4,5 Connective Tissue Flashcards
Components of ECM in CT.
GAGS, water, ions, proteoglycans, glycoproteins, enzymes.
Main cells in CT.
Fibroblasts
Synthesis and digestion of all ECM components
A function of GAGs in ECM of CT.
Bind to high quantity of water therefore effect metabolism
Function of glycoproteins in ECM of CT?
Modulate cells TO ECM connection
CT primary functions?
Cranes shoot my pigs tired dr Connection of different tissues Structural support Medium of transport - met diff Protection of organs Trophic function Defence functions Repairation
ECM Fibrially components?
Collagen, reticular fibres, elastic fibres
2 types of cells in CT?
Resident remain in CT
Fibroblats, adipocytes, pericytes, mast cells
Transient temp in CT
Macrophages/histocytes, leukocytes, plasma cells,granulocytes
Fibroblast to fibrocyte located in?
Loose CT - Adipose, areolar, reticular
Dense CT - Regular, Irregular, Elastic
Chrondroblasts -> chrondrocytes present in?
Hyaline, elastic, fibrocartilage.
Fibroblasts contain high amount of?
Golgi and RER.
Formed from Undifferentiated mesenchymal cells
Inactive fibroblasts?
Flattened more electron dense nucleus therefore greater amount of heterochromatin.
Less protein synthesis
Activated by polypeptide activates.
Defence functions of macrophages? Which differentiate from monocytes. What else differentiates from monocytes?
Antigen presenting cell involved in Immune response.
Phagocytosis - degradation of debris, ecm components, damaged/aged cells
Osteoclast
What do macrophages secrete?
How do macrophages go from inactive (fixed) to active?
Cytokines and enzymes
Removal of attached collagen fibres with small finger like projections
Life span of macrophage?
2 months
Inactive fixed macrophage?
Kidney shaped nucleus, 19-30um in diameter, spindle/stellate shape.
Macrophages are present in….and increase in no. during…
CT
Inflammation
What are histocytes?
Macrophages specialised in different types of cells
Name type of histocyte in each organ?
Liver, spleen, peritoneal cavity, lung, bone, CNS
Kuppfer cells Red pulp cells Perotioneal macrophages Dust cells Osteoclasts Microglia
Adipoctyes structure?
Thin cytoplasm and nucleus Lipid droplet (liposome) dissolved
Leukocytes increase during inflammation. Name three types?
Granulocytes.
Neutrophils, eosinophils, basophills (similar to mast cells except circulate in the blood)
How neutrophil from blood into CT?
Diapedisis Bind to glycoprotein on endothelial cell surface Form pseudopodia (polymerisation of actin filaments) Move between endothelial cells
Mast cell structural feature?
Large no of granules containing histamine, heparin, proteases.
20-30um on EM.
Ig receptors
Function of IG E receptors on mast cells?
Inflammatory process
Immediate hypersensitivity reaction - first exposure become sensitive. Second exposure primary and secondary (phospholipids - arachitonic acid) released.
Plasma cell life span and differentiate from?
Diameter?
B lymphocytes
2-4 weeks
20um
Plasma cells have large no, of … To produce immunoglobins?
RER
Plasma cells involved in …
antibody synthesis and secretion (constitutive) continuous.
Main constituents of collagen?
Proline, glycine, hydroxyproline
Collagen in EM structure starting from a chain?
Single A chain A1-A2 helix Tropocollagen Microfibrils Fibrils
Collagen extra EM features?
Tropocollagen head to tail arrangement. Specific lateral arrangement.
Collagen striated - dark = gaps and lacuna, stain allowed to pass thru.
- length of lacuna and overlapping region (light) 64nm
Length of 1 a chain?
95kDa there 3 a chain in a helix = 285kDa
Which cells synthesise collagen and outline 8 steps?
Fibro, chrondro, osteo - blasts
Intracellular: Transcription, translation, hydroxylation, glycosylation, pro collagen form helix, secretion of procollagen by TGN.
Extracellular: cleavage if pro-peptides form tropocollagen molecules, self assembly - tropocollagen form collagen fibrils
Importance of cross links?
Improve strength
Not easily digested by enzymes and not removed
Importance of hydroxylation of proline and glycine in RER?
Form specific AA residues - form lateral cross-links
Collagen maturation (sif)
Stronger than steel, inelastic, flexible
Which processes collagen synthesis occurs in RER
Translation of procollagen
Hydroxylation
Glycosylation
Procollagen triple helix formed
Relationship between reticular fibres and collagen?
Different arrangement and length of collagen - similar chemical properties
Degradation of collagen 2 methods
1) fibroblasts undergo phagocytosis - phagosome - lysosome - residual body
2) MMP - Matrix metalloproteinases - these include collagenases (degrade type 1,2,3,10 collagen) - synthesised by cancer cells, fibroblasts, chondrocytes, neutrophils, macrophages, monocytes, epithelial cells (keratinocytes).
Which type of MMP do cancer cells produce?
Membrane-type mmp
Potent peri cellular fibrolytic activity
What degrades elastin, type 4 collagen and laminin?
Macrophage metalloelastases
What are collagen crimps?
Waves in tendons 50um long.
Relationship between structure and biomechanical properties.
Reticular fibres organs?
Liver, lymph nodes, spleen, bone marrow
Retucular fibre stain?
High carb - silver stain - argyrophillic fibres
Reticular fibres structural info?
Type 3 collagen 0.5-1.0um in diameter.
Loose 3d network.
Parallel fibrils form reticular fibre
How much is dry weight is collagen?
30%
Macrophages - function of release of cytokines?
Stimulate immune response
Collagenopathy most common in type 3 collagen?
Ehlers-danlos syndrome.
Pathology : defective procollagen peptidase. Non helical procollagen ends. Defective collagen fibrils
Symptoms : hyper-elasticity of skin. Joint dislocation
Marfan syndrome?
Protein fibrillin 1 deficiency. Therefore elastin fibre irregularity. Defects in blood vessels. May lead to aneurysm of Aorta. Patients tall, skinny, shrimpy
5 pathologies associated with MMPs?
Wound healing, inflammation, atherosclerosis, tumour invasion, fibrosis
MMP
What stimulates cell to produce pro MMP - via enzymes - active MMP leading to degradation of ECM?
Growth factors and cytokines.
MMP cause ECM remodelling.
What do gelatinases degrade?
Denatured collagen, fibronectin, elastin, laminin.
Where are elastin fibres found?
Lungs, blood vessels ( marfan syndrome ), bladder, skin
In grazing animals - nuchal ligament
Elastin fibres what colour stain?
Black lines
Characteristics of elastic fibres?
Elastic
Stretched 150% of resting length
Non striated
Maybe branched - anastomosed - form a network
Elastic fibres structure?
Amorphous - elastin
Microfibril component - fibrilin sheets
Elastin = core
What 2 AA allows covalent bonding between elastin molecules?
Desmosine and isodesmosine.
Specific AA to elastin.
Derived from. 4 lysine residues.
Name the 4 main structural glycoproteins in CT?
Fibronectin
Laminin
Entactin
Nidogen
Fibronectin function in CT/ECM?
Binding site for ecm components
Recptors on cell membrane surface
Proteoglycans structure?
Monomer - GAGs attached to central protein
Covalently linked to hyaluronic acid
Function of proteoglycans in ecm of ct?
Form proteoglycan aggregates - bind to water and collagen
Covalently linked to hyaluronic acid
Laminins size and function?
800kda in the bm
Regulate interaction between ecm and cell
Function of SPARC?
Regulate cell cycle
Modulate growth factors and cell-ecm interaction.
When is sparc high produced highly?
Tissue remodelling
Sparc pathogensis
Cell detached from ECM components.
Fibrosis. Tumour occurs.
May metastasise into blood.
Sparc, where found in cell?
Nuclear matrix of proliferatingcytosol in neurons
3 types of connective tissue (broad terms with subtypes)?
Proper - dense, reg/irregular, loose, adipose, reticular, elastic,
Supportive - bone, cartilage
Fluid - blood and lymph