Transplant and

Tumor
immunology

Organ transplantation and Cancer- Two Cancer: suppressed immune respose give
situations in which host immune system birth to tumor.
plays and important role in the survival of
such tumor or transplants.
Organ transplantation-Immune raspone is a
barrier for acceptance,suppression of
immune response –key for transplantation
survival.

Transplantation
Definition: Transfer of a graft or transplant(cells, tissue or organ) from one site
to another.

Classification of transplantation

Autograft : Transfer of an individuals own tissue to another site in the

body. Skin, Bone graft.

Isograft : Transfer of Tissue between genetically

identical(Identical twin) individuals.

Allograft : Transfer of Tissue between genetically

different members of the same species e.g.
Human to human
Autograft & isograft are always accepted, owing to the
genetic identity between graft & host.
Xenograft : Transfer of tissue between different species.
Baboon to human Most common Transplantation is Blood Transfusion
The most commonly transplanted organ is the kidney & Bone
marrow

1
 • Rejection refers to damage done by immune system to
a transplanted organ.
• Rejection is a very complex process in which both the
CMI(T cells) & circulating Ab against the graft plays role.

GRAFT • Transplant rejection occurs when a transplanted

organ or tissue is not accepted by the body of the
transplanted recipient .

REJECTION Antigen responsible for such rejection are those of the

major histocompatibility antigen system(MHC).

The loci responsible for the most vigorous allograft

Transplantation antigens rejection reaction are located within MHC

Histocompatible: Tissue that are antigenically similar–

Antigen of allograft against which the
do not induce an immunologic reaction
recipient mount an immune response.
MHC molecules.HLA-A, HLA-B, HLA-DR are Histoincompitable: Tissue that display significant
mostly responsible for graft rejection. antigenic difference - induce an immunologic reaction

ABO and Rh blood group system.

Minor HA-peptides derived from normal
cellular protein of donated organ.Less
immunogenic.

Classification of graft rejection

A. Hyper acute rejection:
Autograft acceptance
occur within minutes to hours after transplantation
which cause thrombosis of graft vessels and inchaemic
necrosis.
• Day 3 to 7 you will have revascularization
• Preexisting antibody in the reciepient.(preformed anti-ABO • Days 7 to 10 you have healing.
Ab.)
B. Acute rejection reaction: Most common type • By the day 14 you will have resolution.
usually begin within days or weeks after transplantation.
Mediated by mainly T cell mediated reaction (Tc and also Th)
.Vascularization of graft is normal initially but in 11 to 14 days
marked reduction in blood flow and immune cells infiltrate the
graft with eventual necrosis.(Mismatched donor receipent HLA )
C. Chronic rejection reaction:
occur from month to year after transplantation.Occur
due to DTH reaction.Manifested fibrosis of graft and gradual
narrowing of graft blood vessel ,called graft athrosclerosis.

2
 Graft rejection occur in two phases.
Mechanisms of graft rejection
1. T-cell mediated rejections A. Direct pathways- sensitization phase:Dendritic
cell of donor present peptide associated with MHC
2. Antibody mediated rejections
class11 and class1 to CD4& CD8 cells of recepient.
• Effector phase:TH-1 cells of receipent is activated
1. T-cell mediated rejections and activate the CD8 cells and destroy the graft
by secreting perforin and granzyme.Th1 also
 Both CD4 helper cells and CD8 CTL are involved. activate macrophage to enhance inflammation
 Mainly CD8 T cells play active role. and damage the graft.
B. Indirect pathways:Sensitization phase: Recipient
Dendritic cell take up the proteins released by
damaged graft cell and process ag to peptide
associated with class 11 MHC and present to CD4
helper T cell of receipient.

Effector phase of indirect pathway:Th cell is Both direct and indirect pathway contribute
activated and differentiate into Tfh and to acute rejection. Indirect pathway is
produce Ab and damage the graft tissue by primarily responsible for chronic rejection.
complement mediated lysis and ADCC and
activated Th differentiate to DTH and
secrete cytokines and activate macrophages
and cause inflammation and release of lytic
enzyme and damage graft tissue.

Prevention of Graft rejection

MHC +
Antigen Determine Histocompatability.
Immunosuppresive therapy.
Determine histocomptability
Laboratory tests
TCR A. Blood grouping and cross matching
B. HLA typing – Is performed to determine
the closest MHC match between donor and
recipient

3
 Therapy
General Immunosuppressive therapy

Mitotic inhibitor T cell proliferation:

Azathioprine
Blood grouping and crossmatching and HLA Methotrexate
typing. Cyclophosphamide
Corticosteroids suppress inflammation: Prednisolone
Phenotypic method(not in use now) Dexamethasone
Calceneurin inhibitors Cyclosporin A
Serology: Microcytotoxicty Tacrolimus
Tissue typing: Mixed lymphocyte reaction. Specific Immunosuppressive therapy
Genotyping method
Monoclonal antibody(Belatacept) can suppress graft rejection
PCR detecting HLA genes. response by blocking Co-stimulatory signals can induce Anergy.

Immunosuppressive therapy-contd.
Immunosuppressive therapy-contd
The recipient’s susceptibility to opportunistic
infection and neoplasm. Cancer after Immunosuppressive therapy
Common opportunists are: reduces graft versus malignancy effect.
1. Cytomegalovirus
2. Varicella zoster virus 1. Lymphomas
3. Herpes simplex virus 2. Squamous cell carcinoma
4. Pneumocystis carinii 3. Kaposi’s sarcoma
5. Aspergillus spp.
6. Gram negative rods

Fetus an “Allograft”

The fetus is an allograft that is not rejected tolerance of fetal antigens.

A fetus has MHC genes inherited from father
that are foreign to mother.
Mother forms antibodies against the foreign
paternal MHC protein.Mothers immune system
does not reject fetus as foreign.
One possible explanation 1) placenta does not
allow maternal T cells to enter the
fetus.2)Maternal T cell within placenta are
biased to T regulatory T cell promotes

4
 Graft-Versus-Host Reaction(GVHR)
Well matched transplant of Bone Marrow may be establish
themselves initially in 85% of recipient, but subsequently
in about 2/3rd of them develops GVHR reaction.
tolerance to fetal antigen.
Grafted mounts an immune response against host.

i) Graft must contain immunocompetent T cell

ii) Host must be immuocompromised
iii) Recipient must express Ag( MHC protein) foreign
to the donor( e.g. T cells recognize recipient cells
as foreign).

GVH
If GVH reaction occurs treating with
immunosuppressive drug often for
entire lives.
Immunosuppression increases the risk of
disease relapse and increases the risk of
developing malignancy and opportunistic
infection.

TH cells

IL-2
IL-2,4,5,6
IL-2
TDTH
Activated MQ CD4Tc B cell

INF-γ &TNF-β CD8 Tc

Plasma cell

Complement NK cell
Lytic enzymes LYSIS

ADCC
MHC-I MHC-II

Graft

Effector mechanisms involved in allograft rejection