Download Human Tissues III

CLASS: FUND2
DATE: 11.2.10
PROFESSOR: Dr. Cotlin
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INTRO TO HUMAN TISSUES 3
Scribe: Megan Guthman
Proof: Bo Bradford
Page 1 of 6
INTRODUCTION TO HUMAN TISSUES #3 [S1]
CONNECTIVE TISSUE [S2]
a. Connective tissue is the material that’s not epithelial, muscle, or nerve. It’s everything else.
CONNECTIVE TISSUE [S3]
a. It maintains the shape of our body, gives us structure that we look like.
b. Provides structural support, and metabolic support as well.
c. Connective tissue has a huge range of activities involved in defense, protection, storage of fat and energy,
tissue repair, immune reaction. It’s the environment that transmits signals and information from all the other
tissue types.
d. Provides a medium in which cells can move around outside of the circulation in the body.
GENERAL FEATURES OF CONNECTIVE TISSUE [S4]
a. All connective tissue is mesodermal in origin. It consists of a diverse group of cells with a tissue-specific
ECM.
b. We saw epithelial cells are all connected to one another. Muscle cells (besides skeletal) are connected in a
continuum with one another. Connective tissue is unique in that the cells are isolated, they don’t contact one
another. They are cells living in their environment, and they reside as individual cells.
c. Connective tissue is highly vascular, usually lots of nerves (except in cartilage). Forms a continuum with
everything else in the body.
CLASSIFICATION OF CONNECTIVE TISSUES [S5]
a. Embryonic connective tissue – loose assortment of cells that are undifferentiated stem cells.
b. Connective Tissue Proper can be loose or dense defined by the presence and amount of connective tissue
fiber, in particular collagen.
i. Loose is loose arrangement of fibers,
ii. Dense is a dense concentration of fibers. Dense can be classified as dense irregular or dense regular.
c. Specialized Connective Tissue includes cartilage, bone, blood, and adipose tissue – all have the same
characteristics. They have specialized cells and matrix.
LINEAGES OF CONNECTIVE TISSUES CELLS [S6]
a. Where do connective tissue cells come from? There are 2 major lineages.
b. First is Hematopoietic lineage, stem cell populations. These give rise to blood cells and some immune type
cells (plasma cells, mast cells, macrophages).
c. All of the others – osteocytes, chondrocytes, fibroblasts, adipocytes – come from undifferentiated
mesenchymal cells. These cells migrate during embryogenesis to a site and factors stimulate them to be
fibroblasts, etc.
COMPOSITION OF CONNECTIVE TISSUE [S7]
a. Comprised of cells and matrix. Picture indicates all cells are individual free-floating cells. See fibroblats, mast
cells, plasma cells, adipocytes, macrophages, and see blood vessels coursing though. The little green turtle
shapes are pericytes.
b. Also collagen bundles and elastic fibers. Collagen type 1 is the primary fiber in connective tissue. See elastic
fibers as well
c. The matrix is all of those fibers as well as the ground substance.
CONNECTIVE TISSUE UNDERLYING EPITHELIUM [S8]
a. This is what epithelial tissue looks like. See collagen bundles, elastic fibers. This kind of connective tissues is
everywhere.
EMBRYONIC MESENCHYME [S9]
a. This is what mesenchymal embryonic, undifferentialed stem cells look like. Compare to next slide…
LOOSE CONNECTIVE TISSUE [S10]
a. This is what we define as loose connective tissue. It’s usually underlying an epithelial layer. For example,
under skin, underneath the epidermis you’ll see loose connective tissue called lamina propria. Also might see
dense connective tissue. It’s a gradient within.
b. The orange structures are collagen, Black/purple thin fibers are elastic fibers, middle is blood vessel. See
loose arrangement – more space and ground substance than anything else (white space is filled with ground
substance material).
CELLS OF CONNECTIVE TISSUE [S11]
a. Some of our resident cells – fibroblasts, adipocytes, pericytes, mast cells, macrophages, and stem cells.
i. Resident meaning there will always be populations of these cells hanging around.
b. Transient cells are WBCs, they just roam trough. If there’s some kind of wound/breach in tissue, then you see
influx of WBCs to the area.
FIBROBLASTS [S12]
CLASS: FUND2
Scribe: Megan Guthman
DATE: 11.2.10
Proof: Bo Bradford
PROFESSOR: Dr. Cotlin
INTRO TO HUMAN TISSUES 3
Page 2 of 6
a. Fibroblasts are principle cells of connective tissue. These cells lay down all of our collagen and elastic fibers,
and reticular fibers (collagen type 3). Fibroblasts also lay out all the material that makes up ground
substance.
b. Fibroblasts don’t readily divide. Don’t go through a lot of cell division except in the process of wound healing.
i. After damage to connective tissue, fibroblasts get the signal to get out of G0 stage. They go back into cell
cycle and can be rapidly triggered to proliferate to repair the damage site.
c. Usually spindly in shape, have long processes because they’re making collagen fibers.
XIII.
FIBROBLASTS/FIBROCYTES [S13]
a. In general, when a cell is a -blast it’s an immature cell that’s turning out a lot of matrix, while a -cyte is more a
mature cell.
b. Fibroblast – a lot of books use this term even though they aren’t rapidly dividing. Fibroblasts put out
processes and lots of collagen.
c. In fibrocytes, they’re more resting and not exhibiting a lot of activity.
XIV.
PERICYTES [S14]
a. All of our blood vessels have a thick layer of smooth muscle and connective tissue around them.
b. Except for capillaries – capillaries have almost no structure except for endothelial layers. This is for
exchanging gasses, you want thin squamous endothelium.
c. Pericytes have a supporting role in capillaries, they will surround capillary and put out processes for support.
When a capillary bed is damaged, pericytes will activate and help reestablish the damaged capillary bed.
d. Doesn’t totally surround the capillary, just puts out processes to support it.
XV.
MAST CELLS [S15]
a. Mast cells – develop in the bone marrow, are very large cells. Large basophilic staining granules.
b. Always hanging around. Two types of immune cells, mast cells and plasma cells, are always present.
c. Involved in allergic type reactions
d. Secretory products
i. Heparin is an anticoagulant
ii. Histamine increases vascular permeability
iii. Chemoattractant factors – attract more WBCs. Secrete factors locally to combat antigens and activates
things that participate in wound healing and clearance of antigens.
e. We have an antigen with a high affinity for FcR (the Fc component of an antibody).
XVI.
MAST CELLS [S16]
a. See pixilated granules, packed with secretory products. This would be regulated secretion. Preformed
granules wait to get signal.
XVII. MAST CELL DEGRANULATION [S17]
a. What is the signal? Antigen binds and activates this IgE receptor, which triggers the signaling cascade. Goes
through adenylyl cyclase that will increase the level of cAMP, which increases calcium, allowing fusion of the
vesicles to release their molecules. This is mediated by antibody binding and antigen binding. As soon as
antigen is there, it triggers secretion of factors to recruit and stimulate a response. Mast cells will always be
an immune cell hanging around the connective tissue.
b. Most abundant near orifices like respiratory passages, skin cells. They’re ready if anything breaches the area
that we need to respond to.
XVIII. MACROPHAGES [S18]
a. Macrophages are also a blood lineage, derived from monocytes in the blood. Monocyes are going to migrate
into tissues where they become macrophages. Macrophages are the major phagocytic cell of connective
tissues. They clear cell debris, bacteria, and scar build-up. Lots of them around connective tissue.
b. In some places in our body they become more specialized. Macrophages are all over the body, but they have
special names in certain places:
i. Liver has special macrophages called Kupfer cells because it helps filter the blood. All of the blood from GI
tract immediately goes to the liver. Nice to have a bunch of macrophages in there to help scavenge and
take up harmful things.
ii. Lung has dust cells – clear pollutins in respiratory tract
iii. Epidermis – Langerhans cells proactively take up anything trying to cross that epidermis barrier
iv. Bone – osteoclast is macrophage lineage. Degrades bone.
v. CNS – microglia are the macrophage population
XIX.
MACROPHAGES [S19]
a. Macrophage on left has taken up a RBC. Don’t have a special name in the spleen, where RBCs are
processed. Have ruffled border to engulf large molecules
XX.
ALVEOLAR MACROPHGES OR DUST CELLS [S20]
CLASS: FUND2
Scribe: Megan Guthman
DATE: 11.2.10
Proof: Bo Bradford
PROFESSOR: Dr. Cotlin
INTRO TO HUMAN TISSUES 3
Page 3 of 6
a. Slice of respiratory tract, shows alveolar macrophages that have collected carbon deposits. There’s limit to
how much we degrade things, dust cells take up as much as they can. Diseased lungs – see deposits of
things we can’t break down, accumulated in macrophages.
XXI.
LANGERHANS CELLS [S21]
a. Langerhans cells in skin. At bottom see basement membrane and lamina propria. This is a keratinized
example. See langerhans cells in brown with long processes. If something breaches this, it will be picked up
by macrophages.
XXII. KUPFER CELLS [S22]
a. This picture is from the liver. Lots of blood flowing through, see macrophages helping in the initial filtration of
the blood coming from our GI tract.
XXIII. PLASMA CELLS [S23]
a. Plasma cells are the other immune cells, derived from B lymphocytes. They are committed antibody secreting
cells. After an antigen is seen, we make a population of B cells producing the antibody to it. Then the plasma
cells go out into the tissue to combat an antigen as it’s seen.
b. Stay near underlying epithelium.
c. Have a distinct morphology - clock shaped nucleus. They have a central nucleolus and heterochromatin in
distinct patches.
d. This picture is from the GI tract. Hang out in the lamina propria underneath epithelium.
XXIV. EXTRACELLULAR MATRIX [S24]
a. ECM is composed of ground substance and fibers.
XXV. GROUND SUBSTANCE [S25]
a. Ground substance – see collagen fibrils and ground substance in this figure. Ground substance is comprised
of proteoglycans and glycosaminoglycans (GAG). Hyaluronan is a GAG. They can be long or short.
XXVI. GROUND SUBSTANCE [S26]
a. Glycosaminoglycans are long, unbranched, acidic, polyanionic – this is important for their movement of fluid.
Proteoglycans are GAGs + proteins, versus a glycoprotein that is a protein glycosylated in the secretory
pathway. A proteoglycan is predominantly sugar chains with a protein, while a glycoprotein is a very large
protein with a sugar modification.
XXVII. EXAMPLES OF GAGS [S27]
a. Examples of GAGs – repeating disaccharides. Very negatively charged.
XXVIII. AGGRECAN [S28]
a. Example of hyaluronan – this itself is glycosaminoglycans. It’s the scaffold for the linker protein that is the
scaffold for more GAGs  huge network of polysaccharides and proteins.
XXIX. FIBERS [S29]
a. Fibers – collagen, elastic, reticular fibers
XXX. COLLAGEN [S30]
a. Collagen type 1 is the predominant collagen in loose connective tissue, triple helix conformation
XXXI. FIBRILLAR [S31]
a. Collagen classified into categories:
i. Fibrillar – long fibrous.
ii. Fibril-associated collagens are shorter, processed a similar way. Supporting collagens.
iii. Collagen Type 7 anchors connective tissue to basal lamina.
iv. Collagen Type 4 is major component of basement membrane.
XXXII. PROCESSING OF COLLAGEN MOLECULES [S32]
a. A unique step in collagen biosynthesis is hydroxylation of prolines and lysines.
b. Distinct intracellular vs extracellular processing. Constitutive secretion – fibroblasts make this collagen and
secrete it as soon as it’s made.
c. In ER and golgi, synthesis of the pro-chain. Hydroxylation step, then glycosylation of several residues and
then self assembly. This is the initial processing of the triple helix. These are packaged into a secretory
vesicle. Cells make these and secrete it immediately.
d. Extracellularly those pro-peptide ends are cleaved, then self assemble into what we know as a fibril.
XXXIII. AGGREGATE OF COLLAGEN MOLECULES [S33]
a. Another picture of the same process: Intracellular hydroxylation and glycosylation, and the formation of
procollagen and then packaging. Extracellularly we see the cleavage event. Bottom of figure is the initial
polypeptide with glycosylation and hydroxyprolines (D) is the triple formation, and then these polymerize.
Collagen molecule is the triple helix. Collagen fibrils or bundles are multiple triple helixes bound together.
b. Collagen bundle is many, many collagen molecules. Collagen molecule = triple helix molecule. Collagen
bundle is lots of helices.
XXXIV. ELASTIC FIBERS [S34]
CLASS: FUND2
Scribe: Megan Guthman
DATE: 11.2.10
Proof: Bo Bradford
PROFESSOR: Dr. Cotlin
INTRO TO HUMAN TISSUES 3
Page 4 of 6
a. Elastic fibers are produced by fibroblasts in a similar way. They have an accessory molecule called fibrillin.
b. A collagen bundle is a bundle of ONLY collagen. An elastin bundle is bundle of elastin molecules and fibrillin.
These bundles are thinner than collagen and require a special stain to visualize.
XXXV. ELASTIN MOLECULES [S35]
a. Green strands are elastin molecules. Fibrillin (red) is covalently bound to 2 different elastin molecules. See
that its not a tight packaging, it’s a loose arrangement. The molecules have an expansion property. When
relaxed they coil up, when stretched they expand and contract at both monomer level and whole elastin level.
Fibrillin gives it it’s elastic properties.
b. As we age, elastic fibers get looser - breakdown of some fibrillins, don’t expand and contract.
c. Emphysema – lots of elastic fibers located in respiratory connective tissue for lungs to expand and contract.
With damage in emphysema, you lose elasticity and lose the ability to respond to the pressure in the lungs
and contract accordingly.
XXXVI. RETICULAR FIBERS [S36]
a. Reticular fibers are collagen type 3, but they have a unique orientation. Fibroblasts secrete reticular fibers.
b. Found in specific places like bone marrow, lymph nodes, spleen.
c. Bone marrow is a loose, diffuse bunch of cells. The lymph node is lots of immune cells. In these organs, you
see no organ structure. Structure is by reticular cells and fibers. These cells secrete reticular fibers and hold
on to them. Fibers are extracellular. See black fibers between cells. Secrete reticular fibers extracellularly but
hold on to it and another cell holds on to it. Makes a nice meshwork. No structure to a lymph node except
cells and reticular fibers make “cheesecloth” mesh pattern.
XXXVII. RETICULAR FIBERS [S37]
a. This picture is of the inside of a lymph node, showing cells and reticular fibers. B and T cells move thorough
these spaces. Reticular fibers give structure without having stable, static structures. They are collagen type 3,
specialized type where fibers stay associated with cell.
XXXVIII.
MOVEMENT OF FLUID IN CONNECTIVE TISSUE [S38]
a. Blood vessels course through connective tissue, but only exchange molecules at capillary beds. Exchange at
these areas is a result of pressure.
b. Order: arteries, arterioles, capillaries, venules and veins. Arterioles are the tail end of the arteries right before
the capillary bed. No direct communication with these cells in the blood vessel. As the diameter of these
vessels gets smaller, hydrostatic pressure goes up and small molecules flow out. Then the pressure inside
get so much that it draws water back in. Movement is based on pressure surrounding the capillary system.
On the left we have water and fluid flowing out, and on the right we have water and fluid flowing in.
c. Also see lymphatic capillaries called “blind ended lymphatics.” You’re not going to take up all the fluid you’ve
released from the blood, so a lot will drain in lymphatic capillaries. They are a place for excess fluid and a
dumping place for debris. The lymphatics end up returning fluid and contents into venous circulation. The
pressure around the capillary system feeds all the cells in the area.
XXXIX. RAT MESENTERY [S39]
a. Polarized images – see bundles. Both are considered loose connective tissue. Red are collagen fibers, and
the thin ones are elastin. Notice the variation in thickness. Collagen is thicker than elastic fibers.
XL.
AREOLAR (LOOSE) CONNECTIVE TISSUE [S40]
a. Loose connective tissue. Most of these cells are fibroblasts, no blood vessels around.
XLI.
LOOSE CONNECTIVE TISSUE [S41]
a. Loose connective tissue again, see blood vessel branches. Most of these cells are generic fibroblasts.
XLII.
DENSE IRREGULAR CT [S42]
a. Dense irregular – compare to previous picture that has thick collagen but lots of ground substance around.
This picture is epidermis of skin. Underlying the epidermis is dermis, filled with dense, irregular connective
tissue. Pink material is collagen bundles.
XLIII. DENSE IRREGULAR CONNECTIVE TISSUE [S43]
a. Closer picture – shows how thick, dense bundles are. Irregular because patterning is less organized than
something we’d see in a tendon. Connective bundles going every which way.
XLIV. COLLAGEN AND ADIPOCYTES [S44]
a. Again, dense, irregular connective tissue. Seeing adipocytes. In skin, we have epidermis (epithelium), dermis,
and hypodermis. Hypodermis is spongy, full of collagen and also adipose tissue.
XLV. TENDON (DENSE REGULAR) [S45]
a. Dense, regular connective tissue, prominent in tendons. All of these are collagen bundles. See dense
bundling and very regular pattering.
XLVI. MUSCLE TENDON JUNCTION [S46]
CLASS: FUND2
Scribe: Megan Guthman
DATE: 11.2.10
Proof: Bo Bradford
PROFESSOR: Dr. Cotlin
INTRO TO HUMAN TISSUES 3
Page 5 of 6
a. Skeletal muscle – muscles joined to adjacent bones by tendons which is dense, regular connective tissue.
See striations of skeletal muscle (bottom right), bottom left is collagen bundle connective tissue. If the picture
was bigger you’d see all of these collagen bundles are very regular in their arrangement.
XLVII. ELASTIC CT [S47]
a. Elastic connective tissue – see elastin underlying skin, also seen in arteries. Why? Picture is slice of aorta,
with smooth muscle and lots of elastic fibers. Elastic fibers in arteries because of the pressure of blood
flowing through. Elastic fibers allow it to contract and relax just like a rubber band. Not contracting like a cell
would, but elastic molecules give it elastic property.
XLVIII. RETICULAR CONNECTIVE TISSUE [S48]
a. Lots of elastic fibers in parenchyma of the lungs. Always going to see reticular fibers lining up with cells.
Maintain association with cells like a lattice.
XLIX. RETICULAR FIBERS IN THE LYMPH NODE [S49]
a. This shows lymph node reticular fibers. No structure here. Only structure is this network of fibers. Like a
sieve. Cells moving through, reticular fiber network that is drainer, filtration. Cells are loose individual
lymphocytes.
L.
DISEASES INVOLVING CONNECTIVE TISSUES [S50]
a. Atherosclerosis – when you have plaque buildup of connective tissue and lipids.
b. Diabetes causes a thickening of basement membrane, resulting in an inability to move things across. Causes
problems in kidney because basement membrane helps to filter things. In the lung, you impede gas
exchange.
c. Metastasis is highly dependent on connective tissue. A metastasizing cancer cell has to roam around in the
connective tissue. If you have a cell that can evade all the molecules in the connective tissue, it can enter
somewhere else.
d. Fibrosis is buildup of connective tissue (also cirrhosis)
e. Periodontal disease involves ligaments, which are connective tissue.
BEGIN NEXT LECTURE
I. INTRODUCTION TO HUMAN TISSUES #4 [S1]
II. CLASSIFICATION OF CONNECTIVE TISSUE [S2]
a. Cartilage, bone, blood and adipose are all considered connective tissues.
b. Cartilage is cells sitting in the matrix. Bone is cells sitting in a matrix. Same with adipose. Always cells sitting
in a loose connective tissue.
c. Blood itself is connective tissue. Again, cells sitting in the matrix – its matrix is fluid of the blood.
III. ADIPOSE TISSUE [S3]
a. Adipose tissue – cells store fatty acids. Adipocytes have a unique look.
IV. ADIPOCYTES [S4]
a. Adipocyte functions: energy stores, insulation, cushioning of organs. Insulates and cushions everything in our
body. Adipocytes also secrete hormones, sometimes classified as an endocrine organ.
b. White fat is unilocular, brown fat is multilocular. Brown fat is used for temperature regulation and we have
less as adults.
c. Hormones involved: Two hormones help regulate our weight control in the short term.
i. Ghrelin stimulates appetite.
ii. Peptide YY induces a sense of fullness – we hope our cells respond to this. If we’re full but we keep on
eating, we start storing. If we stimulate appetite and don’t eat, apidocytes release energy to provide energy
to the body.
d. Hormones for long-term weight control:
i. Leptin is exclusively produced by adipocytes. Thought to reduce appetite. Adipocytes can tell body we
have enough stored, produces leptin to suppress appetite. Obese people have high levels and are resistant
– secrete this and body is not responding, get sense that you’re not full. Take in food and accumulate it.
ii. Insulin involved when we need to modify our glucose. Adipocytes can take up glucose and generate more
triglycerides.
V. FAT ABSORPTION AND RELEASE [S5]
a. How do we store these? We can’t store free fatty acids as free fatty acids, so we store them as triglycerides.
b. Adipose tissue is highly vascularized – exchanging molecules directly with blood cells. When adipocytes get a
signal that the body needs energy, they take triglycerides and break them down with lipase to release fatty
acids. Fatty acids are taken up into the blood stream where they’re processed and carried away. Once fatty
CLASS: FUND2
Scribe: Megan Guthman
DATE: 11.2.10
Proof: Bo Bradford
PROFESSOR: Dr. Cotlin
INTRO TO HUMAN TISSUES 3
Page 6 of 6
acid contents get very high in the vasculature, they leech out of the capillary beds and adipocytes take them
up and repackage them as triglycerides. Always cycling. When there’s not enough free fatty acids in the
blood, adipocytes release some. When there’s too much, the reverse happens.
c. Lots of capillaries in adipose tissue.
VI. WHITE ADIPOSE TISSUE [S6]
a. Picture of white adipose tissue – unique look, can’t miss them. Filled with pure lipid droplets. Nucleus is
pushed to side, usually look very white.
[End 48:22 mins]