Transplantation immunology

• Replacement of irreversibly damaged

tissue [by accident or disease]
or organ by healthy ones to restore
the
function .
• Tissue or organ transplanted is known as
the transplant or graft.
• The individual from whom the
transplant is obtained is known as the
donor .
• The individual to whom it is applied ,the
recipient.
 Classification of grafts
• Based on the organ or tissue involved :
• Based on the viability of the organ
involved :
• Based on the site of origin or site of
placement of the transplant :
• Based on the genetic reltionship
between the donor and recipient :
 Based on the organ or tissue
involved
• Eg: kidney transplant
heart transplant
skin graft /transplant
live transplant
Based onthe site of origin or site
of placement of the transplant
• Grafts are classified as :
• 1. orthtopic : Grafts are applied in
anatomically ‘normal’ sites as in skin
grafts.
• Heterotopic grafts : Grafts are applied
in anatomically ‘ abnormal’ sites as
when thyroid tissue is transplanted in a
subcutaneous pocket .
 Based on the viability of the
organ involved :
• Viable / vital grafts - live grafts ,such as
the kidney or heart , which are expected
to survive and function physiologically
inthe recipient .
• Non-viable / structural graft / static –
non living transplants like bone or atery
which merely provide a scaffolding on
which new tissue is laid by the
recipient .
Based on the genetic relationship
between the donor and recipient
• Autograft - An organ or tissue taken
from an individual and grafted on him /
herself .
• Isograft - graft between genetically
similar individuals of the same species .
Eg : graft between identical twins .
• Allograft - graft between genetically
dissimilar individuals of the same
species eg: man and women
• Xenograft - graft between members of
different species eg . Animal to man .
 Allograft reaction

• Mechanism of Allograft reaction - CMI

• 1. Graft APC migrate to host lymph
node .
• 2. Present graft antigen to host T cells
• 3. Host T cell activation
• 4. Migration of activated antigraft T
cells to the grafted tissue and
destruction occurs .
• Occurs in two stages .
1. Sensitization phase
2. Effector stage
 Sensitization phase
• Antigen reactive lymphocytes of the
recipient proliferate , in response to
alloantigens on the graft.
1. CD4 + T cells , CD8+ T cells recognise
alloantigens .
2. Proliferate .
 Effector phase
• Immune destruction of the graft .
• Different mechanisms :
• 1. CMI involving Delayed Hypersensitivity .
• 2. Cytotoxic T Lymphocyte mediated
cytotoxicity .
• 3. Antibody – complement lysis .
• 4. ADCC – Antibody Dependent Cell
mediated Cytotoxicity .
• Permeability of T cells and Macrophages
into the graft .
• Cytokines secreted by helper T cells .
eg: [ IL -2 , IFN –ϒ, TNF- β]
• IL -2- promotes T cell proliferation
especially for CTLs.
• IFN –ϒ , DTH reponse , promote influx
of macrphages into the graft .
• TNF- β , direct cytotoxic effect on the
cells of a graft .
 Primary or first set reaction
• Vascularisation of the graft is normal
initially
• But in 11-14 days ,there is marked
reduction in circulation and
mononuclear cell infiltration occurs with
eventual necrosis .
• Helper T cells ------- activate
cytotoxic cells ,macrophages ,B cells .
• Rejection occurs before the
development of high titres of antibodies .
 Accelerated or second set
reaction
• Second allograft from the same donor
is applied to a sensitized recipient .
• Rejected in 5- 6 days .
• Caused by presensitized Cytotoxic T
cells .
• Along with CMI ,Antibodies formed
rapidly ,abundantly.
Properties of allograft rejection
1.Rejection is due to genetic dissimilarity .
Here HLA antigens are involved .
2.Rapidity of rejection depends upon :
a. Degree of disimilarity between
donor and recipient .
b. Immunocompetency of the recipient .
c. Prior sensitization .
 Clinical manifestations of graft
rejection
• Rejection can be classified as :
1. Hyperacute
2. Acute
3. Chronic
Hyperacute rejection / white graft
response
• Occurs with in few mts to a few hours .
• Transplant destructed by preformed
antibodies & CMI.
• Some produced by recipient before
transplant .
• Generated by previous transplants ,blood
transfusions , pregnancies .
• Antibodies activate complement system
then platelet activation and deposition
causing haemorrhage and swelling .
 Acute rejection
• Seen witin days or weeks .
• Involves the targeting of transplanted
tissue by the CD4 and CD8 host T cells.
• Mechanism –
• T cell activation & proliferation ----
massive infiltration of macrophages &
lymphocytes and tissue destruction ----
graft rejection.
 Chronic rejection
• Occurs months to years of post
transplant .
• Involves both AMI and CMI by the
recipient.
 Prevention of Allograft Rejection
• 1.Blood grouping
• 2.HLA typing
• 3.Tissue matching or Antigen matching by
Mixed Lymphocyte Culture .
• 4.Prevention of infection by antibiotics .
• 5.Immunosuppression of the recipient.
• 6.Transplantation in privileged sites -
cornea, cartilage , testicle are safe for the
survival of allografts.
 Important question
1.Histocompatible antigens
2.Histocompatability testing – 1. Blood
grouping
2.HLA compatability – a.Microcytotoxicity
test
b. RFLP with southern blotting
c. PCR
d. Tissue matching
 Immunosuppression of the
recipient
• General immunosuppressive therapy.
• Specific immunosuppressive therapy.
 General immunosuppressive
therapy
• Mitotic Inhibitors – cyclophosphamide
• Corticosteroids – dexamethasone
• Fungal immunosuppresssant metabolites
-
cyclosporin A
• Total Lymphoid irradiation .
 Specific Immunosuppressive
therapy
• Monoclonal antibodies against various
surface molecules .
• Blocking co-stimulatory signals .
 Graft Versus Host Reaction [GVH ]

• Rejection of immunosuppresed recipient

by immnuocompetant graft./ Graft
mounts an immune response against the
antigen of the host .
• GVH reaction brings damage to host
cells and host.
 Mechanism
• Graft lymphocytes [ T – lymphocytes ]
aggregate inthe host lymphoid organs.
• Graft lymphocytes are stimulated by
host lymphocyte .
• Stimulated graft lymphocytes produce
lymphokines .
• Lymphokines activate host T cell and
poduce polyclonal B cell activation.
• Activated B cell react with self antigens
& cause damage to the host cell.
 Clinical manifestations
• Maculopapular rash,jaundice ,
hepatoslenomegaly , diarrhea , infections ,
death.
 Necessities of GVH
• The graft must contain immunocompetant
T cells.
• Host – immunocomprimised .
• Recipient must express antigens foreign
to the donor .
 Reduction of GVH
• Treating the donor tissue with
antilymphocyte globulin or monoclonal
antibodies before grafting .This
eliminates mature T lymphocytes from
the graft.
• Cyclosporine also used to reduce the
GVH .
Thank you