Figure 138

Schematic diagram of T cell activation leading to elimination of a virus-infected host cell. The TCR-CD3 complex on a helper CD4+ T lymphocyte recognizes foreign antigen displayed on a MHC II molecule on the surface of a macrophage. This recognition triggers a rapid response from B lymphocytes and release of interleukin-2 (IL-2). The same macrophage also expresses MHC I molecules (like every other cell in the body) that interact with the appropriate TCR on the surface of a cytotoxic CD8+ T lymphocyte. The cytotoxic CD8+ T lymphocyte also possesses IL-2 receptors. IL-2 binding to these receptors stimulates the cell to divide and differentiate. The newly formed cytotoxic CD8+ T lymphocytes migrate to the site of viral infection. There the TCRs recognize the viral antigens displayed on the surface of MHC I molecules of infected cells. After successfully recognizing these "non-self" proteins, the cytotoxic CD8+ T lymphocytes secrete perforins and fragmentins, killing the infected cells.

Activated T lymphocytes synthesize a variety of cytokines

Cytokines are soluble polypeptide substances, synthesized mainly by activated T lymphocytes, which affect the function of other immune system cells. These substances also stimulate the activity of monocytes and macrophages in cell-mediated immunity. Included among these substances are chemotactic and mitogenic agents, migration inhibitory factors, interferon, and interleulcins.

Interleukins are synthesized mainly by helper CD4+ T lymphocytes and to a lesser extent by monocytes, macrophages, and endothelial cells. Interleulcins promote growth and differentiation of T cells, B cells, and hematopoietic cells. Presently, more than 17 interleukins have been identified. Interleukin-2 was the first cytokine to be discovered and characterized. The major functions of known interleukins are summarized in Table 13.3.

Antigen-Presenting Cells

APCs interact with helper CD41 T lymphocytes to facilitate immune responses

The interaction between most antigens and the antibodies on the surface of B cells is insufficient to stimulate B cell proliferation, differentiation, and secretion of antibodies. For B cell stimulation to occur, the antigen must be broken into small peptides and presented in conjunction with MHC II molecules by APCs to the appropriate helper CD4+ T lymphocytes. Most APCs belong to the mononuclear phagocy-totic system (MPS) (described in Chapter 5, page 144). APCs include macrophages, perisimisoidal macrophages (Kupffer cells) of the liver, Langerhans' cells in the epidermis, and reticular dendritic cells of spleen and lymph nodes. Two APCs that do not belong to the MPS are B lymphocytes and type II and type III epithelioreticular cells of the thymus.

Human immunodeficiency virus (HIV) is a RNA retrovirus; it contains an enzyme called reverse transcriptase. HIV is the virus that causes acquired immunodeficiency syndrome (AIDS). HIV has an incubation period that may be as long as 11 years before symptoms of clinical AIDS occur. The great majority of HIV-infected individuals eventually develop AIDS. HIV gains entry to helper T cells by binding to CD4 molecules. The virus then injects its own genetic information into the cell cytoplasm (Fig. 13.9 ). This injected genetic information consists of single-stranded RNA. The viral RNA is incorporated into the infected T cell genome through reverse transcription of the RNA into DNA. The transcribed DNA is then incorporated into the host DNA. The T cell then makes copies of the virus, which are extruded from the T cell through exocyto-sis. These HIV particles then infect other helper T cells, greatly re ducing their number. The helper CD4+ T cell count is used as a clinical indicator of the progress of HIV infection. Infected individuals eventually become incapable of generating an immune response against bacterial or viral infections. They usually die of secondary infections caused by opportunistic microorganisms or of malignancies.

Anti-HIV treatment is the major strategy against HIV infection and AIDS. Currently, the most effective is multiple drug therapy known as highly active antiretroviral therapy (HAART), which uses a combination of several chemotherapeutic agents. These include nucleoside and nonnucleoside reverse transcriptase inhibitors and HIV protease inhibitors. HAART offers several advantages over monotherapy such as synergistic dosage effects and reduced side effects as well as reduced drug resistance.

reverse transciptase gp 120

gp 120

chemokine receptor reverse transciptase

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