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HISTOLOGY BOOK JUNQUEIRA PDF

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PDF | This new edition of the best-selling English edition of Junqueira's With the best art program of any histology textbook and the most. CONTENTS i FOURTEENTH EDITION Junqueira's Basic Histology . regard to any aspect of the book's features. used throughout the text and supplemented by . Junqueira's Basic Histology: Text and Atlas, 15e. Anthony L. Mescher. Go to Review Questions. Search Textbook Chapter 1: Histology & Its Methods of Study.


Histology Book Junqueira Pdf

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As with the previous edition, the book facilitates learning by its organization: With these new features, I am confident that Junqueira 's Basic Histology will. edition Junqueira's Basic Histology continues as the preeminent source of from a few of the many excellent review books published by. Histology · Related Human Medical Books For more than three decades, Junqueira's Basic Histology has been unmatched in its ability to explain the function of cell and tissue PDF MB Password: resourceone.info Help.

Acid phosphatases are frequently used to demonstrate lysosomes, cytoplasmic organelles that contain acid phosphatase Figure Photomicrograph of a rat kidney section treated by the Gomori method to demonstrate the enzyme alkaline phosphatase.

The sites where this enzyme is present are covered by a black precipitate arrows. Detection of acid phosphatase. Electron micrograph of a rat kidney cell showing three lysosomes ly close to the nucleus N. The dark material on the lysosomes is lead phosphate that precipitated on places where acid phosphatase was present. C ourtesy of E Katchburian. Dehydrogenases remove hydrogen from one substrate and transfer it to another.

There are many dehydrogenases in the body, and they play an important role in several metabolic processes. Dehydrogenases are detected histochemically by incubating nonfixed tissue sections in a substrate solution containing a molecule that receives hydrogen and precipitates as an insoluble colored compound. By this method, succinate dehydrogenasea key enzyme in the citric acid Krebs cyclecan be localized in mitochondria.

Peroxidase, w hich is present in several types of cells, is an enzyme that promotes the oxidation of certain substrates w ith the transfer of hydrogen ions to hydrogen peroxide, forming molecules of w ater. In this method, sections of adequately fixed tissue are incubated in a solution containing hydrogen peroxide and 3,3'diaminoazobenzidine. The latter compound is oxidized in the presence of peroxidase, resulting in an insoluble, brow n, electrondense precipitate that permits the localization of peroxidase activity by light and electron microscopy.

Peroxidase activity in blood cells, w hich is important in the diagnosis of leukemias, can be detected by this method. Because peroxidase is extremely active and produces an appreciable amount of insoluble precipitate in a short time, it has also been used for an important practical application: Molecules of peroxidase can be purified, isolated, and coupled w ith another molecule.

Later in this chapter, applications of tagging molecules w ith peroxidase are presented.

In the combined state, they constitute an extremely complex heterogeneous group. Polysaccharides can be demonstrated by the periodic acidSchiff PAS reaction, w hich is based on the transformation into aldehyde of 1,2-glycol groups present in the sugar molecules.

These aldehydes are then revealed by Schiff's reagent, w hich produces a purple or magenta color in areas of the section w ith an accumulation of polysaccharides. A ubiquitous free polysaccharide in the body is glycogen, w hich can be demonstrated by the PAS reaction in liver, striated muscle, and other tissues w here it accumulates.

Glycoproteins are protein molecules associated w ith small, branched chains of sugars oligosaccharides. The protein chain predominates in w eight and volume over the oligosaccharide chain. Because both glycogen and neutral glycoproteins are PAS positive, the specificity of the PAS reaction can be improved by comparing the staining of regular sections w ith that of sections pretreated w ith an enzyme that breaks glycogen eg, amylase present in the saliva.

Structures that stain intensely w ith the PAS reaction but do not stain after treatment w ith amylase contain glycogen. Figure show s examples of structures stained by the PAS reaction. Photomicrograph of an intestinal villus stained by PAS. Staining is intense in the cell surface brush border arrows and in the secretory product of goblet cells G because of their high content of polysaccharides.

The counterstain was hematoxylin. Glycosaminoglycans are strongly anionic, unbranched long-chain polysaccharides containing aminated monosaccharides amino sugars. The complex molecules formed by the attachment of glycosaminoglycan chains to a protein core constitute the proteoglycans. Some of the significant constituents of connective tissue matrices are proteoglycans see Chapter 5: Connective Tissue and Chapter 7: Unlike the glycoproteins, the carbohydrate chains in proteoglycans constitute the major component of the molecule.

Glycosaminoglycans and acidic glycoproteins are strongly anionic because of their high content of carboxyl and sulfate groups.

For this reason, they react strongly w ith the alcian blue dye. Lipids Lipids are best revealed w ith dyes that are soluble in lipids. Frozen sections are immersed in alcohol solutions saturated w ith the dye. Sudan IV and Sudan black are the most commonly used dyes. The dye dissolves in the cellular lipid droplets, w hich become stained in red or black. Additional methods used for the localization of cholesterol and its esters, phospholipids, and glycolipids are useful in diagnosing metabolic diseases in w hich there are intracellular accumulations of different kinds of lipids.

Examples are Perls' reaction for iron eg, hemochromatosis, hemosiderosis , the PAS-amylase reaction for glycogen glycogenosis , alcian blue staining for glycosaminoglycans mucopolysaccharidosis , and lipid staining sphingolipidosis.

The compounds that w ill interact w ith the molecule must be tagged w ith a label that can be detected under the light or electron microscope Figure The most commonly used labels are fluorescent compounds w hich can be seen w ith a fluorescence or laser microscope , radioactive atoms w hich can be detected w ith autoradiography , molecules of peroxidase w hich can be detected after demonstration of the enzyme w ith hydrogen peroxide and 3,3'-diaminoazobenzidine or other enzymes w hich can be detected w ith their respective substrates , and metal usually gold particles that can be observed w ith light and electron microscopy.

These methods are mainly used for detecting sugars, proteins, and nucleic acids. C ompounds that have affinity toward another molecule can be tagged with a label and used to identify that molecule. The label can be a fluorescent compound, an enzyme such as peroxidase, a gold particle, or a radioactive atom. Phalloidin, protein A, lectins, and antibodies are examples of compounds that interact specifically w ith other molecules.

Phalloidin, w hich is extracted from a mushroom Amanita phalloides , interacts strongly w ith actin and is usually labeled w ith fluorescent dyes to demonstrate actin filaments. Protein A is a protein obtained from Staphylococcus aureus that binds to the Fc region of immunoglobulin antibody molecules. W hen protein A is tagged w ith a label, immunoglobulins can be detected. Lectins are proteins or glycoproteins that are derived mainly from plant seeds and that bind w ith high affinity and specificity to carbohydrates.

Different lectins bind to specific sequences of sugar molecules. They may bind to glycoproteins, proteoglycans, and glycolipids and are w idely used to characterize membrane molecules containing defined sequences of sugars. Immunocytochemistry A highly specific interaction betw een molecules is that betw een an antigen and its antibody. For this reason, methods using labeled antibodies have proved most useful in identifying and localizing specific proteins and glycoproteins.

The body has cells that are able to distinguish its ow n molecules self from foreign ones. W hen exposed to foreign molecules called antigensthe body may respond by producing proteinsantibodiesthat react specifically and bind to the antigen, thus helping to eliminate the foreign substance. Antibodies are proteins of a large family, the immunoglobulin family. In immunocytochemistry, a tissue section or cells in culture that may contain a certain protein is incubated in a solution containing an antibody to this protein.

The antibody binds specifically to the protein, w hose location can then be seen w ith either the light or electron microscope, depending on the type of compound used to label the antibody.

One of the most important requirements for immunocytochemistry is the availability of an antibody against the protein that is to be detected.

This means that the protein must have been previously purified and isolated so that antibodies can be produced. Some methods for protein isolation can be seen in Figures and Ultracentrifugation A and chromatography B: A mixture of proteins obtained from homogenized cells or tissues is submitted to centrifugation at high speed for several hours.

The proteins separate into several bands, depending on the size and density of the protein molecules. The ultracentrifugation medium is drained and collected in several fractions that contain different proteins, which can be analyzed further.

A solution containing a mixture of proteins obtained from homogenized cells or tissues is added to a column filled with beads that have different chemical properties. For instance, the beads may have different electrostatic charges attracting proteins according to their charge or different sizes of pores acting as sieves for different-sized molecules. As the proteins migrate through the column, their movement is slowed according to their interaction with the particles. When the effluent is recovered, the different groups of proteins may be collected separately.

Gel electrophoresis: Isolation of proteins. They are usually treated with a strong detergent sodium dodecyl sulfate and with mercaptoethanol to unfold and separate the protein subunits. The proteins migrate along the gel according to their size and shape.

Detection and identification of the proteins. All proteins will stain the same color. The color intensity is proportional to the protein concentration. Radioactive proteins can be detected by autoradiography.

An x-ray film is apposed to the gel for a certain time and then developed. Radioactive proteins will appear as dark bands in the film. The proteins can be transferred from the gel to a nitrocellulose membrane. The membrane is incubated with a labeled antibody made against proteins that may be present in the sample. If protein x is already isolated, it is injected into an animal of another species eg, a rabbit or a goat. If the protein is sufficiently different for this animal to recognize it as foreignthat is, as an antigenthe animal w ill produce antibodies against the protein eg, rabbit antibody against rat x or goat antibody against human x.

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These antibodies are collected from the animal's plasma and used for immunocytochemistry. Several groups clones of lymphocytes of the animal that w as injected w ith protein x may recognize different parts of protein x and each group produces an antibody against each part. These antibodies constitute a mixture of polyclonal antibodies. It is possible, how ever, to furnish protein x for lymphocytes maintained in cell culture actually, lymphocytes fused w ith tumor cells.

The different clones of lymphocytes w ill produce different antibodies against the several parts of protein x. Each clone can. Each clone can be isolated and cultured separately so that the different antibodies against protein x can be collected separately. Each of these antibodies is a monoclonal antibody. There are several advantages to using a monoclonal antibody rather than a polyclonal antibody: Therefore, there w ill be less nonspecific binding to other proteins similar to the one being looked for.

In the direct method of immunocytochemistry, the antibody either monoclonal or polyclonal must be tagged w ith an appropriate label. A tissue section is incubated w ith the antibody for some time so that the antibody interacts w ith and binds to protein x. The section is then w ashed to remove the unbound antibody Figure Depending on the label that w as used fluorescent compound, enzyme, gold particles , the section can be observed w ith a light or electron microscope.

The areas of the tissue section that contain protein x w ill become fluorescent or w ill be covered by gold particles or by a dark precipitate if an enzyme w as used as a marker.

Direct method of immunocytochemistry. Protein x from a rat is injected into a rabbit. Several rabbit Igs are produced against protein x. The rabbit Igs are tagged with a label. The rabbit Igs recognize and bind to different parts of protein x. The indirect method of immunocytochemistry is more sensitive but requires more steps. Let us suppose that our objective is to detect protein x, present in rats. Before proceeding to the immunochemical reaction, tw o procedures are needed: Rabbit immunoglobulins are considered foreign by a goat and are thus capable of inducing the production of an antibody an antiantibody or antiimmunoglobulin in that animal.

Indirect immunocytochemical detection is performed by initially incubating a section of a rat tissue believed to contain protein x w ith rabbit anti-x antibody. After w ashing, the tissue sections are incubated w ith labeled goat antibody against rabbit antibodies. The antiantibodies w ill bind to the rabbit antibody that had previously recognized protein x Figure Protein x can then be detected by using a microscopic technique appropriate for the label used in the secondary antibody.

There are other indirect methods that involve the use of other intermediate molecules, such as the biotin-avidin technique. Indirect method of immunocytochemistry. Several rabbit immunoglobulins Ig are produced against protein x.

Ig from a nonimmune normal rabbit is injected into a goat. Goat Igs http: The goat Igs are then isolated and tagged with a label. Goat Igs against rabbit Ig are produced. Labeled goat Igs recognize and bind to different parts of rabbit immunoglobulin molecules, therefore labeling protein x.

Figures , , , and show examples of immunocytochemical detection of molecules. Table 11 show s some of the routine applications of immunocytochemical procedures in clinical practice. Table Antigens Intermediate filament proteins Cytokeratins Glial fibrillary acid protein Vimentin Desmin Other proteins Protein and polypeptide hormones Carcinoembryonic antigen CEA Steroid hormone receptors Antigens produced by viruses Protein or polypeptide hormoneproducing tumors Glandular tumors, mainly of the digestive tract and breast Breast duct cell tumors Specific virus infections Tumors of epithelial origin Tumors of some glial cells Tumors of connective tissue Tumors of muscle Diagnosis.

Photomicrograph of a mouse decidual cell grown in vitro. The protein desmin, which forms intermediate filaments, was detected with an indirect immunofluorescence technique. A mesh of fluorescent intermediate filaments occupies most of the cytoplasm. The nucleus N is stained blue. C ourtesy of FG C osta.

Junqueira's Basic Histology Text & Atlas (14th Ed.), Anthony Mescher

Photomicrograph of a section of small intestine in which an antibody against the enzyme lysozyme was applied to demonstrate lysosomes in macrophages and Paneth cells. The brown color, indicating the presence of lysozyme, results from the reaction done to show peroxidase, which was linked to the secondary antibody. Nuclei were counterstained with hematoxylin. C arcinoembryonic antigen is a protein present in several malignant tumors mainly of the breast and intestines.

This photomicrograph is an immunocytochemical demonstration of carcinoembryonic antigen in a section of large intestine adenocarcinoma. The antibody was labeled with peroxidase and the brown precipitate indicates tumor cells. Electron micrograph showing a section of a pancreatic acinar cell that was incubated with antiamylase antibody and stained by protein A coupled with gold particles.

Protein A has high affinity toward antibody molecules. The gold particles appear as very small black dots over the secretory granules. C ourtesy of M Bendayan.

Mescher Anthony L. Junqueira's Basic Histology. Text and Atlas

Hybridization Techniques The central challenge in modern cell biology is to understand the w orkings of the cell in molecular detail. This goal requires techniques that permit analysis of the molecules involved in the process of information flow from DNA to protein.

Many techniques are based on hybridization. The greater the similarities of the. The greater the similarities of the sequences, the more readily complementary strands form "hybrid" double-stranded molecules. This technique is ideal for determining if a cell has a specific sequence of DNA such as a gene or part of a gene , for identifying the cells in w hich a specific gene is being transcribed, or for determining the localization of a gene in a specific chromosome.

The DNA inside the cell must be initially denatured by heat or by denaturing agents so that both strands of the DNA separate. They are then ready to be hybridized w ith a segment of single-stranded DNA or RNA that is complementary to the sequence to be detected. This sequence is called a probe. The probe may be obtained by cloning, by polymerase chain reaction PCR amplification of the target sequence, or by synthesis if the desired sequence is short.

The probe must be tagged w ith a label, usually a radioactive isotope w hich can be localized by autoradiography or a modified nucleotide digoxygenin , w hich can be identified by immunocytochemistry. In in situ hybridization, the tissue section, cultured cells, smears, or chromosomes of squashed mitotic cells must first be heated to separate the double strands of their DNA.

A solution containing the probe is then placed over the specimen for a period of time necessary for hybridization. After w ashing off the excess probe, the localization of the bound probe is revealed through its label Figure Tissue section of a benign epithelial tumor condyloma submitted to in situ hybridization. The brown areas are places where DNA of human papillomavirus type 2 is present.

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C ourtesy of JE Levi. After electrophoresis, the fragments of nucleic acids are transferred to a nylon or nitrocellulose sheet by solvent drag: This technique of DNA identification is called Southern blotting. W hen electrophoresis of RNA is performed, the technique is called Northern blotting.

Hybridization techniques are highly specific and are routinely used in research, clinical diagnosis, and forensic medicine. Several steps of this procedure may distort the tissues, delivering an image that may differ from how the structures appeared w hen they w ere alive. One cause of distortion is the shrinkage produced by the fixative, by the ethanol, and by the heat needed for paraffin embedding.

Shrinkage is decreased w hen specimens are embedded in resin. A consequence of shrinkage is the appearance of artificial spaces betw een cells and other tissue components.

Another source of artificial spaces is the loss of molecules that w ere not properly kept in the tissues by the fixative or that w ere removed by the dehydrating and clearing fluids.

Glycogen and lipids are often lost during tissue preparation. All these artificial spaces and other distortions caused by the section preparation procedure are called artifacts. Other artifacts may include w rinkles of the section w hich may be confused w ith blood capillaries , precipitates of stain w hich may be confused w ith cytoplasmic granules , and many more.

Students must be aw are of the existence of artifacts and try to recognize them so as not to be confused by these distortions. Totality of the Tissue Another difficulty in the study of histological sections is the impossibility of differentially staining all tissue components on only one slide.

Thus, w hen observing cells under a light microscope, it is almost impossible to see the nuclei, mitochondria, lysosomes, and peroxisomes, surrounded by a basement membrane as w ell as by collagen and elastic and reticular fibers. It is necessary to examine several preparations, each one stained by a different method, before an idea of the w hole composition and structure of a tissue can be obtained. The transmission electron microscope, on the other hand, allow s the observation of a cell w ith all its organelles and inclusions surrounded by the components of the extracellular matrix.

This often leads observers to err if they do not realize that a sectioned ball looks like a circle and that a sectioned tube looks like a ring Figure W hen a section is observed under the microscope, the student must alw ays imagine that something may be missing in front of or behind that section, because many structures are thicker than the section.

It must also be remembered that the structures w ithin a tissue are usually sectioned randomly. How different three-dimensional structures may appear when thin sectioned. Different sections through a hollow ball and a hollow tube. A section through a single coiled tube may appear as sections of many separate tubes. Sections through a solid ball above and sections through a solid cylinder below may be very similar.

To understand the architecture of an organ, it is necessary to study sections made in different planes. Sometimes only the study of serial sections and their reconstruction into a three-dimensional volume make it possible to understand a complex organ. Molecular Biology of the Cell, 3rd ed. Garland, Bancroft JD, Stevens A: Theory and Practice of Histological Techniques, 2nd ed. Churchill Livingstone, Cuello ACC: W iley, Molecular Cell Biology, 2nd ed.

Scientific American Books, Hayat MA: Stains and Cytochemical Methods.

Plenum, James J: Light Microscopic Techniques in Biology and Medicine. Martinus Nijhoff, Junqueira LCU et al: Arch Histol Jpn ; Meek GA: Practical Electron Microscopy for Biologists. Pease AGE: Theoretical and Applied, 4th ed. Rogers AW: Techniques of Autoradiography, 3rd ed. Elsevier, Rubbi CP: Light Microscopy.

Essential Data. Spencer M: Fundamentals of Light Microscopy. Cambridge University Press, All rights reserved. Privacy Notice. Any use is subject to the Term s of Use and Notice. Additional Credits and Copyright Inform ation. There are tw o fundamentally different types of cells, but so many biochemical similarities exist betw een them that some investigators have postulated that one group evolved from the other. Prokaryotic Gr.

These cells are small 15 m long , typically have a cell w all outside the plasmalemma, and lack a nuclear envelope separating the genetic material DNA from other cellular constituents. In addition, prokaryotes have no histones specific basic proteins bound to their DNA and usually no membranous organelles. In contrast, eukaryotic Gr.

Histones are associated w ith the genetic material, and numerous membrane-limited organelles are found in the cytoplasm. This book is concerned exclusively w ith eukaryotic cells.

The ultrastructure and molecular organization right of the cell membrane. The dark lines at the left represent the two dense layers observed in the electron microscope; these are caused by the deposit of osmium in the hydrophilic portions of the phospholipid molecules. The first cellular divisions of the zygote originate cells called blastomeres, w hich are able to form all cell types of the adult. Through this process, called cell differentiation, the cells synthesize specific proteins, change their shape, and become very efficient in specialized functions.

For example, muscle cell precursors elongate into spindle-shaped cells that synthesize and accumulate myofibrillar proteins actin, myosin. The resulting cell efficiently converts chemical energy into contractile force. The main cellular functions performed by specialized cells in the body are listed in Table Cellular Functions in Some Specialized Cells.

Function Movement Synthesis and secretion of enzymes Synthesis and secretion of mucous substances Synthesis and secretion of steroids Ion transport Intracellular digestion Specialized Cell s Muscle cell Pancreatic acinar cells Mucous-gland cells Some adrenal gland, testis, and ovary cells Cells of the kidney and salivary gland ducts Macrophages and some w hite blood cells.

Transformation of physical and chemical stimuli into nervous impulses Sensory cells Metabolite absorption Cells of the intestine.

Mescher A.L. Junqueira's Basic Histology Text & Atlas

CELL ECOLOGY Because the body experiences considerable environmental diversity eg, normal and pathological conditions , the same cell type can exhibit different characteristics and behaviors in different regions and circumstances.

Thus, macrophages and neutrophils both of w hich are phagocytic defense cells w ill shift from oxidative metabolism to glycolysis in an anoxic, inflammatory environment. Cells that appear to be structurally similar may react in different w ays because they have different families of receptors for signaling molecules such as hormones and extracellular matrix macromolecules.

For example, because of their. For example, because of their diverse library of receptors, breast fibroblasts and uterine smooth muscle cells are exceptionally sensitive to female sex hormones.

Individual cytoplasmic components are usually not clearly distinguishable in common hematoxylin and eosin-stained preparations; the nucleus, how ever, appears intensely stained dark blue or black. Cytoplasm The outermost component of the cell, separating the cytoplasm from its extracellular environment, is the plasma membrane plasmalemma.

How ever, even if the plasma membrane is the external limit of the cell, there is a continuum betw een the interior of the cell and extracellular macromolecules. The plasma membrane contains proteins called integrins that are linked to cytoplasmic cytoskeletal filaments and to extracellular molecules. Through these linkages there is a constant exchange of influence, in both w ays, betw een the extracellular matrix and the cytoplasm. The cytoplasm is composed of a matrix, or cytosol, in w hich are embedded the organelles, the cytoskeleton, and deposits of carbohydrates, lipids, and pigments.

The cytoplasm of eukaryotic cells is divided into several distinct compartments by membranes that regulate the intracellular traffic of ions and molecules. These compartments concentrate enzymes and the respective substrates, thus increasing the efficiency of the cell.

Plasma Membrane All eukaryotic cells are enveloped by a limiting membrane composed of phospholipids, cholesterol, proteins, and chains of oligosaccharides covalently linked to phospholipids and protein molecules. The cell, or plasma, membrane functions as a selective barrier that regulates the passage of certain materials into and out of the cell and facilitates the transport of specific molecules. One important role of the cell membrane is to keep constant the intracellular milieu, w hich is different from the extracellular fluid.

Membranes also carry out a number of specific recognition and regulatory functions to be discussed later , playing an important role in the interactions of the cell w ith its environment. Membranes range from 7. The line sometimes seen on the light microscope betw een adjacent cells is formed by the membranes of the tw o cells plus extracellular molecules. These three components together reach a dimension visible on the light microscope. Electron micrographs reveal that the plasmalemmaand, for that matter, all other organellar membranesexhibit a trilaminar structure after fixation in osmium tetroxide Figure Because all membranes have this appearance, the three-layered structure has been designated the unit membrane Figure The three layers seen in the electron microscope are apparently produced by the deposit of reduced osmium on the hydrophilic groups present on each side of the lipid bilayer.

Electron micrograph of a section of the surface of an epithelial cell, showing the unit membrane with its two dark lines enclosing a clear band. The granular material on the surface of the membrane is the glycocalyx.

Membrane phospholipids, such as phosphatidylcholine lecithin and phosphatidylethanolamine cephalin , consist of tw o long, nonpolar hydrophobic hydrocarbon chains linked to a charged hydrophilic head group. Cholesterol is also a constituent of cell membranes. W ithin the membrane, phospholipids are most stable w hen organized into a double layer w ith their hydrophobic nonpolar chains directed tow ard the center of the membrane and their hydrophilic charged heads directed outw ard Figure 2 1.

Cholesterol breaks up the close packing of the phospholipid long chains, and this disruption makes the membrane more. Cholesterol breaks up the close packing of the phospholipid long chains, and this disruption makes the membrane more fluid. The cell controls the fluidity of the membranes through the amount of cholesterol present. The lipid composition of each half of the bilayer is different. For example, in red blood cells erythrocytes , phosphatidylcholine and sphingomyelin are more abundant in the outer half of the membrane, w hereas phosphatidylserine and phosphatidylethanolamine are more concentrated in the inner half.

Some of the lipids, know n as glycolipids, possess oligosaccharide chains that extend outw ard from the surface of the cell membrane and thus contribute to lipid asymmetry Figures 23A and The fluid mosaic model of membrane structure.

The membrane consists of a phospholipid double layer with proteins inserted in it integral proteins or bound to the cytoplasmic surface peripheral proteins. Integral membrane proteins are firmly embedded in the lipid layers. Some of these proteins completely span the bilayer and are called transmembrane proteins, whereas others are embedded in either the outer or inner leaflet of the lipid bilayer.

The dotted line in the integral membrane protein is the region where hydrophobic amino acids interact with the hydrophobic portions of the membrane. Many of the proteins and lipids have externally exposed oligosaccharide chains. Membrane cleavage occurs when a cell is frozen and fractured cryofracture.

Most of the membrane particles 1 are proteins or aggregates of proteins that remain attached to the half of the membrane adjacent to the cytoplasm P, or protoplasmic, face of the membrane. Fewer particles are found attached to the outer half of the membrane E, or extracellular, face.

For every protein particle that bulges on one surface, a corresponding depression 2 appears in the opposite surface. Membrane splitting occurs along the line of weakness formed by the fatty acid tails of membrane phospholipids, since only weak hydrophobic interactions bind the halves of the membrane along this line. Modified and reproduced, with permission, from Krstc RV: Ultrastructure of the Mammalian Cell. SpringerVerlag, Schematic drawing of the molecular structure of the plasma membrane.

Note the one-pass and multipass transmembrane proteins. The drawing shows a peripheral protein in the external face of the membrane, but the proteins are present mainly in the cytoplasmic face, as shown in Figure Biologia Celular e Molecular, 6th ed. Editora Guanabara, Integral proteins are directly incorporated w ithin the lipid bilayer, w hereas peripheral proteins exhibit a looser association w ith membrane surfaces.

The loosely bound peripheral proteins can be easily extracted from cell membranes w ith salt solutions, w hereas integral proteins can be extracted only by drastic methods that use detergents. Some integral proteins span the membrane one or more times, from one side to the other. Accordingly, they are called one-pass or multipass transmembrane proteins Figure Freeze-fracture electron microscopic studies indicate that many integral proteins are distributed as globular molecules intercalated among the lipid molecules Figure 23B.

Some of these proteins are only partially embedded in the lipid bilayer, so that they may protrude from either the outer or inner surface. Other proteins are large enough to extend across the tw o lipid layers and protrude from both membrane surfaces transmembrane proteins.

The carbohydrate moieties of glycoproteins and glycolipids project from the external surface of the plasma membrane; they are important components of specific molecules called receptors that participate in important interactions such as cell adhesion, recognition, and response to protein hormones.

As w ith lipids, the distribution of membrane proteins is different in the tw o surfaces of the cell membranes. Therefore, all membranes in the cell are asymmetric. Integration of the proteins w ithin the lipid bilayer is mainly the result of hydrophobic interactions betw een the lipids and nonpolar amino acids present on the outer shell of the integral proteins.

Some integral proteins are not bound rigidly in place and are able to move w ithin the plane of the cell membrane Figure How ever, unlike lipids, most membrane proteins are restricted in their lateral diffusion by attachment to the cytoskeletal components.

In most epithelial cells, the tight junctions see Chapter 4: Epithelial Tissue prevent lateral diffusion of transmembrane proteins and even the diffusion of membrane lipids of the outer leaflet. Experiment demonstrating the fluid nature of the cell membrane.

The plasmalemma is shown as two parallel lines representing the lipid portion in which proteins are embedded. In this experiment, two types of cells derived from tissue cultures one with a fluorescent marker [right] and one without are fused A B through the action of the Sendai virus.

Minutes after the fusion of the membranes, the fluorescent marker of the labeled cell spreads to the entire surface of the fused cells C. However, in many cells, most transmembrane proteins are stabilized in place by anchoring to the cytoskeleton. The mosaic disposition of membrane proteins, in conjunction w ith the fluid nature of the lipid bilayer, constitutes the basis of the fluid mosaic model for membrane structure show n in Figure 23A.

Membrane proteins are synthesized in the rough endoplasm reticulum, their molecules are completed in the Golgi apparatus, and they are transported in vesicles to the cell surface Figure The proteins of the plasmalemma are synthesized in the rough endoplasmic reticulum and then transported in vesicles to the Golgi complex, where they may be modified and transferred to the cell membrane.

This example shows the synthesis and transport of a glycoprotein, which is an integral protein of the membrane. Biologia Celular e Molecular, 7th ed. In the electron microscope the external surface of the cell show s a fuzzy carbohydrate-rich region called the glycocalyx Figure This layer is composed of carbohydrate chains linked to membrane proteins and lipids and of cell-secreted glycoproteins and proteoglycans.

The glycocalyx has a role in cell recognition and attachment to other cells and to extracellular molecules. The plasma membrane is the site at w hich materials are exchanged betw een the cell and its environment. Mass transfer of material also occurs through the plasma membrane. This bulk uptake of material is know n as endocytosis Gr. The corresponding name for release of material in bulk is exocytosis. How ever, at the molecular level, exocytosis and endocytosis are different processes that utilize different protein molecules.

Pinocytotic vesicles about 80 nm in diameter pinch off from the cell surface Figure and most eventually fuse w ith lysosomes see the section on Lysosomes later in this chapter. In the lining cells of capillaries endothelial cells , how ever, pinocytotic vesicles may move to the surface opposite their origin.

There they fuse w ith the plasma membrane and release their contents onto the cell surface, thus accomplishing bulk transfer of material across the cell Figure The receptors are either originally w idely dispersed over the surface or aggregated in special regions called coated pits.

Binding of the ligand a molecule w ith high affinity for a receptor to its receptor causes w idely dispersed receptors to accumulate in coated pits Figure The coating on the cytoplasmic surface of the membrane is composed of several polypeptides, the major one being clathrin.

These proteins form a lattice composed of pentagons and hexagons very similar in arrangement to the struts in a geodesic dome.

The coated pit invaginates and pinches off from the cell membrane, forming a coated vesicle that carries the ligand and its receptor into the cell. Schematic representation of the endocytic pathway and membrane trafficking. Ligands, such as hormones and growth factors, bind to specific surface receptors and are internalized in pinocytotic vesicles coated with clathrin and other proteins.

After the liberation of the coating molecules, the pinocytotic vesicles fuse with the endosomal compartment, where the low pH causes the separation of the ligands from their receptors. Membrane with receptors is returned to the cell surface to be reused. The ligands typically are transferred to lysosomes. The cytoskeleton with motor proteins is responsible for all vesicle movements described. The coated vesicles soon lose their clathrin coat and fuse w ith endosomes, a system of vesicles Figure 27 and tubules located in the cytosol near the cell surface early endosomes or deeper in the cytoplasm late endosomes.

Together they constitute the endosomal compartment. W hether early and late endosomes are separate compartments or one is a precursor of the other is still an open question. The clathrin molecules separated from the coated vesicles are moved back to the cell membrane to participate in the formation of new coated pits.

Molecules penetrating the endosomes may take more than one pathw ay Figure Receptors that are separated from their ligand by the acidic pH of the endosomes may return to the cell membrane to be reused. For example, low -density lipoprotein receptors Figure 28 are recycled several times. The ligands typically are transferred to late endosomes. How ever, some ligands are returned to the extracellular milieu to be used again.

An example of this activity is the iron-transporting protein transferrin. LDL, which is rich in cholesterol, binds with high affinity to its receptors in the cell membranes.

This binding activates the formation of pinocytotic vesicles from coated pits. The vesicles soon lose their coating, which is returned to the inner surface of the plasmalemma: In the next step, the LDL is transferred to lysosomes for digestion and separation of their components to be utilized by the cell. For example, after a bacterium becomes bound to the surface of a macrophage, cytoplasmic processes of the macrophage are extended and ultimately surround the bacterium.

The edges of these processes fuse, enclosing the bacterium in an intracellular phagosome. Exocytosis is the term used to describe the fusion of a membrane-limited structure w ith the plasma membrane, resulting in the release of its contents into the extracellular space w ithout compromising the integrity of the plasma membrane.

A typical example is the release of stored products from secretory cells, such as those of the exocrine pancreas and the salivary glands Figure The fusion of membranes in exocytosis is a complex process. Because cell membranes exhibit a high density of negative charges phosphate residues of the phospholipids , membrane-covered structures coming close to each other w ill not fuse but w ill rather repel each other, unless specific interactions facilitate the fusion process.

Consequently, exocytosis is mediated by a number of specific fusogenic proteins. During endocytosis, portions of the cell membrane become an endocytotic vesicle; during exocytosis, the membrane is returned to the cell surface. This phenomenon is called membrane trafficking Figures 27 and In several systems, membranes are conserved and reused several times during repeated cycles of endocytosis.

Signal Reception Cells in a multicellular organism need to communicate w ith one another to regulate their development into tissues, to control their grow th and division, and to coordinate their functions. Many cells form communicating junctions that couple adjacent cells, allow ing the exchange of ions and small molecules see Chapter 4: Epithelial Tissue.

Through these channels, also called gap junctions, signals pass directly from cell to cell w ithout reaching the extracellular fluid. In other cases, cells display membranebound signaling molecules that influence other cells in direct physical contact. Extracellular signaling molecules, or messengers, mediate three kinds of communication betw een cells. In endocrine signaling, hormones are carried in the blood to target cells ie, cells w ith specific receptors to a hormone throughout the body; in paracrine signaling, chemical mediators are rapidly metabolized so that they act on local cells only; and in synaptic signaling, neurotransmitters act only on adjacent nerve cells through special contact areas called synapses see Chapter 9: In some cases, paracrine signals act on the same cell type that produced the messenger molecule, a phenomenon called autocrine signaling.

Each cell type in the body contains a distinctive set of receptor proteins that enables it to respond to a complementary set of signaling molecules in a specific, programmed w ay Figure C ells respond to chemical signals according to the library of receptors they have. In this schematic representation, three cells appear with different receptors, and the extracellular environment contains several ligands that will interact with the appropriate receptors.

C onsidering that the extracellular environment contains a multitude of molecules, it is important that ligands and the respective receptors exhibit complementary morphology and great affinity. Signaling molecules differ in their w ater solubility. Small hydrophobic signaling molecules, such as steroid and thyroid hormones, diffuse through the plasma membrane of the target cell and activate receptor proteins inside the cell.

In contrast, hydrophilic signaling molecules, including neurotransmitters, most hormones, and local chemical mediators paracrine signals , activate receptor proteins on the surface of target cells. These receptors, w hich span the cell membrane, relay information to a series of intracellular intermediaries that ultimately passes the signal to its final destination in either the cytoplasm or the nucleus.

The numerous intercellular hydrophilic messengers rely on membrane proteins that direct the flow of information from the receptor to the rest of the cell. The best studied of these proteins are the G proteins, so named because they bind to guanine nucleotides. Once a first messenger hormone, neurotransmitter, paracrine signal binds to a receptor, conformational changes occur in the receptor; this, in turn, activates the G proteinguanosine diphosphate complex Figure A guanosine diphosphateguanosine triphosphate exchange releases the subunit of the G protein, w hich acts on other membrane-bound intermediaries called effectors.

Often, the effector is an enzyme that converts an inactive precursor molecule into an active second messenger, w hich can diffuse through the cytoplasm and carry the signal beyond the cell membrane.

Second messengers trigger a cascade of molecular reactions that leads to changes in cell behavior. The examples listed in Table 22 illustrate the diversity of G proteins present in various tissues and their roles in regulating important cell functions. Diagram illustrating how G proteins switch effectors on and off.

G proteins. Sci Am ; Epinephrine, glucagon Liver cells Epinephrine, glucagon Fat cells Luteinizing hormone Antidiuretic hormone Acetylcholine Enkephalins, endorphins, opioids Angiotensin Odorants Light Pheromone Ovarian follicles Kidney cells Heart muscle cells Brain neurons Smooth muscle cells in blood vessels Neuroepithelial cells in nose Rod and cone cells in retina Baker's yeast.

Calcium and potassium channels, Changed electrical activity of adenylyl cyclase neurons Phospholipase C Adenylyl cyclase Cyclic GMP phosphodiesterase Unknow n Muscle contraction; elevation of blood pressure Detection of odorants Detection of visual signals Mating of cells.

For example, pseudohypoparathyroidism and a type of dw arfism are due to nonfunctioning parathyroid and grow th hormone receptors. In these tw o conditions the glands produce the respective hormones, but the target cells do not respond, because they lack normal receptors.

Signaling Mediated by Intracellular Receptors Steroid hormones are small hydrophobic lipid-soluble molecules; binding reversibly to carrier proteins in the plasma transports them in the blood.

Once released from their carrier proteins, they diffuse through the plasma membrane lipids of the target cell and bind reversibly to specific steroid hormonereceptor proteins in the cytoplasm or the nucleus.

The binding of hormone activates the receptor, enabling it to bind w ith high affinity to specific DNA sequences; this generally increases the level of transcription from specific genes. Each steroid hormone is recognized by a different member of a family of homologous receptor proteins.

Thyroid hormones are modified lipophilic amino acids that also act on intracellular receptors. Mitochondria Mitochondria Gr. They tend to accumulate in parts of the cytoplasm at w hich the utilization of energy is more intense, such as the apical ends of ciliated cells Figure , in the middle piece of spermatozoa Figure , or at the base of ion-transferring cells Figure Photomicrograph of the stomach inner covering.

The large cells show many round and elongated mitochondria in the cytoplasm. The central nuclei are also clearly seen. These organelles transform the chemical energy of the metabolites present in cytoplasm into energy that is easily accessible to the cell. Through the activity of the enzyme ATPase, ATP promptly releases energy w hen required by the cell to perform any type of w ork, w hether it is osmotic, mechanical, electrical, or chemical.

Mitochondria have a characteristic structure under the electron microscope Figures and A. They are composed of an outer and an inner mitochondrial membrane; the inner membrane projects folds, termed cristae, into the interior of the mitochondrion. These membranes enclose tw o compartments. The compartment located betw een the tw o membranes is termed the intermembrane space. The inner membrane encloses the other compartmentthe intercristae, or matrix, space.

Compared w ith other cell membranes, mitochondrial membranes contain a large number of protein molecules. Most mitochondria have flat, shelflike cristae in their interiors Figures and A , w hereas cells that secrete steroids eg, adrenal gland; see Chapter 4: Epithelial Tissue frequently contain tubular cristae Figure The cristae increase the internal surface area of mitochondria and contain enzymes and other components of oxidative phosphorylation and electron transport systems. The adenosine diphosphate ADP to ATP phosphorylating system is localized in globular structures connected to the inner.

The chemiosmotic theory suggests that ATP synthesis occurs at the expense of a flow of protons across this globular unit Figure Three-dimensional representation of a mitochondrion with its cristae penetrating the matrix space. Note that two membranes delimiting an intermembrane space form the wall of the mitochondrion. The cristae are covered with globular units that participate in the formation of ATP.

Structural lability of mitochondria. Electron micrograph of a section of rat pancreas. A mitochondrion with its membranes, cristae C , and matrix M is seen in the center. Numerous flattened cisternae of rough endoplasmic reticulum with ribosomes on their cytoplasmic surfaces are also visible. Electron micrograph of striated muscle from a patient with mitochondrial myopathy. The mitochondria arrows are profoundly modified, showing marked swelling of the matrix. The chemiosmotic theory of mitochondrial energy transduction.

The flux of protons is directed from the matrix to the intermembranous space promoted at the expense of energy derived from the electron transport system in the inner membrane.

Half the energy derived from proton reflux produces ATP; the remaining energy produces heat. The protein thermogenin, present in multilocular adipose tissue, forms a shunt for reflux of protons. This reflux, which dissipates energy as heat, does not produce ATP see C hapter 6: Adipose Tissue. The number of mitochondria and the number of cristae in each mitochondrion are related to the energetic activity of the cells in w hich they reside.

Thus, cells w ith a high-energy metabolism eg, cardiac muscle, cells of some kidney tubules have abundant mitochondria w ith a large number of closely packed cristae, w hereas cells w ith a low -energy metabolism have few mitochondria w ith short cristae. Betw een the cristae is an amorphous matrix, rich in protein and containing circular molecules of DNA and the three varieties of RNA. Enzymes for the citric acid Krebs cycle and fatty acid -oxidation are found to reside w ithin the matrix space.

The DNA isolated from the mitochondrial matrix is double stranded and has a circular structure, very similar to that of bacterial chromosomes.

These strands are synthesized w ithin the mitochondrion; their duplication is independent of nuclear DNA replication. Mitochondria contain the three types of RNA: Mitochondrial ribosomes are smaller than cytosolic ribosomes and are comparable to bacterial ribosomes. Protein synthesis occurs in mitochondria, but because of the reduced amount of mitochondrial DNA, only a small proportion of the mitochondrial proteins is produced locally.

Most are encoded by nuclear DNA and synthesized in polyribosomes located in the cytosol. Elsevier's Integrated Histology, Concise, includes cross-references to other disciplines. Your choice of a text at this level may be based on availability or on personal preference for style which can differ markedly among texts. Just as a single snapshot cannot the convey the impact of a landscape or the personality of friend, so a single micrograph is seldom sufficient to catch the full character of a tissue.

Histology atlases some are examples listed below are quite useful for this purpose. Personal possession of an atlas should not be necessary; several different atlases are available in the MRC. Rhodin, An Atlas of Histology This is an excellent source for electron microscope images, organized by organ system.

Note that each section begins with low-magnification images and leads through higher and higher magnification, making it easy to appreciate images in organ and tissue context. This book is usefully kept alongside your light microscope and treated as if it were an "extra-high power" objective.

Although this book is out of print, multiple copies are available in the MRC. An excellent resource for images of particular pathologies. A new CD resource just published by Sinauer. Like the out-of-print atlas by Rhodin above , a laptop running this CD might be useful alongside your light microscope and treated as if it were an "extra-high power" objective.

Color Atlas of Histology, 5th edition, Any book labelled as a "atlas" of histology will offer a useful collection of images, for comparison and contrast with other sources and with real specimens. The following are much more substantial heavier, much more detail, vs. Students should be aware that such resources exist, but personal ownership is not recommended. Stevens et al. Concise introduction to the application of histology to pathology.

May be appropriate if you have already had a course in histology, or if you wish to read beyond the basics of normal histology. Mills, Histology for Pathologists, 3rd ed. New edition of Sternberg below.The authors of this text recognize that students of biologic structure share a common goal, namely, to better understand how structure and function are integrated into the molecules, cells, tissues, and organs of a living creature.

The sections are floated on w ater and transferred to glass slides to be stained. Because of this, every attempt has been made to present the information as concisely as possible and organize it in a way that facilitates learning.

Indirect immunocytochemical detection is performed by initially incubating a section of a rat tissue believed to contain protein x w ith rabbit anti-x antibody. This technique is also useful in the study of parasites that grow only w ithin cells, such as viruses, mycoplasma, and some protozoa Figure