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
endogenous
from
antigens
and present them to Tcell / 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 transplantationB. 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 as1.Hyper acutewithin 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.