T_C (cytotoxic) Cells (CD8 cells):

Cytotoxic T cell provides protection against intracellular pathogens such as viruses and some bacteria and parasites that multiply in the host-cell cytoplasm, where they are sheltered from attachment by antibodies.

Under the influence of T_H a T_C that recognizes an antigen-MHC molecule complex  proliferates and differentiates into an effector called a cytotoxic T lymphoctye (CTL) which can eliminate cells that display antigen, such as virus infected cells, tumor cells and cells of a foreign tissue graft.

In general, CTLs are CD8+ and are class I MHC restricted, although in rare instances CD4+ class II restricted T cells have been shown to function as CTLs. CD8+ T cells recognize viral peptides associated with MHC class I molecules on the surface of infected cells. They lyse these cells and produce IFNγ and other antiviral molecules. To proliferate and differentiae into effector cells, naive CD8+ T lymphocytes, however, first require antigen presentation by dendritic cells (DC).

Since virtually all nucleated cells in the body express class I MHC molecules, CTLs can recognize and eliminate almost any altered body cell.

Types of CD8 T lymphocytes

CD8 T lymphocytes are composed of different subpopulations on the basis of their stage of differentiation, activation state, cellular phenotype, and functional capacity. CD8 T cells can be subdivided into different maturation lineages on the basis of the expression of the different isoforms of the leukocyte common antigen CD45.

The high molecule weight isoform, CD45RA is expressed on both naive and antigen-primed effector CD8 T cells.

The low-molecular weight isoform, CD45RO is expressed predominantly on activated CD8 T cells.

CD8+CD11b+T cells have been reported to be recently activated effector cells.

Niave CD8+CD11b-T cells are naive or memory T cells.

T cytotoxic Cell Activation:

Resting T_C cells are incapable of killing target cells. DC8 T Cells require three steps to become activated.

• First, the T cell receptor and CD8 and the CTL must interact with an antigenic peptide-class I MHC complex on the membrane of a target cell. CD8+ T cells are usually activated by antigens on DCs, which have been acquired endogenously (e.g., viral protein synthesis in the DCs cytoplasm). These proteins are cleaved into peptides, transported into the ER via ATP-dependant TAP transmembrane transporters and loaded onto MHC class I molecules for export to the cell surface.
• Co-stimulatory molecules: B7-1 and B7-2
• CD8 Tells require a third signal such as IL-12. If miss this third signal get tolerance instead of activation of CTL. Could there also be a third signal with respect to CD4 T cell activation? The answer is not in yet on this question. Interesting, memory CD8 T cells (OT-I) do not require a third signal.

CD4+ T_H cells are also believed to assist CD8 T cells after initial activation by producing IL-2. Antigen activation induces a CTL to increase its expression of the IL-2 receptor. IL-2 produced by proliferating T_H cells binds to this receptor and induces the CTL to proliferate and differentiate into effector CTLs.

How CD8 T lymphocytes Recognize Cells

Surface interactions between the T cell receptor (TCR) and peptides of 8-11 amino acids (eptiopes) bound to MHC class I molecules form the basis for CTL recognition of cells expressing foreign or dysfunctional proteins. Peptide peitopes are generatd primarily by proteolytic cleavage in the cytosol, and associate with MHC class I molecules in the ER prior to externalization. Virally infected cell thus present an array of nonself epitopes capable of stimulating specific CTL responses.

How do T Cytotoxic Cells Kill?:

How do CTLs kill target cells? One mechanisms is through expression of the Fas gene. Activation of CTLs through T cell-receptor interaction with viral antigens induces the expression of the FasL gene. The FasL expressed on the surface of the effector cells binds to Fas on the target cell and causes apoptosis by activating caspases.

Another mechanism is the perforin/granzyme pathway. Similar activation of CTLs through T cell receptor releases perforins and granzymes stored in granules. Perforin makes pores in the plasma membrane of the target cells. One of the granzymes (granzyme B) is a serine protease caspase, which activates some of the caspase family members by proteoysis.