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Connective Tissue
Organisation of the Body
| Question | Answer |
|---|---|
| What is connective tissue | A complicated tissue below the endothelium which contains: Collagen, capillaries, elastic fibres, mast cells, hyaluronan, proteoglycans, glycoproteins, fibroblasts, macrophages and the basal lamina |
| Functions of connective tissue | Mechanical - Supporting matrix, transmission of forces Metabolic - route for exchange between blood and fluid, fat storage Defence and repair - Insulation, cushioning, injury, infection and repair Growth and morphogenesis - control cell behaviour |
| Types of tissue in connective tissue | Loose connective tissue (areolar tissue) Dense connective tissue - regular and irregular Elastic tissue Adipose tissue - white and brown |
| Loose connective tissue (areolar tissue) | Component of most of the body. Delicate, flexible and not very resistant to stress. Supports structures under low pressure and friction. Fills space between muscle cells, supports epithelial cells, sheaths lymphatic and blood cells |
| What cells and fibres are in loose connective tissue | Cells - numerous fibroblasts and macrophages Fibres - moderate amount of collagen, elastic and reticular fibres |
| Dense connective tissue | For resistance and protection Fewer cells, predominance of collage fibres Less flexible but more resistant to stress Split into regular and irregular tissue |
| Dense irregular connective tissue | Collagen fibres with no predominant orientation 3D network forms resistance to stress in all directions e.g. dermis of the skin |
| Dense regular connective tissue | Collagen fibres aligned with linear orientation of fibroblasts along lines of prolonged stress in one particular direction e.g. tendon attaching striated muscle to bone |
| Connective tissue under the skin | Dense irregular - superficial dermis anchoring the epithelium Loose - deeper, allowing skin to move over underlying muscle Adipose - areas of fat in loose layer |
| White adipose tissue | Mature adipocytes have a single large droplet of triglyceride fat and very little cytoplasm For energy storage, insulation and padding Also serves an endocrine function in secreting hormones Immature cells have smaller lipid droplets |
| Brown adipose tissue | Brown adipocytes have more cytoplasm, many mitochondria, multiple small fat droplets Innervated by the sympathetic nervous system Mitochondria generate heat when activated |
| Elastic tissue | Bundles of thick parallel elastic fibres These fibres are elastin associated with a glycoprotein called Fibrillin |
| Basement membrane | Specialised sheets of extracellular matrix proteins and GAGs associated with epithelial layers, muscle cells and blood vessels. Functions: cell adhesion, regulation of cell organisation and to act as a diffusion barrier |
| What is the basal lamina | A substructure of the basement membrane |
| Role of basement membrane in cell adhesion | Cells anchored to basement membrane Hemidesmosomes (through intermediate filaments) connect the cell to the extracellular matrix Actin-linked cell-matrix adhesion anchors also play a role |
| Role of basement membrane as a diffusion barrier | Molecular sieve or permeability barrier, with pore size dependant on the GAGs present. e.g. in kidneys to prevent protein loss from filtered blood |
| Role of basement membrane in regulation of cell growth | Through cell surface receptors and the extracellular matrix |
| Cells present in loose connective tissue | Fibroblasts Macrophages Mast cells Leukocytes |
| Fibroblasts | Most nuclei in connective tissue are from fibroblasts Cytoplasm elongates along the line of the fibres they produce Lays down fibres in a particular orientation e.g. in the cornea the regular layers of collagen are what gives translucency to the tissue |
| What molecules do fibroblasts secrete | Collagen Elastin GAGs Proteoglycans Glycoproteins Growth factors |
| Macrophages | Tissue phagocytes often derived from blood monocytes, but can be resident so made internally.They engulf dead cells and invading organisms and both initiate and regular the inflammatory response and recruit polymorphonuclear leukocytes to kill pathogens |
| Different types of macrophage | Kupffer cells - liver Microgila - CNS Langerhans cells - skin |
| Mast cells | Secretory granules containing many bioactive molecules e.g. histamines, serotonin, heparin, prostaglandins Activation of IgE receptors activates mast cells to release the mast cell granules. |
| Roles of mast cells | Phagocytose bacteria Stimulated to release their granules Vasodilation Increase capillary permeability Breakdown extracellular matrix Contract smooth muscle |
| 3 types of white blood cell | Basophil - release pharmacological compounds e.g. histamine Eosinophil - allergic and vasoactive reactions and control mast cells and inflammation Neutrophil - phagocytosis |
| Process of inflammation | Microbial colonies on epithelium migrate below the epithelium. These are phagocytosed by mast cells/macrophages which release cytoxic agents and pro inflammatory cytokines. Basophils also release these cytokines |
| Migration of a neutrophil to inflammation | Endothelium activated and bind neutrophils to ICAM - intercellular cell adhesion molecule that binds to integrin on neutrophil membrane. The neutrophil is trapped, activated and undergoes adhesion to the cell before invading the connective tissue below |
| Development and differentiation of white adipose cells | Starts as a fibroblast like precursor cell. Fat cells form as lipid droplets which accumulate, fuse and enlarge. Very large fat cells result (up to 120um diameter). Cytoplasm remains only as a thin layer around the edge |
| Brown adipose tissue in babies | Babies are born with brown adipose tissue as 2-5% of their body weight, mainly concentrated at the stomach and neck. These is metabolised to produce heat during the neonatal period and so is mainly lost after childhood |
| Fibrous components of connective tissue | Fibrous protein e.g. collagens (25% of body protein mass) Glycosaminoglycans (GAGs) - polysaccharide chains covalently linked to protein proteoglycan. Highly hydrated gel like substance |
| Major connective tissue fibres | Collagen Reticular Elastic |
| Collagen | The major protein of the extracellular matric with 42 different collagen genes and 27 proteins transcribed, Different collagens have different properties e.g. Type 1 is found in bones, skin, tendons while type VI is found in the basal lamina |
| Structure of collagen | String of glycine repeating motifs that assemble in 3s to form collagen fibres. Collagen molecules assemble end to end and staggered to form a fibril that self assemble to form a banded collagen fibre Mature collagen has a regular structure |
| Weird facts on collagen | 300 nm long 35nm gap between molecules 67 nm overlap between adjacent molecules |
| Production of mature collagen | Synthesis of pro-alpha chain. Prolines and lysine's are hydroxylated whilst hydroxylysines are glycosylated. Self assembly of three chains which form pro collagen triple helix. This is secreted and cleaved to form mature collagen which forms fibrils |
| Specialisations of fibroblasts | Contain transfer vesicles, large quantities of Golgi, secretory vesicles, mitochondria, RER to allow collagen synthesis. |
| Diseases due to mutations in Collagen | Ehlers-Danlos V - decreased cross linking - skin and joint hyperextensibility Osteogenesis imperfecta - decrease in type I - blue sclerae and bone deformities Scurvy - decreased hydroxyproline -pour wound healing, deficient growth and capillary weakness |
| How vitamin C deficiency contributes to scurvy | Prevents proline hydroxylation. Collagen chains fail to form the stable triple helix so are degraded. Normal collagen turnover of weeks or months fails |
| Reticular fibres | Reticulin - type 3 collagen. Short and thin to form the delicate meshwork holding tissue elements together. Highly evident in haemopoietic tissue e.g. lymph nodes, spleen, bone marrow |
| Elastic fibres | Made of an elastin core strongly crosslinked to form a 3D network. On the surface are microfibrils of a glycoprotein called fibrillin. Mutation in fibrillin weakens fibres and causes marfan syndrome - tall, thin, flexible joints, heart valve defects |
| How do elastic fibres work | Relaxed state - random coil structure Elastin can reversibly stretch and recoil due to covalent cross links between molecules to form fibres or sheets Present on lung, skin and blood vessel walls. |
| Glycosaminoglycans (GAGs) | Very long unbranched polysaccharide chains. Highly anionic so attract Na+ ions and water. This allows for swelling, turgor, resistance to compression e.g. in joints. Strongly hydrophilic so form porous hydrated gels. |
| 4 main types of GAGs | Hyaluronic acid - no sulphur and not protein linked, found in cartilage Chondroitin/dermatan sulphate - cartilage, bone, skin, heart Heparin/Heparan sulphate - basement membrane, lung, skin, mast cell granules Keratan sulphate - cartilage, cornea |
| Proteoglycans | GAGs (except Hyaluronan) are covalently attached to proteins. These can be huge e.g. aggrecan in cartilage is 3x10^6 Da with 100 GAGs or can be smaller e.g. decorin 1-10 GAG chains. |
| Role of proteoglycans | Form gels of varying pore size to act as molecular sieves e.g. thick basal lamina of kidney glomerulus Resist mechanical compression forces Act as a lubricant |
| Connective tissue glycoproteins | RGD - arginine, glycine, asparagine Binds to integrins (small RGD peptides used therapeutically to block in metastasis) Include Fibronectin (2 polypeptide chains) and Laminin (two alpha and two beta chains) |
| Integrin | Integrin receptors on the plasma membrane link the cytoskeleton to extracellular glycoproteins and collagen. Allow for mechanosensing and cell movement. |
| Cell movement | Occurs via progressive binding of integrins to extracellular matrix proteins. The extracellular matrix contains actin, which integrin bind to and moves along, pulling the collagen (which it is also bound to) in the cell along |
| Extracellular matrix signalling molecules | Long range cues - chemoattraction e.g. Netrins and chemorepulsion e.g. Semaphorins Short range cues - Contact attraction e.g. Eph ligands and contact repulsion e.g. Cadherins |
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