Connective Tissue I Flashcards
Connective tissues are basically
a big continuous compartment separated form other tissues by various basal laminae (they differ in locations with their composition/properties)
Connective tissue (CT) shared structural/functional feature?
they produce a prominent extracellular matrix (ECM) of structural fibers, glycoproteins, polysaccharides.
ECM’s vary, helps make connective tissues distinct.
Connective tissue fx.
- 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).
Regulatory fx of CT/ECM?
- 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
Is CT dynamic?
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
2 categories of cells in CT & general fx.?
- ) Core “resident” cells: produce and secrete components of ECM and can proliferate to make new CT. Have common developmental origin.
- ) 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
Core “resident” CT cells
- 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*
Mesenchymal cells
PRECURSORS to all CT members. Primarily in embryogenesis. Small # in adulthood to fx. as stem cells for generation of new CT.
Smooth muscle cells (some)
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.
Myofibroblasts
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.
Immigrant blood-derived cells
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.
Regulatory fx. of macrophages?
secrete/respond to numerouse extracell signals.
Macrophage produced signals can: induce angiogenesis, immune cell migration and fx, fibroblast activation (CT precursor), blood vessel permeability
Macrophage physiological fx.
Phagocytose invaders, promote angiogenesis, remodel damaged tissue, removed normal developing tissues/organs
Fibroblast features
- 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*
Developmental flexibility of fibroblasts?
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…)
ECM and components
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
Collagen
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.
Types of collagen structures?
Fibrilar
Fibril-associated
Network-forming
Fibrilar
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.
Fibril-associated collagen
Decorate surface of collagen fibrils. Link fibrils to each other and other tissue components.
Network-forming collagen
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.
Loose connective tissue
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.
Dense connective tissue
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)
Collagen synthesis?
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)
N-telo peptides
N-terminal fragments that are generated. Used for clinical diagnosis via urine levels. Imp for formation of bundles etc.
Elastic fibers
In CT that need distensibility/resiliency.
Contain elastin and fibrilin (make fibers and sheets).
Elastin and fibrilin
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!
Ground substance is made of…
Proteoglycans
Other secreted proteins/glycoproteins (proteases that process collagen, growth factors…)
Inorganic and small organic mlcs (ions carbs etc.)
Water
Proteoglycans
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)
Why is GAG hydration important?
Important for diffusion (small easier, large mlcs limited). Also creates high swelling pressure so you can resist large compression forces (your knee)
Inflammation and blood clotting
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
New tissue formation
Fibroblasts stimulated ot divide/secrete ECM. Can happen from signals from multiple cell types (like macrophages…angiogenesis)
Tissue remodeling
In response to wounds cell density reduced, ECM thinner and altered. If extensive damage get imperfect remodeling..scarring.
Inflammation
tied to crohn’s, IBD, cancer
