Histology 1 notes first year anatomy PDF

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Lior OnnHistology I1stSCT:EpithelialandConnectiveTissues*These notes are based on: Ross Histology book 7th edition, lectures slides,and notes from class (taught by Professor Antal).Good luck!Epithelial tissueOverview Epithelium covers body surfaces, lines body cavities, and constitutes glands. Avasc...

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Histology I st

1 SCT: Epithelial and Connective Tissues *These notes are based on: Ross Histology book 7th edition, lectures slides, and notes from class (taught by Professor Antal). Good luck!

Lior Onn

Epithelial tissue Overview • • • • •

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Epithelium covers body surfaces, lines body cavities, and constitutes glands. tissue. Form ( ) of glands and their ducts. Specialized epithelial cells function as receptors for the special senses (smell, taste, hearing and vision). Three principal characteristics of epithelial cells: 1. Attach closely to one another via specialized , . Adjacent cells are separated by a very narrow EC space which can’t even be seen in light microscope resolution. 2. Functional and morphological polarity: three surface domains each with specific properties and different functions: a. Free surface, apical domain b. Lateral domain c. Basal domain 3. in the basal surface ( , layer) : . Typical of s( of in the testis, of the ovary, in pancreas, etc.). also formed by . Creates a selective barrier between external environment and underlying CT.

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Classification • Based on two factors: 1. : a. Simple: one cell layer b. Stratified: two or more cell layers c. Pseudostratified: appears stratified, but all cells rest on basement membrane. 2. (in stratified epithelium, the shape of the cells is used to classify): a. : width >> height I. – only in the (covering epithelium) II. ( ) b. : width ~ depth ~ height c. : height width (low columnar is when height width) • Classification into four main groups: 1. epithelium: covers body surfaces 2. epithelium: produce and secrete substances 3. epithelium: associated with senses (taste, vision, olfactory, hearing) 4. epithelium: found in the retina of the eye, in charge of eye pigmentation. • Reflects on structure, not on function.

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There are also cells in some exocrine glands, but they’re classified as . Specialization of the apical domain may also be added to classification: ciliated, keratinized/non keratinized. ): epithelium lining the ( x. ). epithelium with special ability to . When the bladder is full the epithelium is flattened due to hydrostatic pressure, but when it’s empty the hydrostatic pressure drops and the epithelium becomes columnar and there are even more cells. : s. : is in . : epithelial lining of ventricles and atria of the heart. : simple squamous epithelium that lines the walls and covers the contents of the closed s cavities of the body ( , , and = ). Functions: 1. Secretion (columnar epithelium of the stomach). Glandular epithelium. 2. Absorption (columnar epitheliu of the intestines) 3. Transportation: a. of materials or cells along the surface of an epithelium by motile cilia b. of materials across an epithelium to/from CT 4. protection (epidermis of the skin, SSE). Lining epithelium. 5. receptor function: receive and transduce external stimuli (taste buds, olfactory epithelium, retina). Sensory and pigment epithelium.

Cell polarity • epithelial cells have three surfaces/domains, each with specific biochemical characteristics and functions. • Polarity is needed to create a fully functional barrier between adjacent cells

The apical domain and its modifications May contain specific enzymes, ion channels, and carrier proteins. Three structural surface modifications: 1. cytoplasmic processes with core of actin filaments 2. : microvilli of unusual length 3. cytoplasmic processes containing microtubule bundles 1. Microvilli (small intestine slide):

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Fingerlike cytoplasmic projections, 1-3 µm length Number and shape vary, and correlate with the cell’s absorptive capacity: i. Transport fluid and absorb metabolites àmany closely packed tall microvilli ii. Less active trans-epithelial transport àsmaller, irregular shape microvilli (may escape light microscope) Create in the ( , ), and in .

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of these cytoplasmic projections is than that of the ! Contain core of actin filaments, cross-linked by s: , , and . anchor the end of villi (also an actin-bundling protein) : network of filaments, with and , just below the base of the microvilli. Seen in slides. Contractile property à cause an increase in inter-microvillous space. • binds the to the plasma membrane of the microvillus. 2. Sterocilia (stereovilli): • Microvilli that are unusually long (up to 120 µm) and immotile (can’t move).

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Found only in: 1. Epididymis (of ductus deferens): absorptive structures. • Arise from an apical cell protrusion with

thick stem portions that are connected by aactinin cytoplasmic bridges. • Similar to microvilli: internal actin bundles cross-linked by fimbrin. • Differences from microvilli: 1. ezrin protein anchors the actin filaments to the plasma membrane. 2. Longer (lateral additions of actin) 3. No villin at the tip (plus end) 4. Larger diameter 2. Sensory (hair) cells of the inner ear: serve as sensory mechanoreceptors. • Uniform in diameter, show staircase pattern of increasing height. • High density of actin, cross-linked by espin. • Lack ezrin and a -actinin. • Can be easily damaged à have molecular mechanism of regeneration = treadmilling effect (actin monomers are removed from the base and added to the tip, and everything is pushed down). 3. Cilia (trachea slide): • • •

Present on nearly all cells of the body Extensions of the apical plasma membrane (not a cytoplasmic protrusion) Axoneme: internal core of microtubules, which extends from a basal body (a centriole-derived, microtubule organizing center MTOC located in the apical region of a ciliated cell. Dark-staining band at the base of the cilia). The basal bodies appear as a continuous band in light microscope but in electron microscope the basal body of each cilium appears.

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Ciliogenesis: o the first stage is generation of centrioles, which then assume function of basal bodies. Then there is an elongation stage of motile cilia, polymerization of tubulin molecules, creating 9+2 arrangement. Then axenome grows upward from the basal body, cell membrane is pushes outwardàmature cilium. o Ciliogensis depends on the bidirectional intraflagellar transport mechanism that supplies precursor molecules to the growing cilium.

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Classification according to functional characteristics: 1. Motile cilia: • • • •

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Move fluid and particles along epithelial surfaces. Trachea, bronchi (sweep mucus and other junk toward oropharynx for elimination), oviducts. Short, fine, hairlike structures, sit on basal bodies. 9+2 axonemal organization, from tip of cilium to its base: 9 pairs/doublets of circularly arranged microtubules, surrounding two center microtubules (which are separate but partially enclosed by a central sheath projection). Microtubules of axenome are highly stable and can resist depolymerization. Ciliary dynein: motor protein, shown on each of the 9 microtubule doublets. Uses energy from ATP. Radial spokes: extend from microtubule doublets toward the central ones, allowing movement. Basal body: 9 short microtubule triplets in a ring. No central microtubules. A and B continue into the axenome as (the) pairs, C microtubules extend into the transitional zone. Transitional zone: transition between basal body and the axenome. Origin of the two central microtubules. Basal body-associated structures: 1. Alar sheet: transitional fiber, from top end of the basal body C microtubule and into the cytoplasmic domain of the plasma membrane. 2. Basal foot: midregion of basal body. Coordinate ciliary movement. Associate with myosin. 3. Striated rootlet: protofilaments that anchor basal body within the apical cytoplasm. Contain rootletin protein. Ciliary movement originates from the sliding of microtubule doublets, which is generated by the ATPase activity of the dynein arms. Effective stroke (a rapid forward movement featured by a cilium doesn’t have enough ATP and remains rigid) and recovery stroke (slower, return movement of the previously rigid cilium, after enough energy is accumulated).

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Motile cilia beat in a synchronous pattern, creating a wave across the epithelium called metachronal rhythm which allows moving mucus over epithelial surfaces or facilitating flow of fluid through tubules and ducts. Basal feet of basal bodies are responsible.

2. Primary cilia: • • • • • •

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Non-motile=no active movement (lack microtubule-associated motor proteins needed to generate motile force) àpassively bend due to fluid flow 9+0 pattern of microtubules No central pair of microtubules Its formation is synchronized with the cell cycle and with centrosome duplication Found in a variety of cells called primary cilia/monocilia. Each cell has only one such cilium. Also found in epithelial cells. In many mammalian cells, signaling through the primary cili seems to be essential for controlled cell division and gene expression. Function in secretory organs (kidney, liver, pancreas) as signal receptors, sensing a flow of fluid. Example: mechanoreceptors in glomerulus and tubular cells of the kidney. Fluid flow in renal tubules àcilia bendàCa2+ influx initiated. Polycystic kidney disease, as well as cysts in the pancreas and liver, may be caused by mutations in genes that affect development of primary cilia.

3. Nodal cilia: • • • •

Found in embryos during early embryonic development 9+0 microtubule pattern (like primary cilia) Motile: contain motor proteins (dynein and kinesin)àmove in full circles, creating a course resembling a full cone (motile cilia did only half cone movement. Shown in table 5.2 on next page). Important for embryonic development: generate left-right asymmetry of internal organs. Without nodal cilia (or if nodal cilia are immotile)ànodal flow doesn’t occuràno flow detection by sensory receptors on the left side of the bodyàrandom placement of internal organsàprimary cilia dyskinesiaàsitus inversus (position of heart/abdominal organs are reversed).

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Lateral domain and its specializations in cell-to-cell adhesion • • • •

The lateral domain is characterized by having special proteins called cell adhesion molecules (CAMs) which are part of junctional specialization. Molecular composition of lipids and proteins of the lateral cell membrane is very different from the apicals. Later cell surface membrane of some epithelia may form folds and processes àtongue-and-groove margins between neighboring cells. Junctional complex: specific structural components that make up a barrier to the passage of substances between adjacent epithelial cells and attaches between the cells. There are three types:

1. Occluding junctions=zonula occludens (aka tight junctions): o Impermeableàform the primary intercellular diffusion barrier between adjacent cellsàmaintain physicochemical separation of tissue compartments. o Located at most apical point between adjoining cells àprevent migration of lipids and membrane proteins between apical and lateral surfacesàmaintain integrity of apical and lateral domains (example: Na/K ATPase is restricted to the lateral plasma membrane, below zonula occludens). o Recruit signaling molecules to the cell surface and link them with actin filaments of the cytoskeleton o Features network of anastomosing particle strands in which protein particles from opposing (adjacent) cell membrane surfaces cause complementary grooves in each otheràfunctional seal in intercellular space. o Three major groups of transmembrane proteins of the zonula occludens: 1. Occludin: a. Maintains barrier between adjacent cells AND between lat. And apical domains b. Present in most occluding junctions BUT without it cells may still have fully functional zonula occludentes 2. Claudin: a. family of about 24 proteins that form the backbone of zonula occludens strands b. able to form extracellular aqueous channels for paracellular passage of ions and other small molecules

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c. mutation in claudin-14 gene à hereditary deafness 3. Junctional adhesion molecule (JAM): a. protein of the immunoglobulin family b. associates with claudins in endothelial cells These three proteins have amino acid sequences in their cytoplasmic portions which attract PDZ-domain proteins (ZO-1, ZO-2, ZO-3) which they interact with during the formation of the zonula occludens and they also help the transmembrane proteins interact with actin cytoskeleton. Play an important role in selective passage of substances from one side of an epithelium to the other. Two distinct pathways of transport across epithelium: 1. Transcellular: across the plasma membrane, via active transport and energy-dependent transport proteins and channels. Movement across apical plasma membraneà cytoplasmàacross lateral membrane, below level of occluding junctionà intercellular space 2. Paracellular: across zonula occludens between two epithelial cells. The amount of substances transported is relative to the tightness of the zonula occludens=regulation. Permeability of the zonula occludens depends not only on the complexity and number of strands but also on the presence of functional aqueous channels formed by various claudin molecules. Combination and mixing ratios of claudins to occludins and other proteins found within individual paired zonula occludens strands determine tightness and selectivity of the seal between cells! Although it is the job of zonula occludens to restrict free passage across epithelium, the adhesive properties of zonulae and maculae adherents guard against physical disruption of this barrier.

2. Anchoring junctions: o Provide mechanical stability to epithelial cells by linking the cytoskeleton of one cell to the cytoskeleton of an adjacent cell. o Lateral adhesions, found on both lateral cell surface and basal domain as well o Signal transduction capability à important roles in cell-to-cell recognition, morphogenesis, and differentiation. o Two types of anchoring cell-to-cell junctions: 1. Zonula adherens: interacts with actin filament network in the cell 2. Macula adherens or desmosome: interacts with intermediate filaments in the cell o Two types of cell-to-connective tissue matrix anchoring junctions: 1. Focal adhesions 2. Hemidesmosomes

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Cell adhesion molecules (CAMs): § Essential part of anchoring junctions on both lateral and basal cell surfaces. § CAMs of neighboring cells interact with one another either in heterotypic binding (binding between two different types of CAMs) or homotypic binding (between two CAMs of same type). § CAMs have selective adhesivenessàcells easily join and dissociate § CAMs bind their cytoplasmic domains to the cytoskeleton of the cellàcontrol and regulate intracellular processes associated with cell adhesion, proliferation, and migration § Four major families, based on molecular structure: 1. Cadherins: -transmembrane Ca2+-dependent CAMs -within zonula adherens (àlinked to actin) -homotypic interactions with similar proteins from neighbor cells -transmit signals that regulate mechanisms of growth and cell differentiation (embryonic cell migration) -E-Cadherin (transmembrane protein) acts as suppressor of epithelial tumor cells, working as Ecadherin-catenin complex bound to Ca2+ (no Ca à dissociation) to interact with actin filaments. 2. Integrins: -two transmembrane glycoproteins -heterotypic interactions -interact with: ECM molecules (collagens, laminin, etc.), actin, intermediate filaments -regulation of cell adhesion, control cell movement and shape, participate in cell growth and differentiation 3. Selectins: -expressed on WBC and endothelial cells -Mediate neutrophil-endothelial cell recognitionàinitiate neutrophil migration through endothelium of blood vessels into ECM -direct lymphocytes (WBC) into accumulations of lymphatic tissue (aka homing) -Heterotypic binding 4. Immunoglobulin superfamily (IgSF): -mediate homotypic cell-to-cell adhesions -play a role in differentiation, cancer and tumor metastasis, angiogensis, inflammation, immune responses, and microbial attachment. Fascia adherens: broad faced, cell-to-cell attachments (desmosomes + broad adhesion plates that resemble zonula adherens of epithelial cells) between non-epithelial cells, i.e. cardiac muscle cells. Contains zonula occludens ZO-1 protein (found in tight junctions of epithelial cells).

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Macula adherens is found in small, localized sites of the later cell surface and is thus different than zonula adherens which is a continuous structure around the cell à a section perpendicular to the cell surface will often not include a macula adherens but will always include zonula adherens. In the area of the macula adherens, desmogleins and desmocollins provide the linkage between the plasma membranes of adjacent cells. The intercellular space of the macula adherens is much wider than that of the zonula adherens and is occupied by a dense medial band called the intermediate line. This line represents the extracellular portions of transmembrane glycoproteins of the cadherin family of Ca2+-dependent cell adhesion molecules (called desmogleins and desmocollins). The desmogleins and desmocollins create a cadherin zipper in the area of the desmosome, as seen in between the cells in the above figure.

3. Communicating junctions (aka gap junctions or nexuses): o Intercellular communication: only cellular structure that allows direct passage (diffusion) of signaling molecules between adjacent cells ( providing specificity to basal lamina of different tissues. -Type XV collagen stabilizes external lamina in skeletal and cardiac muscles cells -Type XVIII collagen in vascular and epithelial basal laminae, angiogenesis -Type VII collagen links basal lamina to underlying reticular lamina. 2. laminins: glycoproteins, 15 different variations. Initiate assembly of basal lamina, involved in many cell-to-ECM interactions, and have binding sites for integrin receptors in the basal domain of the overlaying epithelial cells. 3. glycoproteins: entactin/nidogen (rodlike, sulfated). Link between laminin and the type IV collagen network. Bind calcium, support cell adhesion, and promote neutrophil chemotaxis and phagocytosis. 4. proteoglycans: most of the basal lamina volume. -Protein core to which heparin sulfate, chondroitin sulfate, or dermatan sulfate side chains are attached. -Very anionicà regulate passage of ions across the basal lamina. -Perlecan (400Kd, heparin sulfate). Most common. Binds to all other proteinsà additional cross-linkage. -Agrin: almost exclusively in the glomerular basement membrane, kidney. Major role in renal filtration and cell-toECM interaction.

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The molecular structure of type IV collagen determines its role in the formation of the basal lamina network suprastructure. Structure is 3 polypeptide chains, each with: a.

short amino-terminus domain (7S domain)

b. long middle collagenous helical domain c. carboxy-terminus globular non-collagenous domain (NC1 domain). •

There are 6 known chains of type IV collagen (named a1 to a6), and they form three sets of triple helical molecules known as collagen protomers.

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The different collagen protomers are found in different kinds of

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basal lamina: 1. [a(IV)]2a2(IV): all basal laminae. 2. a3(IV) a4(IV) a5(IV): mainly kidney and lungs 3. [a5(IV)]2a6(IV): only in skin, esophagus, and Bowman capsule (kidney).

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Type IV collagen and laminins initiate the process of the self-assembly of the basal lamina. The first step is calciumdependent polymerization of the laminin molecules, on the basal surface of the epithelial cells. Aided by Integrins. A...