Fig. 1.31 Mechanism of host defense against intracellular infection by viruses. Cells infected by viruses are recognized by specialized t cells called cytotoxic t cells, which kill the infected cells directly. the killing mechanism involves the activation of enzymes known as caspases, which contain cysteine in their active site and cleave target proteins at aspartic acid. the caspases in turn activate a cytosolic nuclease that cleaves host and viral dnA in the infected cell. Panel a is a transmission electron micrograph showing the plasma membrane of a cultured CHo cell (the Chinese hamster ovary cell line) infected with influenza virus. many virus particles can be seen budding from the cell surface. Some of these have been labeled with a monoclonal antibody that is specific for a viral protein and is coupled to gold particles, which appear as the solid black dots in the micrograph. Panel b is a transmission electron micrograph of a virus-infected cell (V) surrounded by cytotoxic t lymphocytes. note the close apposition of the membranes of the virus-infected cell and the t cell (t) in the upper left corner of the micrograph, and the clustering of the cytoplasmic organelles in the t cell between its nucleus and the point of contact with the infected cell. Panel a courtesy of m. Bui and
A. Helenius; panel b courtesy of n. rooney.
MHC class I molecules bearing viral peptides are recognized by CD8-bearing cytotoxic T cells, which then kill the infected cell (Fig. 1.32).
CD4 T cells recognize antigen presented by MHC class II proteins, which are expressed by the predominant antigen-presenting cells of the immune system: dendritic cells, macrophages, and B cells (Fig. 1.33). Thus CD4 T cells tend to recognize antigens taken up by phagocytosis from the extracellular environment. CD4 T cells are the helper T cells mentioned earlier in the chapter. They develop into a variety of different effector subsets, called TH1 (for T helper type 1), TH2, TH17, and so on, and they produce cytokines in patterns similar to the subsets of ILCs mentioned earlier that activate effector modules protective against different pathogens. These subsets act primarily at sites of infection or injury in peripheral tissues. In the lymphoid tissues, a subset of CD4 T cells, called the T follicular helper (TFH) cell, interacts with B cells to regulate antibody production during the immune response. The various T helper subsets are described later, in Chapter 9.
For example, the TH1 subset of CD4 T cells helps to control certain bacteria that take up residence in membrane-enclosed vesicles inside macrophages. They produce the same cytokine as ILC1 cells, IFN-γ, which activates macrophages to increase their intracellular killing power and destroy these bacteria. Important infections that are controlled by this function are tuberculosis and leprosy, which are caused by the bacteria Mycobacterium tuberculosis and M. leprae, respectively. Mycobacteria survive intracellularly because they prevent the vesicles they occupy from fusing with lysosomes, which contain a variety of degradative enzymes and antimicrobial substances (Fig. 1.34). However, on its surface, the infected macrophage presents mycobacteriaderived antigens that can be recognized by activated antigen-specific TH1 cells, which in turn secrete particular cytokines that induce the macrophage to the effector mechanisms of immunity.
Fig. 1.33 CD4 T cells recognize antigen presented by MHC class II molecules.
on recognition of their specific antigen on infected macrophages, tH1 cells activate the macrophage, leading to the destruction of the intracellular bacteria (top panel). When t follicular helper (tFH) cells recognize antigen on B cells (bottom panel), they activate these cells to proliferate and differentiate into antibody-producing plasma cells (not shown).