Transplantation
Dr. Karzan Mohammad
PhD. MSc. BSc.
Medical Biologist
Faculty of Education
Ishik University
100M Road
Erbil-Iraq
Tel.: 07504095454
Research Fellow
Manchester Fungal Infection Group
The University of Manchester
Institute of Inflammation and Repair
Manchester, UK
M13 9NT
Tel. 07927133678
GBD Expert
Global Burden of Disease IHME
Institute for Health Metrics and
Evaluation
University of Washington
Seattle, WA 98121, USA
INTRODUCTION
DEFINITION OF TERMS
An organ transplant is a surgical procedure in which a failing
organ is replaced by a functioning one from a donor with a compatible
tissue type.




Autograft
Allograft
Isograft
Xenograft
Tissues that can be transplanted


Bones
Heart valves

Tendons  Cornea

Skin of leg

Vein
Number opted-in on the NHS Organ Donor Register at 31 March
25.0
22.5
21.1
20.2
19.5
Number on the ODR (millions))
20.0
18.7
17.1
17.8
16.1
15.1
15.0
14.2
10.0
5.0
0.0
2007
2008
2009
2010
2011
2012
2013
Year
Source: Transplant activity in the UK, 2015-2016, NHS Blood and Transplant
2014
2015
2016
Age and gender of total people registered as opt-in on the NHS Organ Donor
Register by 31 March 2016
30%
Percentage of people registered
25%
23.8%
22.9%
21.9%
21.3%
20.3%
19.2%
20%
18.6% 18.2%
17.9%
14.3% 14.1%
13.8%
15%
Male
Female
Total
10.1%
9.9%
9.7%
8.6%
10%
7.6%
6.8%
5%
2.6%
2.2%2.3%
3.3%
2.9%
2.5%
1.4%1.8% 1.6%
0%
<11
11-15
16-20
21-30
31-40
Age group (years)
41-50
Source: Transplant activity in the UK, 2015-2016, NHS Blood and Transplant
51-60
61-70
71+
Major Histocompatibility
Complex (MHC)

Major function of MHC- bind to peptide
fragments derived from foreign antigen and
display them on cell surface for recognition
by appropriate T cell.

MHC determines the compatibility between
donor and recipient for organ transplantation.
Characteristics of MHC

Responsible for strong rejection

MHC class I molecules - almost all
nucleated cells

MHC class II molecules – APCs, B cells,
Macrophages
Antigen processing and display by MHC Molecule

Major histocompatibility complex MHC:
o
They are clusters of genes on the short arm of
chromosome 6 expressed on the cell surface as
HLA (Human Leukocyte Antigen) i.e. genes that
encode HLA.

ABO:
o
These blood group antigen are expressed not only
on red blood cells but by most cell types as well.
o
Incompatibility leads to hyperacute rejection
GRAFT REJECTION
Rejection of transplanted organs is a
bigger challenge than the technical expertise
required to perform the surgery. It results
mainly from HLA and ABO incompatibility
through MHC classes.



Hyperacute
Acute
Chronic
GRAFT REJECTION (Contd…)
Hyper acute rejection
 Immediate graft destruction due to ABO or
preformed anti- HLA antibodies.
 Characterized by intravenous thrombosis and
interstitial hemorrhage.
 Risk factors are previous failed transplant and
blood transfusions
 Kidney transplant is vulnerable to hyperacute
rejection
GRAFT REJECTION (Contd…)
Acute rejection
 Usually occurs during the first 6 months.
 May be cell mediated (T-cell), antibody mediated or
both
 Characterized by cellular infiltration of the
graft(cytotoxic, B- cells, NK cells and macrophages)
GRAFT REJECTION (Contd…)
Chronic Rejection:
 It occurs after 6 months.
 Most common cause of graft failure
 Antibodies play important role
 Non- immunological factors contribute to the
pathogenesis
 Characterized by myointimal proliferation in
graft arteries leading to ischemia and fibrosis
CELLULAR REJECTION




It is caused by T-cell mediated reactions.
Destruction of grafts occurs by
1. CD8+ CTLs
2. CD4+ helper cells
Delayed hypersensitivity is triggered by CD4+
helper cells.
2 pathways
1. Direct pathway
2. Indirect pathway
Non rejection complications
Transport injury
 Drug toxicity
 Infection
 Malignancy
 Recurrence of disease

METHODS OF INCREASING GRAFT
SURVIVAL

Immunosuppressive agents
1. Cyclosporin
2. Azathioprine
3. Steroids
4. Rapamycin
5. Monoclonal antibodies.
ANOTHER METHOD:

Prevention of host T cells from receiving costimulatory signals (B7-1&2) from dendritic
cells.
DISADVANTAGES:
 EBV induced lymphoma
 HPV induced squamous cell carcinoma
 Sarcoma
PRINCIPLES

PRE-OPERATIVE

Patient selection and Evaluation

Counseling

Informed written consent

Optimization
PATIENT SELECTION & EVALUATION
(Recipient)
1. RECIPIENT

Clinical evaluation; history and physical
examination

Immunological evaluation

Infection screening – septic work-up

Others ; CBC, clotting profile, ECG, tumour
markers.
Patient selection & evaluation (DONOR)

Contra-indications for living donor
o
Mental disease
o
Diseased organ
o
Morbidity and mortality risk
o
ABO incompatibility
o
Cross matching incompatibility
o
Transmissible disease
Patient selection & evaluation (DONOR)

II. Deceased donor
- Brain dead donors:
o
Normothermic patient.
o
No respiratory effort by the patient.
o
The heart is still beating.
o
No depressant drugs intake should be there while evaluating
the patient.
o
Individual should not have any sepsis, cancer (except brain
tumour).
o
Not a HIV or hepatitis individual.
TISSUE TYPING

The tissue typing laboratory carries
out 3 tasks :

To determine the HLA type of blood for both
donor and recipient by PCR.

Lymphocyte cross-matching.

HLA antibody screening and specificity
CROSS MATCHING



Positive cross matching;
o
Recipient antibodies attacks donor’s.
o
Not suitable for transplant
Negative cross matching;
o
Recipient antibodies do not attack donor
o
Suitable for transplant
Methods;
o
Micro-cytotoxic assay, mixed lymphocytes, flow cytometry,
DNA analysis.
Thank you