The Connective Tissues

Question 1

Simple columnar epithelia/Pseudostratfield

Answer 1

Elongated cells-including mucus-secreting cells and absorptive cells (lining of small intestine)
Micro villi-on apical surface
Favours max surface of absorption/secretion

Question 2

Simple squamous epithelia

Answer 2

Thin cells-including cells lining blood vessels (endothelial cells/endothelium) and many body cavities .
Favours gas and molecules exchange

Question 3

Transitional epithelia

Answer 3

Several layers of cells with different shapes-lining certain cavities (urinary bladder)
Favouring expansion and contraction (elasticity)

Question 4

Stratified squamous

Answer 4

Line surfaces such as mouth and vagina
Resist abrasion & favours protection

Question 5

Animal tissues

Answer 5

Epithilea
Connective
Muscular
Neuronal
Blood

Question 6

Epithelia

Answer 6

Adhesion structures
Adhesion molecules

Question 7

Connective tissues

Answer 7

Loose and dense
Hold organs together
Low in cells and high in collagens,reticular and elastin fibres
Specialised :adipose,cartilage,blood,lymph

Question 8

Extra cellular matrix

Answer 8

Basal lamina
Connective tissues
-loose and dense
How

Question 9

Functions of the extracellular matrix

Answer 9

1-Anchoring &surrounding cells to maintain solid tissue3d architecture and define tissue boundaries ,connects epithelial to basal structure
Heterogeneous family of integrins from basal side of epithelia bind to fibronectins,elastins and collagen

Question 10

FOEM

Answer 10

Determining the biomechanical properties(stiffness/elasticity,porosity,shape) of the extracellular environment

Question 11

FOEM-3

Answer 11

Controlling cellular polarity,survival,proliferation,differentiation and fate(e.g-asymmetric division of stem cells)&this embryonic and neonatal development and adult function and response to environment and disease

Question 12

FOEM-4

Answer 12

Inhibiting or facilitating cell migration (e.g-serving as either a carrier to movement or conversely,as a ‘track’ along which cells -or portions of cells -can move

Question 13

FOEM-5

Answer 13

Binding to & acting as a reservoir of growth factors ;in some cases ,the ECM
1-helps generate an extra cellular concentration gradient of the growth factor
2-serves as a co-receptor for the growth factor
3-aids in proper binding of the growth factor to its receptor (ECM component and growth factor jointly serve as a receptors combined ligand)

Question 14

FOEM-6

Answer 14

Activating cell surface signalling receptors

Question 15

How is th extracellular matrix

Answer 15

Formed by basal lamina and underlying connective tissues

Question 16

ECM componanats

Answer 16

Proteoglycans
Collagens & Elastin
Multi-adhesive matrix proteins

Question 17

What are proteoglycans ?

Answer 17

A unique type of glycoproteins,hydration and mechanic protections

Question 18

What do collagen and elastin do ?

Answer 18

Form fibres and give elasticity

Question 19

What are multiadhesive matrix proteins?

Answer 19

Important organisers of the extra cellular matrix
Fibronin and laminin
-long,flexible molecules that contain multiple domains
-bind various types of collagen other matrix proteins,polysaccharides and extracellular signalling -molecules as well as adhesion receptors
:Regulate cell matrix adhesion and cell shape and behaviour

Question 20

What is the Laminin molecule ?

Answer 20

Heterotrimeric multi-adhesive matrix protein found in all basal laminate

-16 vertebrae laminin isoforms -assembled from 5a,3b &3y chains
-coiled-coil regions-3 peptides covalently linked by several disulfide bonds
-Globular domains-bind to/crosslink adhesion receptors and various matrix components
-5 a subunits C-terminal globular LG domains -mediate Ca2+ dependent binding to cell surface laminin receptors including certain integrins (hemi desmosome),sulfated glycolipids,syndecan,and dystroglycan
-inset: laminins assemble into a lattice via interactions between their N-terminal globular domains

Question 21

Structure of Laminin molecule

Answer 21

-Charectireristic cross-shape
Carbohydrate -binding LG domains near the C-terminus

Question 22

Structure & assembally of type 4 collagen

Answer 22

Sheet-forming type IV collagen is a major structural component of the basal lamina
a
-400 nm long molecule
-N-terminus - small globular domain
-C-terminus-large globular domain
-collageneous triple helix -interrupted by nonhelical segments that introduce flexible kinks into the molecule

Question 23

Formation of diners,tetramers,& higher order sheet -like networks ?

Answer 23

-lateral interactions between triple-helical segments
-head-to-head and tail-to-tail interactions between the globular domains
-multiple,unusual sulfilimine (-S=N-) or thioesther bonds between hydroxylysine (or lysine) & methionine residues covalently cross-link some adjacent C-terminal domains and contribute to the stability of the network

Question 24

Type IV collagen network formed in vitro (EM) ?

Answer 24

-Side to side triple helical segment binding
C-terminal globular domain interactions

Question 25

Extra-cellular matrix and connective tissues

Answer 25

-Connectve tissues are diverse depending on the organs -the ration between cells & ECM components ,varies greatly -connnective tissue including tendons and cartilage is mostly ECM Fibres dense and cell scares (chondrocytes,fibroblasts,lymphocytes,endothelial cells)

Question 26

Main molecular component of ECM of connective tissue ?1

Answer 26

Collagens-from Latin colla are trimeric molecules that are often bundled together into fibres( fibrillar collagen);very abundant in all connective tissues & very heterogenous

Question 27

Main molecular component of ECM of connective tissue ? 2

Answer 27

Proteoglycans : glycoproteins containing one or more covalently bonding GAG chains .Play an important role in cell-matrix adhesion.They can be cell-surface linked (Perlecans) or secreted in extra-cellular space

Question 28

Main molecular component of ECM of connective tissue ?3

Answer 28

Glycosaminoglycans (GAGS) specialised linear polysaccharides chains of specific repeating disaccharides ,negatively charged ,that can be highly hydrated and confer diverse binding and physical properties (e.g: resistance to compression :ie hyaluronate)

Question 29

Main molecular component of ECM of connective tissue ? 4

Answer 29

Multi-adhesive proteins large multi domain proteins often compromising many copies (repeats) of a few distinctive domains that bind to and crosslink a variety of adhesion receptors and ECM compants

Question 30

Main molecular component of ECM of connective tissue ?5

Answer 30

Elastin a rubber like protein that forms the amorphous core of elastic fibres ,typically high in organs that stretch like the heart ,tendons ,vessels ,bladder and skins Most compacts are produced and re modelled by resident fibroblasts

Question 31

Types of callogens ?

Question 32

collagen

Answer 32

Trimeric protein made of 3 polypeptide -can be identical (homotrimer) or different (heterotrimer) Peptides- encoded by one of at least human 43 collagen a chain genes

Question 33

Structure of collagen

Answer 33

LONGITUDINAL Polypeptide fragment -contains repeating sets of Gly-X-Y amino acids characteristic of collagen a chains -each chain is twisted into a left handed helix -3 chains wrap around one another in a right handed triple helix -triple-helical structure with left handed twist of the individual collagen a chain

Question 34

COLLAGEN STRUCTURE 2 - Cross sectional view

Answer 34

Glycine proton side chains-located in the very narrow space between the polypeptide chains in the center of triple helix Collagen glycine mutations -larger R group disrupt trimer chain packing of the chains—destabilise the triple-helical structure

Question 35

Proteoglycans (PG)

Answer 35

Subset of secreted and cell surface (perlecans & sydecans in basal lamina) glycoproteins containing covalently linked GAG - GAG are linear polymers of repeating disaccharides - Generally glucuronic & ioduronic /galactose linked to N-acetyl-glucosamine/galactosamine -PG are produced by cells with the protein core produced in RER and GAG assembled in the Golgi before secretion (O-linked oligosaccharides)

Question 36

Proteoglycans 2

Answer 36

Mucin glycoproteins on surface of epithelia help -curvature of cells aka form microvilli Others bind to cadherins to stabilise the cell-matrix interaction Heparan sulphate controlling the blot clotting cascade

Question 37

Hyaluronic acid

Answer 37

Hyaluronon is a non-suphated GAG made by plasma membrane bound enzyme called HA synthase -secreted directly into extracellular space as its synthesised Resists compression ,fascilliates cell migration ,and provides cartlidge its gel-like properties -surrounds migrating &proliferating cells -embryonic -forms background of complex proteoglycans aggregates found in many ECMs including cartlidge Some HA molecules range to 10 micrometers

Question 38

Fibronectins

Answer 38

Fibroblasts expressing fibronectins on their surface adhere to Petri dishes -cancer cells-lose expressions,detach and float -20 isoforms -pave route for embryogenesis &differentiation -essential in healing process-regulate clotting&lead way for macrophages

Question 39

Tissue modelling & remodelling

Answer 39

ECM needs to to be responsive to changes in the environment -moving in cells,during inflammation, Metalloproteases are secreted by fibroblasts and tissues like elastases ,collagenenases and help breaking down the ECM network to fascillitate cell movement in physiology &pathology -Secretion or activation in response to stimuli-growing factors / cytokines

Question 40

Tissue modelling & remodelling

Answer 40

Fibroblasts are most common cell type Central mediators of pathological fibrotic accumulation of ECM & cellular proliferation and differentiation that occurs inn response to prolonged tissue injury and chronic inflammation

Question 41

Tissue modelling & remodelling

Answer 41

Fibroblasts sensitive to signals like cytokines,chemokines and growth factors which instruct to manipulate ECM fibres physically close open wounds , fibroblasts have multiple concomitant biological roles, such as in wound healing, inflammation, and angiogenesis, which are each interwoven with the process of fibrosis. many common fibroblast-related features across physiological and pathological role of non-cancerous fibroblast interactions with tumors in cancer progression.