deck_4748117 Flashcards
Repair occurs by what two types of reactions?
regeneration of the injured tissue and scar formation by the deposition of connective tissue
How does regeneration of injured tissue work?
Some tissues are able to replace the damaged cells and essentially return to a normal state; this process is called regeneration. Regeneration occurs by proliferation of residual (uninjured) cells that retain the capacity to divide, and by replacement from tissue stem cells.
Regeneration is the typical response to injury where?
In the rapidly dividing epithelia of the skin and intestines, and some parenchymal organs, notably the liver.
How does scar formation work?
If the injured tissues are incapable of regeneration, or if the supporting structures of the tissue are severely damaged, repair occurs by the laying down of connective (fibrous) tissue, a process that results in scar formation.
What is the main benefit for scar tissue?
Although the fibrous scar cannot perform the function of lost parenchymal cells, it pro- vides enough structural stability that the injured tissue is usually able to function.
What is fibrosis?
process of extensive deposition of collagen that occurs in the lungs, liver, kidney, and other organs as a consequence of chronic inflammation, or in the myocardium after extensive ischemic necrosis (infarction).
What is ‘organization’?
When fibrosis develops in a tissue space occupied by an inflammatory exudate
Several cell types proliferate during tissue repair, namely:
1) remnants of the injured tissue (which attempt to restore normal structure), 2) vascular endothelial cells (to create new vessels that provide the nutrients needed for the repair process), and 3) fibroblasts (the source of the fibrous tissue that forms the scar to fill defects that cannot be corrected by regeneration).The proliferation of these cell types is driven by proteins called growth factors
The ability of tissues to repair themselves is critically influenced by their intrinsic proliferative capacity. On the basis of this criterion, the tissues of the body are divided into three groups:
1) Labile (continuously dividing) tissues2) Stable tissues3) Permanent tissues
What are labile tissues?
Cells of these tissues are continuously being lost and replaced by maturation from stem cells and by proliferation of mature cells.Labile cells include hematopoietic cells in the bone marrow and the majority of surface epithelia, such as the stratified squamous surfaces of the skin, oral cavity, vagina, and cervix; the cuboidal epithelia of the ducts draining exocrine organs (e.g., salivary glands, pancreas, biliary tract); the columnar epithelium of the gastrointestinal tract, uterus, and fallopian tubes; and the transitional epithelium of the urinary tract. These tissues can readily regenerate after injury as long as the pool of stem cells is preserved.
What are stable tissues?
Cells of these tissues are quiescent and have only minimal replicative activity in their normal state. However, these cells are capable of proliferating in response to injury or loss of tissue mass. Stable cells constitute the parenchyma of most solid tissues, such as liver, kidney, and pancreas. They also include endothelial cells, fibroblasts, and smooth muscle cells; the proliferation of these cells is particularly important in wound healing. With the exception of liver, stable tissues have a limited capacity to regenerate after injury.
What are permanent tissues?
The cells of these tissues are considered to be terminally differentiated and nonproliferative in postnatal life. Most neurons and cardiac muscle cells belong to this category. Thus, injury to brain or heart is irreversible and results in a scar, because neurons and cardiac myocytes cannot regenerate. Limited stem cell replication and differentiation occur in some areas of the adult brain, and there is some evidence that cardiac stem cells may proliferate after myocardial necrosis. Never- theless, whatever proliferative capacity may exist in these tissues, it is insufficient to produce tissue regenera- tion after injury. Skeletal muscle is usually classified as a permanent tissue, but satellite cells attached to the endomysial sheath provide some regenerative capacity for this tissue. In permanent tissues, repair is typically dominated by scar formation.
With the exception of tissues composed primarily of non-dividing permanent cells (e.g., cardiac muscle, nerve), most mature tissues contain variable proportions of three cell types: continuously dividing cells, quiescent cells that can return to the cell cycle, and cells that have lost replicative ability.
With the exception of tissues composed primarily of non- dividing permanent cells (e.g., cardiac muscle, nerve), most mature tissues contain variable proportions of three cell types: continuously dividing cells, quiescent cells that can return to the cell cycle, and cells that have lost replicative ability.
Stem cells are characterized by what two important properties?
self- renewal capacity and asymmetric replication
What is asymmetric replication? Self-renewal?
Asymmetric replication means that when a stem cell divides, one daughter cell enters a differentiation pathway and gives rise to mature cells, while the other remains an undifferentiated stem cell that retains its self-renewal capacitySelf-renewal enables stem cells to maintain a functional population of precursors for long periods of time.
What are the two fundamental kinds of stem cells?
1) Embryonic stem cells (ES cells)2) Adult stem cells
What are ES cells?
are the most undifferentiated stem cells. They are present in the inner cell mass of the blastocyst and have extensive cell renewal capacity. Hence they can be maintained in culture for over a year without differentiating. Under appropriate culture conditions, ES cells can be induced to form specialized cells of all three germ cell layers, including neurons, cardiac muscle, liver cells, and pancreatic islet cells.
What are Adult stem cells?
also called tissue stem cells, are less undifferentiated than ES cells and are found among dif- ferentiated cells within an organ or tissue. Although, like ES cells, they also have self-renewal capacity, this property is much more limited. In addition, their lineage potential (ability to give rise to specialized cells) is restricted to some or all of the differentiated cells of the tissue or organ in which they are found.
What keeps ES stem cells quiescent and undifferentiated?
signals from other cells in stem cell niches
Where are mesenchymal stem cells found and what can they form?
Found in bone marrow and can give rise to a variety of mesenchymal cells, such as chondroblasts, osteoblasts, and myoblasts
Why would introduction of ES cells into a recipient body as part of regenerative therapy be bad?
ES cells are derived from blastocysts (typically produced from in vitro fertilization), their progeny carry histocompatibility molecules (human leukocyte antigen [HLA] in people) of the donors of the egg and sperm. Thus, they are likely to evoke immunologi- cally mediated rejection by the host, just as organs trans- planted from genetically disparate hosts do.
Induced pluripotent stem cells (iPS cells)?
The expressed genes in ES cells and differentiated cells have been compared and a handful of genes that are critical for the “stem-cell-ness” of ES cells have been identified. Introduction of such genes into fully differentiated cells, such as fibroblasts or skin epithelial cells, leads, quite remarkably, to reprogramming of the somatic cell nucleus, such that the cells acquire many of the properties of ES cells.
Most growth factors are proteins that stimulate the survival and proliferation of particular cells, and may also promote migration, differentiation, and other cellular responses.
Most growth factors are proteins that stimulate the survival and proliferation of particular cells, and may also promote migration, differentiation, and other cellular responses.
How do most growth factors work?
Most growth factors function by binding to specific cell- surface receptors and triggering biochemical signals in cells. The major intracellular signaling pathways induced by growth factor receptors are similar to those of many other cellular receptors that recognize extracellular ligands. In general, these signals lead to the stimulation or repres- sion of gene expression. Signaling may occur directly in the same cell that produces the factor (autocrine signaling), between adjacent cells (paracrine signaling), or over greater distances (endocrine signaling).
On the basis of their major signaling transduction pathways, plasma membrane receptors fall into three main types:
1) Receptors with intrinsic kinase activity2) G protein–coupled receptors.3) Receptors without intrinsic enzymatic activity
Receptors with intrinsic kinase activity.
Binding of ligand to the extracellular portion of the receptor causes dimer- ization and subsequent phosphorylation of the receptor subunits. Once phosphorylated, the receptors can bind and activate other intracellular proteins (e.g., RAS, phos- phatidylinositol 3[PI3]-kinase, phospholipase Cγ [PLC- γ]) and stimulate downstream signals that lead to cell proliferation, or induction of various transcriptional programs.Growth factors such as epidermal growth factor (EGF) and hepatocyte growth factor (HGF) bind to receptors with intrinsic kinase activity, triggering a cascade of phos- phorylating events through MAP kinases, which culminate in transcription factor activation and DNA replication.Think EGF, VEGF, FGF, and HGF
G protein–coupled receptors.
These receptors contain seven-transmembrane α-helix segments and are also known as seven-transmembrane receptors. After ligand binding, the receptors associate with intracellular gua- nosine triphosphate (GTP)-binding proteins (G proteins) that contain guanosine diphosphate (GDP). Binding of the G proteins causes the exchange of GDP with GTP, resulting in activation of the proteins. Among the several signaling pathways activated through G protein– coupled receptors are those involving cyclic AMP (cAMP), and the generation of inositol 1,4,5-triphosphate (IP3), which releases calcium from the endoplasmic reticulumChemokines utilize such receptors.
Receptors without intrinsic enzymatic activity.
These are usually monomeric transmembrane molecules with an extracellular ligand-binding domain; ligand interaction induces an intracellular conformational change that allows association with intracellular protein kinases called Janus kinases (JAKs). Phosphorylation of JAKs activates cytoplasmic transcription factors called STATs (signal transducers and activators of transcription), which shuttle into the nucleus and induce transcription of target genes.Cytokines generally bind to receptors without kinase activity; such receptors interact with cytoplasmic transcription factors that move into the nucleus.
