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 Antigen- presenting 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 Transmission EM Scanning EM Light microscopy

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 class- II 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. CD4+ T cell CD8+ 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 self- nonself 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 Lymphocyte Clone Both in the thymus and bone marrow, auto-reactive clones are deleted upon encounter with self-Ag

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