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CELL AND TISSUE BIOLOGY EXAM #2
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BONE AND CARTILAGE
CARTILAGE: Consists of chondrocytes in lacunae, in an extracellular matrix.
- MATRIX: Consists of FIBERS + GROUND SUBSTANCE
- Ground Substance: Consists of Proteoglycans non-covalently linked to
- CORE Protein is covalently attached, via Link Proteins, to Keratan
Sulfate and/or Chondroitin Sulfate.
- Many Core Proteins are non-covalently linked to Hyaluronic Acid.
- BASOPHILIC: The matrix ix relatively basophilic, thanks to Chondroitic
Acids: Chondroitin-4-Sulfate and Chondroitin-6-Sulfate.
- AVASCULAR: All cartilage is relatively avascular.
- Nutrients are received, via passive diffusion, from blood vessels in the
- PERICHONDRIUM: Dense connective tissue around the cartilage.
- Perichondrium is not found on the articular surfaces of long bones.
- It contains blood vessels which provides nutrients to the cartilage.
- They are located within little caves called lacunae, in the ECM.
- SYNTHESIS: They are heavily synthetic. They have lots of ER. They
secrete the extracellular matrix components.
- They produce matrix components.
- They produce CHONDRONECTIN: Increases adhesiveness of
chondrocytes to matrix.
- DEVELOPMENT: Mesenchymal cells aggregate to start formation. The
Perichondrium is formed.
- INTERSTITIAL GROWTH: Formation of Isogenous Groups leads to an
expansion of the cartilage from within the cartilage.
- APPOSITIONAL GROWTH: Adding cells from the Perichondrium. Layers
from the perichondrium are added from the outside perimeter.
- ISOGENOUS GROUPS: Mitotic clusters of chondrocytes in mature cartilage,
formed by interstitial growth during cartilage development.
- CARTILAGE REGENERATION: Regeneration is limited because cartilage is
- Some appositional regeneration can occur from chondroblasts around the
- Cartilage Deficiencies:
- Vitamin-A Deficiency:
- Scurvy: Vitamin-C Deficiency leads to cessation of matrix formation (needed
to make collagen).
- Rickets: Vitamin-D Deficiency leads failed calcification of Epiphyseal
Cartilage (cartilage at epiphyseal plate).
- Growth Hormone Deficiency: Growth Hormone stimulates synthesis of matrix
components by chondrocytes. In deficiency, growth hormone therapy will
return you to normal.
- Hydrocortisone: It inhibits proteoglycan synthesis.
TYPES OF CARTILAGE:
- HYALINE CARTILAGE: Most common, basic type.
- FIBERS: College Type II (Cartilaginous Collagen)
- Nasal cartilage
- Trachea, bronchi, larynx (Cricoid Cartilage)
- Articular ends of bones
- ELASTIC CARTILAGE: Hyaline cartilage with elastic fibers are added to the matrix.
- FIBERS: Collagen Type II plus Elastins
- MICROSCOPIC APPEARANCE: Under low light, when you focus in and out,
you can see refraction of the elastic fibers under the microscope.
- Auditory tube + Auricle of ear
- Laryngeal Cartilages (Corniculate, Cuneiform, Arytenoid)
- FIBROCARTILAGE: Found in places where high stress occurs.
- DISTRIBUTION: It never occurs alone. It is closely associated with either
dense connective tissue or with hyaline cartilage.
- Intervertebral Disks
- Articular Disks
- Pubic Symphysis
- Insertions of some tendons and ligaments
- STRUCTURE: It has no perichondrium
- GROWTH: It grows more like connective tissue (i.e. interstitial growth) due
to the absence of a perichondrium.
- FIBERS: Collagen Type I
UNIQUE QUALITIES OF BONE:
- HYDROXYAPATITE: Calcium Phosphate crystals.
- It prevents diffusion of metabolites.
- It prevents interstitial growth -- all bone growth occurs from the periosteum.
- A CANALICULAR SYSTEM: Tiny canals connect one haversian system to the
- VASCULARITY: All bone cells are in close proximity to vessels!
- APPOSITIONAL GROWTH: All growth occurs by appositional growth.
- BONE RECONSTRUCTION: Bone is dynamic tissue, constantly changing shape.
GENERAL PROPERTIES OF BONE:
- TYPES OF BONE
- COMPACT, CORTICAL, LAMELLAR BONE: Bone arranged in concentric
layers called lamellae, with Haversian Canals containing blood vessels in
the center. Often found around the outside of large bones.
- CANCELLOUS, SPONGY BONE: Often found on inside, composed of
trabeculae, unorganized extensions of bone, around the bone-marrow
- LONG-BONE GROSS STRUCTURE:
- DIAPHYSIS: The shaft, with a medullary cavity on inside.
- EPIPHYSIS: The ends.
- METAPHYSIS: The site of ossification, between the diaphysis and
- ARTICULAR CARTILAGE: Hyaline cartilage covering compact bone at the
ends of long bones. It lacks perichondrium.
- PERIOSTEUM: Osteogenic potential around the outside.
- ENDOSTEUM: Lines the marrow cavity and also has osteogenic potential.
- In Skull, the endosteum is the dura mater, and it has limited
osteogenic potential which is important in fracture healing.
Bone Cell Types:
- OSTEOPROGENITOR CELLS: The Stem-Cells of bone.
- Found on the inner lining of the periosteum and endosteum.
- Found lining vascular canals.
- OSTEOBLASTS: They are secretory cells.
- They secrete the bone matrix.
- ALKALINE PHOSPHATASE which calcifies the matrix.
- They have polarity and resemble other secretory cells.
- OSTEOCYTES: They are osteoblasts that have become trapped in their own
- They are found in lacunae, between layers of lamellae, in the matrix of
- The lacunae are potential spaces, filled with extracellular fluid in real
- CANALICULI: Fine cytoplasmic extensions of the osteocytes running
perpendicular to the haversian canals.
- OSTEOCLASTS: Large, multinucleate cells derived from monocytes.
- They have acid hydrolases which have a Mannose-6-Phosphate
Receptor that targets them to lysosomes within the osteoclasts.
- Osteoclasts have many lysosomes and are eosinophilic.
- HOWSHIP'S LACUNAE: The spaces for bone resorption, between the
osteoclast and the bone resorption surface.
- RUFFLED BORDER of osteoclasts faces the Howship's Lacunae..
- Sealing Zones are contractile proteins that close off the Howship's
- SECONDARY LYSOSOME ANALOGY:
- Osteoclasts PUMP PROTONS into the sealed off space to acidify the
- The Proton Pump is driven by a Na+-K+ ATPase pump on the
basolateral surface of the cell.
- Thus the potential space is like a secondary lysosome except that it
- BONE-LINING CELLS: Found in the periosteum and endosteum. They can rapidly
transfer Ca+2 into and out of the bone.
- Morphologically they are like osteoblasts, except that they serve the special
Ca+2 transport function because they are located at the periosteal border.
BONE-MATRIX PROTEINS: Following are constituents of the bone-matrix.
- COLLAGEN: Type I Collagen = 85% - 90% of total bone protein.
- NON-COLLAGEN PROTEINS: Small percentage but very important.
- Cell Attachment Proteins: Fibronectin, Osteopontin
- OSTEOCALCIN: Contains gamma-Carboxyglutamic Acid residues.
Important in bone turnover.
- GROWTH-Related Proteins: TGF-beta, Insulin-Like-Growth-Factor-beta
- HYDROXYAPATITE: Bone salts (Calcium Phosphate) composes the non-protein
COMPACT BONE ULTRASTRUCTURE:
- Haversian Lamellae: Lamellae around central Haversian Canals, which contain
blood vessels and nerves.
- Osteocytes are within the lamellae, with canaliculi radiating toward the
central haversian canal.
- Volkmann's Canals: Run perpendicular (transverse) to the Haversian Canals, they
connect the haversian canals to each other, or to the marrow cavity.
- Interstitial Lamellae: Remnants of older haversian lamellae. They are not
concentrically arranged, but lie in between the haversian systems.
- Circumferential Lamellae: The external and internal borders of cortical bone.
- Outer Circumferential Lamellae: Occur adjacent to the periosteum.
- Inner Circumferential Lamellae: Occur adjacent to the endosteum.
- SYNARTHROSES: Poorly moveable (fibrous) joints.
- Syndesmosis: Bones linked by dense fibrous connective tissue, as in
- Synchondrosis: Bones linked by cartilage, as in the PUBIC SYMPHYSIS.
- DIARTHROSES: Moveable joints
- Articular Cartilage made of hyaline cartilage, without perichondrium, covers
the moving bone-ends.
- Joint Capsule is continuous with the periostea.
- Synovial Membrane lines the joint capsule. It secretes synovial fluid into
the joint space.
- Proprioception Nerve Receptors are located in the joint capsule.
- ARTHRITIS: Inflammation or degeneration of the joints, impairing joint mobility.
- Rheumatoid Arthritis: Auto-immune attack against joints. Swelling of
synovial membrane, hypertrophy of articular cartilages.
- Osteoarthritis: Non-inflammatory degeneration of joints.
- Hypertrophy of articular cartilages occurs.
General Characteristics of Ossification:
- OSTEOID: Unmineralized "Pre-Bone." It is the early matrix that is secreted by
osteoblasts, before it is mineralized.
- WOVEN BONE: Osteocytes are uniformly distributed and randomly oriented
throughout the bone. All Bone starts as Woven Bone.
- Bone first appears as little spikes called spicules, which then form
- From there, the woven bone is reformed to make either Cortical Bone or Spongy
INTRAMEMBRANOUS OSSIFICATION: Formation of bone directly from osteoblasts, with
no cartilage intermediate.
- Mesenchymal Cells ------> Osteoblasts
- Osteoblasts secrete the Osteoid Matrix.
- Osteoblasts then secrete Alkaline Phosphatase to calcify the matrix, trapping
themselves in it, and thereby forming Osteocytes.
- NEUROCRANIUM: Flat bones form by intramembranous ossification. The bone
spicules coalesce in the calcified matrix to form parallel, strong, trabeculae that
make up flat bones.
- Exceptions: Occipital, Temporal, and Sphenoid bones are both endochondral
ENDOCHONDRAL OSSIFICATION: Bone is formed on a cartilage model. The formation
of the bone itself is identical to intramembranous ossification.
- GENERAL PROCESS:
- Cartilage matrix is laid down.
- Perichondrium then becomes periosteum, when a vascular bud invades
the perichondrial space.
- The Vascular Bud contains blood cells, bone marrow cells,
macrophages, endothelial cells.
- GROWTH IN LENGTH: Occurs by proliferation of chondrocytes at the
epiphyseal plates and at the primary ossification front.
- GROWTH IN DIAMETER: Occurs by deposition of new bone under the
periosteal collar along with simultaneous osteoclastic resorption, in order
to maintain bone shape.
- The osteoclastic resorption is necessary to enlarge the medullary
- PRIMARY OSSIFICATION CENTER: Occurs in the center of the diaphysis, and
extends toward both epiphyses.
- Thus there are two fronts of primary ossification.
- Primary Ossification Centers close around the time of birth. Thereafter, long-bone growth occurs from the secondary ossification centers.
- SECONDARY OSSIFICATION CENTER: Forms at the epiphyseal plate.
- The orderly columns of chondrocytes are not seen here.
- Growth occurs from the epiphysis downward, toward the epiphyseal plate.
- EPIPHYSEAL CLOSURE: The end of longitudinal growth in long bone, when the
primary ossification center overtakes (i.e. calcifies) the secondary ossification
center, and hence long-bone growth ceases.
- OSSIFICATION ZONES: At the ossification front, the following zones can be seen:
- RESERVE / QUIESCENT ZONE: This is the zone farthest away from the
ossification front. Little cellular activity or cell division is occurring.
- PROLIFERATIVE ZONE: Chondrocytes are multiplying and arrange
themselves in long parallel columns.
- This is the main zone responsible for growth of the long axis of the
- MATURATION ZONE: Chondrocytes are hypertrophying and secreting
- CALCIFICATION ZONE: Matrix around the hypertrophied cells solidifying,
trapping the chondrocytes in the matrix. Chondrocytes are dying here.
- BONE DEPOSITION ZONE: The chondrocytes die once calcification is
complete, due to no nutrients. New osteoblasts are recruited from the blood
supply in the vascular bud.
- OSTEOBLASTS come into calcified cartilage and deposit bone
proteins into the matrix.
- FORMATION OF THE MARROW CAVITY: Develops from the early cavities in
trabecular bone, formed by erosions in the trabeculae.
- FORMATION OF HAVERSIAN SYSTEMS: Trabeculae of the long bone appear
as stalactites, hanging down from the epiphyses. These trabeculae enclose tunnels
where chondrocytes once resided.
- The vascular bud enters through those tunnels, and haversian canals form
around those tunnels.
- Bone builds up on either side of the vascular tunnel.
- The two ridges then fuse, enclosing the vascular tunnel.
- What was periosteum forming on both sides has now become the
endosteum of the tunnel.
- Ossification proceeds inward. Endosteal cells deposit bone until the vessel
is completely enclosed.
THE ARF CYCLE: The process of BONE-REMODELING, which occurs during growth and
in mature bone. It explains the interdependence between osteoclastic and osteoblastic
activity in bone-remodeling, which explains why Osteoporosis is difficult to treat.
- Activation: Osteoclasts are activated and begin secreting acids to resorb bone.
- Resorption: Osteoclastic resorption occurs.
- Reversal: Resorption stops and osteoblasts take over.
- Formation: Osteoblasts form bone on the opposing surface to complete the bone
PARATHYROID HORMONE: Enhances the rate of bone-turnover. Ultimately it takes Ca+2
from the bone and puts it into the blood.
- PTH indirectly stimulates Osteoclasts to resorb bone. PTH stimulation of
Osteoclasts is mediated by Osteoblasts. Again this shows interdependence of the
two cell types.
- PTH stimulates the release of soluble factors from osteoblasts. Those
factors stimulate the osteoclastic activity.
- Osteoclasts have no PTH-Receptors.
- PTH also stimulates the differentiation of monocytes into osteoclasts, and
increases the amount of osteoclastic ruffled borders.
- PTH also directly stimulates Bone-Lining Cells to transfer Ca+2.
- We need Parathyroid Hormone to survive and maintain Calcium homeostasis. We
can live without Calcitonin.
VITAMIN-D: 1,25-Dihydroxy-Vit-D stimulates osteoblasts to synthesis the bone matrix and
CALCITONIN: Takes Ca+2 from the blood and deposits it into the bone.
- Calcitonin inhibits osteoclastic activity by binding directly to osteoclasts.
- Osteoclasts do have Calcitonin receptors.
- Calcitonin also directly stimulates osteoblastic activity.
- Although Calcitonin opposes PTH, it does not completely counteract PTH. The
effect of PTH is more important.
TRANSFORMING GROWTH FACTOR (TGF-beta): This is one connection between
osteoblasts and osteoclasts.
- TGF-beta is found in bone in its inactive form.
- Osteoclastic activity stimulates TGF-beta ------> increased acid production
------> activation of TGF-beta in bone.
- TGF-beta, in turn, inhibits further osteoclastic activity (negative feedback) and
promotes osteoblastic activity.
- TGF-beta, as well as other cytokines, (IL-1, Tumor Necrosis Factor), appear to
be involved in differentiation of monocytes into osteoclasts.
MECHANISMS OF CALCIFICATION:
- MATRIX VESICLES: Matrix vesicles are inside the osteoblasts. They accumulate
the mineral and control the rate at which calcification proceeds.
- Intravesicular Calcium Accumulation: Ca+2 binds to vesicle and combines
with phosphates from the phospholipids to form the calcium salt.
- Extravesicular Calcium Accumulation: The hydroxyapatite crystals get
exposed to the extracellular space.
- Vesicular Alkaline Phosphatase is required for external calcification to
CHILDHOOD OSTEOPOROSIS: A deficiency in Carbonic Anhydrase II in children.
- This leads to incompetent osteoclasts, as no acid can form in the ruffled borders.
- Results = no marrow cavity formation, among other things.
FRACTURE HEALING: Healing recapitulates development.
- Clot Formation occurs in the Haversian vessels that were damaged by the bone
- A Callus is formed where the clot was, as new capillaries, fibroblasts, and
osteogenic cells invade the area.
- Cartilaginous Callus: It forms before a bone callus forms.
- Bony Callus: Forms from the Cartilaginous Callus as blood vessels
reperfuse the area.
- Woven bone is formed before lamellar bone, just like in development.
- BONE GRAFTS: They are used to bridge large fractures. Osteogenic Cells from
the host contribute to healing.
- The graft serves as a temporary transplant, to aid in the replacement of real
bone from the host.
DR. LUKERT'S CLINICAL LECTURE: OSTEOPOROSIS, defined as the decrease in bone
mass to the point that a fracture may occur with normal activity.
- NET RESORPTION: Whenever you have an increased number of sites of
resorption, you will have net bone loss.
- ESTROGEN: Estrogen inhibits the production of Interleukin-1 and Interleukin-6
by monocytes, which prevents them from differentiating into osteoclasts.
- WOMEN RUNNER'S: Why are they at higher risk for stress-fractures?
- High stress ------> Low Gonadotropins (as a teleological assurance that
pregnancy doesn't occur during stress) ------> Lower estrogen levels
------> more Ca+2 resorption from bone.
- GLUCOCORTICOIDS: They promote Ca+2 resorption from bone. They cause the
most rapid bone loss known. Why bone loss? Glucocorticoids have multiple bad
- Glucocorticoids inhibit Ca+2 absorption in gut ------> negative Ca+2-Balance
------> PTH is stimulated to restore Ca+2 in the blood ------> Ca+2 is
taken from bone.
- Glucocorticoids inhibit the gonadotropins ------> inhibit estrogen ------>
more Ca+2 resorption.
- This effect also holds for men. Testosterone levels are down-regulated, and Ca+2 resorption increases as a result.
- Glucocorticoids inhibit collagen synthesis in osteoblasts.
- VIT-D DEFICIENCY (RICKETS): Once again, inhibition of Ca+2 absorption from the
gut is the result.
- This results in a calcification defect which results in both osteoporosis (low
bone mass) and osteomalacia (inadequate bone calcification).
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THREE LAYERS OF VASCULATURE:
- TUNICA INTIMA: Endothelium + Subendothelial loose connective tissue.
- TUNICA MEDIA: Smooth Muscle primarily
- Also connective tissue with Collagen III (Reticular Collagen), and some
- Smooth muscle can also synthesize ECM components such as fibronectin,
- TUNICA ADVENTITIA: Outer connective tissue layer.
- CT contains Collagen I
- Vasa Vasorum: The tissue that supplies blood to the vasculature itself.
PERICYTES: Covers the outer surface of the capillary.
- Pericytes can contract. They aid in the blood flow of the capillary system.
- Help in INJURY -- the pericyte is pluripotential and can replace damaged tissue.
THREE TYPES OF CAPILLARIES:
- CONTINUOUS: Tight Junctions; lowest permeability.
- All tissues with blood-tissue barriers = brain, thymus, eye, gonads
- FENESTRATED: Capillary wall has little openings (fenestrations) that are covered
by little diaphragms.
- There is usually a complete basement membrane.
- DISTRIBUTION: GI-Tract, Ciliary Body, Choroid Plexus, Endocrine glands
- Diaphragm Permeability: The diaphragms are rich in heparin sulfate
which is anionic. Hence the diaphragm is impermeable to anionic plasma
proteins (which most plasma proteins are).
- The diaphragm is permeable to water and small solutes.
- Anionic Proteins can get through by transcytosis through endothelial
- DISCONTINUOUS: Basement membrane may be discontinuous or sporadic. There
are large gaps between endothelial cells.
- DISTRIBUTION: Sinusoids of the liver, spleen, and bone marrow.
- Non-Specific Endocytosis: Heme, Decapeptides
- Receptor-Mediated Endocytosis: Insulin, Transferrin, LDL.
TRANSCYTOSIS: Endothelial cell transports some plasma constituents out of the blood.
There are different methods (pathways) by which this can be done:
- Cell-Membrane Pathway: Transport permeable stuff through the cell, as in water
and lipophilic substances.
- Vesicular Pathway: Transcytosis of vesicles through the cell.
- Intercellular Junctions for transport of water and permeating solutes.\
- The Channel Pathway: Fusion of Vesicles.
- Open Fenestra (Glomerular Capillaries)
- Closed Fenestra: (Visceral Capillaries)
METABOLIC FUNCTIONS OF ENDOTHELIAL CELLS: Endothelial cells make lots of
- Production of basal lamina and other ECM components.
- Production of oligosaccharide moieties, which may function as recognition sites for
some molecules in the blood.
- Monoamine Oxidase (MaO) is made in endothelial mitochondria, to inactivate
- Angiotensin Converting Enzyme is made in endothelial cells, (presumably in the
- It has specific anionic sites on exoplasmic surface, to prevent platelets from sticking
to endothelial wall.
- Produces Prostacyclin, a potent antagonist of TXA2. It is an anti-coagulant.
- Endothelial cells also produce some coagulant factors: Antihemophilic Factor,
von Willebrand Factor, Plasminogen Activator
- Production of Nitric Oxide.
- Production of Endothelin.
ATHEROSCLEROSIS: Deposition of fatty tissue, usually on a muscular artery, to form a
lesion called an atheroma. Progression of damage is as follows:
- Endothelium gets injured ------> endothelium somehow gets detached (via
inflammatory mediators, mechanical damage, etc.), and underlying tissue gets
- Exposed subendothelial tissues attract blood cells and platelets.
- Smooth muscle cells accumulate lipid.
- Platelets can stimulate smooth muscle proliferation.
- Repeated injuries result in formation of an intimal plaque.
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- Inner (palpebral) epithelium is stratified columnar.
- Outer epithelium is stratified squamous keratinized (i.e. skin).
- Has Meibomian (sebaceous) and Sweat Glands (of Moll) associated with
THE SCLERA: Dense collagenous tissue. Like the cornea, but it is moe opaque.
THE CORNEA: Collagenous tissue but it is more translucent.
- The Cornea has five layers:
- Corneal Epithelium: Outermost epithelium, stratified squamous.
- BOWMAN'S MEMBRANE: Basement membrane of the corneal epithelium.
- CORNEAL STROMA: This is continuous with the sclera.
- All the collagen fibers in the stroma are parallel to each other.
- Proteoglycans in the cornea take up a lot of water, aiding the
translucence of the stroma.
- Descemet's Membrane: Basement membrane of the endothelial layer.
- Corneal Endothelium: Innermost epithelium, cuboidal.
- FNXN: It pumps excess water out of the corneal stroma. It is critically
important in keeping the cornea transparent.
- LIMBUS: The very edge of the cornea, where the cornea meets the sclera.
- FUNCTION: The cornea is responsible for stationery refraction of light. It refracts
about 70% of light, and the lens the other 30%.
CILIARY EPITHELIUM: The epithelial bilayer lining of the ciliary body.
- The epithelia are arranged apex to apex. Each respective basement membrane
- Non-Pigmented Layer faces the vitreous.
- It is continuous with the Neural Retina.
- Pigmented Layer faces the sclera.
- It is continuous with the Retinal Pigmented Epithelium.
- ORA SERRATA: The junction of the ciliary epithelium with the retina, where the two
epithelial layers become respective retinal layers.
- FUNCTION: Production of aqueous humor, to fill the anterior and posterior
chambers of the eye.
- Evidence says that the non-pigmented layer is the primary layer to secrete
the aqueous humor.
- BLOOD SUPPLY: The stromal layer has fenestrated capillaries that supply the
- AQUEOUS HUMOR:
- Trabecular Meshwork is around the iris angle.
- Canal of Schlemm drains the aqueous humor.
- GLAUCOMA: High intraocular pressure, usually from blockage of the drainage
pathway of the aqueous humor.
- SYMPTOM: This results in cupping of the optic disc.
- TREATMENT is very difficult, because its hard to get a drug into the ciliary
epithelium because of the blood-retina barrier.
- RESEARCH is currently being done on the connective-tissue
properties of the trabecular meshwork and Canal of Schlemm, to see
if their resistance to excessive aqueous humor can somehow be
RETINAL PIGMENTED EPITHELIUM (RPE): The underlying epithelia of the neural retina.
- Choroid: The name of the underlying layer, consisting of the RPE plus the
capillaries that supply the RPE.
- STRUCTURE: Cuboidal or columnar epithelia, with tight junctions.
- Villi: The RPE tightly interdigitates with the outer segment of the rods and
cones, so there is lots of surface area contact between the two layers.
- FUNCTION: There are four functions of the RPE.
- To supply the overlying photoreceptor cells and transport nutrients. The
photoreceptor cells are completely avascular.
- Phagocytosis of materials shed from the rods and cones, on a daily basis.
This is very important function -- the RPE disposes of and reprocesses the
shed disk-membranes of the photoreceptor cells.
- Storage of Vitamin-A
- Pigment (melanin) absorbs any stray light that is not absorbed by the
- BRUCH'S MEMBRANE: A double-layer membrane, consisting of the basement
membrane of the RPE, + the basal lamina of the underlying choroidal capillaries.
- Things leaving the retina are transported through this membrane system.
- MACULAR DEGENERATION can occur when waste accumulates
and Bruch's Membrane and diffusion through the membrane fails to
- MULTIPLE LAYERS: From capillary to retina, we have:
- Basal Lamina of the Capillary
- A layer of collagen
- A layer of elastic fibers
- Basal Lamina of the RPE
- Blood Retinal Barrier: It is a multi-layer system
- The choroidal capillaries that serve the outer retina are fenestrated. For
these guys, the RPE serves as the barrier.
- The capillaries that serve the inner layer of the retina are continuous. This
is the blood-retinal barrier for the inner retina.
- Epithelia: The anterior surface has no epithelium! POSTERIOR SURFACE has
two layers of epithelium.
- The posterior surface epithelium
- The anterior layer of myoepithelial cells: This forms the dilator muscle of
the pupil, which is innervated by sympathetics.
THE LENS: It's pretty translucent.
- FNXN: Primary function is accommodation. It also does some refraction, but so
does the cornea.
- Lens changes shape to accommodate for near-vision by contraction of the
ciliary muscle ------> zonular ligaments let go lens ------> it restores its
- Relax ciliary muscle ------> zonular ligaments grab onto the lens ------>
flatten it out for far vision.
- EQUATOR: New cells differentiate from the edges and proliferate inward.
- Lens cells never and are never replaced. This has implications for aging.
- CRYSTALLIN: Protein that gives the lens its translucent quality. There are three
- alpha-Crystallin: This seems to be the primary form that is responsible for
- alpha-proteins decrease a lot with age. This helps to explain the
occurrence of cataracts in old people.
- beta-Crystallin: These don't decrease with age so much as alpha-proteins
- gamma-Crystallin: Neither do these decrease with age.
THE RETINA: From the back of the eye (outer limit of eye) to the inner most layer...
- Retinal Epithelium: Not officially part of the retina.
- Choroid -- Not officially part of the retina. It is the blood supply to the retina.
- Retinal Pigmented Epithelium -- Not officially part of the retina.
- Neural Retina: Photoreceptor Layers
- OUTER SEGMENT: Photoreceptor Cells.
- It contains the disk membranes of the rod-cells, which contains
- These disk membranes contain 1:1 phosphatidylcholine to
phosphatidylethanolamine, giving them unusual amount of
- Experiments show that these disk membranes are continually
synthesized at the inner limit of the segment, and they are
continually turned over via phagocytosis in the RPE.
- This is also the demarcation point between Bruch's Membrane and
the beginning of the Neural Retina.
- EXTERNAL LIMITING MEMBRANE really isn't a membrane, but
consists of tight junctions between the cytoplasmic extensions of
- RODS -vs- CONES
- Rod-Cells harvest low-intensity, monochromatic light. Dark-adapted eyes are using primarily rod-cells.
- Cone-Cells harvest high-intensity, colored light.
- INNER SEGMENT LAYER: Continuation of the Photoreceptor Cell layer.
- It contains the mitochondria and other support organelles for
- OUTER NUCLEAR LAYER: Contains the cell-bodies of the photoreceptors.
- Neural Retina: Second-Order Neurons
- OUTER PLEXIFORM LAYER: Contains synaptic connections between the
photoreceptor-cells and the integrating neurons (amacrine and horizontal
- INNER NUCLEAR LAYER: Contains the cell-bodies of the integrating cells.
There are three integrating cell types:
- Amacrine Cells
- Horizontal Cells: Process lateral information.
- Bipolar Cells: This is the basic second-order neuron. The "Standard
Synapse" is photoreceptor cell ------> bipolar cell ------> ganglion
- Muller Cells: This cell extends almost the entire length of the retina.
- Their tight junctions form the external limiting membrane on
the outer surface of retina.
- They extend all the way through retina, and parts actually lie
on the internal limiting membrane.
- INNER PLEXIFORM LAYER: Contains synaptic connections between the
integrating cells and the Ganglion Cells.
- Neural Retina: Ganglion Layers
- GANGLION CELL LAYER: Contains the cell-bodies of the Ganglion Cells.
They're afferent fibers make up the optic tract.
- INTERNAL LIMITING MEMBRANE: Separates the neural retina from the
FUNDUS OF THE EYE:
- Optic Disk: An indentation right in the middle of the optic nerve. This is the blind
spot of the eye.
- Glaucoma patients, again, have cupping of the optic disk due to high
- Vascular Supply to the inner retina enters and exits through the optic disk,
along with ganglion cells.
- These vessels supply the secondary neurons of the inner retina -- they don't
supply the photoreceptors. Those are supplied by the RPE!
- Macula Lutea: Area on retina, lateral to optic nerve, where the retina is at its
- Fovea: In the Macula, the region of highest visual acuity, as it contains the greatest
concentration of rods and cones, without overlying neural structures.
CLINICAL STUFF FROM DR. WARREN:
- Anatomical Considerations: Attachment of the Retina: the Retina is only attached
to the eye-socket at two places: the ora-serrata and the optic nerve -- nowhere
- Those are the only mechanical attachments. Beyond that, the retina is held
in place by its interdigitations with the RPE.
- CLINICAL THINGS:
- Retinitis Pigmentosa: Good central vision because the cones are fine, but
peripheral vision is bad.
- Macular Degeneration
- Diabetic Retinopathy: Scar tissue on the retina from poor blood supply or
blood clots in the microvasculature. The scars can be surgically removed for
- THE ROD CELL:
- The INNER SEGMENT is like a neuron, with synaptic vesicles that will
synapse with secondary neurons at the inner plexiform layer.
- Synthesis of Rhodopsin occurs in the inner segment.
- Mitochondria and other supporting structures are in the inner segment.
- The cell operates a Na+-K+-ATPase pump at full speed, hence it
needs lots of E.
- The OUTER SEGMENT contains the disk-membranes which contain studs of rhodopsin
- STRUCTURE: It is a seven-alpha-helix transmembrane receptor that sits on
the disk-membranes in the inner segment of the rod-cells.
- RETINAL (Vit-A derivative) sits in the "pocket" of the receptor, inside
the membrane, covalently attached to the Rhodopsin via the Lys-296
- ACTIVATION of Rhodopsin occurs when a Photo of Light strikes. It is a
multi step reaction, but the reaction that is important in biological time is
Rhodopsin ------> ------> Meta-Rhodopsin-II.
- Once Activates, the Retinal, in all-trans-form, detaches from the
rhodopsin, at which point we have fully active rhodopsin.
- RETINAL: It is sits in the "pocket" of the Rhodopsin receptor.
- Photon of Light CHANGES THE CONFIGURATION of RETINAL from 11-cis-Retinal ------> all-trans-Retinal. This is the chemical basis for
- TRANSDUCTION PROCESS: Light causes the Rod-Cell to hyperpolarize, via a
cGMP-mediated signal transduction pathway.
- TRANSDUCIN: The G-Protein on the disc-membrane. It is activated by a
photon of light ------> conversion of Rhodopsin to Meta-Rhodopsin (R*)
- When activated, its alpha-subunit-GTP-Complex aids
phosphodiesterase (the target enzyme) in converting 3',5'-cGMP
- This is the opposite of what normally happens!
- The loss of the cGMP then causes cGMP-activated Na+-Channels
on the plasma membrane of the rod-cell to close ------>
hyperpolarization of the rod-neuron.
- The GTP is auto-hydrolyzed, in time, from the alpha-subunit, thus
deactivating it. So activation is temporary, just like other transduction
- MODULATING RHODOPSIN: In intense light, we don't Rhodopsin to be
- Rhodopsin Kinase can phosphorylate Rhodopsin, decreasing its
- ARRESTIN: It also inhibits Rhodopsin, to accommodate the eyes to
intense light. This makes it so Rhodopsin is not being continually
activated in light.
- IN THE DARK: The rod-cell is depolarized.
- High levels of cGMP are in the rod-cells.
- Na+-Ca+2-Channels are open. The channel accommodates both Na+ and
Ca+2, although Na+ is the major ion to come in.
- The cell is depolarized as Na+ continually comes in, and is pumped back out
via Na+/K+-ATPase located in the inner segment.
- The cell is releasing excitatory neurotransmitter (glutamate, aspartate) onto
the secondary neurons.
- IN THE LIGHT: The rod-cell becomes hyperpolarized.
- cGMP gets cleaved to GMP by phosphodiesterase.
- The Na+-Channels close.
- Na/K-ATPase quickly restores the cell to what we normally think of as resting
potential -- cell is hyperpolarized.
- The cell stops releasing neurotransmitter.
- RETINITIS PIGMENTOSA: It is multifactorial. Some of its genetic forms appear to
be mutations in the Rhodopsin molecule itself.
- CONE CELLS: There are at least four different Opsin Molecules involved in color
- Each opsin molecule has a different lambdamax and thus responds to different
- COLOR BLINDNESS occurs from a mutation in one of the opsin molecules.
- BLUE OPSIN resides on Chromosome #7
- RED OPSIN and GREEN OPSIN reside on the X-Chromosome
(hence X-Linked RG-Color Blindness)
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BLOOD AND BONE MARROW
HEMATOPOIESES: Development of erythrocytes and leucocytes
- HEMATOPOIESES DURING DEVELOPMENT:
- First it occurs in the Yolk Sac.
- Then it occurs in the Liver and Spleen.
- Then it occurs in the Bone Marrow
- Red Marrow (hematopoietic) is replaced by Yellow Marrow in the adult, in
the peripheral bones. Hematopoieses continues to occur in the axial
- Yellow Marrow may convert back to red marrow in disease or severe
- Extramedullary Hematopoieses: Spleen and liver can revert back to being
hematopoietic in some pathological conditions.
- STEM CELL DIFFERENTIATION:
- STEM CELL: It is pluripotential and divides by asymmetrical
division (i.e. division results in one differentiated daughter cell and
one undifferentiated stem cell.)
- PROGENITOR CELL: Multipotential cell that also divides by
- LYMPHOID will form B-Cells and T-Cells
- MYELOID will form erythrocytes, megakaryocytes, monocytes,
- PRECURSOR CELL: The blast cell. It is monopotential.
- MATURE BLOOD CELL: Only the mature blood cell will exit the
sinusoids and enter the blood stream.
Microenvironmental Factors that Regulate Cell Differentiation:
- Colony Stimulating Factors (CSF):They stimulate the formation of specific cell
colonies from multipotential stem cells.
- Granulocytes CSF's: Stimulates Neutrophils (G-CSF), or Neutrophils,
Eosinophils and Monocytes (GM-CSF)
- Monocyte/Macrophage CSF (m-CSF): Stimulates differentiation of
monocytes and macrophages.
- Erythropoietin (EPO): Produced in kidneys, it induces globin synthesis and
promotes differentiation of rubriblasts into erythrocytes.
- Interleukins (IL):
- IL-1: Stimulate granulocytic cells.
- IL-3: Stimulates growth in all phagocytes.
- IL-6: Stimulates multiple cell-types to differentiate.
- Stem Cell Factor (SCF):
- Stimulates early stem cells to differentiate.
- Stimulates the proliferation of mast cells.
- Transforming Growth Factor (TGF-beta): Inhibits hematopoieses.
- Directly inhibits proliferation of progenitor cells.
- Inhibits expression of GM-CSF, G-CSF, and IL-3 receptors.
- Interrupts the function of other local factors.
- Extracellular Matrix (ECM): Fibronectin, collagen, laminins. These ECM proteins
are essentially for the proper binding of other local factors.
HOMING: In bone-marrow transplants, the process of stem-cells finding their way to the
- Sinus Endothelial Cells express specific glycoproteins that the stem cells
- Stem Cell transport into the bone marrow occurs by transcytosis through the sinus
endothelial cells. That is, the stem cell travels through an endothelial cell -- not
- Once inside, the stem cell interacts with stromal cells in the bone marrow, also by
ligand-ligand interactions of glycoproteins on each respective cell membrane.
- B0NE MARROW SINUSES contain hematopoietic cords of mitotically identical
- Adventitial Cells are the structural components of the sinuses. They form
the barrier between the bone-marrow sinuses and the blood stream.
- Mature blood cells displace the adventitial cells to enter the blood stream;
at the same time the basement membrane depolymerizes.
- STRUCTURE: Biconcave disk, of size 7.0 - 7.2 micron.
- Poikilocytosis: A general term meaning anemia from abnormal RBC size, such as
- Hypochromic Anemia: Reduction in cell size or hemoglobin resulting in
anemia, as in microcytic anemia.
- Hyperchromic Anemia: Anemia from cells that are too large, such that there
are too few cells, as in pernicious anemia.
- The Red Blood Cell Hematopoietic Series:
- RUBRIBLAST: Most immature cell has a nucleus, nucleolus, and blueish
- PRORUBRICYTE: Nucleus compacts a little. It appears smaller.
- RUBRICYTE: Becomes more red (as basophilia is changed to hemoglobin).
Nucleus continues to get compacted.
- METARUBRICYTE: Full complement of hemoglobin, compacted nucleus,
eosinophilic pigmented cytoplasm.
- Mature ERYTHROCYTE: The nucleus is lost, and the cell is, by definition,
in the blood stream.
- Types of Transplantation:
- Syngeneic Transplantation: Transplant stem cells from an identical twin.
- Allogenic Transplantation: Transplant stem cells from someone other than
- Autologous Transplantation: Transplant stem cells from one's self.
- Aplastic Anemia is an auto-immune disease against stem-cells.
- Chronic Myeloid Leukemia: Disorder of the stem cell, from characteristic
chromosomal abnormality, the Philadelphia Chromosome.
- SYMPTOMS patient will have enlarged spleen, and one will find immature
myeloid cells in the bloodstream where they shouldn't be.
LEUCOCYTES: White blood cells, composed of Granulocytes and Mononuclear
- GRANULOCYTES: Granules in these cells means lysosomes and lysosomal
- NEUTROPHILS: Most prominent of the granulocytes. Constitutes about
70% of the WBC-count.
- FNXN: Inflammatory response to tissue injury. Particularly digestion
- MORPHOLOGY: Multilobed nucleus, granular, somewhat neutral
(yeah, right) color.
- You can see a BARR BODY as a "drumstick chromosome" in
the nucleus, in female cells. It is the extra X-chromosome
which is quiescent and condensed.
- MORPHOLOGY: Sometimes the nucleus is obscured by the same-color cytoplasm.
- It is a bilobed nucleus, when you can see it.
- It is bright red, i.e. eosinophilic.
- FNXN: They function in the allergic response. They are thought to
attack some parasites.
- They also counteract the histamine granules released by
basophils and mast cells. Thus they serve to balance the
effect of the basophils.
- BASOPHILS: They resemble mast cells. There are very few of them in
- MORPHOLOGY: It is basophilic and it again has a bilobed nucleus
which may be difficult to see.
- FNXN: Again, immunological responses to parasites.
- Basophils and Mast Cells release histamine granules to
cause vasodilation and inflammatory response.
- MONONUCLEAR LEUCOCYTES:
- LYMPHOCYTES: They are agranular.
- MORPHOLOGY: Lymphocytes are divided into small, medium, and
large, according to size.
- MONOCYTES: They are precursors of Macrophages.
- MORPHOLOGY: It looks agranular, but it actually does have
- Key to identification is a HORSESHOE-SHAPED NUCLEUS,
or Nuclear Indentation.
- The cell is largest of the leucocytes, and the nucleus is
relatively large and eccentrically placed.
MEGAKARYOCYTES: They shed fragments of their cell bodies to form Platelets.
- MEGAKARYOCYTES Morphology: They're huge. Ya can't miss 'em.
- MORPHOLOGY: Cytoplasm is purple and agranular. They are small and
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- Skin and Mucous Membranes = First line of defense
- Enzymes and pH effects are second-line defense.
- COMPLEMENT SYSTEM: Soluble, circulating proteins that interact in a sequential
manner, to help cell-mediated immunity. At the end of the cascade, the effects are
- Cell Lysis
- Opsonization: Coating cells with protein that makes them easier targets for
- Leucocyte Attraction (Chemotaxis)
- Monocytes / Macrophages: Natural, non-specific, phagocytic immunity that is
always in effect, to attack critters once they penetrate the skin.
- Granulocytes: Non-specific immunity that kicks in when you get an acute
CELL-MEDIATED IMMUNITY: T-LYMPHOCYTES
- DEVELOPMENT: They migrate from the bone-marrow to the thymus where they
- In the Thymus, the majority of T-Cells are destroyed or suppressed, resulting
- Macrophages dispose of the dead T-Cells.
- T-Cells acquire T-Cell-specific markers (CD2+CD3, and CD4 or CD8)
- Naive T-Lymphocytes are T-Cells in the thymus that have not yet come into
contact with antigen.
- PRE-PROGRAMMING: Humans are genetically pre-programmed for every possible
antigen you could be presented with.
- SUBGROUPS of T-CELLS: All T-Cells have the Pan-T-Cell-Markers of CD2, CD3,
and T-Cell-Receptor (TcR) markers.
- HELPER (TH) T-CELLS:
- FNXN: They help other T-Cells perform their function by secreting
- They activate B-Cells to produce antibody.
- TH1-CELL: Preferentially activates Cytotoxic T-Cells.
- TH2-CELL: Preferentially activates B-Cells.
- MARKER: CD4+ is the distinguishing marker for a T-Helper Cell.
- CYTOTOXIC (TC) T-CELLS:
- FNXN: They kill host-cells infected by viruses or bacteria.
- MARKER: CD8+ is the distinguishing marker for TC Cells.
- They require help from T-Helper Cells in order to become activated.
- SUPPRESSOR (TS) T-CELLS:
- MARKER: Also CD8+
- FNXN: Thought to be responsible for switching off the immune
HUMORAL IMMUNITY: B-LYMPHOCYTES
- DEVELOPMENT: B-Cells undergo differentiation in the bone-marrow.
- Stem-Cells mature into Pre-B-Cells which contain IgM in cytoplasm
- Pre-B-Cells ------> Immature B-Cells which contain IgM on cell surface.
- Immature B-Cells ------> Mature B-Cells which may express any antibody.
Antigen specificity is determined by gene rearrangement.
- Maturation process is facilitated by bone-marrow stromal cells and the
growth factors they secrete.
- ANTIGEN-EXPOSURE: When B-Cells are exposed to antigen, they differentiate
into two cell-types:
- PLASMA CELLS: Antibody-secreting cells that circulate the blood.
- B-MEMORY CELLS: They mediate secondary immunity.
- FNXN: They make antibodies or immunoglobulins. Once made, the antibodies
can do one of two things:
- They can be secreted into the general circulation where they travel as free
- They can stay bound to the plasma membrane of the B-Cell, where they
- With the help of TH-Cells, the antigen-receptor will activate the B-Cell
when the appropriate antigen is bound.
- B-CELL ACTIVATION: B-Cells are activated in the Primary Immune Response,
the first time an antigen is encountered.
- Once activated, B-Cells will clone themselves, creating multiple cells of the
same antigen specificity.
- At this point the B-Cell has two fates:
- Many of these B-Cells will become Plasma Cells and secrete that
- A few of them will become B-Memory Cells and will remain dormant,
and keep the antigen-specificity, until the same antigen comes along
in the future to reactivate the B-Cells.
- This reactivation of B-Cells is the secondary immune response.
ANTIGEN-PRESENTING CELL (APC): They control the activation of T-Cells.
- They are usually monocytes or macrophages. They can also be B-Cells.
- FNXN: They ingest foreign material, reprocess it, and put it on their plasma
membrane in a form that is recognizable by the T-Cell Receptors on T-Cells.
- REPROCESSING involves combining the antigen with HLA markers.
- HLA Class II markers are combined with the antigen to present to T-Helper
LYMPHOCYTE SURFACE ANTIGENS: These are really just surface markers on T and/or
B Cells. There are four general types of surface antigens.
- IMMUNOGLOBULINS: "Antibodies" secreted by or found on B-Cells.
- Has a huge range of specificities achieved by DNA rearrangement.
- Five general types (see below): IgG, IgA, IgE, IgD, IgM
- MAJOR HISTOCOMPATIBILITY (HLA) ANTIGENS: These are the antigens that are
integral to acceptance or rejection of transplanted organs.
- HLA Class I: Found on virtually all cells, except erythrocytes.
- FNXN: They activate Cytotoxic T-Cells. They combine with
intracellular antigenic proteins, such as viral proteins and
tumorigenic proteins, to present the antigen to T-Cells.
- STRUCTURE: One transmembrane heavy chain.
- APC: HLA Class-I APC's will secrete Interleukin-1 (IL-1) to initiate
the immune response.
- HLA Class II: Present on B-Cells, Activated T-Cells, and Antigen-Presenting
- FNXN: They aid in activation of both Cytotoxic T-Cells and B-Cells.
They combine with exogenous proteins from phagocytic and
lysosomal degradation products.
- STRUCTURE: It has two transmembrane chains.
- FNXN: These molecules function in Antigen Presentation.
- They combine with the antigen, in APC-Cells, and then the HLA-Antigen Complex is presented to the T-Cells.
- VARIABILITY: Genetically it is expressed codominantly, giving it a huge
variability in structure. That's what makes organ transplantation so tough.
- T-CELL (TcR) RECEPTORS: They bind to the Antigen-Presenting Cell.
- VARIABLE REGIONS are on the T-Cell Receptor. They allow us to develop
variability and diversity in the immune response.
- They give us specificity.
- "CD" ANTIGENS: Systematic classification of surface-antigens with diverse
functions. Cell-surface markers.
THYMUS: Site for maturation of T-Cells.
- STRUCTURE: Thymus has multiple lobules, each containing a cortex and medulla.
- THYMIC CORTEX: Primordial T-Cells are found at the outer edge of the
- Thymic Epithelial Cells help the T-Cells in the maturation and
- The cortex is highly basophilic.
- THYMIC MEDULLA: Has fewer lymphocytes and is less basophilic.
- THYMIC CAPSULE: Blood-Thymus Barrier. Blood vessels are enclosed
within the extracapsular space. The only supply to the inside of the thymus
is via the epithelia.
- HASSALL'S CORPUSCLES: Characteristic of the thymus, but their function
- INVOLUTION: Thymus in adult is largely fatty. However the thymus continues to
operate no matter how much fat has infiltrated.
LYMPH NODES: Filters both blood and lymph, trapping antigenic substances and
- Afferent Lymph Vessels: They come in under the lymph capsule all over
- They have valves to provide directional flow.
- Efferent Lymph Vessels: One or two efferent vessels exit at the hilus and
enter venous blood.
- Lymph Capsule: Made of connective tissue. Vessels come in under the
- Lymph Cortex: Contains Lymphoid Follicles, with germinal centers in the
- The Follicles contain lots of B-Cells.
- The germinal centers are sites of B-Cell proliferation.
- Paracortical Zone: Rich in mature T-Cells.
- The T-Helper-Cells secretes lymphokines which the neighboring B-Cells (in the follicles) can detect. This is a part of B-Cell activation.
- HIGH ENDOTHELIAL POST-CAPILLARY VENULES can be seen in the
paracortical zone, specialized for the entrance of T-Lymphocytes into the
- This directed entrance of lymphocytes is mediated by adhesion
- WEAK ADHESION AND ROLLING: The early stage is mediated by
- STRONG ADHESION AND EMIGRATION: The later stage is
mediated by integrins.
- Lymph Medulla: Contains primarily Plasma Cells
- Contains medullary sinuses that converge on the hilum.
- Also contains medullary cords consisting of Plasma Cells.
- PATHWAY OF LYMPH: Afferent vessels enter around cortex ------> travels from
the cortex toward the medulla, where it is filtered through multiple layers ------>
out the hilum.
- Lymphocytes tend to stick around the nodes for a while, because of
selectins. Then they will exit again and continue circulating.
- LYMPH-NODE PATHOLOGIES:
- Thymic Hyperplasia: No T-Cell in the lymph nodes are present.
- The Paracortical Zone of lymph node is missing -- There is only the
medulla and outer cortex.
- Agammaglobulinemia: Antibodies cannot be produced.
- The medulla of the lymph nodes is missing.
- Combined Immunodeficiency (SCID): Both T and B cells are missing.
SPLEEN: Filters only blood, not lymph.
- Immunological responses against blood-born antigens.
- Collection and removal of particulate matter (old RBC's) from the blood.
- Red Pulp: Contains dead and living erythrocytes.
- Old RBC's express a sugar-marker on surface, which macrophages
recognize and bind to bring them out of circulation.
- White Pulp: T-Lymphocytes centered around a "central artery." The central
arteries have been demonstrated well in animals but not humans.
- The White Pulp, then, is the site of immunological activity against
- RETICULAR FIBERS: They stain silver. They are prevalent in the spleen.
The reticular fibers hold the lymphocytes in place in the spleen.
- SPLEEN CIRCULATION: Trabecular Artery ------> branches into Central
Arteries ------> Smaller Branches ------> Sinusoids
- The smaller branches may have closed or open circulations.
- Either way, lymphocytes can exchange with each other in the white pulp of
MUCOSA-ASSOCIATED LYMPHOID TISSUE (MALT): Lymphoid tissue found along the
GI and Respiratory tracts, there to protect from outside antigens.
- PEYER'S PATCHES are streaks of lymphoid tissue found along the GI-Tract. They
are like MALT, except they are not diffuse -- they are concentrated areas of
- LOCATION: They are directly under the epithelial cells of the GI lining.
- The Colon in particular has lots of Peyer's Patches (because it has lots of
- HOMING to the region of the patches occurs. The patches don't just spring
up from nowhere!
- These patches start as T-Cells that originated in Lymph-Nodes.
- Macrophages or other APC's travel to the lymph node from the site of
infection and present the Antigen at the lymph node.
- The T-Cells then migrate back to the infection by the process of
THE PRIMARY IMMUNE RESPONSE: This occurs in lymph nodes, at the interface
between T and B-cells (paracortical area and follicles).
- Antigen Presenting Cell presents the antigen to T-Helper Cell.
- TC ACTIVATION:
- HLA Class I and II are combined with antigen before presentation.
- TH1 is the specific T-Helper cell for Cytotoxic T-Cell activation.
- TH1 also produces interferon-gamma (inflammatory mediator)
and Tumor Necrosis Factor, both of which further aid the
- B-CELL ACTIVATION:
- Only HLA II is combined.
- TH2 is the specific T-Helper cell for B-Cell activation.
- APC binds with the T-Helper Cell: INITIATION OF IMMUNE RESPONSE. IL1 and
IL2 are crucial to initiation.
- Interleukin-1 (IL-1): It is the cytokine that activates the T-Helper Cell. The
APC makes IL-1 in response to the binding of the naive T-Helper Cell.
- Interleukin-2 (IL-2): An autocrine growth factor, made and recognized by the
T-Helper Cell after activation.
- PROLIFERATIVE PHASE: T-Helper cells proliferate and lymph nodes swell.
- Each of the TH cells is identical to the original activated one.
- CYTOTOXIC ACTIVATION: T-Helper cells activate Cytotoxic T-Cells via expression
- B-CELL ACTIVATION: T-Helper cells specifically activate B-Cells via expression
- This stimulates the B-Cells to turn into Plasma Cells and B-Memory Cells,
and then to secrete antibodies.
IMMUNOGLOBULIN STRUCTURE AND FUNCTION:
- GENERAL STRUCTURE: Two identical heavy chains and two identical light chains,
covalently linked to each other. The different classes have different numbers of
these basic units, connected to each other in different ways.
- Antigen-Binding Regions are in both heavy and light chains. The genes
coding for this region come from multiple places on the genome, with
sophisticated RNA-Splicing going on to come up with the final product . IN
the genome we have:
- Variable Region: One gene from this region is used.
- Diversity Region: One gene from this region is used.
- Joining Region: One gene from this region.
- Constant Region: This region determines the anti-body class.
- IgD: Made in tiny amounts and no one is certain what it does.
- IgM: It is the earliest antibody produced, and it is prevalent early in the primary
- STRUCTURE: Five monomers held together by the J-Chain.
- FNXN: It is a wonderful activator of the Complement System
- Immature B-Cells have IgM on their plasma membranes.
- IgM has a low affinity (hence it is early on) but it can sweep up a lot of
- IgG: Most common mature antibody. It is the main antibody found in secondary
immune responses, in the blood.
- It has a very high affinity and hence high specificity.
- IgA: It is the main antibody found in secretions.
- SECRETION: First it forms a dimer and then combines with a secretory
component from the secretory epithelial cell. This component aids in the
transcytosis of the globulin to the lumen of the gland.
- IgE: It is the main antibody involved in allergic reactions.
- ALLERGY: IgE binds non-specifically to Mast Cells, causing degranulation.
If the Mast-Cell has a particular antigen and there is enough IgE around,
then an allergic reaction will ensue.
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Copyright 1999, Scott Goodman, all rights reserved