HLA & TISSUE TRANSPLANTATION K R.pptx

1. HLA & TISSUE
TRANSPLANTATION
K R MICRO NOTES 1

2. MAJOR HISTOCOMPATIBILITY
COMPLEX :
• Group of genes coding for a set of host surface
molecules that bind to a peptide fragments
derived from pathogens & foreign antigens, &
display them on host cell surface for recognition
by the T cells.
• Also called Human Leukocyte Antigens (HLA).
• Serves as a unique identification marker for every
individual.
• Following transplantation of a graft the recipient
mount an immune response against the graft’s
MHC molecules & vice versa.
• Also called histocompatibility antigens.
K R MICRO NOTES 2

3. HLA COMPLEX ( MHC GENES) & THEIR
PRODUCTS :
• In humans, HLA complex coding for MHC proteins are located on
short arm of 6th chromosome
• Around 4000 kbp in length coverings >100genes. Genes are
clustered in three regions namely MHC region-Ⅰ, ⅠⅠ & ⅠⅠⅠ.
K R MICRO NOTES 3

4. TISSUE TYPING
• In this test donor’s antigens expressed on the surface of
leukocytes or their genes are matched with that of the recipient.
• The closer the HLA antigens on the transplanted organ match the
recipient, the more likely that the recipient’s the body will not
reject the transplant.
• Value of HLA matching between donor & recipient varies in
different solid organ transplantation. In kidney transplants, there
is substantial benefit if all the polymorphic HLA alleles are
matched.
• Every person inherits each of the following antigens from each
parent: HLA-A,B,C,DR,DQ,DP antigens.
• When performing an HLA typing test for kidney transplant, the
following HLA antigens are looked at: HLA-A, HLA-B, HLA-DR.
• Six HLA antigens are looked at for each person.
K R MICRO NOTES 4

5. TISSUE TRANSPLANTATION
• AUTOGRAFT: self tissue transferred from one part of the body
site to another in the same individual ( e.g transferring healthy
skin to a burned area in burned patients.
• ISOGRAFT OF SYNGENEIC GRAFT: tissue transferred between
genetically identical individuals (e.g monozygotic twins).
• ALLOGRAFT: tissue transferred between genetically non-
identical members of the same species. (e.g kidney or heart
transplant).
• XENOGRAFT: tissue transferred between different species (e.g
the graft of a baboon heart into a man .
K R MICRO NOTES 5

6. AUTOGRAFT ISOGRAFT
ALLOGRAFT
XENOGRAFT
K R MICRO NOTES 6

7. IMMUNE SYSTEM
REJECTION:
Often a transplanted organ is not identified by the immune system
as the tissue of the organism .
It can be attacked & destroyed .
Against this effect, the patient has to swallow
immune suppressive which cause symptoms like
suffering from AIDS.
In 15-20 minutes the organ dies, unable to
withstand the immune system attack.
K R MICRO NOTES 7

8. GRAFT VS. HOST REACTION
(GVHR):
• When grafted tissue has mature T cells, they will attack host
tissue leading to GVHR.
• Major problem for bone marrow transplant.
• Methods to over come GVHR :
a. Treat bone marrow to deplete T cells.
b. Use autologous bone marrow.
c. Use umbilical cord blood.
• The graft possesses transplantation antigens that are absent
in the graft.
• In contrary graft mounts an immune response against the
antigens of the host (GVH).
K R MICRO NOTES 8

9. GRAFT-VS-HOST DISEASE:
• Graft-vs-host disease can occur in special
case in which immunocompetent tissue(fresh
whole blood, thymus or bone marrow) is
transplanted into an immunocompromised
host. T cells from the transplant recognize
the host MHC molecules as non-self & attack
the host. This is a type Ⅳ hypersensitivity
reaction ;antibody plays no role at all.
K R MICRO NOTES 9

10. WHAT HAPPENS AFTER 2-3 DAYS
• The site arounds transplantation is inflamed, invaded by
lymphocytes, macrophages.
• Blood vessels occluded by thrombi
• Vascularity to graft diminishes
• Ischemic changes set in
• Scabs like changes appears, sloughs out 10th day
• Above response is called 1st set response
K R MICRO NOTES 10

11. PREVENTION OF GRAFT REJECTION:
• It is not possible to get donors of exactly similar antigenicity except in case
of monozygotic twins.
• In practice its not possible to match more than 5% of individuals for 3 or 4
HLA antigens.
• For prevention of graft rejection the donor individuals are selected
antigenically closely related.
• Certain grafts are placed at privileged sites where the lymphocytes of host
cannot reach & thus survive longer .
• E.g., corneal graft, trophoblast & fetus in uterus .
• Deficiency of C.M.I in recipient will allow acceptance of graft for longer
period.
• Clinically graft rejection can be suppressed by immune suppressive drugs
e.g., cyclophosphamide, 6-mercaptopurine, & azathiopurine,
adrencorticosteroids or antilymphocytic serum are used prior to
transplantation.
• The residual serum can make the graft tolerant to lymphocytes of the host
K R MICRO NOTES 11

12. REFERENCES:
IMMUNOLOGY 4TH EDITION – K.R. JOSHI/N.O. OSAMA
IMMUNOLOGY 2ND EDITION – S.S LAL & KUMAR S.
BASIC CLINICAL & IMMUNOLOGY – D.P. STITAS , JD. STOBO, H.H FUDENBERG
IMMUNOLOGY 5TH EDITION – RICHARD A. GOLDSBY, THOMAS, BARBARA A.,
JANIS KUBY
WEBSITES : WWW.MICROBIONOTES.IN
WWW.SCIENCEDIRECT.NET
K R MICRO NOTES 12

13. THANK YOU
K R MICRO NOTES 13