Dr.

Mejbah Uddin Ahmed

Lesson plan
• HLA
• MHC
• MHC Protein
• Diseases associated with HLA
• Transplant
• Measures to be taken for successful
transplantation
• Graft versus reaction (GVH))
 Human leukocyte antigens”/
Major Histocompatibility Complex
• HLA means “human leukocyte antigens”
• These proteins are encoded by HLA genes,
clustered in the major histocompatibility
complex (MHC), located on the short arm
of chromosome 6.
• HLA antigens are alloantigens i.e, differ
among the members of the same species.
• The success of tissue and organ transplant
depends on the donor's HLA.
 Human leukocyte antigens”/
Major Histocompatibility Complex
MHC: Stands for Major histocompatibility
complex located on the short arm of
chromosome 6. There are three clusters
of genes.
•Class I MHC: HLA-A, B, C
•Class II MHC: HLA-DR, DP and DQ.
• Class III MHC: Complement.
HLA/ MHC
Uses of HLA typing:
•Used primarily for determination of HLA
compatibility prior to transplantation. The
better the match in HLA -D, the higher the
probability of graft survival.
• Paternity testing.
• Anthropologic studies.
• For establishing HLA related disease.
MHC proteins:
¤These are the glycoproteins found on
different types of cell surface.
¤Class I MHC protein: Expressed on
all nucleated cells.
¤Class II MHC protein: Expressed on
the surface of professional antigen
presenting cells, I.e; B lymphocyte,
Macrophages, Dendritic cell.
 MHC-I Molecules
MHC-I molecules bind
with peptides from
endogenous antigens
and present them to T-
cell / CD8 molecules on
T8-lymphocytes.
 MHC-II Molecules
MHC-II molecules
bind with peptides
from exogenous
antigens and
present them to
CD4 molecules on
T4-lymphocytes.
 Biological significance of MHC
1. T cell recognition of macrophage processed

antigen. 2. T cell collaboration with B cells.

3. Killing of virally infected cells. 4. Recognition of

foreign antigens during graft rejection.

5. Related with complement system.

6. Associated with many diseases.

Binding of Peptide Epitopes from Endogenous Antigens to
MHC-I Molecules
Antigen-Presenting Cell Presenting MHC-I with
Bound Peptide to a Naive T8-lymphocyte
Binding of Peptide Epitopes from Exogenous
Antigens to MHC-II Molecules
T4-Lymphocyte Recognizing MHC-II
on an Antigen-Presenting Cell (APC)
 Diseases associated with HLA:

• Ankylosing spondylitis B27

• Juvenile rheumatoid arthritis Dw 14

• Reiter's syndrome B27

• Insulin dependant diabetes mellitus DQw 8

• Graves disease ( RR 04%) DR3

• SLE ( RR 03%) DR2

 TRANSPLANTATION IMMUNITY:
• Transplantation: Process of implanting an
organ or part from one site to another site either
within the same animal or from one animal to
another animal either to the same or different
species.
• Prosthesis: Replacement of any tissue by
artificial material.
• Transfusion: Transfusion refers to transfer of
blood or blood products from one individual to
another.
Classification of grafts
On the basis of animal of origin:
1. Autograft 2. Isograft
3. Allograft 4. Xenograft or heterograft.

Autograft: A graft or transplant from one area to

another area of the same individual, e.g.
transplantation of skin from one area of an
individual to another area of the same
individual.
Classification of grafts:
Isograft: A graft between two genetically
identical individuals, as in identical twins.
Allograft: The graft between two genetically
dissimilar individuals of same species. e.g.
transplantation of kidney from one person to
another HLA mismatched person.

Xenograft: A graft between a donor and a

recipient from different species e.g.
transplantation of heart from monkey to human.
HLA /MHC and Transplantation
• Due to thymic education, the T-cell recognizes
any antigen self or non-self by MHC
molecules.

• Individual of same species differs from other

member; HLA molecule leads immunological
phenomenon. This is the main hazards of
transplantation.
Measures to be taken for successful
transplantation-
 Blood grouping and cross matching
 Cross matching of recipients serum with
donors leukocytes.
 HLA typing and matching.
 Complement dependent lymphocytes toxicity
test for class 1 MHC.
 Mixed lymphocyte reaction for class II.
Measures to be taken for successful
transplantation-
B. Immunosuppression of the host by
*Total body irradiation by X-ray.
*Total lymphoid irradiation.
*Cytotoxic and corticosteroid drug therapy.
*Lymphoid cell ablation.
*Administration of excessive amount of
antigens like those antigens shed from the
grafted tissue in the circulation.
Classification of graft rejection
If immunosuppressive measures are not taken
allograft is rejected by a process called graft
rejection.
On the basis of timing, morphology & underlying
mechanism it is classified as-
1.Hyper acute- within minutes after
transplantation
2.Acute - within days after transplantation but
suddenly
3.Chronic- progressive over a period of 4-6
months.
Graft versus reaction (GVH)
• Immunological reaction showed by the
immunocompetent cells of graft tissue to
the immunologically crippled tissue.
• Before transplantation the recipient
undergo irradiation by which all ICC of
recipient become devitalized.
• Grafted tissue from the donor contain
competent T cell.
• They recognize the recipient tissue as
foreign and produces typical cell mediated
and humoral immune response.
GVH can be prevented by–
o • By better HLA typing and matching.
o • By removing the T-cell from the grafted
tissue.
o • By treatment with cytotoxic drugs after
reaction is seen.