Immunomodulating Agents - Drug Design and Discovery - page 362

Infected cell

Viral

Vira

Viral peptide

MHC class I

Peptide

CD8

TCR

Cytotoxic

T cell

FIGURE 22.2 Schematic representation of an antigen (peptide) displayed at the cell surface of an APC in the
class I histocompatibility molecules leading to the activation of a cytotoxic T cell.

The best understood CD8 + T cells are cytotoxic T-lymphocytes (CTLs). They secrete molecules that
destroy the cell to which they are bound. In general, the role of the CD8 + T cells is to monitor all the
cells of the body after they have been primed by APCs in the thymus or in the lymph nodes, ready
to destroy any cell that express foreign antigen fragments in their class I molecules.
CD4 + T cells bind an epitope consisting of an antigen fragment lying in the groove of a class II
histocompatibility molecule. CD4 + T cells are essential for both the cell-mediated and antibody-
mediated (humoral branch) branches of the immune system.

22.2.1.2.1 Cell-Mediated Immunity
CD4 + cells bind to antigen presented by APCs like phagocytic macrophages and DCs. The T cells
then release lymphokines that attract other cells to the area. The result is an inl ammation where
immune cells and molecules accumulate and attempt to protect from and destroy the antigenic
material.

22.2.1.2.2 Antibody-Mediated Immunity
These CD4 + cells, called helper T cells, bind to antigen presented by B cells. The result is the devel-
opment of clones of plasma cells secreting antibodies against the antigenic material (as described
above).

22.2.1.2.3 Building the T Cell Repertoire
After the naive T cell (N) encounters an antigen in the context of an APC (1) it becomes activated
and begins to proliferate (divide) into many clones or daughter cells. (2) Some of the T cell clones
will differentiate into effector T cells (E) that will perform the function of that cell (e.g., produce
cytokines in the case of helper T cells or invoke cell killing in the case of cytotoxic T cells). (3)
Some of the cells will form memory T cells (M) that will survive in an inactive state in the host for
a long period of time until they reencounter the same antigen and reactivate (Figure 22.3).
T helper (Th) 17 cells represent a newly identii ed subset of CD4 + T cells that protects against
extra cellular microbes, but are responsible for autoimmune disorders in mice. However, their