Cyclophosphamide
Fungal & bacterial derivatives
-Cyclosporine A
-FK506
-Rapamycin
Drug
Mechanism of action
Cyclosporine & FK 506
Block Tcell cytokine production
Rapamycin
Inhibits IL-2 signaling which inhibits
lymphocyte proliferation
Corticosteroids
Reduce inflammation by inhibiting
MQ cytokine secretion
Anti IL-2 receptor
Inhibit T cell proliferation by
inhibiting IL-2 binding
Anti-CD40 ligand
Inhibit cellular activation by blocking
co-stimulation
Monoclonal Ab against Tcell surface
markers
Depletion of Tcells

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Infections
Malignancies: especially lymphomas &
carcinoma of the skin

Anaphylaxis or serum sickness

Graft verus host disease (GVHD)

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A successful therapy for tumors derived
from marrow precursors such as leukemia
& lymphomas
It may be also successful in treatment of
some primary immunedefficiency disease
such as severe forms of thalassemias

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In leukemia therapy, the source of leukemia
must be first destroyed by aggressive
cytotoxic chemotherapy. The patient is thus
severely immunocompromised
Bone marrow cells are highly immunogenic&
can elicit a strong IR
Therefore, very careful donor/recipient HLA
matching is critical

If mature donor Tcells are transplanted
with the marrow cells, these mature Tcells
recognize the tissues of the recipient as
foreign causingsevere inflammatory disease
called:
GVHD
Graft Versus Host Disease
-Rashes
-Diarrhea
-Pneumonitis
-Liver
dysfunction
-Wasting
-Death
1- The most crucial factor is donor selection
&MHC compatibility: an identical twin is the
ideal donor
2- From poorly matched grafts, T lymphocytes
can be removed using monoclonal Abs. to
avoid induction of an immune response by the
immune competent (mature) donor Tcells
against the tissues of the
immunocompromised recipient & hence GVHD
3-Malignant cells should be eliminated from
the recipient blood to avoid recurrence of
the underlying malignancy which
necessitated the BMT in the first place
4- Methotrexate, cyclosporin & prednisone
are often used to control GVHD