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186 Cards in this Set

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Describe Pseudomonas Aeruginosa.
Gram negative rod shaped bacteria; can cause disease in almost every organism; mainly lives in water and soil, have been found in dH2O; don't require oxygen but can use it; have been used to clean up toxic waste; able to form biofilms
What are biofilms?
Clusters of cells; form on surfaces and almost look like mushrooms

Organized structure: bacteria at different levels have diff fxns (ie bacteria on inside will form channels to desctroy toxins/antibiotics

Takes acetic acid/bleach to get rid of
What are some diseases that Pseudomonas Aeruginosa can cause?
Hot tub folliculitis, green nail, and gangrene
What environment does Pseudomonas aeruginosa love?
warm, oxygen, glucose (humans)
What do we need a respiratory system?
1. Air conduction
- movement of air from
the room to our organs
- from nasal cavity -> sinus

2. Gas Exchange
- Respiratory Bronchioles
- Alveolar Ducts
- Alveoli
3. Mechanism for Ventilation
- Rib cage, intercostals,
and diaphragm
With regards to air conduction, describe the role of the larynx, trachea and bronchi.
Larynx - important both for making sounds and maintaining the development and sterility of the lungs

Trachea and Bronchi - plumbing which carries gas to the lungs; also important in keeping lungs sterile and humidified
Describe Mucous (snot. Where is it secreted and what does it contain.
Secreted by glands in the epithelium lining of the nasal cavity; contains antimicrobial peptides, WBCs, sloughed epithelium

can contain a lot of DNA from microbes and WBCs that stuck in the mucous
What is the purpose of the hair in the nose?
important for filtering large particles

the turbinates (3) help mix, warm, and humidify that air going into the respiratory tract
What is our oldest, most well developed sense?
smell
What are the cell types found in the olfactory epithelium?
1. Olfactory neurons (mature/immature)

2. basal cells
3. sustentacular cells - support cells
(T/F) Is the neuron in the epithelium myelinated
FALSE. The neurone is not myselinated in the epithelium, becomes myelinated as it goes deeper into the mucose, it then travels through the cribiform plate into the first cranial nerve
What is the purpose of the olfactory glands of Bowman?
Glands produce odorant binding protein that will be secreted into the epithelium
What is the purpose of the odorant binding proteins?
Odorant binding protein binds to odorants and presents them to the odorant receptors and causes the neuron to fire

Odorants are what we actually smell and there are odorants for different characteristic smells
How do we taste a variety of foods when we only can taste about 5 tastes?
We can taste a variety of foods based on diff combinations of odorants
(T/F) Each neuron produces receptors for numerous types of odorants, which will give you the sense of smell
FALSE. EAch neuron produces receptors for only ONE type of odorant

Cell might produce 10,000 copies of the receptor but they are all ONE TYPE
What can cause sinus congestion and how do you relieve this congestion?
Sinus congestion can be caused by the engorgement of this plexus with blood. Vasoconstrictors can be used to reduce congestion.
Describe the venous plexus in the nasal cavity. What regulates it? Describe the blood flow.
The venous plexus/nasal lamina propria contains cavernous or erectile tissue.

It is regulated by nitric oxide and cGMP.

Blood flow in sinuses is cyclical - it changes every 30-40 minutes.
Larynx: Epiglottis

What is the function of the epiglottis? Describe the epithelium.
The epiglottis protects the vocal cords in the larynx.

It has 2 surfaces, with two different types of epithelium.
1. Lingual/tongue surface - stratified squamous
epithelium

2. Pharyngeal: pseudo. strat ciliated epithelium

Certain viruses will infect only one side of the epiglottis.
What type of cartilage does the epiglottis have?
elastic
What happens when a particle hits the vocal cords?
cough
What are the false vocal cords?
folds of tissue above the vocal cords
Embryologically, where does the lung come from?
The lung comes from the foregut, or what would be the esophagus; thus, it shares a lot of the same biological principles as the gut.
What is the purpose of the ciliated epithelium in the respiratory system?
cilia beats quikly in a coordinated manner to clear particles, mucous, and spread growth factors
Where do you find basal cells and what is their function
Nuclei are at the base of the epithelium and are possible progenitor cells for the epithelium
What is the purpose of the trachea? What type of epithelium is found in the trachea?
Trachea connects the oral phaynx and larynx to the lungs

Pseudostratified columnar epithelium
What is the purpose of goblet cells?
Glandular type cells that are full of mucins and other secretions

Mucins are a component of mucous, which forms a thin layer on the top of cilia
What is the purpose of the submucousal glands? Where are they found?
Secrete mucous, antimicrobial peptides, and other factors which keep the airway clean

Found in the trachea and NOT throughout the lung!!
What is unique about the cartilage found in the trachea?
The cartilaginous rings of the trachea do not go all the way around the trachea. The back layer of the trachea has only a layer of membrane
What type of cartilage is found in the trachea?
hyaline
What is tracheomalacia?
disease which results from the collapse of the posterior wall of the trachea
Why is important to have seperation of ligand and receptor in epithelium?
Tight junctions found between apical and basolateral surface of epithelium.

Epitehlial cells make AND respond to Heregulin. When they respond to Heregulin, they proliferate.

the same cell makes the ligand and the recpetor

the tight junctions block the two from interacting unless the epithelium is damaged
What is Heregulin?
epidermal growth factor
What part of the cell makes Hergulin?
apical
What part of the cell makes the Heregulin receptor?
basolateral
What occurs when Heregulin binds to its receptor? What type of epithelium does this occur in?
When it is bound to the receptor it signals cell proliferation and healing of the epithelium.

This occurs anywhere there is pseudostratified columnar epithelium with tight junctions.
Describe the relationship of healthy cilia and pseudomonas. What happens to cilia if elastase is released from pseudomonas?
Cilia is moving and beating and doesnt allow pseudomonas to settle on the cells.

Without cilia, pseudomonas would be able to from biofilms on the cells.

If elastase from pseudomonas is added, the cilia will no longer beat
What is found on the terminal ends of all glycoproteins that allows for pseudomonas to stick
sialic acid

thats why its important for the cilia to continue beating to ensure pseudomonas does not stick
What gene is required from cilia formation?
HFH-4
What happens to mice when HFH-4 gene is knocked out
Knockout mice have non functional cilia and also have Situs Inversus (organs are on the wrong side of their bodies)
Why are cilia important in embryogenesis? How is this shown with mice?
Cilia regulate how a signal moves, probably by beating factors from one place to another.

In knockout mice, they had situs inversus
What is Kartagener's Syndrome (Primary Ciliary Dysmotility)?
Defect in how dynein arms assemble in cilia - dont assemble or beat correctly
What are the symptoms of Kartageners syndrome?
Bronchiectasis - chronic infection of the bronchus

Rhinitis - chronis infection of the nose

Situs Inversus
How many cartilage rings are found in the human trachea?
16-20

sometimes babides have 12 and this is bad
What animal has the most submucousal glands amond mammals
Ferrets
What is the diameter of trachea
same diameter as your thumb
What are bronchi?
Bronchi are divisions off the trachea
Describe the formation of bronchi and their structure
Bronchi are surrounded by PLATES of cartilage.

they are formed by dichotomous branching with an exact spatial orientation -- trachea branches into 2 bronchi which will divide into 2 secondary bronchi at the exact time and spatial arrangement

MAIN POINT: everyone has the exact same bronchial tree
Where do you find blood vessels in relation to the bronchus and bronchial branches?
Arteries and veins that run along with the bronchus and bronchial branches. Vessels form about the same time as, and run parallel to, the branches.
What type of epithelium is found on the bronchi?
ciliated pseudostratified columnar epithelia, which includes ciliated columnar cells, goblet cells, and basal cells
How are the epithelia in the bronchi arranges?
They are arranged in crypt-like structures -- dont know why but may be important for reducing turbulence of airflow
What is the purpose of the smooth muscle surrounding the bronchus?
SM allows constriction and causes bronchconstriction or broncho-spasm and makes people wheeze when they have an asthma attack
How are bronchioles different than bronchi?
Bronchioles are smaller; they don't have cartilage

there are no submucousal glands in bronchioles (only in trachea and bronchi)

They DO have ciliated epithelia and are lined by smooth muscle -- can contribute to airway obstruction by constriction
How do you know when you are at the terminal bronchiole?
When you reach point in bronchial tree divisions where there is no more cartilage, that is a terminal bronchiole
Is the terminal bronchiole part of the conduction system or the respiratory system?
Conduction system

No much flow in this area so hopefully pseudomonas has not made it down to this area
What is the purpose of alveoli?
Allows for diffusion of oxygen into the blood and carbon dioxide out of the blood

This is where the capillary plexus of the lungs is located
What is the gas exchange unit of the lung?
alveoli
What type of epithelium is found at the level of the respiratory bronchiole?
simple cuboidal epithelium w/o invaginations

terminal bronchiole has invaginations
Respiratory bronchioles branch into _____________. Is this dichotomous branching?
Branch into alveolar ducts.. this branching is random and not dichotomous
What type of epithelium is found at the alveolar ducts?
non-ciliated simple cuboidal
Premature babies have ________ ___________ that will become alveoli and alveolar ducts with one cell layer of cuboidal epithelium and lots of mesenchym around them
terminal saccules
Alveolar ducts lead to ____________ ______
alveolar sacs
Why are lungs better than animals that have gills and rely on counter-current exchange?
A plexus of capillaries created a huge surface area across almost all of the alveolus, which allows us to use a lot more oxygen a lot more quickly than animals that don't have lungs
What is the determinanat of viability -- factor that determines whether or not a pre-term baby will survive?
presence of an alveolar capillary plexus
When does the alveolar plexus form?
Forms at about 23 weeks
How many lipid bilayers does the gas have to diffuse through?
4 lipid bi-layer think

1. thin apical membrane
2. basement membrane of type
1 cell
3. Very thin apical
4. Basement membrane of capillary endothelial cell
(T/F) There is very little mechanical flow through this area.
True. The alveolus would rupture or be damaged with much flow
Damage of the alveoli that allows fluid from the blood or blood itself, into the alveoli is caused by:
1. Near drowning
2. Adult respiratory distress syndrome.
3. Heart failure causing pulmonary edema
What are the holes between alveoli called?
Pores of Kohn
What are type 1 epethelial cells?
flat and squamous like cells.

these cover most of the surface area of the lung.
What are type 2 epithelial cells?
Cuboidal

these make surfactant
there are MORE type 2 cells in the lumb

they have dark lamellar bodies inside
What are lamellar bodies?
They contain surfactant.
What is surfactant?
It is a combination of surfactant protein and a lot of lipids.
When do you start to make surfactant?
20-25 weeks.. made by immature cuboidal epithelial cells of the terminal saccules
What is the fxn of surfactant?
surfactant allows us to maintain equal surface tension throughout the lung.

upon secretion from type 2 cells, the surfactant unrolls to coat the entire surface of the alveolus
What happens if there is damage to the lung epithelial?
Type 2 cells repopulate the area and then differentiate into type 1 cells.
When are type 2 cells present?
32 weeks of gestation
What is beta-mathazone?
Mothers who are in pre-term labor (before 32 weeks) get a shot of beta-methazone (steroid) to increase the maturation of type 2 cells

this reduces the risk of respiratory distress syndrome in the infant
What is respiratory distress syndrome?
Aleveoli can't maintain the surface tension to stay open.
What was the cause of death of the Kennedy's baby?
Respiratory distress syndrome
Who discovered that surfactant was missing in the lungs of premature babies?
Mary Ellen Avery and John Clements
What happens in Emphysema?
destruction of respiratory tissue

The alveoli become large and there is less surface area

type of emphysema determines what part of the structure is destroyed
When smoking, the particles inhaled will be concentrated at what location?
Since the flow of air stops at the terminal bronchiole, the particles inhaled will be concentrated at the terminal bronchiole and respiratory bronchiole, in addition to the to trachea and vocal cords and nose
What is centriacinar emphysema?
It's due to inhalation of toxins or things that cause damage and inflammation. Primarily results in destruction of the respiratory bronchiole where air flow is decreased
What is the cause of alpha-1 anti-trypsin and panacinar emphysema
genetics and affects the alveolar ducts
What is the concentration (%) of oxygen and carbon dioxide that is found in the atmosphere?
21% oxygen
0.03% or 300ppm carbon dioxide
What is the concentration (%) of oxygen and carbon dioxide that is found in exhaled breath?
18-19% oxygen
5% carbon dioxide
What do epithelial cells of the lung make when something irritates it?
cytokines
Describe the function of cytokines.
They have components of and are active participants of the immune system.

They have chemotactic mediators to recruit neutophils, WBCs, etc to the area

they make anti-microbial peptides that are always lining our airways
Are alevolar cells good at killing or moving pathogens?
NO!
Where do alveolar macrophages come from?
Think that these come from developing lung mesenchyme and not the bone marrow
What is the function of alveolar macrophages?
They get rid of foreign particles or call for help with signaling molecules.

Send signal to neutrophils that are circulating in the cpaillary plexus.
What is the action of the neutrophil wants it receives a signal from an alveolar macrophage?
A neutrophil will go to the site of infection and recruit many more immune cells (this is the cellular mechanism for pneumonia.)

Neutrophils will kill off the foreign species even if it means destroying some of the lung tissue or walling off an area and forming consolidations
What is a pulmonary effusion?
a collection of fluid on the outside of the lung. There is so much inflammatory damage inside lung that is causes leakage of liquid, usually lymph, to the outside of the lung.

Staphylococcus is likely in causing effuecions.

Most of the time its a trasudative collection of fluid -- serum and some WBCs
where are clara cells epxressed
bronchioles and terminal bronchioles
what type of epithelia do clara cells have?
columnar but not ciliated
What do clara cells secrete?
Clara Cell secretory protein (CCS10), which is probably very important in innate immunity
what is the fxn of clara cells?
Important role in regenerating the lung epithelium in resopse to injury. If you expose lung to napthalene, it will destroy a lot of the epithelial cells.. involved in the repopulation of the epithelium
What is the controversy about lung stem cells?
debate on whether or not stem cells that reside in the lung can regenerate lung following injury

suggest that there are hematopoetic stem cells in the bone marrow that can go into the lung and repopulate it

other data suggests that mesenchymal stem cells from various tissues can repopulate the lungs
What is CF?
Autosomal Recessive Disease; been called the most lethal inherited single gene disorder among Caucasians (1/23 to 1/25 carry the diseased gene)

There is no way to determine carriers except with a genetic test.
How does CF show up at a doctor's office?
failure to thrive
What is the hallmark characteristic of CF regarding sweat?
sweat test - salty sweat is the hallmark characteristic of CF

Collect sweat off the skin of the child by using an agonist that draws out sweat and then the salt concentration is then measured.
What is the exocrine part of the pancreas?
The part that makes the digestive enzymes that get carried down the ductular system into 2nd part of the duodenum and then to the small intestines where they aid in digestion
Describe the progressive issues that CF causes in the pancreas.
The secretions from the exocrine part of the duodenum are called concretions because they are so thick. These block the ducts and fluid formed cavities form called cysts. The digestive enzymes that are building up become activated and begin autolysis and the exocrine part of the pancreas digests itself. Since digestive enzymes are't getting where they need to, you cant digest foods, gte diarrhea, and fail to thrive.

concretions->cysts->autolysis
What is the real name of CF and why was it called this?
Real Name: Cystic Fibrosis of the Pancreas because the cysts cause scarring and fibrosis until the function of the exocrine part of the pancreas is lost.

One of the hallmarks of CF is pancreatic insufficiency.
Is the endocrine part of the pancreas compromised in CF?
Endocrine part of the pancreas (contains the Islets of Langerhans which make insulin) is spared for a long time but it is not unusual for CF patients to develop diabetes later in life because the Islets also become compromised. The whole pancreas can be destroyed by this process.
What must CF patients do since the digestive enzymes are not getting to the right place in order to digest foods?
Must take exogenous pancreative supplements --- these have cox and pig digestive enzymes
How are the lungs affected in CF patients?
Some of the thick secretions that clog the pancreas show up in the lungs and cause pulmonary compromise. Bacteria grow in the mucous plugs and thrive there. They bring imflammatory immune cells into the lungs and fill them up. The inflammatory response with the immune cells also causes damage to the normal tissues of the lung.
Using pseudomonas, describe how CF patients are more likely to develop an infection.
Pseudomonas is normally cleared by muco-ciliary clearance. But in a CF patient the muco-ciliary mechanism is defective because the mucous plasters the cilia on the airways preventing clearance. The bacteria grow while the lung disease progresses, which makes it harder and harder to breathe.
What are therapies that CF patients use?
Chest physical therapy 2-3 times a day which involves someone beating on their back to break up the mucous and bring it up

Clean outs - 10 day stay in which they are given large amounts of antibiotcs so their bacteria can be knocked down and they can regain some lung function.
What is the current life expectancy of CF patients due to the advances?
37 years old

before advancements: 21 or 22
What is meconium illeus?
Meconium is the first stool passed by a baby. Illeus means a blockage of the intestines. This is basically the same obstructive disease that can happen in the lungs, pancreas, and sweat glands.
How does CF affect the reproductive tract?
There is a loss of the vas deferens as result of obstruction which results ultimately in infertility in 99% males of CF. Also high rate of infertility among women.
Why has CF been called a "generalized exocrinopathy?"
Because CF is a disease in which all the exocrine glands, including those important in digestion, mucous clearance and reproduction, are impaired.
Why is CF so prevalent in Caucasians?
heterozygote advantage (similar to relationship of SCA and malaria)

Villages were swept with cholera and those who were not carriers of CF had secretory diarrhea and died. Those that were carriers often had meconium illeus, which is when the stool is thickened. So the carrier frequency continued to increase.
What does it mean for a disease to be autosomal recessive?
Means one gene somewhere in the genome is causing problems.

1 gene = 1 protein, then the protein could be found in any of the disease tissue and be understood everywhere in the body
CF: With the experiment with sweat glands, what did scientist find?
Deep in the skin in the coil of the gland the secretion is made and then travels down a duct to appear on the surface of the skin.

Everyone's sweat comes out salty when it is made in the coil, but as it travels down the duct salt is removed before it reaches the surface.

In CF, the salt is never pulled out so the same amount of saltiness in the coil is the same that is secreted on the surface of the skin.

Using the patch clamp technique, pple found out that it was a problem with Cl-reabsorption and since no Cl- could not leave no Na+ could leave.
CF: What was determined by the experiments with airway cells?
Using patch clamp technique and exposing the ion channels to different situations, found out that in CF patients there is an epithelial Cl- channel that is not present.
What is the underlying cause of CF?
Lack of Cl- channel that lines the airways and sits on the face that points towards the lumen. It lines the ducts of the pancreas, reproductive tract, intestines, and all the other affected organs.
Mechanism of CF.
The way things are mobilized is by secreting Cl- through a channel. If there no Cl- channel, then Cl-, Na+ or water can moved so there is no ability to move secretions along. The absence of this Cl- channel means that you cant properly mobilize your secretions.
After determining the gene that caused CF, what did it look like and what gene family did it belong to?
It belonged to the ABC (ATP Binding Cssette) genes. Didn't look like an ion channel.
What gene is responsible for CF?
defect in the Cystic Fibrosis Transmembrane Regulator Gene (CFTR)
What is the structure of the CFTR protein?
Intracellular C domain and N domain.

Two transmembrane domains (TM1 and TM2).

Two cytosolic Nucleotide Binding Domains (NBD1 and NBD2) -- this is the ATP binding cassette

Regulatory domain (R) - has numerous sites for phosphorylation of Protein Kinase A. Phosphorylation results in a more negative R-domain
What is the function of the CFTR protein?
PKA is required for CFTR function. PKA is activated by cAMP.

As the transmembrane regions line up in the membrane they form a channel for Cl- to pass.

R domain is at the intracellular asepct of the pore. When it gets phosphorylated (now has negative charge) it pops out and lets Cl- to pass through.

Dephosphorylation causes the ball to pop back in like a plug.

NBDs act like a fine gate on the channel. Once the R-domain is phosphorylated, the NBD's move closer together and form an ATP sandwich changes the conformation of the NBD so Cl- can flow easier.
What would happen if the R-domain of the CFTR were removed?
Cl- would flow because the channel would always be open.

No other ABC protein has an R domain.
What is the most common mutation in the CFTR gene?
delta F508

Phenylalanine is missing at amino acid 508
Describe the mutation delta F508 in the CF gene?
Accounts for 70% of all CF alleles.

Although this mutation in the CFTR protein was functional on the cell surface, it could never make it to the surface because it did not fold right in the ER. Thus, ERAD did not allow it to leave the ER for further processing. The protein is sent to the proteasome instead.

This mutation is temperature sensitive. At 27oC, the mutated CFTR can get to the cell surface
Describe the R553X mutation in the CFTR gene.
Arginine at amino acid 553 has a nonsense mutatino. It is replaced by a stop codon.

Early truncation occurs which leads to a shortened non-functional protein; if it does make it to the cell surface it is non-functional.
Describe the G551D mutation.
Glycine at position 551 is replaced with aspartic acid.

CFTR is actually made and actually gets to the cell surface, but it is non-functional.
Where are all the CFTR mutations?
NBD1 domain

nucleotide binding domain 1
How many mutations exist that cause CF?
1000 mutations
Why is important to know the underlying mechanism of CF for each patient?
It allows for tailoring the therapy. For example, a therapy for processing CFTRR would not be effective for the R553X mutation.
Describe High Throughput Drug Screening.
HTDS just screens millions of synthetic organic compounds using robots to see if they have any effect on certain diseases. These drugs are tested w/o any scientific rationale

HTDS has found many potential therapeutics called correctors.

For R553X - Bedwell has found a non-sense mutation supressor in which there is suprresion of the ribosome's ability to recognize a non-sense mutation.
What are the 7 functions of skin?
Barrier and Seal
Immunological
Sensation
Biotransformation
Social-Sexual
Thermoregulation
Water Regulation (evaporative colling and electrolyte balance)
Describe the epidermis. (thickness, function, vascular/avascular, cells present)
Usually thinner than other layers
Fuctions as exterior barrier
avascular and no lymph vessels

Cells Present: keratinocytes, melanocytes, merkel cells, langerhan cells
Describe the dermis.
Thickness varies.
Mainly connective tissue collagen matrix (~75% collagen)
Dermis supports epidermal appendage structures

Blood, lymph, and nervous supply

Cells: mainly fibroblasts and cells recruited to be around blood vessels (endothelial cells of lymph and blood vessels, mast cells, dermal dendritic cells, lymphocytes and PMNS in pathological state)
What are some examples of epidermal appendange structures?
hair follicles
sweat glands
other sensory structures
Describe the hypodermis.
Mainly made up of adipocytes.
Supported by loose connective tissue

Has blood, lymph, sensory, and nervous supply
What is the purpose of having the hypodermis filled with fat?
Fat layers provide insulation, cushioning, and mobility of skin.

Energy storage function
What are the different layers of the epidermis?
Basement Membrane
Stratum Basal
Stratum Spinosum
Stratum Granulosum
Stratum Corneum
What types of cells will you find in the Stratum Basale?
Made up of dividing keratinocytes

As these cells proliferate, they are pushed into the upper layers, as they change their protein expression profile to acommodate each specific layer's needs
What types of cells will you find in the Stratum Spinosum?
Keratinocytes express proteins to:
1. allow movement through the skin
2. provide tensile strength
What types of cells will you find in the Stratum Granulosum?
Keratinocytes here express proteins to:
1. accumulate granules with lipids
2. crosslink their proteins with each other
What types of cells will you find in the Stratum Corneum?
Keratinocytes:
1. completely hollow husks
2. function as body's armor
What is the difference between thick and thin skin?
Depends on the thickness of the epidermal layer

Thick: found on palms and soles; no hair follicles, lots of sweat glands, thinner dermis relative to thin skin, hypodermis quite large

thin skin: continous epidermis like thick; hair follicles
Describe keratinocytes.
- 95% of epidermal cells
- stratified differentiation of squamous epithelial cells
- generates keratin and cross linking enzymes
- makes lipids which are the barrier to the moisture inside the body
- Melanin produced by melanocytes and used to protect from UV damage
- skin constantly regenerates new cells and sloughs off damaged cells
- generates cytokines to signal barrrier breaches of the skin or infection in the body
What is cytomorphogenesis?
Keratinocytes change their shape as they move up the epidermis.

cuboidal columnar -> cuboidal polygonal -> flattened polygonal -> empty husks
Describe the keratinocyte maturation in the stratum basale.
K5 (acidic) and K14(basic) keratins

smaller keratins allow these cells to divide but remain attached to the BM
Describe the maturation of keratinocytes in the stratum spinosum.
K1 (acidic) and K10 (basic)

Bind to each other via desmosomes, which provides tensile strength but does not inhibit movement

high MW keratin needed for the desmosomes
Describe the maturation of the keratinocytes in the stratum granulosum.
keratinohyaline granules - contain filament aggregating protein - proflaggrin - allow for crosslinking in stratum corneum

Has lamellar granules - lipid that will be secreted in extracellular space

cell nuclei being to disintegrate
Describe the maturation of the keratinocytes in the stratum corneum.
Regular, overlapping structure; anuclear

cytoplasm completely replaced with keratinocyte tonofibrils

cells are glued together with lipids
How long does it take to move from the basal to the corneal layer?
5-14 days depending on cell type
How long does it take for the stratum corneum layer to slough off?
2-4 weeks
What keratins are found in what layer? What does this say about protein expression?
K5 and K14 -- low MW are only expressed in basale layer

after cell division, protein expression changes to express K1 and K10 in all other layers
Where are the melanocytes found?
binds to the basement membrane
compromise 1-3% of epidermal cells
How does melanin get in the keratinocytes?
Dendritic process of the melanocytes feed surrounding keratinocytes with melanin granules, which protect cell nuclei from UV mutagenesis

cytocrine process
Where are melanocytes derived from?
Neural crest cells (8th week of gestation)

thus, damage to melanocyte population does not repair quickly
What enzyme is only found in melanocytes?
tyrosinase - catalyzes the initial reaction of melanin synthesis

Tyr -> DOPA ---> Melanin
What are the two types of melanin?
Eumelanin: brown/black

Phaeomelanin: yellow/red
What is a melanocyte unit?
Each melanocyte prived 36 keratinocytes with melanin via dendrite processes
How do melanocyte granules undergo cytocrine secretion?
Mature melanin granules are pushed up vis processes and taken up by keratinocytes.
What is the purpose of melanin?
Melanin is organized in a polarized umbrella like fashion protecting nucleus from UV. UV will eventually degrade melanin, it is then taken up by lysosomes and replaced.
Where are langerhan cells found?
stratum spinosum, not connected to BM
What are the langerhan cells derived from?
derived from bone marrow precursors and seed the epidermis at 12 weeks of gestation
What are the actions of langerhans cells in a resting and activated state?
Resting: survey the health of the skin and take up possible antigens in intracellular space

Activated (if they find an antigen): will leave skin and go into lymph vessel to get to lymph node to present the antigen and activate the immune system
Describe the general action of the langerhan cells.
Antigen presenting cells, especially dendritic cells (cells with class II MCH molecules) are cells that pick up pathogens and then turn on the immune system by activating T-cells, which coordinate the appropriate immune response.
What are dendritic cells?
professional antigen presenting cell
What are Birbeck granules?
They are found in langerhan cells and presumbaly this organelle takes special skin antigens and puts them on the MHC
What are the functions of dermoepidermal junctions?
This is basically the basement membrane.

1. Attaches epidermis to dermis
2. Support and tensile strength to skin
3. provides filter for the epidermis
4. Regulates premeability across DEJ
5. Important for embryonic differentation: BM separates ectoderm (epidermis) and mesoderm (dermis)
6. Supports appendage structures
What are the 3 layers of the DEJ?
1. Lamina Lucida
2. Lamina Densa
3. Sub-lamina densa
Describe the lamina lucida.
Mainly made up of laminin
electron permeable
hemidesmosome (type 17 collagen) anchors basal cell to lamina lucida
Describe the lamina densa.
electron impermeable
has type 4 collagen and proteoglycans; type 7 collagen anchros lamina densa into dermis
What is the main cell of the dermis?
fibroblasts is the main cell

will have mast cells found next to capillaries that release histamine and cause an influx of leukocytes
What do fibroblasts secrete?
proteoglycans, elastin, collagen
What type of collagen is found in the dermal papillary layer?
type 3 collagen
What type of collagen is found in teh dermal reticular layer?
type 1 collage
What are Meissner's corpuscles?
for high touch sensitivity
What are Merkel Cells?
high resolution tactile receptor
What are free nerve endings sensing?
respond to pain and temperature
Where are stem cells of the found?
Stem cells found in hair follicles in region next to sebaceous gland called the buldge or bulb

These cells can differentiate into cells of epidermis, sebaceous gland, or dermal papilla structure (hair follicle)
Describe the sebaceous glands.
Secrets sebum via holocrine secretion.

The gland cells fill up with the lipid and then die as relasing contents

These glands arise from differentiated basal cells.
Describe the eccrine system.
Important for thermoregulation - produce hypotonic solution from isotonic plasma needed for evaportaive cooling

Highly active in resorbing Na+ in exchange for potassium (3rd kidney)

Sweat is acidic/has antibacterial properties
When sweat glands made?
Made during development; so at birth the body has a set number of sweat glands (300-400 million)
Describe cytocrine secretion and give an example.
Delivery of melanin granules by having dendritic tips pinched off by receiving keratinocyte.

Melanocytes
Describe apocrine secretion and give an example.
Deliver vesicles by cell budding, lipid rich, pheromones

Now thought that this is actually merocrine secretion

Special sweat glands found around the nipples, gland of Moll-eyes, ear glands
Describe merocrine secretion and give an example.
Secretion of liquid.

Example - Sweat glands
Describe holocrine secretion and give an example.
Secretion of and disintegration of lipid filled whole cells. Whole cell dies and dumps it contents into the lumen of the gland.

Example - Sebaceous glands