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Difference betwen Extracellular matric and connective tissue?
Similarities: structure and support
ECM: basal lamina included; proteoglycan, glycoprotein and polysaccharide macromolecules included
CT: principal function is connection/anchorage for medium of transport; very few cells embedded but main resident is fibroblast
Basic structural unit of collagen?
Secondary structure of collagen?
- triple alpha-chain
Fibrillar collagen types and general characteristics?
Types: I, II, III
fibrillar, linear, self-assemble
Type I collagen characteristics?
most common (90%), form large fibers bundles (fibrils < fibers < fiber bundles), strongest, seen in bone, skin, dentine, ligaments/tendons
**found in tissues that need to overcome high amounts of stress
Type II collagen characteristics?
Fibrils (never forms higher order structures), found in cartilage
Type III collagen characteristics?
Fibers (fibril < fiber < bundle), forms 3-D mesh network to resist stress in all directions (found in lymph nodes, blood vessels), associated with reticular fibers (means meshwork)
Type IV collagen characteristics?
Forms networks (not fibrils, fibers, or bundles b/c has kink in it) in basal lamina
Type VII collagen characteristics?
Achoring fibril, connect basal lamina to deep CT
FACIT (fibril-associated collagens with interrupted helices) characteristics?
they associate on surface of already made collagens to allow higher order structures (like in Type I collagen)
Transmembrane collagen XVII (BPAG2, BP 180) is used for what?
In hemidesmosomes to provide strong linkage to ECM (transmembrane)
What is bullous pemphigoid?
Mutation in collagen XVII (skin blistering)
What is osteogensis imperfecta? Which collagen is affected?
Fragile bones (break easily from daily activities)
Collage type I
Elastic fiber formation formed from microfibrils and elastin. Microfibrils are made form which glycoprotein? Microfibril fxn?
Fibrillin; fxn is to anchor elastic fibers
Elastin is solube or insoluble? High or low turn over rate? Why?
Insoluble; Low turn over rate b/c due to hydrophobic A.A.'s
What is the function of having many proteoglycans and aggregates (diversity)?
The diverse amount of PGs allows for the encirclation of many types of molecules with negative charges. This is because PGs have negative charged and will encircle water in the body. PGs are never free (2 exceptions).
Difference between aggrecan (i.e. hyaladherans) and GAGs?
The amount of PG's attached to core protein
Structural and Regulatory roles of PGs?
Structural role = organize ECM matrices (cartilage) and help link different ECM compartments
Reg. role = storage site for signaling molecules, act as co-factors to modify ligand sfor receptor recognition
Different between glycoproteins and proteoglycans?
glycoproteins generally on cell-surface for cell-cell communication
proteoglycans are in ECM, carry negative charges from sulfonation that allow them to contain water, signaling molecules, etc.
Fibronectin is an example of PG or glycoprotein? Fxn?
Glycoprotein; links cells to ECM, multiple binding sites for integrins (cell adhesion) and collagen (ECM)
Laminin is an example of PG or glycoprotein? Characteristics? Fxn?
Glycoprotein; 3 protein chains (many isoforms), multiple genes make each chain, links cell to ECM, different forms of laminin expressed during rissue formation/remodeling
Similarities and differences of laminin and fibronectin?
Fib: single gene but multiple isoforms via post-trans. modificatios, di-sulfide bond linkage, cell-cell communication (cell adhesion, ECM)
Laminin: 3 protein chains, many isoforms, multiple binding sites, cell adhesion to ECM (IF/actin), expression of dif. isoforms during tissue formation/remodeling
What is the resident cell in CT? Fxn?
Fibroblasts; synthesize and maintain all of the ECM components
(info slide) Cells in CT?
fibroblasts, osteoblasts, stromal cells, epithelial cells, adipose cells
Cells that can come into CT are?
Macrophages (fixed migrants), Mast cells (fixed resident), and plasma cells (free migrants)
Function of macrophages?
Phagocytose antigens, present antigens on cell surface
What is the function of mast cell?
inflammatory mediation- granulated cell type that monitors what's going on, cause leakage to allow other cells to come into that area, release histamines
what is function of plasma cells?
release antibodies (protein factory), so it has a lot of RER in cell membrane
Dense regular CT vs. Dense IR CT?
Dense R CT: no vasculature (fibers in one direction), fibers very close together
Dense IR CT: no vasculature (fibers in many directions)
Loose vs. dense CT?
loose: vasculature is present (lumens, capillaries), easily repairable
dense: no vasculature
where will you see Reticular CT? type of collagen present?
You will see this is in blood vessels. Type III
Adipose cells are either brown or white because?
white fat: highly vascular, energy
brown: they have lots of mitochondria to burn fat to generate heat (seen in fetuses)
Three layers of basement membrane starting form the top?
- Lamina Lucida
- Lamina densa
- Lamina reticularis
**First two make basal lamina...all three make basement membrane
What types of collagen are found in lamina lucida, densa, and reticularis?
- Lucida (Collagen type XVII [transmembrane one])
- Densa (Collagen type IV)
- Reticularis (Collagen type VII [loop deep in CT])
(info slide) ECM acts to give cells polarity (apex vs. basal), filtration barrier (limits what can cross), and physical barrier (doesn't let cancerous epithelial cell pass, or bacteria)...exception to bacteria passing is?
Staph. aureous infection
(info) ECM components can provide signals via interactins with cell surface integrins or other receptors to?
allow maturation, differentiation, repair
What protein is responsible for monitoring what is going on outside cells and around cells?
integrins surface proteins
(info) integrins on cell surface bind to ECM or not bind depending on the situation. Integrins also use signal transduction pathways to allow cell survival, migration, etc.
Matrix Metalloproteases (MMPs) characteristics?
In the pro-form and are activated via proteases.
Tightly regulated with alot of inhibitors (tissue inhibitor of MMPs [TIMPs]).
When ECM is degraded the left over part is matrikine which can regulate stuff via cell siginaling (like cytokine)
a novel (cryptic) binding site is revealed as a result of MMP cleavage of ECM and cell can bind to it
Function of MMPs?
MMPs degradate ECM to allow cell movement (i.e. inflammatory response cells, growth of new cells (angiogenesis), tissue formation)
Tissue Inhibitor Matrix Metalloproteases (TIMPs)?
Inhibit MMPs (i.e. don't allow degradation of ECM)
(info) ECM and cancer: anchorage independence, angiogenesis, metasis
anchorage independence: tumor cell survives even with MMP degrading ECM
angiogenesis: cancer therapy is to block angiogenesis (i.e. block the MMPs ability to degrade ECM for angiogenic purposes so new blood vessels wont feed tumor cells)
Metasis: tumor cells become metastatic because they release more MMPs that degrade the ECM to allow them to go whereever they want to go