Chapter 5: T cells, cell mediated immunity and the immune system

Chapter 5: T cells, cell mediated immunity and the immune system

T cells and cell-mediated immunity:

Development of T lymphocytes

·        T lymphocytes originate from the multipotent hematopoietic stem cells in the bone marrow.

·        These progenitor cells migrate from the bone marrow via the blood to the thymus, where they mature.

·        The progenitor cell receives a signal, most probably from stromal cells of the thymus that instructs the precursor to commit to the T-cell lineage rather than the B-cell lineage.

Development of T lymphocytes in the thymic cortex

·        The cortex consists of immature thymocytes, branched cortical epithelial cells and scattered macrophages. It has a high cellular density and is packed with immature T cells awaiting positive (functional) selection.

·        Positive selection ensures that the T cells will have the bare minimum functionality of binding the cell surface proteins major histocompatibility complex class (MHC) I or II. Of note, most immature T cells that undergo this process never make it past this step and subsequently undergo apoptosis.

·        The scattered macrophages are involved in clearing of the apoptotic cells.

·        It is of critical importance that these thymocytes are able to bind MHC. When mature, they will bind MHC I if they differentiate into CD8+ T cells and MHC II if they differentiate into CD4+ T cells.

Development of T lymphocytes in the corticomedullary junction

·        In this region, T cells undergo negative selection. Negative selection destroys cells that see the body's own normal antigens as foreign invaders.

·        Negative selection is highly important in preventing autoimmune disease by destroying T cells that could potentially start an attack on the body's own cells. A T cell that has made it through positive selection is presented with self-antigen. If the specificity of binding is too strong, an apoptotic signal will be given to that particular T cell leading to clonal deletion.

·        Of note, some autoreactive T cells are able to make it through the negative selection phase, but are eliminated by peripheral mechanisms (e.g., anergy, regulatory T cells). However, if peripheral mechanisms also fail, then this sets the stage for potential predisposition to autoimmunity.

What is anergy?

·        Co-stimulatory molecules are crucial in initiating an immune response.

·        Without accompanying co-stimulatory molecules, naive lymphocytes are inactivated.

·        This inactive state is known as anergy. (Mnemonic: No energy received for immune response is anergy.)

Medulla

·        Medulla consists of a pale, low cellular density with mature T cells having already gone through positive and negative selection.

·        Medulla also contains Hassall corpuscles, which are remnants of apoptosed T-cells seen on histology.

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