T lymphocytes have a central role in the generation of immune responses by acting as helper cells in both humoral and cellular immune responses and by acting as effector cells in cellular responses. T cells can be distinguished from other types of
Figure 6.1 External stimuli affect the cell, which has a specific coordinated response.
lymphocytes by their cell surface phenotype, based on the pattern of expression of various molecules, as well as by differences in their biologic functions.
● There are two major subsets of mature T cells that are phenotypically and functionally distinct: T-helper/inducer cells, which express the CD4 cell surface marker, and the T-suppressor/cytotoxic cells, which express the CD8 marker. TH1 and TH2 are two helper T-cell subpopulations that control the nature of an immune response by secreting a characteristic and mutually antagonistic set of cytokines: Clones of TH1 produce interleukin-2 (IL-2) and interferon-γ (IFN-γ), whereas TH2 clones produce IL-4, IL-5, IL-6, and IL-10.
Advances in molecular biology and genetics have improved our understanding of basic biologic concepts and disease development. The knowledge acquired with the completion of the human genome project, the data available through The Cancer Genome Atlas (TCGA), the development of novel diagnostic modalities, such as the microarray technology for the analysis of DNA and proteins, and the emergence of treatment strategies that target specific disease mechanisms all have an increasing impact on the specialty of obstetrics and gynecology.
Normal cells are characterized by discrete metabolic, biochemical, and physiologic mechanisms. Specific cell types differ with respect to their mainly genetically determined responses to external inﬂuences (Fig. 6.1). An external stimulus is converted to an intracellular signal, for example, via a cell membrane receptor. The intracellular signal is transferred to the nucleus and generates certain genetic responses that lead to changes in cellular function, differentiation, and proliferation. Although specific cell types and tissues exhibit unique functions and responses, many basic aspects of cell biology and genetics are common to all eukaryotic cells.
Normal Cell Cycle Adult eukaryotic cells possess a well-balanced system of continuous production of DNA (transcription) and proteins (translation). Proteins are constantly degraded and replaced depending on the specific cellular requirements. Cells proceed through a sequence of phases called the cell cycle, during which the DNA is distributed to two daughter cells (mitosis) and subsequently duplicated (synthesis phase). This process is controlled at key checkpoints that monitor the status of a cell, for example, the amount of DNA present. The cell cycle is regulated by a small number of heterodimeric protein kinases that consist of a regulatory subunit (cyclin) and a catalytic subunit (cyclin-dependent kinase). Association of a cyclin with a cyclindependent kinase (CdkC) determines which proteins will be phosphorylated at a specific point during the cell cycle.
Figure 6.2 The cell cycle.
The cell cycle is divided into four major phases: M phase (mitosis), G1 phase (period between mitosis and initiation of DNA replication), S phase (DNA synthesis), and G2 phase (period between completion of DNA synthesis and mitosis) (Fig. 6.2). Postmitotic cells can “exit” the cell cycle into the so-called G0 phase and remain for days, weeks, or even a lifetime without further proliferation. The duration of the cell cycle may be highly variable, although most human cells complete the cell cycle within approximately 24 hours. During a typical cell cycle, mitosis lasts about 30 to 60 minutes, the G1 phase 7 to 10 hours, S phase 10 hours, and G2 phase 5 hours. With respect to the cell cycle, there are three subpopulations of cells: 1.
Terminally differentiated cells cannot re-enter the cell cycle.
2.
Quiescent (G0) cells can enter the cell cycle if appropriately stimulated.
3.
Dividing cells are currently in the cell cycle.