Lecture 4 - Connective Tissue & ECM Flashcards
List the parts of the ECM.
Fibers, amorphous ground substance, & tissue fluid
List the functions of CT.
1) structural support 2) exchange medium between blood and tissues 3) defense and protection 4) fat storage
What type of cells do fibroblasts arise from?
Mesenchymal cells
What is the difference between a fibroblast and a fibrocyte?
Fibroblasts = active/high synthesis; Fibrocyte = inactive/low synthesis (slimmer in appearance as a result)
What type of cells do adipocytes arise from and what are they surrounded by?
Mesenchymal cells, basal lamina
What type of receptors do unilocular adipocytes possess?
Insulin, growth hormone, norepinephrine, glucocorticoid
What type of tissue and cell do macrophages arise from?
originate from bone marrow as monocytes
Macrophages migrate from blood into connective tissue & various organs and take on different phenotypes. What are 3 primary sites of migration and what are the names for the specialized macrophages at each site?
Liver - Kuppfer cells
Osteoclasts - bone
Microglia - CNS
Macrophages have two primary functions. What are they?
1) Phagocytic
2) Regulate immune system
What type of immune regulators to macrophages secrete?
Prostaglandins, interleukins, TNF-alpha
What type of cells do Mast cells arise from?
Myeloid stem cell
What specific type of hypersensitivity reaction do Mast cells mediate?
Type 1 hypersensitivity (asthma, hay fever, eczema)
What effect to Mast cell immune mediators have?
Increase inflammatory response (vasoactive)
What mediators do Mast cells release? (There are 7 listed in the notes)
Leukotriene C, heparin, histamine, eosinophil chemotactic factor, neutrophil chemotactic factor, aryl sulfatase, neutral protease
What tissues do Mast cells occur in?
Respiratory or GI (mucosal) and connective tissue
How to Mast cells interact with IgE?
Possess Fc receptor for Fc on IgE
From what type of cells do plasma cells arise? What is their function?
Activated B lymphocyte, antibody producing (humoral immunity)
What imaging characteristic is a hallmark of plasma cells?
Hemotoxylin (basophilic) stained cytoplasm (protein of rER) and negative staining golgi (adjacent to nucleus)
What cells do lymphocytes arise from and what cell types do they produce?
Arise from lymphoid stem cells. Produce T cells (cell mediated immunity), which differentiate in thymus, and B cells (humoral immune response).
What type of cell possesses a characteristic trilobed nucleus?
Neutrophil
What immune cell appears first at the site of inflammatory reaction?
Neutrophil
What immune cell type is biolobed?
Eosinophil
What specific enzymes do eosinophils contain and what is their job upon secretion?
Leukotriene C and histamine - moderate allergic reaction
What immune cell type is integrally involved in parasite immune response? Additionally, how do these immune cells associate/mitigate parasites?
Eosinophil, bind to antigen-Ab complex on parasite surface and release cytotoxins
Where are pericytes found?
Around capillaries
What cell types can pericytes differentiate into?
Fibroblasts & smooth muscle
List the types of embryonic connective tissue (2) and state where these types are found.
1) Mesenchymal CT - present in embryos
2) Mucous CT (aka Wharton’s jelly) - main component of umbilical cord
What makes up mesenchymal CT?
amorphous matrix with some reticular fibers and mesenchymal cells (a small sub-pop may be stem cells)
What makes up mucous CT?
collagen and fibroblasts (jelly like)
List the types of connective tissue proper.
1) Loose (areolar) CT
2) Dense CT - regular (only found in ligaments, tendons) and irregular
3) Reticular tissue
4) Adipose tissue
Lists type of specialized CT.
bone, cartilage, blood
What does ECM consist of (3 parts)?
1) ground substance 2) fibers 3) tissue fluid
What does ground substance consist of?
proteoglycans
What is a proteoglycan?
core protein with a covalently linked glycosaminoglycan
What is a glycosaminoglycan?
unbranched polymer of repeated disaccharides (can be sulfated or non-sulfated)
Lists the GAGs discussed in class.
Chondroitin sulfate, heparan sulfate, heparin, hyaluronic acid, dermatan sulfate, keratan sulfate (CHHHDK)
What GAG is made up of repeating disaccharide units of D-glucuronic acid and N-acetyl-D-galactosamine?
Chondroitin sulfate
In chondroitin sulfate what position is the N-acetyl-D-galactosamine sulfated at?
4 or 6
Where is chondroitin sulfate abundant (structures/fluids)?
hyaline & elastic cartilage, adventitia of arteries
What structures/fluids is heparan sulfate associated with?
reticular fibers, blood vessel walls, heart valves
How sulfated is heparin relative to heparan sulfate?
Heparin is MORE sulfated.
What structures/fluids is heparin associated with?
lung, skin, liver, mast cells
What structures/fluids is hyaluronic acid associated with? Is it sulfated?
cartilage, synovial fluid, vitreous humor. NOT SULFATED.
What functional role does hyaluronic acid play in cartilage structure?
Binds H2O with help of aggrecan and maintains hydration.
What structures/fluids is dermatan sulfate associated with?
skin, blood vessels, heart valves
What structures/fluids is keratan sulfate associated with?
cornea, nucleus pulposus, cartilage
List the types of glycoproteins (GP) in the ECM.
Fibronectin, laminin, entactin, tenascin, chondronectin, osteonectin (FLETCO)
What is the molecular weight of fibronectin and how many subunits does it have? What holds these subunits together?
460K MW, 2 subunits, a disulfide
Where is the cellular form of fibronectin found? Where is the plasma form found?
Cellular form - find in CT cells and cell surfaces
Plasma form - dissolved in blood and involved in clotting and wound healing
Where is laminin primarily found & what structures does it bind at this site?
Basement membranes, binds to heparin sulfate, type 4 collagen, entactin, and INTEGRINS
What is the role of entactin?
Component of basement membrane. Binds laminin and links it to type IV collagen.
What are the roles of tenascin?
Adhesive GP found in embryonic tissues. Functions in cell migration. Secreted by glial cells of developing nervous system.
What is the role of chondronectin?
Attaches chondrocytes to type II collagen. Functions in development and maintenance of cartilage.
What is the role of osteonectin and where is it found?
Link minerals to type I collagen and influences calcification by inhibiting crystal growth. Found in bone.
List the types of ECM fibers (3).
1) Collagen
2) reticular (type III collagen)
3) elastic (consist of elastin and fibrillin)
List the steps of collagen synthesis and modification.
1) Synthesis of pro-alpha chains
2) Hydroxylation of Pro and Lys
3) Glycosylation of hydroxylysines
4) Assembly into procollagen
5) Transport to cell surface
6) Cleavage into tropocollagen
7) Assembly of tropocollagen into fibrils
What step in collagen synthesis requires ascorbate (vit C)?
Hydroxylation of Pro and Lys.
What percentage of total body collagen is Type I collagen? Where is type of collagen present?
- 90% of collagen in body
- Present in: bone, skin, tendons, dentin, scar tissue
What cells produce type I collagen?
Fibroblast, osteoblast, odontoblast
Where is type II collagen found?
HYALINE CARTILAGE & some in elastic cartilage. Also, vitreous body of eye & nucleus pulposus.
What is the chain make-up of type I collagen?
Two alpha-1(I) and one alpha-2(I)
What is the chain make-up of type II collagen?
Three alpha-1(II)
What is the chain make-up of type III collagen?
Three alpha-1(III)
Where is type III collagen found?
Fetal skin, reticular fibers, granulation tissue
What cells secrete type II collagen?
Chondroblast
What cells secrete type III collagen?
Fibroblast, Schwann cell, hepatocyte
What is the primary role of Type IV collagen?
BASEMENT MEMBRANES.
What is the chain make-up of Type IV collagen?
Two alpha-1(IV) and one alpha-2(IV)
What cells secrete type IV collagen?
Endo and epithelial cells, muscle, Schwann cell
What is unique about type IV collagen fibrils?
They have no striations.
Where is type VII collagen found?
beneath epithelial basement membranes.
What is the role of type VII collagen?
Its fibrils anchor basement membrane to connective tissue.
What is the chain make-up of type VII collagen?
Three alpha-1(VII)
Where is type X collagen found?
hypertrophic zone of developing bones.
What two unusual amino acids does elastin contain?
desmosine and isodesmosine
What is the role of elastin?
amorphous structural protein
What crosslinks elastin?
highly cross-linked by lysine residues
What component surrounds elastic fibers?
Fibrillin I & II
What helps link fibrillin together?
Microfibril associated glycoprotein (MAGP)
What is the main class of proteolytic enzymes involved in ECM remodeling? What characterizes these enzymes?
matrix metalloproteinases (MMPs) characterized, in part, by a requirement for zink
Genetic defect involving Type I collagen that leads to bone fragility and poor collagen production.
Osteogenesis imperfecta
Genetic defect in cystathionine synthetase enzyme that result in abnormal collagen cross-linking
Homocystinuria
Genetic defect in fibrillin I that results in weakend tunica media of aorta & arachnodactyly.
Marfan syndrome
Produced by vitamin C deficiency. Decreases proline hydroxylation of collagen.
Scurvy
Genetic defect involving type IV collagen that result in a combination of nephritis, cataracts, and deafness.
Alport syndrome
Genetic defect involving petidyl lysine hydroxylate needed for type III collagen synthesis. Results in rupture of large bowel / arteries. HYPERELASTICITY OF SKIN AND HYPERMOBILITY OF JOINTS.
Ehlers-Danos syndrome
What changes in fibronectin are often observed in cancerous cells?
1) Increased production of matrix metallo proteinases
2) Decreased production of tissue inhibitors of metalloproteases (TIMPs)
