Connective Tissue I

Question 1

Connective tissues are basically

Answer 1

a big continuous compartment separated form other tissues by various basal laminae (they differ in locations with their composition/properties)

Question 2

Connective tissue (CT) shared structural/functional feature?

Answer 2

they produce a prominent extracellular matrix (ECM) of structural fibers, glycoproteins, polysaccharides.
ECM’s vary, helps make connective tissues distinct.

Question 3

Connective tissue fx.

Answer 3

• Mechanical strength/support for organs
• Conduct/control exchange of nutrients, metabolites, and signaling ligands b/w diff. cell types of organs and b/w organ cells and blood
• Directly control behavior/fx of cells that contact the CT matrix (ECM).

Question 4

Regulatory fx of CT/ECM?

Answer 4

• Control of epithelial cell polarization and shape
• Guidance/regulation of cell migration through matrix
• Control of cell prolif, differentiation, metabolism
• Defense against infectious agents
• Control of tissue formation, organization, modification of tissue structure after stimulation or disease
• Control of inflammation and repair due to injury

Question 5

Is CT dynamic?

Answer 5

Yes. CT cells can be stimulated to prolif/differentiate throughout life.
ECM is continually secreted/modified by CT cells (and it affects fx etc of cells

Question 6

2 categories of cells in CT & general fx.?

Answer 6

1. ) Core “resident” cells: produce and secrete components of ECM and can proliferate to make new CT. Have common developmental origin.
2. ) Immigrant blood-derived cells: WBC’s derived from hematopoietic cells, migrate from blood to CT. Often part of immune system and also respond to tissue damage, allergic hypersenitivities

Question 7

Core “resident” CT cells

Answer 7

• Mesenchymal cells*
• Fibroblasts: pre-eminent cells of most CT’s in body
• Myofibroblasts*
• Adipocytes (fibroblast derviatives. Fat. White or brown).
• Osteoblasts and osteocytes (make bone)
• Chondrocytes: make cartilage
• Some smooth muscle cells*

Question 8

Mesenchymal cells

Answer 8

PRECURSORS to all CT members. Primarily in embryogenesis. Small # in adulthood to fx. as stem cells for generation of new CT.

Question 9

Smooth muscle cells (some)

Answer 9

Particularly in walls of blood vessels. Make some ECM components in which they are embedded. Derive (not all smooth muscle) from CT cells… why they can secrete ECM.

Question 10

Myofibroblasts

Answer 10

derived from fibroblasts. Capable of smooth-muscle like fx. Found in CT that require a contractile fx.
Often generated at wounds to retract/shrink scar tissue.

Question 11

Immigrant blood-derived cells

Answer 11

Lymphocytes: acquired immunity

• Macrophages: phagocytosis, regulatory
• Neutrophils & Eosinophils: imp for defense against microorganisms
• mast cells: secretory cells (imp in edema/allergies)
• Osteoclasts: phagocytic, specific to bone resorption/remodeling.

Question 12

Regulatory fx. of macrophages?

Answer 12

secrete/respond to numerouse extracell signals.
Macrophage produced signals can: induce angiogenesis, immune cell migration and fx, fibroblast activation (CT precursor), blood vessel permeability

Question 13

Macrophage physiological fx.

Answer 13

Phagocytose invaders, promote angiogenesis, remodel damaged tissue, removed normal developing tissues/organs

Question 14

Fibroblast features

Answer 14

• Secretory machines that make ECM components
• Capable of cell division to make new fibroblasts/ other CT types
• Actually not a single cell type (in diff CT’s have diff markers/regulatory proteins) responsible for variation in ECM structure/composition
• Developmentally flexible*

Question 15

Developmental flexibility of fibroblasts?

Answer 15

Can differentiate into other CT types (adipocytes, chondrocytes etc.)… but evidence now suggests it may be mesenchymal stem cells (MSC)
Fibroblasts or MSCs differ in their developmental potential, given fibroblast diversity (hard to tell apart fibroblasts and MSCs with histology…)

Question 16

ECM and components

Answer 16

Dominant feature of CT is that most components are extracellular. These are organized into ECM. Distinct with each type of CT.

a. ) Structural fibers (strength/resiliency)
b. ) Hydrated gelatinous material, ground substance (where structural fibers are enmeshed)
c. ) Numerous other Extracell macromlcs embedded w/in or diffusing the ECM

Question 17

Collagen

Answer 17

Structural fiber. Most abundant. Fibrous protein.
Made of 3 intertwined polypep chains (alpha chains) that form a fairly rigid rope-like triple-helix. There are many diff chains.
Each collagen mlc can be aligned/cross-linked with other collagen to make higher order fibrous structures.

Question 18

Types of collagen structures?

Answer 18

Fibrilar
Fibril-associated
Network-forming

Question 19

Fibrilar

Answer 19

Some collagen assemble head to tail (long) and are stacked in large bundles called fibrils. Lots of type I.
Rope-like. Great strength to resist tensile strength. Show banding pattern under microscope. Most abundant type of collagen.

Question 20

Fibril-associated collagen

Answer 20

Decorate surface of collagen fibrils. Link fibrils to each other and other tissue components.

Question 21

Network-forming collagen

Answer 21

Form very thin fibers, assemble into interlaced networks that form porous sheets.
Found in basal laminae, anchoring fibers that attach basal lamina to ECM.
Some fx as filtration barriers (kidney).
Collagen type IV is common component.

Question 22

Loose connective tissue

Answer 22

Contain thin collagen fibrils that are sparse, arranged in irregular lattices.
Cell densities and ground substance components are relatively high.
Blood/lymph capillaries and nerves are abundant.

Question 23

Dense connective tissue

Answer 23

Thick collagen fibrils in irregular orientations (or in parallel in ligaments/tendons)
Less ground substance and low cell number.
Great strength. Resist shear forces (tendons/ligaments)

Question 24

Collagen synthesis?

Answer 24

Made intracellularly by CT (in ER translocated to ER lumen) glycosylated and hydorxylated, put into triple helix then…
secreted and further modified (N and C termini cleaved by proteases) extracellularly. Formation of bundles/end-to-end polymers, enzymes catalyze cross-links b/w collagen mlcs (increase tensile strength)

Question 25

N-telo peptides

Answer 25

N-terminal fragments that are generated. Used for clinical diagnosis via urine levels. Imp for formation of bundles etc.

Question 26

Elastic fibers

Answer 26

In CT that need distensibility/resiliency.

Contain elastin and fibrilin (make fibers and sheets).

Question 27

Elastin and fibrilin

Answer 27

In random coils (unstructured) can be stretched. Secreted by fibroblasts (sometimes smooth muscle).
Form filaments/sheets with mlcs highly cross-linked to generate extensive network. Networks interwoven with fibrilin (organizes elastin elements in the fiber and with other components of the ECM).
Can stretch and recoil like rubber-band!

Question 28

Ground substance is made of…

Answer 28

Proteoglycans
Other secreted proteins/glycoproteins (proteases that process collagen, growth factors…)
Inorganic and small organic mlcs (ions carbs etc.)
Water

Question 29

Proteoglycans

Answer 29

Core protein attached to large acidic polysaccharide (glycosaminoglycan, GAG) that has lots of sugar. Many diff GAGs, most covalently attach to protein, but some don’t attach to core.
3 imp properties of GAGs:
-Negative (hydrophilic)
-Rigid extended structure allows them to form gels (promote hydration)
-Can bind/inactivate other proteins (like GF’s and ECM modifying enzymes)

Question 30

Why is GAG hydration important?

Answer 30

Important for diffusion (small easier, large mlcs limited). Also creates high swelling pressure so you can resist large compression forces (your knee)

Question 31

Inflammation and blood clotting

Answer 31

In response fibroblasts/mast cells and blood derivatives signal for: increased water permeability of capillaries…swelling, increased cellular permeability of endothelia for migration, attract migration of WBCs, stimulate fibroblast prolif/differentation of monocytes into macrophages
Histamines (increase endothelial permeability) and cytokines

Question 32

New tissue formation

Answer 32

Fibroblasts stimulated ot divide/secrete ECM. Can happen from signals from multiple cell types (like macrophages…angiogenesis)

Question 33

Tissue remodeling

Answer 33

In response to wounds cell density reduced, ECM thinner and altered. If extensive damage get imperfect remodeling..scarring.

Question 34

Inflammation

Answer 34

tied to crohn’s, IBD, cancer