Antigens & HLA Dr.Ghada Boghdadi. Objectives: * Define antigen and hapten. * Define immunogenicity &...
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Transcript of Antigens & HLA Dr.Ghada Boghdadi. Objectives: * Define antigen and hapten. * Define immunogenicity &...
Antigens & HLA
Dr.Ghada Boghdadi
Objectives:
* Define antigen and hapten.
* Define immunogenicity & antigenicity.
* Define epitope.
* Describe the chemical nature and different classes of Ag.
* Discuss various determinants of antigenicity. * Describe the major classes of MHC molecule.
* Explain the role of MHC in immune mechanism (antigen processing, antigen presentation & immune response).
Anantha NarayananCh 15
Immunogen: A substance that induces a specific immune response.
Antigen (Ag): A substance that reacts with the products of a specific
immune response.
Hapten: A substance that is non-immunogenic but which can react with the products of a specific immune response. Haptens are small molecules which could never induce an immune response when administered by themselves but which can when coupled to a carrier molecule.
Epitope or Antigenic Determinant: That portion of an antigen that combines with the products of a specific immune response. Any given antigen may have several epitopes. Each epitope is recognized by a different antibody.
Antibody (Ab): A specific protein which is produced in response to an immunogen and which reacts with an antigen.
Epitopes: Antigen Regions that Interact with Antibodies
FACTORS INFLUENCING IMMUNOGENICITY
A- Immunogen:
1. Foreignness
2. Size
3. chemical composition
4. Physical form
5. Degradability
B- Biological system:
1. Genetic factors.
2. Age.
C- Method of administration:
1. Dose.
2. Route.
3. Adjuvants.
Substances which are added to or emulsified with an Ag so as to enhance the Ab production.
They can be - Inorganic salts : Aluminium hydrooxide- Bacterial products: Bordetella pertussis (with Diphtheria, Tetanus toxoids)
The chemical nature of immunogens:
1. Proteins.
2. Polysaccrides.
3. Nucleic acids.
4. Lipids.
Types of Antigens:
T-dependent Ag:
-Do not directly stimulate the production of antibody without the
help of T cells.
- Proteins.
- Immunogenic over a wide dose range and do not cause tolerance.
- Produce immunological memory
- Requires processing by APCs.
T-independent Ag:
- Can directly stimulate the B cells to produce antibody without the requirement for T cell help.
- Polysaccharides.
- Immune response is dose dependent. Too little – non immunogenic Too much – tolerance
- Do not produce immunological memory.
- Do not require processing by APCs.
Antigen processing and presentation
Exogenous Ag Endogenous Ag
Superantigens
Not processed.Interact with the MHC class II molecule outside of the peptide - binding groove.Bind only to the Vβ segment of TCR.
Antigenic specificity:
Species Specificity.
Isospecificity. (Human blood group)
Autospecificity.
Heterogenetic (heterophile) Specificity.
Major histocompatibility complex (MHC)
• The MHC is a large complex region of highly polymorphic genes located on the short arm of chromosome 6.
• Also known as human leukocyte antigens or HLA.
• There are 3 classes of MHC molecules: MHC Class I, Class II and Class III.
. They differ among members of the same species.
. Each person has two haplotypes.
T cell receptor only recognize antigens combined with major histocompatability (MHC) proteins on the surface of cells.
• MHC Class I: Found on all cells.
• MHC Class II: Found on phagocytes.
• MHC class I & II play role in antigen presentation
For T cell activation, T cell receptor (TCR) must recognize the processed antigens (in peptide fragment forms) which bound to MHC class I or II molecules
(MHC restriction).
Table 1. Polymorphism of class I MHC genes
LocusNumber of alleles
(allotypes)
HLA-A 218
HLA-B 439
HLA-C 96
HLA-E, HLA-F and HLA-G Relatively few alleles
Table 2. Polymorphism of class II MHC genes
LocusNumber of alleles
(allotypes)
HLA-DPAHLA-DPB
1288
HLA-DQAHLA-DQB
1742
HLA-DRAHLA-DRB1HLA-DRB3HLA-DRB4HLA-DRB5
226930712
HLA-DM and HLA-DO Relatively few alleles