IDTH 201 Epithelia PDF

**IDTH 201 -- Exam 3 Material** **Epithelium** Epithelia lines body surfaces and cavities and constitutes the secretory portion of glands (parenchyma) and their ducts. It is a tightly cohesive sheet of cells, and it is avascular. There are specialized epithelial cells that are receptors for spec...

**IDTH 201 -- Exam 3 Material** **Epithelium** Epithelia lines body surfaces and cavities and constitutes the secretory portion of glands (parenchyma) and their ducts. It is a tightly cohesive sheet of cells, and it is avascular. There are specialized epithelial cells that are receptors for special senses. I. **Epithelial Cell Characteristics:** 1. Closely adhering to one another by means of specific cell-to-cell adhesion molecules (junctions). 2. They exhibit functional and morphological polarity. Different functions are associated with 3 distinct morphological surface domains: a. Free surface domain or apical domain open towards lumen. b. Lateral domain. c. Basal domain attached to BM a non-cellular protein polysaccharide layer. The properties of each domain are determined by specific lipid surface membrane proteins. Example of **thick ascending limb** and **distal convoluted tubule**: the apical domain contains different transporters and channels. The thick ascending limb has different distribution of transporters and channels compared to the distal convoluted tubule. In the same nephron, we can see two different distributions of cells which means two different functions. 3. Epithelia can be classified as simple or stratified. A single layer Used for exchange mainly. Multiple layers More involved in protection. Note epithelia has high innervation, high mitotic rate, and lies on BM. II. **We can classify cells based on:** 1. Number of cell layers (simple or stratified) 2. Shape of the cell (Squamous, Cuboidal, or Columnar) Cells in some exocrine glands are more or less pyramidal. Their apical side (apsis) is directed toward the lumen. However, these cells are still classified as either cuboidal or columnar depending on their height relative to their width at the base of the cell. In some instances, there is specialization of the apical cell surface domain. Simple: one layer. Columnar: there are the lateral sides which are longer than the apical and basal side. If they have cilia or not. Simple columnar ciliated when the apical domain has cilia. Same principle applies to stratified squamous epithelium, in which the surface cells can be keratinized or non-keratinized. Stratified squamous keratinized epithelium because keratinized cells are on the apical side. Stratified columnar has two layers, a basement membrane another cuboidal layer then another columnar layer. **It is the last layer towards the apical side or the lumen that will dictate the name of the epithelium.** Here the last layer towards the lumen is the columnar stratified columnar.  **Some special categories of epithelia:** **Pseudostratified epithelium:** Simple epithelium that appears stratified. All of the cells rest on the basement membrane, yet some of them will not reach the lumen. The distribution of pseudostratified epithelium is limited in the body. It is often difficult to distinguish whether all of the cells contact the lumen. Identification of pseudostratified epithelium will depend on where it is normally found. **Specific classes of epithelium:** Endothelium: Epithelium lining the blood and lymphatic vessels. Endocardium: Epithelium lining ventricles and atria of heart. Mesothelium: Epithelium lining walls and covering content of closed cavities of the body. These are almost always simple squamous epithelia; an exception is the postcapillary venules of certain lymphatic venules which have cuboidal endothelium. III. **Structure-Function Relationship:** An epithelium may serve one or more function depending on the activity of the cell type that are present. **Secretion**: as in the **columnar epithelium of the stomach and the gastric glands**. **Absorption**: **columnar epithelium of the intestines and proximal convoluted tubules** in the kidney. **Transportation**: transport of materials or cells along the surface of the epithelium by motile cilia or in the transport of materials across an epithelium to and from the connective tissues. **Protection**: several layers, **stratified squamous epithelium of the skin** (epidermis) and the **transitional epithelium of the urinary bladder** because urine contains all the toxins of our body. **Receptors**: epithelium receives and transduces external stimuli as in the taste buds of the tongue, olfactory epithelium of the nasal mucosa and the retina of the eye. Epithelia involved in secretion or absorption are typically simple, in some cases they are pseudostratified which is also simple. The height of the cells often reflects the level of secretory or absorptive activity. Simple squamous small distance between the basal and the apical side are compatible with high rate of transepithelial transport. Stratification of the epithelium usually correlates with transepithelial impermeability. In some pseudostratified epithelia, basal cells are the stem cells that give rise to the mature functional cells of the epithelium thus balancing cell turn-over. IV. **Cell Polarity: Apical Domain** - Apical domain (towards lumen). - Lateral domain communicates with adjacent cells and it is characterized by specialized attachment areas **tight junction** which is always towards the apical side and the lumen. It can be used to distinguish whether we are on the apical side or not. Also, there are **gap junctions** that allow communication between cytoplasm of the epithelium which allows calcium to move for example between one cytoplasm to the other. - Basal domain rests on the basal lamina anchoring the cell to the connective tissue. Specific biochemical characteristics are associated with each cell surface. Toward the lumen on the apical domain there are special structure surface modifications, and any structural change is going to be transducing a functional change. These structural changes are: A. **Microvilli**: cytoplasmic processes containing a core of **actin filaments**. B. **Stereocilia** or stereovilli: microvilli of unusual length. C. **Cilia**: cytoplasmic processes containing bundle of **microtubules**. A. **Microvilli**  They are fingerlike cytoplasmic projections which are found on the apical surface of most epithelial cells. Microvilli vary widely in appearance: The number and shape of microvilli correlate with the absorptive state of the cell. When they are uniform, numerous, tall and regularly arranged their main goal is to increase the free cell surface area for absorption. Cells that transport fluid and absorb metabolites have many closely packed tall microvilli intestine cells are absorptive cells and microvilli play a major role in exchange. Cells in which transepithelial transport is less active have smaller more irregular shaped microvilli. Microvilli that are uniform, numerous, and regularly arranged form a straited border or a brush border. A cell cannot increase in size except when it undergoes hypertrophy so to increase the surface of exchange they have microvilli.  20-30 actin filaments, anchored to **villin** on the top. Actin bundles extend down into the apical cytoplasm, and they interact with a horizontal network of actin filaments called the **terminal web**. They are cross-linked by ABP like **espin** and **fimbrin**. This cross-linkage provides support and give rigidity to the microvilli. In addition, the core of actin filaments is associated with **myosin I**, a molecule that binds the actin filaments to the plasma membrane of the microvillus. The addition of villin to epithelial cells growing in culture induces formation of microvilli on the free apical surface. The terminal web is composed of actin filament stabilized by **spectrin**. The presence of **myosin II and tropomyosin** in the terminal web explain the contractile ability of the microvilli. These proteins decrease the diameter of the apex of the cell causing the microvilli to spread apart and increase the inter-microvillus space allowing more exchange. B. **Stereocilia** They are long, non-motile microvilli. They are not widely distributed through epithelia, they mostly belong to the **epididymis**, the **proximal part of the ductus deferens** of the male reproductive system and the **sensory cells of the inner ear**. They extend from the apical surfaces of the cell and in some cases, they facilitate absorption. They are supported by internal bundles of actin filaments, crosslinked by **fimbrin**. They are bound to the membrane by ABP **ezrin**, and they **do not have villin**! They are anchored to the apical site of cytoplasm by **alpha actinin** in the terminal web. Microvilli are present in many epithelial cells, they increase absorptive surface of the cells, they are visible in light microscopy as **straited borders or brush borders**. Stereocilia have limited distribution, they are found in the male reproductive system and in sensory hair cells in the inner ear and they function as mechanoreceptors. C. **Cilia** Common surface modification present on nearly every cell in the body. They are hair-like extensions of the apical plasma membrane, and contain an **axoneme**, a **MT**- based internal structure. They are much longer and different in structure than microvilli.  Axoneme of cilium extends from the basal body MTOC. Basal bodies are associated with several accessory structures that help them in anchoring. Functions of cilia: Based on functional characteristics, we can classify cilia into: 1. Motile cilia Found in large numbers and have a 9+2 axonemal arrangement. 2. Primary cilia Immotile solitary projections found on almost all eukaryotic cells. They function as chemosensors, osmosensors, and mechanosensors. 3. Nodal cilia Found on embryo bilaminar disk at gastrulation, area around primitive node. They have similar axonemal architecture as primary cilia, but they can also rotate! 1. *Motile Cilia* - Motile cilia possess an internal structure that allows them to move fluid and particles along epithelial surfaces (i.e. trachea, bronchi, oviduct). - Motile cilia appear as short, thin hair like structures and in the middle we see a thin dark staining band which is known as the **basal body**. - Internal core of microtubule is called axoneme. - A cross sectional view will reveal a characteristic configuration of motile cilia made of nine pairs or doublets of circular arranged microtubules surrounding two central microtubules. - The wall of one MT (B) appears incomplete because it shares a portion of the wall of MT (A). - Elastic band of **nexin** links A to B. - The central MTs are enclosed partially by an **inner sheath**, and the **radial spoke** extends from each doublet to the central MTs. - Cilia movement originates from the sliding of microtubule doublets which is generated by the ATPase activity of the **outer and inner dynein arms** that go from A to B. Cilia beat in a synchronous pattern, they display a precise and synchronous movement. 2. *Primary Cilia* - Immotile, move passively by fluid motion. - Have an arrangement of 9+0 no central MTs. - Lack microtubules-associated motor proteins needed to generate motile force. - The axoneme originates from a basal body that ressembles a mature centriol positioned orthogonally in relation to its immature counterpart. - Primary cilium formation is **synchronized with cell cycle progression** and centrosome duplication events. - Found in epithelial cells of the biliary tract, kidney tubules, etc. - Function as receptors sensing fluid flow. - Function in secretory organs (kidney, liver, pancreas) as sensors of body flow. 3. *Nodal Cilia* - Motile. - 9+0 pattern of microtubules. - Play a role in early embryonic development since they generate the left-right asymmetry of internal organs. - Contain motor proteins and capable of rotational movement. Correlate structure with function of human cilliary disease genes. D. **Flagella** They are present in human body only in spermatozoa. They are similar in structure to cilia, longer, and are limited to one per cell. V. **Cell Polarity: Lateral Domain** Lateral domain of epithelial cells is in close contact with other lateral domain of adjacent cells. Characterized by presence of specific cell adhesion molecules CAMs. The molecular composition of lipids and proteins forming the cell membrane of the lateral domain are significantly different from those that form the apical cell membrane.  Lateral cell surface may form folds and processes, invaginations and evaginations that create interdigitating and interleaving tongue-and-groove margins between neighboring cells. Junctional complex: Zonula occludens or tight junction Zonula adherens or belt desmosomes Macula adherens or desmosomes Hemidesmosomes Note that occluding or tight junctions indicate polarity of the cell. A. **Occluding Junctions** In some places of the body, they are permeable and allow cells to function as a barrier leaky. Form the primary intercellular diffusion barrier between adjacent cells. Main functions: - Form a tight seal and prevent migration of lipids and specialized membrane proteins between the apical and lateral surfaces = they prevent the paracellular route of transport maintaining the integrity of these two domains + they mantain physiochemical seperation of tissue compartments. - Recruit signaling molecules to the cell surface and link them to the actin filaments of the cell cytoskeleton. Tight junctions in EM: you will see a region in the plasma membrane of adjoining cells that come in close contact to seal off intercellular space. The zonula occludens appear not as a continuous series but as a series of focal fusion between the cell. This focal fusion are created by transmembrane proteins of adjoining cells that join in the intercellular space. The presence of the tight junction and its ability to create a diffusion barrier will create two distinct pathways: Transcellular: Exchange goes through the apical and basal sides. It requires energy. Example of active transporter Na+/K+ pump on basolateral membrane. Paracellular: Capable of diffusing ions based on the tightness of zonula occludens. B. **Zonula Adherens and Macula Adherens** Anchoring junctions provide lateral adhesions between epithelial cells, using proteins that link into the cytoskeleton of adjacent cells: Zonula adherens: Interact with actin filaments. Macula Adherens: Interact with IF. Other anchoring junctions where epithelial cells rest on CT are focal adhesions and hemidesmosomes. **Zonula** **Adherens** An adherens junction is defined as a cell junction whose cytoplasmic face is linked to the **actin cytoskeleton**. They can appear as bands encircling the cell (zonula adherens) or as spots of attachment to the extracellular matrix (adhesion plaques).  The cell adhesion molecules form an essential part of every anchoring junction on both lateral and basal cell surfaces. The extracellular domain of cell adhesion molecules interact with similar domains belonging to the cell adhesion molecules of neighboring cells. If the binding occurs between different types of CAMs it is described as heterotypic binding. When the binding occurs between the same type of CAMs it is described as homotypic binding. CAM have a selective adhesive characteristic of relatively low strength which will allow cells to easily join and dissociate. The cytoplasmic domains are linked through a variety of intracellular proteins to components of the cell cytoskeleton. Through the cytoskeleton connections, CAMs are able to control and regulate diverse intracellular processes associated with: - Cell adhesion - Cell proliferation - Cell migration The three CAMs are integrated in many cellular functions such as: - Intercellular and intracellular communication - Cell recognition - Regulation of intercellular diffusion barrier - Generation of immune response - Apoptosis **CAMs are divided into four major factors:** 1. **Cadherins**: Transmembrane calcium dependent CAMs localized mainly within the zonula adherens. At this site they maintain homotypic interactions with similar protein from the neighboring cells. They are associated with a group of proteins **catenin** that links cadherin molecules to actin filaments of the cell cytoskeleton. Through this interaction, cadherins convey signals that regulate mechanism of growth and cell differentiation. Cadherins control cell to cell interaction, they participate in cell recognition and embryonic cell migration. E-cadherin is the most studied member of this family, it maintains the zonula adheren junction between epithelial cells. It also acts as an important suppressor of epithelial tumor cells. 2. **Integrins**: Represented by two transmembrane glycoprotein subunits consisting of 15 alpha and 9 beta chains. This composition allows for the formation of different combination of integrin molecules that are able to interact with various proteins. Integrin interacts with EM molecules and with actin and intermediate filaments of the cell cytoskeleton. By these interactions, integrin regulates: cell adhesion, control cell movement and shape, participate in cell growth and differentiation. 3. **Selectins**: Expressed on white blood cells and endothelial cells. They mediate neutrophil endothelial cell recognition. This heterotypic binding initiates neutrophil migration through the endothelium of blood vessel into the extracellular matrix. They are also involved in directing lymphocytes into accumulation in lymphatic tissues. 4. **Immunoglobin Superfamily**: many molecules involved in immune reactions share a common precursor element in their structure. Yet, several other molecules with no known immunological function also share the same repeat element. Together the genes encoding these related molecules have been defined as the immunoglobulin gene family. It is the largest gene families in the human genome and its glycoproteins perform a wide variety of important biological functions. **Macula Adherens or Spot Desmosomes** They represent a major anchoring cell-to-cell junction that provides a particularly strong attachment. The macula adherence was originally described in epidermal cells where we start calling them desmosomes. These junctions localize on the lateral domain of the cells. They are much like a series of spot wells and they mediate direct cell-to-cell contact by providing anchoring site for **intermediate filaments.** They are distributed in patches along cell lateral membrane of most epithelial cells. Also called anchoring junctions, we have cell-to-extracellular-matrix junction. They maintain the **morphological integrity** of the epithelium connective tissue interface. You have the **focal adhesions** that anchor actin filament of the cytoskeleton into the basement membrane, and you have **hemidesmosomes** that anchor intermediate filaments of the cytoskeleton into the basement membrane. C. **Communicating Junctions or Gap Junctions** Gap junctions are the only known cellular structure that permits a **direct passage of signaling molecules from one cell to another**. Calcium can go from one cytosol to the other cytosol using gap junction. They are present in a wide variety of tissues, including **epithelia**, **smooth and cardiac muscle**, and **nerves**. Cardiac junction are important tissue in which activity in adjacent cell must be coordinated very tightly. The gap junction consists of an accumulation of transmembrane channels or pores in a tightly packed area. It allows cells to exchange ions, regulatory molecules, and small metabolites through the pores. The number of pores in gap junction can vary widely, as can the number of gap junction between adjacent cells. They are pores, and these pores are formed by 12 subunits of the connexin protein family to form the connexins. So when you view gap junction under electron microscope, they appear as an area of contact between the plasma membrane of adjacent cells, and they reveal groups of tightly packed channels, each formed by two half channels called connexins embedded in the facing membrane. The connexin in one cell membrane is precisely aligned to dock with the corresponding connexin on the membrane of an adjacent cell. Each connexin contains six symmetrical subunits of membrane proteins called connexins. VI. **Basal Domains** It is characterized by several features. The basement membrane is a specialized structure located next to the basal domain of epithelial cells and the underlying connective tissues. Cell-to-extracellular matrix junction anchors the cell to the extracellular matrix. They are represented by **focal adhesions** and **hemi-desmosomes**. Basal cell membrane enfolding that increase the cell surface area and facilitate morphologic interaction between adjacent cells and extracellular matrix proteins. The term basement membrane is used to specify a **periodic acid shift positive layer** visible with light microscope beneath epithelial. The basement membrane is usually formed by the **fusion of either two basal laminas or a basal lamina and a reticular lamina/lamina lucida**.  The basement membrane is defined by two layers, a **basal lamina** containing **laminin**, **fibronectin**, **type IV collagen**, **heparensulfate** **proteoglycans**, and a **reticular lamina** containing **type III collagen**, or reticular fibers. The components of these two lamina are **glycoproteins**, and they are **periodic acid shift positive**. VII. **Glandular Epithelia** Glands are classified into two major groups and this classification is based on how their products are released. Glandular epithelia are cells that produce **fluid** secretion. They produce a fluid that is different than the extracellular fluid blood. They produce a fluid that is different than the intracellular fluid. They are characterized by presence of **secretory granules** inside the cell. They may synthesize, store, and secrete: Proteins like the pancreas. Lipid like the adrenal gland. Complexes of carbohydrate plus protein like salivary gland. Also they can secrete proteins, lipids, and complexes of carbohydrates and protein like the mammary gland. Some other epithelial cells are ion-transporting cells, example the striated duct. The types of glandular epithelia are: - Exocrine glands. - The exocrine secrete their products onto a surface directly or through epithelial ducts or tube that are connected to a surface. The ducts convey the secreted material in a unilateral form or may modify the secretion by concentrating it or adding or reabsorbing constituents substances. - Endocrine glands. - The endocrine glands, they lack a duct system. They secrete their product into the connective tissue from which they enter the bloodstream to reach their target cells. The products that you know is called hormones. - Mixed. The liver is one of the best examples. The cells of exocrine gland exhibit different mechanism of secretion: 1. **Merocrine** **secretion**: This secretory product is delivered in **membrane-bounded vesicles** to the apical surface of the cell. The vesicles here fuse with the plasma membrane and extrude their content by exocytosis. This is the most common mechanism of secretion and it is found for example in the **pancreatic acinar cells**. 2. **Apocrine secretion**: The secretory product is released in the apical portion of the cell surrounded by **a thin layer of cytoplasm** within an envelope of plasma membrane. This mechanism of secretion is found in the lactating **mammary gland** where it is responsible for releasing large lipid droplets into the milk. It also occurs in the **apocrine glands of skin**, **ciliary glands of the eyelid** and other places. 3. **Holocrine** secretion: The **secretory product accumulates within the maturing cell** which simultaneously undergoes programmed cell death. Both secreted product and cell debris are discharged into the **lumen of the gland**. This mechanism is found in the **sebaceous gland of skin** and in the **glands of the eyelid**. VIII. **Epithelial Cell Renewal** Most epithelial cells have a finite lifespan. The rate of cell turnover is different, it can be fast like in the intestinal epithelium or slow like in the pancreas. Also it should be emphasized that some cells like special epithelial cells are hard to be renewed like podocyte. Metaplasia is when one type of epithelia transforms into another type (reversible): - In smokers (heavy), the pseudostratified becomes stratified squamous epithelia. - In chronic Vit A deficiency, the epithelium of bronchi or urinary bladder becomes stratified squamous epithelia.