Term
| How to distinguish between epithelium and connective tissue? |
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Definition
| Epithelia are composed of many cells with little extracellular matrix. CTs typically are composed of a few cells, with lots of extracellular matrix. On an H&E slide, CT has much fewer nuclei. Also, epithelial cells tend to have more cytoplasm, which stains eosinophilic, while connective tissue cytoplasm is pale or sparse. |
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Term
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Definition
| It is the embryonic precursor material from which all connective tissues and some other tissues derive. It is composed of mesenchymal cells surrounded by a matrix with that is nearly absent of connective fibers. It has small, spindle-shaped cells of uniform appearance. Osteocytes, adipocytes, fibroblasts and chondrocytes (cells found in cartilage) are derived from mesenchyme. |
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Term
| What is mucous connective tissue? |
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Definition
| It is a type of embryonic connective tissue that is found in the umbilical cord. It consists of a specialized, almost gelatinlike ECM. Its spindle-shaped cells are widely separated. |
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Term
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Definition
| They derived from mesenchymal cells, and are the “resident” generic connective tissue cells that produce most, if not all, of the fibers and matrix. They have an oval nucleus and tapered eosinophilic cytoplasm. If a cell has a round nucleus and a round cytoplasm then it is not a fibroblast. They have elongated nuclei, often elongated nucleoli, and attenuated organelles (rER, Golgi, etc). |
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Term
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Definition
| They derived from monocytes (not mesenchyme) and are found in many tissues throughout the body. The name (big eater) aptly describes their characteristic phagocytic capacity. Macrophages play roles in inflammation and in immune responses. In light microscopy, macrophages can be identified by their indented or kidney-shaped nuclus. In EM, they have an oval nucleus, lots of vacuoles and lots of extensions b/c of constant phagocytosis. |
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Term
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Definition
| Mast cells are immune cells that play a role in inflammation and anaphylaxis, and have large amounts of secretory granules containing histamine and heparin. Mast cells are identified in toluidine blue stain, where the mast cell granules turn the dye purple (metachromasia). They are large, ovoid, and have a spherical nucleus and cytoplasm filled with basophilic granules. They arise from plurpotential hemopoietic stem cells (HSC) in the bone marrow. |
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Term
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Definition
| They are granulocytes that circulate in the bloodstream, representing less than 1% of leukocytes. They develop and mature in the bone marrow. They participate in allergic reactions. |
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Term
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Definition
| They are connective tissue cells that are specialized to store neutral fat and produce a variety of hormones. |
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Term
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Definition
| They are elongated, spindly connective tissue cells not readily identified in routine H&E preparations. They have bundles of actin filament with associated actin motor proteins. |
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Term
| What is ground substance? |
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Definition
| It is the extracellular matrix (ECM) component that fills in the spaces between the fibers and cells. It contains water, ions, GAGs, and other molecules. The components vary considerably, and account for the fact that matrix (and connective tissues) can vary from fluid to solid. |
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Term
| Types of generic connective tissue |
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Definition
| These are Loose (aka areolar, includes reticular, elastic, maybe mesenchyme), Dense irregular (aka dense irregular), and Dense regular (aka dense regular) |
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Term
| Main variables used to distinguish types of generic connective tissue |
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Definition
| The density and thickness of the extracellular fibers (loose vs. dense) and the orientation of the fibers (irregular vs. regular). |
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Term
| Loose connective tissue (aka areolar) |
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Definition
| Contain more space than collagen or reticular fibers. The fibers that are there are thin, so it is loose. The fibers are oriented in all directions. They are not very strong but are usually well vascularized. They are found as filler and are especially useful right under epithelia, which has no blood vessels of its own. It is the initial site where pathogenic agents that have breached an epithelial surface are challenged by the immune system. It is the site of inflammatory and immune reactions. |
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Term
| Is mesenchyme a type of loose connective tissue? |
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Definition
| No, mesenchyme is undifferentiated connective tissue that can give rise to all connective tissue types, including the generic types as well as the specialized ones (e.g. cartilage, bone, etc.). Because it has few extracellular fibers, it’s tempting to call this loose connective tissue, but this is incorrect. Mesenchyme and loose connective tissue are mutually exclusive. |
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Term
| Dense irregular connective tissue |
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Definition
| It has less space and many thick (type I) collagen fibers, which are oriented in all directions. It is strong in multiple directions but usually is not as well vascularized as loose connective tissue. |
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Term
| Dense regular connective tissue |
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Definition
| It has no space. It has many thick (type I) collagen fibers that are packed so tightly that it’s hard to see individual fibers. The collagen fibers oriented in one direction. This is difficult to appreciate because the individual collagen fibers are hard to see, but you can see how the fibroblast nuclei have to orient, narrow and elongate. They are strong in one direction (e.g. tendon, ligament) but are usually very poorly vascularized, which means it takes a long time to heal. |
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Term
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Definition
| They are the most abundant structural components of the connective tissue. They are flexible and have a high tensile strength. In EM, they appear as bundles of fine, threadlike subunits. In light microscopy they stain readily with eosin and other acidic dyes, appearing thick and pink. Collagen type is determined by the polypeptide subunit composition. Collagen forms regular structures. Collagen fibers have high tensile strength (are able to withstand elongation) and have an okay shear resistance. |
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Term
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Definition
| A single collagen molecule consists of three polypeptides known as α chains. These chains intertwine, forming a right-handed triple helix. Every third aa in the chain is a glycine, except at the ends of the α chains. Associated with the helix are sugar groups, making collagen a glycoprotein. Homotrimeric collagen contains three identical α chains while heterotrimeric collagen has two or three genetically distinct α chains. |
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Term
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Definition
| It is found in loose and dense connective tissue. It is heterotrimeric, with two α1 and one α2 chains. It provides resistance to force, tension and stretch. |
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Term
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Definition
Type II collagen
It is homotrimeric and found in cartilage, notochord and intervertebral disk. It provides resistance to intermittent pressure. |
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Term
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Definition
| It is homotrimeric. It is prominent in loose connective tissue and organs, smooth muscle, endoneurium, blood vessels, and fetal skin. It forms reticular fibers, arranged as a loose meshwork of thin fibers, and provides a supportive scaffolding for the specialized cells of various organs and blood vessels. |
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Term
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Definition
| It is heterotrimeric and found in the basal laminae of epithelia, kidney glomeruli, and lens capsule. It provides support and acts as a filtration barrier. Type IV polymerizes into sheets instead of fibers because extension peptides are not removed and there are more substitutions for glycine in “Gly”-X-Y repeated tripeptide. Normally, in collagen extension peptides are cleaved off in formation of fibers. The glycine substitutions create kinks that prevent fibers. |
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Term
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Definition
| In light microscopy, they are present, but not visible without special stains (such as silver stain or PAS) because they are thinner than collagen fibers. Reticular fibers are composed of type III collagen. Networks of reticular fibers are found at the boundary of connective tissue and epithelium. They are prominent in the initial stages of wound healing and scar tissue formation, where they provide early mechanical strength to the newly synthesized ECM. They are normally produced by fibroblasts. Reticular fibers are fine collagen fibrils that connect basal lamina to the connective tissue proper |
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Term
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Definition
| In resorcin stains, they are thin and purple. They are usually not visible with standard H&E, except in some tissues (such as large elastic artery), where they form a prominent sheet. When this occurs, they can be distinguished from collagen fibers because they are shinier and have a wavy appearance. They are arranged in a branching pattern to form a three-dimensional network. They are interwoven with collagen fibers to limit the distensibility of the tissue and to prevent tearing from excessive stretching. Elastin fibers have a central core of elastin and a surrounding network of fibrillin microfibrils. Fibrillin microfibrils are made of a glycoprotein named fibrillin-1 and play a major role in organizing elastin into fibers. |
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Term
| what are glycosoaminoglycans (GAGs) |
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Definition
| They are covalently bound to proteoglycans. They are the most abundant heteropolysaccharide components of ground substance. They are highly negatively charged. |
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Term
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Definition
| It is a multiadhesive glycoprotein. It is formed from dimer molecules that are formed from two similar peptides. Each molecule contains several binding domains that interact with different ECM molecules. Fibronectin is activated by binding to a cell-surface receptor, which then assembles into fibrils. Fibronectin also is important for cell attachment to the ECM. Fibronectin does not polymerize. RGD is the key sequence in fibronectin that binds to cell integrins. While collagen type I, collagen type IV, laminin, and integrin are encoded by a gene family (with different tissue distributions), fibronectin is derived from a single gene. The central cell adhesive region of fibronectin binds to the a5b1 integrin in an interaction that requires at least two distinct sequences: the Arg-Gly-Asp (RGD) site and a Pro-His-Ser-Arg-Asn (PHSRN) sequence that acts in synergy with the RGD site. |
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Term
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Definition
| It is a multiadhesive glycoprotein that is present in basal and external laminae. It has binding sites for collagen IV, heparin sulfate, heparin, entactin, laminin, and the laminin receptor on the cell surface. Laminin is a basal lamina component that plays a key role in nerve regeneration. It is a family of glycoproteins, composed of 3 polypeptides (a, b, g chains) that form a cross-shaped structure. They are good substrates for adhesion of epithelial cells and neurons. Different laminins are found in different basal laminae. |
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Term
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Definition
| It acts as a selective barrier to the movement of cells. It is also important in tissue regeneration after injury. BL components are collagen type IV, laminin/entactin, and perlecan (heparan sulfate proteoglycan). Both collagen IV and laminin can polymerize into layers, but they are not very ordered. After nerve injury, the axon regenerates to the original spot in normal conditions and after irradiation of muscle cell so that the only the basal lamina remains. Something on the basal lamina is recognized by the incoming axon. |
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Term
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Definition
| They are the main receptor proteins that cells use to both bind to and respond to the ECM. An integrin molecule is composed of two noncovalently associated transmembrane glycoprotein subunits. Major cellular receptors for many ECM components are integrins. A given integrin may bind several ligands and several integrins may bind the same ligand. Integrins mediate cell-matrix interactions (binding of itnegrins to fibronectin or laminin) and cell-cell interactions (such as integrin binding to ICAM). Cells express multiple kinds of integrin, and integrins bind multiple ECM ligands. RGD (arginine, glycine, aspartate) is key in binding of ECM ligands in integrins but is not essential for all integrins. |
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Term
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Definition
| Caused by mutation in type IV collagen and ultimately leads to renal failure because the glomerular basement membrane becomes irregularly thickened and fails to serve as an effective filtration barrier. |
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Term
| Leukocyte Adhesion Disorder (LAD) |
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Definition
| Neutrophils are the first cell type to respond to most infections, particularly bacterial and fungal infections. They ingest microbes in the circulation, and they rapidly enter extravascular tissues at sites of infection, where they also ingest microbes and die after a few hours. In LAD, neutrophils cannot leave the bloodstream to go to a site of infection. A hallmark of the disease is lack of pus at the site of infection. Therapies are aggressive antibiotic regimens, bone marrow transplant (cell replacement) and gene therapy (gene replacement). |
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Term
| Normal mechanism of how neutrophils leave bloodstream |
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Definition
| Normally, leukocytes are tethered and begin rolling due to selectin-mucin binding. The integrins present don’t mediate firm attachment because they are in an inactive conformation. Activating factors (chemoattractants) then activate a trimeric G-protein coupled receptor, which via a signaling network activates integrin, which then removes the neutrophils from the bloodstream. |
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Term
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Definition
| Usually, LAD occurs because of a lack of integrin β2. LAD I is caused by structural defects in integrin. LAD II is caused by the absence of the selectin ligand. LAD III is caused by defects in integrin activation. |
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Term
| Why is LAD characterized by delayed separation of the umbilicus? |
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Definition
| Cord separation comes about by infiltration of neutrophils progressing from the edges of the umbilical area towards the centre. This infiltration finally forms a continuous band producing a demarcation zone between the mummified cord stump and the vital tissues of the umbilical area of the abdominal wall from which the cord is in the process of separating. In LAD, the neutrophils take longer to achieve this, making the umbilical cord stay attached longer. |
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Term
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Definition
| This is a complex, autosomal dominant, connective tissue disorder caused by abnormal expression of the fibrillin gene (FBN1), a key component of microfibrils in elastic fibers. Patients are tall with long, thin arms and legs and spider-link fingers and often suffer from aortic dissection |
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Term
| What is the true underlying cause of Marfan’s? What is an experimental treatment? |
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Definition
| The true cause is overexpression of TGF-β. Fibrillin-1 is similar to the structure of a TGF-ß regulatory protein, and TGF-ß regulatory proteins bind to fib-1. Reduced expression of fibrillin-1 leads to a systemic increase in TGF-ß, triggering a whole cascade of inappropriate development. Losartan is an experimental therapy that reduces TGF-ß levels. |
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Term
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Definition
| Anaphylaxis is caused by the rapid release of mast cell granule, which contain bioactive substances, such as histamine, leukotrienes, proteoglycans, ECF-A and proteases. Normally, the slow release of granule contents and cytokines regulates innate immune responses. |
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Term
| mechanism of mast cell degranulation |
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Definition
| Anaphylactic shock may occur upon a second exposure to an allergen. The first exposure to an allergen induces a weak immune response. That is, some lymphocytes are stimulated to proliferate and differentiate into plasma cells, which secrete antibodies (immunoglobulin E or IgE). This takes several days after exposure. The IgE binds to receptors on the surface of mast cells. During a second exposure, two things happen. First, the allergen again triggers an immune response, which is more powerful and slightly quicker (may now occur within 3 days rather than 7-10). Second, in susceptible individuals, the allergen also binds directly to IgE on the “primed” mast cells, causing anaphylaxis, which is rapid (within minutes) and life-threatening. Binding of allergen to IgE triggers immediate release of the cytoplasmic granules, which spill their contents into the area surrounding the cells. The granule contents induce many rapid tissue responses, especially including constriction of airways. |
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Term
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Definition
| Histamine causes bronchoconstriction by inducing contraction of smooth muscle, which can cause death rapidly. It also triggers vasodilation, which lowers blood pressure rapidly and can cause loss of consciousness. |
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Term
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Definition
| Epinephrine acts by binding to a variety of adrenergic receptors and, thus, its actions vary by tissue type depending on expression of adrenergic receptors. It causes smooth muscle relaxation in the airways but causes contraction of the smooth muscle that lines most arterioles. These effects oppose those of histamine. |
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Term
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Definition
| Scleroderma can cause Raynaud’s phenomenon (has red, white and blue color changes occur with exposure to low temperatures). In it, collagen fibers are denser and extend more deeply throughout the dermal and subcutaneous region. The increased collagen makes fingers full and rigid. It also causes vascular problems and autoimmune reactions. Scleroderma can be localized to specific areas but it is usually systemic. Its etiology is thought to involve changes in vasculature, autoimmune responses and fibrosis (formation of excess fibrous CT in a reparative or reactive process. |
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Term
| treatment options for scleroderma |
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Definition
| There are no good treatments. No good anti-fibrotic drugs exist because there is currently no safe and effective method of removing excess insoluble cross-linked collagen fibers without damaging the structural framework of the body and individual organs. The lack of effective treatment options makes support for patients essential |
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Term
| What tests are run to identify Scleroderma |
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Definition
| An ANA (Anti-Nuclear Antibody test) is ordered first to see if the disease is autoimmune. If positive, an anti-centromere antibodies test is run. A positive test indicates scleroderma |
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Term
| How GAGs and proteoglycans contribute to rigidity and porosity of ECM |
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Definition
| The high density of negative charge on GAGs attracts water, forming a hydrated gel. This gel-like ground substance permits the rapid diffusion of water-soluble molecules. Simultaneously, the rigidity of the GAGs provides a structural framework for the cells. |
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Term
| Involvement of ECM in development and homeostasis |
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Definition
| The ECM exerts a regulatory effect on embryonic development and cell differentiation. The matrix can bind and retain growth factors, which modulates cell growth. With the aid of cell adhesion molecules, the ECM also influences the transmission of information across the plasma membrane of the connective tissue cells. |
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Term
| Role of basal lamina in nerve regeneration |
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Definition
| Basal lamina plays a crucial role in development and regeneration of neuromuscular junctions. Muscles in the limbs are innervated by motorneurons whose cell bodies are located in the spinal cord. The place where the neuron contacts the muscle is called the neuromuscular junction. The muscle fiber (a single large multinucleated cell) is surrounded by a basal lamina. At the junction, the muscle is specialized – there is a cleft that is enriched in receptors for the transmitter released by the nerve ending. The ending and muscle are separated by the basal lamina. After injury, the nerve detaches from the muscle, retracts and partially degenerates. During regeneration, the nerve fiber grows back to the muscle and eventually forms a synapse in the same spot where it originally innervated the muscle. |
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Term
| Experiment done to show role of BL in nerve regeneration |
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Definition
| In an experiment done to test whether BL is sufficient for nerve regeneration, Initially, the nerve innervating the muscle is severed. If the nerve is allowed to regenerate without interferance, it reforms a neuromuscular junction at the same place it originally innervated. If, however, the muscle fiber is killed by irradiation, leaving only the basal lamina, the nerve still reinnervates the original spot! |
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