Histology, Cytotoxic T Cells

Excerpt

The innate and adaptive immune systems form the basis of immunity in human beings. Innate immunity is a generalized and non-specific response to pathogens, while adaptive immunity induces pathogen-specific, more sophisticated, and long-term responses. Antibody-mediated and cell-mediated responses carry out adaptive immunity. The antibody-mediated response involves the production of immunoglobulin by B lymphocytes. The response generated by T-cells is called a cell-mediated response. There are two classes of T-lymphocytes, helper and cytotoxic T-cells, also called CD4+ and CD8+ T-cells, respectively.

Helper T-cells activate macrophages and cytotoxic cells and stimulate antibody synthesis in B lymphocytes. Cytotoxic cells are involved in directly killing intracellular and extracellular pathogens and eliminating mutated and cancerous cells. These immune responses are generated by T-cells when they recognize an antigen, which is exposed to them by antigen-presenting cells. The antigen is a peptide fragment generated by antigen-presenting cells when they degrade the foreign protein. To be recognized by a T-cell, the antigen must bind to a protein called the major histocompatibility complex (MHC). MHC proteins aid in T-cell activation and have a vital role in the maturation of T-cells in the thymus.

T-lymphocytes originate from hematopoietic stem cells in the bone marrow and migrate to the thymus for maturation. They enter the thymus at the corticomedullary junction and move towards the cortex while undergoing developmental changes to accumulate in the subcapsular zone. Initially, the newly arrived intrathymic immature T-cells are known as double-negative cells because they lack expression of CD4 or CD8, but during maturation, they develop both CD4 and CD8 receptors and are then called double-positive cells. In the thymus, these immature double-positive cells are presented with various antigens, and a small subset (1%-5%) binds to antigens connected to MHC types 1 or type 2. The rest of the double-positive cells undergo apoptosis. The T-cells that bind to MHC type 1 molecules become CD4-/CD8+ (cytotoxic T-cells), and the T-cells that bind to MHC type 2 molecules become CD4+/CD8- (helper T-cells). This process is called positive selection. Positively selected T-cells enter the medulla, where they undergo negative selection. This process involves eliminating T-cells whose receptors bind strongly to self-antigens or self-MHC proteins (avoiding autoimmunity).