Transcript Power Point

Dental Microbiology #211
IMMUNOLOGY
2006 Lecture 3
Topics
• Antigen Presentation
• Antigen-Presenting Cells (APC)
• The Major Histocompatibility
Complex (MHC)
• MHC Class-I and Class-II Ag
presentation
• Immunological Tolerance
Antigen Presentation
Both B and T lymphocytes become activated as a result of
encounter with specific Ag.
B cells become activated by direct Ag binding,
T cells fail to recognize Ag directly.
T cells bind Ag only when it is presented to them by a
specialized group of cells called collectively Antigenpresenting cells (APC)
B cells are activated by Ag directly. Fig 1
Ignore
T cells recognize Ag only on APC
Fig 2
Ignore
Antigen-Presenting Cells (APC)
Typical APCs:
Macrophages (most tissues)
Dendritic cells (most tissues)
Kupffer cells (liver)
Langerhans cells (skin)
Microglia (CNS)
APCs have in common the ability to phagocytose and digest
the Ag into small fragments (peptides) which are then
deposited on the APC surface for presentation to T cells.
Antigen Presenting Cells. Fig 3
Light
microscopy
Transmission
EM
Scanning
EM
The Major Histocompatibility Complex
(MHC)
Molecules encoded by a group of genes called
the Major Histocompatibility Complex (MHC)
genes.
The proteins encoded by the MHC genes are
called MHC molecules
The Ag fragments are transported to, and
expressed on the APC surface after being
loaded intracellularly onto the MHC
molecules.
MHC-classes
The T cells recognize Ag in the context of either of
two classes of MHC molecules: MHC class-I and MHC
class-II
All cells in the body express MHC class-I molecules,
APCs express both class-I and class-II,
Red blood cells express none.
The function of the MHC is to bind peptide fragments
derived from pathogens and other foreign Ag and
display them on the cell surface for recognition by the
appropriate T cell.
The Major Histocompatibility Complex
Fig 4
Antigen
MHC Contd
The MHC molecules differ from one individual
to another (except in the case of identical
twins),
The MHC preserves the integrity and
individuality of each organism.
In organ transplantation, the recipient’s T
cells, recognize the MHC molecules expressed
by the graft tissue as foreign Ag, resulting in
graft rejection.
Antigen Processing. Fig 5
APC present Ag to T cells in the
context of either MHC-I or MHC-II
The APC takes up Ag, processes it into small fragments,
and loads the fragments onto the MHC class-I or classII molecules.
The MHC-Ag fragment complex is transported to the
APC surface.
The MHC-Ag complex is recognized by a T cell through
its Ag-specific receptor (TCR)
But
CD4+ T cells interact only with Ag on MHC class-II
CD8+ T cells interact only with Ag on MHC class-I
MHC class-I vs Class-II Ag
presentation Fig 6.
CD8+
T cell
CD4+
T cell
CD4 T cell-Ag-APC interaction Fig 7
The CD4 T cell recognizes
Ag fragment only when
loaded in the context of
MHC class-II on an APC.
The CD4 molecule on the T
cell must make contact with
the MHC class-II molecule
on the APC.
Immunological Tolerance
Under normal circumstances, our adaptive immune
system does not react to antigens expressed by our own
tissues and soluble proteins.
Our immune system operates through a process of selfnonself discrimination.
Both B and T lymphocytes are “educated” to recognize
and react only to foreign Ag but not to self (auto) Ag
The process whereby the lymphocytes of an individual
fail to react with self Ag (auto-antigens) is called
immunological tolerance.
The process of immune tolerance takes place during
lymphocyte development in the central lymphoid organs
where the freshly produced Ag-specific receptors on the
developing lymphocyte surface encounter a variety of
self-peptides.
The consequence of this encounter is the death of the
lymphocyte. The process is called clonal deletion
The process of “tolerization” continues in the periphery
whenever new self-reacting clones arise.
Failure of tolerance leads to auto-immune diseases.
E.g. Rheumatoid Arthritis, Juvenile Diabetes, Multiple
Sclerosis, Autoimmune Thyroiditis, Myasthenia Gravis,
etc.
Immunological Tolerance
Fig 8
Both in the thymus and
bone marrow, auto-reactive
clones are deleted upon
encounter with self-Ag
Lymphocyte Clone
END