SIU SOM Histology INTRO
For additional introductory exercises, see Ed      (The Path Guy)'s Basic Histology Gallery .
OVERVIEW of Connective Tissue
Connective tissue forms a framework upon which epithelial tissue rests and      within which nerve tissue and muscle tissue are embedded.  Blood vessels      and nerves travel through connective tissue.  
Connective tissue functions not only as a mechanical support for other tissues      but also as an avenue for communication and transport among other tissues.  Most significantly, connective tissue is the stage for inflammation .  The principal cell types involved in immunological defense are found within connective tissue
Connective tissue is derived  from embryonic mesenchyme (unlike        most epithelial tissue which is derived from ectoderm        and endoderm).
 
Elastic fibers confer            resiliency.  
The matrix is produced by fibroblasts (or      related cell types -- chondroblasts in cartilage and osteoblasts in bone ).
Connective tissue assumes widely varying forms, embracing not only many variations      on " ordinary " (such      as fibrous tissue and adipose tissue )      but also several highly specialized types -- elastic tissue , lymphoid tissue , blood , cartilage , and bone .  
Specific examples of connective tissue vary in proportion        of the several components.  Fibrous tissue such as dermis emphasizes collagen fibers.  Fatty tissue emphasizes adipocytes .  Lymphoid tissue emphasizes lymphocytes .  In specialized forms, some components missing altogether.  In blood , fibers are absent and the ground substance        (also called plasma) is fluid.  In bone ,        several cell types are absent and the ground substance is solidified by        mineral deposits.
Note that connective tissue forms a significant and vitally important component      of nearly every organ.  As we study the human body organ system by organ      system, it is easy to forget the importance of connective tissue simply because      it is ubiquitous and serves universal functions, rather than being special      with novel functions.  Never let this bland familiarity cause you to      lose sight of the existence and significance of ordinary connective tissue.   Inflammation is a principal function for      connective tissue and the blood vessels which pass through it.
Macrophages (which ingest and remove            foreign material or damaged cells).
Immigrant cells include:
lymphocytes , monocytes ,            and neutrophils , which are all involved            in immune defense and inflammation .  
Fibroblasts are the most common resident cells in ordinary connective      tissue.  Fibroblasts are responsible for secreting collagen and other elements of the extracellular matrix of connective      tissue. 
In microscopic appearance, fibroblasts lack obvious specialized features.  And fibroblasts throughout the body all appear similar to one another, wherever      they occur in ordinary connective tissues.  There is thus little about      fibroblasts to attract the attention of an observer. However, fibroblasts      are essential for normal development and repair , and      recent research ( PLoS      Genetics 2006 ) has shown that fibroblasts      from different regions display extensively differentiated patterns of gene      expression which may guide differentiated patterns of tissue organization,      such as different types of skin and hair in different areas.  Indeed,      the single cell type called "fibroblast" may properly represent      many distinctly (but invisibly) different cell types, including "mesenchymal      stem cells" which retain capacity to differentiate into other cell types      (see Science 324:1666, 26 June 2009)..
The name "fibroblast" is something of a misnomer,        since most cells with "blast" in their name are embryonic precursor        cells which subsequently differentiate into specialized cell types.  Fibroblasts        are already a mature, differentiated cell type (although some may have the        capacity to differentiate into other mesenchymal cell types as well).
Resting      fibroblasts typically have so little cytoplasm that the cells commonly appear,      by light microscopy, as "naked" nuclei.  
Fibroblast nuclei appear dense (heterochromatic) and are        usually flattened or spindle-shaped.  The pink material in this thumbnail        image is extracellular collagen .
Fibroblasts are active during growth but are normally quiescent        in the adult.  When active, fibroblasts are actively secretory, manufacturing        the collagen and other components of the extracellular matrix of connective tissue.  Active fibroblasts appear larger than        resting ones, with more cytoplasm and with nuclei that are more euchromatic        (less densely stained).  
Scar formation:  Resting fibroblasts retain the ability to become      active and to multiply when necessary, as during healing after injury.  Scars are formed by fibroblast activity during tissue repair.  The substance      of the scar is collagen deposited by fibroblasts to      replace damaged tissue.  
For an image of scar formation, see WebPath .
For recent research on fibroblast involvement in scar formation, see Science 348:284(17 April 2015) .
Closely related to fibroblasts are the chondroblasts which produce      the matrix of cartilage and the osteoblasts which produce the matrix of bone .  
Terminology:  The appearance of "blast" in a cell name normally indicates an embryonic cell that transforms into a mature cell type (e.g., neuroblast, myoblast).  However, in        the case of "fibroblast", "chondroblast" and "osteoblast",        this designation indicates a cell which secretes fibers, cartilage        or bone.
Adipocytes.  Adipocytes are large connective tissue cells which      contain a substantial amount of lipid stored in the form of conspicuous round      droplets.  Adipocytes function primarily as warehouses for reserve energy.  En masse, they also assist in thermoregulation (maintaining body      temperature) and in a few sites offer some cushioning capacity (e.g., around      kidneys, behind eyeballs).
Since most loose connective tissue contains scattered clusters        of adipocytes, the term adipose tissue is usually reserved for large        masses (grossly visible) of these cells.
The most common type of adipocyte is called the unilocular adipocyte      or white fat.  Each cell contains one single fat droplet (hence, unilocular) surrounded by a thin rim of cytoplasm.
Under        the light microscope, the appearance of an adipocyte is that of a conspicuous        clear space with a very thin border.  The lipid droplet which comprises        the bulk of each adipocytes is not stained by ordinary aqueous stains, and        may even be removed by solvents during specimen preparation.  Furthermore,        adipocyte cytoplasm itself is inconspicuously thin, and the nucleus of any        particular adipocyte is unlikely to be included in any given section (see Viewing Tissues ).
On microscope slides, clusters of adipocytes present an        appearance somewhat like a "foam".  The individual "bubbles",        each representing a lipid droplet within a single cell, are fairly consistent        in the size.  Typically diameter is about 50 micrometers, comparable        to a skeletal muscle fiber or a small (terminal) arteriole.
The        shape of the droplet, in a tissue section on a slide, depends on how carefully        the specimen was prepared.  Ideally the droplets are smooth and round        (as in the image above), but they may also be distorted, shaped more like        jigsaw-puzzle pieces (as in the image at right).
Adipocytes may occur in almost any sample of ordinary connective        tissue, where they may be found as individual cells or in clumps.  Even        when clustered together and apparently touching, adipocytes remain separated        by a thin layer of matrix (ground substance and collagen) which includes        numerous capillaries.
A layer of adipose tissue in the deep layers of skin (variously        called hypodermis or subcutaneous adipose) may provide significant        thermal insulation.
A more specialized and localized type of adipocyte      is called the multilocular adipocyte or brown fat.  These      cells function in thermogeneration, essentially burning fat to produce heat.
Individual        brown fat cells contain numerous small lipid droplets (hence the name multilocular)        and numerous mitochondria (whose cytochromes confer a brownish color).  In        these cells, the metabolic reactions of the mitochondria are uncoupled from        ATP synthesis so that energy produced is simply released as heat.  
Infants have a substantial amount of brown fat, especially        in a pad between the shoulder blades.  Brown fat is scarce in adults        but may be found around the adrenal gland.  Recent research (three        articles in New England Journal of Medicine 360[15], 9 April 2009)        reported brown fat in a region extending from the anterior neck to the thorax;        brown fat activity was positively related to resting metabolic rate and        was significantly lower in overweight or obese subjects than in lean subjects.
Macrophages remove and digest the by-products of both bacterial      warfare and normal growth and degeneration.  Resting macrophages are      difficult to recognize reliably by light microscopy, at least in routine preparations,      because they lack conspicuous distinguishing characteristics.  They tend      to be somewhat larger than fibroblasts, with more cytoplasm.  Macrophages      contain numerous lysosomes which are used for breaking down ingested material.  These lysosomes are usually inconspicuous by light microscopy but readily      visible by electron microscopy.  
In        macrophages which have been active and have accumulated indigestible residue,        the lysosomes may be visible by light microscopy as brown intracellular        granules, as in this image of lung macrophages ("dust cells").  Click here or on the image for a wider-field        view and more information on lung macrophages.
Historical notes:  Macrophages        of liver ( Kupffer cells ) and lung        (dust cells) were named prior to clear understanding that these cells belong        to a more widely distributed cell type.  
The term reticuloendothelial system refers        to the macrophages of the liver , spleen and lymph nodes (i.e., those organs        with elaborate endothelially-lined channels supported by reticular        connective tissue ).  The name reflects former confusion about the        distinction between endothelial cells and the scattered population of macrophages        (monocytes, histiocytes).  Macrophages can be readily labelled experimentally        through their phagocytosis of injected carbon particles.  However,        endothelial cells are also labelled by the same procedure.  Although        endothelial cells are not dramatically phagocytotic, they do shuttle some        materials across the endothelial lining via small endocytotic and exocytotic        vesicles.
Macrophages are mobile (amoeboid movement) over short distances within a      local region of connective tissue.  Most ordinary connective tissue contains      a standing population of resident macrophages.  But when damage or infection      requires reinforcements, monocytes can increase      the macrophage population many-fold.  Monocytes are circulating cells      in the blood (example at WebPath )      which can differentiate into macrophages when they enter connective tissue.  
Macrophages are among the most independent cells        in the body.  Although they respond to the chemical signals which govern        immune responses, individual macrophages are capable of crawling out of        connective tissue, crossing the body's epithelium, and scavenging foreign        material on exposed surfaces such as the alveolar lining of the lung and        the conjunctiva of the eye.
Macrophages can gather and fuse into giant cells at sites of damage or foreign material.  For illustrations, see WebPath example        1 , example        2 , example        3 .
Mast cells are secretory alarm cells.  Upon the slightest disturbance,      they release chemical signals which diffuse through the surrounding ground      substance and trigger the process of inflammation .  
Mast cells occur as small individual cells, scattered rather widely in ordinary      connective tissue.  The cytoplasm of mast cells is packed with secretory      vesicles, which can be fairly conspicuous in high-quality light microscope      preparations.  The granules contain histamine, heparin, and various      other chemical mediators whose release signals a number of physiological defense      responses.
Allergies are caused (in part) by inappropriate sensitivity        of mast cells.  The symptoms are treated with antihistamines, chemicals which interfere with the action of histamine.
Historical note.  The name "mast cell" is a misnomer.  The word "mast" refers to food.  When        first described, the secretory vesicles of mast cells were misinterpreted        as evidence of ingestion by phagocytosis.  So the name suggests a cell        which has eaten its fill of "mast".
Lymphocytes are small cells with round nuclei and minimal cytoplasm (the example shown      here is from a blood smear).  Some lymphocytes circulate throughout the      body, moving freely from blood to ordinary connective tissue and back again.  [ Recent      research suggests that some types of lymphocytes are more compartmentalized.]  Lymphocytes serve both as scouts and as weapons against invading microorganisms.  (View examples at WebPath , WebPath , electron micrograph at WebPath .)
Lymphocytes        occur as inconspicuous individual cells scattered through most ordinary        connective tissues.  They are especially common in lamina propria (i.e.,        the connective tissues of mucous membranes).  Microscopically conspicuous        accumulations of lymphocytes occur in scattered sites around the body, with        special concentrations in spleen , thymus , lymph        nodes , Peyer's patches of ileum,        and tonsils .  These sites include germinal centers where activated lymphocytes proliferate.
Lymphocytes manufacture antibodies, proteins which possess the ability to      recognize and bind to foreign substances.  The antibodies may be either      secreted or bound to the lymphocyte membrane.  Plasma cells are      differentiated lymphocytes which are specialized to manufacture and secrete      relatively large amounts of antibody.  (Electron micrograph      at WebPath .)
[ More on lymphocytes.]
Other connective tissue cell types.  The list above is not exhaustive.
During inflammation , white        blood cells in addition to lymphocytes , such        as neutrophils , may enter connective tissue        from blood.   Eosinophils may be present        in some places (e.g., lamina        propria of gut, especially in the presence of parasites)
Skeletal tissues include        specialized relatives of fibroblasts , the chondroblasts which make cartilage and the osteoblasts which make bone .   Bone also contains osteocytes (resting cells, encased in bony matrix) and osteoclasts ( macrophage relatives, which dissolve bone matrix).
Connective tissue may also contain undifferentiated stem        cells, which are morphologically indistinguishable from fibroblasts        but which (by definition) retain the ability to differentiate along various        routes.
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EXTRACELLULAR MATRIX
The extracellular matrix of connective tissue is composed of ground      substance and fibers .  In ordinary connective      tissue, the ground substanc e consists mainly of water.  The principal fiber type is collagen (the most      abundant protein in the body), with elastic fibers as a minor element.  The extracellular materials which comprise      the matrix are produced by fibroblasts .
More        at Biochemistry website.
Ground substance is the background material within which all other      connective tissue elements are embedded.  In ordinary connective tissue,      the ground substance consists mainly of water whose major role is to provide      a route for communication and transport (by diffusion) between tissues.  This      water is stabilized by a complex of glycosaminoglycans (GAGs), proteoglycans,      and glycoproteins, all of which comprise only a small fraction of the      weight of the ground substance.  
The effect of GAGs in water is quite like that of Jello.  If you've ever made Jello, you know that a couple tablespoons        of powder from the Jello package can turn a quart or more of water        from a flowing liquid into a solid mass.  
Ground substance may be highly modified in the special      forms of connective tissue .  
In blood, the ground substance lacks stabilizing macromolecules.  We call this free-flowing ground substance plasma.
In skeletal tissue ,        the ground substance may become mineralized by deposition of calcium salts.  We call this rigid ground substance bone .
In cartilage ,        the ground substance is much more solid than in ordinary connective tissue        but still retains more resiliency than bone.
The extracellular fibers of connective tissue are traditionally classified      into three types:
Collagen fibers confer main tensile        strength, and are the stuff of scars.
Elastic fibers confer elasticity.
Reticular fibers (really, a special        form of collagen) provide a delicate supporting framework for loose cells.
Collagen is the most common protein in the body.  As an essential structural element in the extracellular matrix of      most connective tissues, including bone and cartilage, collagen confers      toughness and tensile strength.  Scars are made      of collagen.
More than a dozen different varieties of collagen exist        in the body, usually identified by Roman numerals.  These varieties        are produced by different genes, have somewhat different properties, and        occur in different locations.  The most common forms are listed below.  More        at Biochemistry website.
Type I collagen forms the familiar eosinophilic        collagen fibers of ordinary fibrous connective tissue (e.g., dermis, tendon,        organ sheath, fascia).
Type II collagen reinforces cartilage .
Type III collagen forms reticular fibers and also        occurs in basement membranes and bone .
Type IV collagen occurs in the basal lamina around        smooth and skeletal muscle fibers .
Type VII collagen is an interlinking collagen important        for formation of basement membranes .
Collagen pathology:  Because different types          of collagen occur in different locations, various collagen defect disorders          can produce different symptoms depending on which particular gene carries          a mutation.
The      type I collagen fibers of ordinary fibrous connective tissue are colorless, so in most cases their bulk appearance is white (e.g., the "white" of the eye and other organ sheaths, tendons, fascia).  Whiteness results      from scattering of light (the same reason that snow is white, even though      snowflakes are transparent crystalline ice).  Under extraordinary circumstances      of regular fiber arrangement and controlled extracellular fluid, as in the cornea of the eye , bulk      collagen can be transparent.
Although colorless, type I collagen is eosinophilic and so appears pink in      routine H&E stained tissue specimens.  Such pink collagen fibers are the most prominent feature of ordinary      connective tissue.  The ability to locate and identify connective tissue      on slides is largely the ability to recognize collagen fibers.
Collagen is produced by fibroblasts .
Collagen is secreted by fibroblasts as procollagen molecules,        converted extracellularly into tropocollagen which self-assembles into microscopically        visible fibers and grossly evident mechanical structures such as tendons.  (For more on the biochemistry and related pathology of collagen, see        Kierszenbaum, Histology and Cell Biology. )
 Densely packed type I collagen fibers (in dense        connective tissues such as dermis and tendon) provide main strength        with resistance to tearing and stretching.  Loosely packed collagen        fibers (in loose connective tissues , such as hypodermis        or the submucosa of internal organs) allow free movement within definite        limits.  
Reticular      fibers (rete, net), made from type III collagen, provide a very      delicate network (hence the name) supporting individual cells in certain organs      ( lymph nodes , spleen , liver ).  Reticular fibers do not show      up in routine H&E stained specimens,      but they can be demonstrated with silver salts .  
The collagen which reinforces cartilage, bone, basement      membranes , basal lamina, and assorted other structures is not organized      into microscopically visible fibers.
Elastin is another fibrous protein.  As the name suggests, elastin is elastic.  In ordinary connective tissue, elastic fibers help restore normal shape      after distortion.  In high enough concentrations, elastin confers a yellowish      color (as in the elastic ligament, ligamentum flavum, where flavum = yellow)
Like rubber bands, elastic fibers can deteriorate with        age and exposure to sun.  This effect is easily demonstrated by recruiting        two volunteers, one youthful and one elderly.  Pinch up a bit of skin        on the back of each person's hand and then watch how quickly the skin returns        to its original position when released.
In        elastic ligaments, dense elastic fiber concentrations convey strong elastic        properties while a lesser concentration of collagen serves simply as a mechanical        stop to prevent over-stretching under severe stress.
In        addition to its occurrence as a minor constituent in most ordinary connective        tissue, elastin is also characteristic of arterial        walls (especially elastic arteries such as the aorta) and of elastic cartilage (found in        ear and epiglottis).
Elastic fibers are often poorly stained by H&E ,        and so are seen microscopically only with specially stained slides.
Other -- fibrous , elastic , adipose , lymphoid , areolar , blood , bone and cartilage
"Ordinary" connective tissue, or connective tissue "proper",      is a generalized form of connective tissue which contains all of the basic      components of connective tissue in reasonable proportion, including cells (of several types), extracellular fibers , and extracellular ground substance .  Variations in the relative proportions      and arrangements of cells, fibers, and ground substance are used to describe/classify      connective tissues.
Examples of ordinary connective
 
 
"Special" connective tissue.  Within a background texture of      rather universally distributed ordinary connective tissue, there also occur      several very highly differentiated and localized forms of "special" connective      tissue, which nevertheless share many common features (structural components,      cell lineages) with connective tissue proper.  These special forms      include bone , cartilage , lymphoid tissue (spleen and lymph nodes), and blood .  
In routine use, the term "connective tissue" usually refers      to ordinary connective tissue, while the special forms are more commonly referred      to by their specific names (e.g., bone, cartilage, blood).  
Loose / Dense.  Connective tissue may be distinguished as either loose or dense, depending on the proportion of fibers .  
The difference between moderately loose connective tissue and moderately      dense connective tissue is difficult to appreciate by microscopy, since inadvertent      compression or stretching may reduce or exaggerate the space between the fibers.  This difference is better appreciated at the level of gross anatomy.  
If a fresh sample of loose connective were hit with        a hammer, it would "squish".  If a sample of really dense connective tissue, such as tendon, were hit, the hammer would bounce back.
There is no sharp distinction between loose and dense connective tissue;      the labels refer to the extremes of a continuum.  
Dense connective tissue is so named because of        high density of extracellular fibers , and relatively        smaller proportions of ground substance and cells .  
Dense collagenous connective tissue is found wherever the tensile strength          of collagen is of paramount importance.  Examples          include dermis (the layer of the skin which yields leather), tendons and ligaments,          and organ sheaths (such as the sclera, or "white", of          the eye).
Dense elastic connective tissue is found wherever          the elasticity of elastin is of paramount importance,          as in the ligamentum flavum (flavum refers to the yellow          color conferred by the elastin) and the aorta.
Loose connective tissue has        a relatively large proportion of ground substance ,        of cells , or of both cells and ground substance.  In        other words, loose connective tissue lacks the massive fibrous reinforcement        that characterizes dense connective tissue.  Nevertheless, the same        types of fibers are still found, although fewer and        more delicate.
Loose connective tissue is easily distorted, permitting tissues on either side to move freely with respect to one another.  However,          when loose connective tissue is distorted sufficiently, it too becomes          tough and resists further deformation.  The intrinsic strength of collagen is the same in both loose and dense connective          tissue.
Exercise:  To experience the mechanical          quality of loose connective tissue, try the following.  (1) Pinch          the skin of one cheek between thumb and forefinger.  (2) Hold the          lining (mucosa) of that cheek between your teeth.  (3) Then move          the skin relative to the lining.  See how far the two surfaces can          move relative to one another.  The freedom is due to the looseness          of the intervening connective tissue.  The limits are set by the collagen fibers which become straightened until          taut.
Examples of loose connective tissue include hypodermis, lamina propria , submucosa , mesentery , and fascia.  (Fascia [L., band] is the term used in gross anatomy for          the connective tissue that loosely binds together various other structures.)  The textbook "ideal" example of ordinary loose connective          tissue is sometimes called areolar tissue (areolar refers to the small spaces filled with ground substance).
Regular/Irregular.   Dense connective      tissue may be further described as either regular or irregular,      depending on the orientation of the fibers .  
In regular connective tissue (example: tendon)        the fibers are all aligned in a single direction,        conferring tensile strength primarily in that direction.  
 In irregular connective tissue (example: dermis)        the fibers are arranged randomly in all directions.
Fibrocollagenous (or just fibrous) tissue contains a substantial proportion of collagen .  A principal feature of fibrous tissue      is flexibility combined with great tensile strength.
Because collagen is colorless and typically scatters light,        fibrous connective tissue usually appears white.
The sclera (or "white") of the eye is        a readily visible example of dense fibrous connective tissue comprising        an organ sheath.  
Tendons and muscle capsule may also be familiar        from the butcher shop or anatomy lab.  The ends of muscle        fibers are typically attached to dense fibrous connective tissue of        periosteum, tendon, or ligament.
 The dermis of the skin        is also fibrous connective tissue (hence, leather is mostly collagen).
Elastic tissue is a dense connective tissue which contains predominantly elastic fibers rather than collagen.  It is more      elastic (obviously) than dense collagenous connective tissue.
Examples include the wall of the aorta and the elastic        ligament of the spine (called ligamentum flavum [flavum =        yellow] because in sufficient quantity elastin is yellowish).
Adipose      tissue is loose connective tissue which is dominated by fat      cells , or adipocytes .  Since most loose      connective tissue contains scattered clusters of adipocytes ,      the term adipose tissue is usually reserved for large masses (grossly      visible) of these cells.
Lymphoid      tissue is loose connective tissue with large numbers of lymphocytes that have accumulated in the tissue.   Lamina      propria (the loose connective tissue of mucosal surfaces) often shows      lymphatic tendencies, or even fairly well-developed lymph nodules.  The      immune cells in these locations form a vital second line of defense (the epithelium      with its continuous but rather easily broken wall was the first line) against      invading microorganisms.  
A separate page describes the lymphatic      system , including lymphoid tissues in several specialized lymphoid organs      -- spleen , thymus , lymph nodes , and tonsils .  Lymphoid organs are also sometimes called reticular tissue because of      the supporting framework of reticular fibers (a delicate,      branching form of collagen).  
For more on lymphoid tissue, visit " Lymphoid        Tissues "at Blue        Histology .
Areolar tissue.  The ideally generalized      form of connective tissue, with unspecialized proportions of the various matrix      components and cells, receives its own name: areolar tissue.  Mesentery      is usually given as the standard example.
Areolar        tissue is often introduced with a whole-mount preparation of mesentery.  The term "areolar" refers to the many small spaces (filled with ground        substance ) visible in this tissue.
Blood is traditionally classified as a specialized      form of connective tissue, with no fibers, highly fluid ground substance,      and mobile cells.  Blood is thus distinct from ordinary connective tissue.  However, blood may also be usefully regarded as simply a fraction of      ordinary connective tissue that is free to gallop around from place to place      along differentiated highways.  (Follow the links for a more extensive      discussion of blood .)
Only the red blood cells ,        like trolley cars, are confined to the highways (i.e., blood vessels).  All        other cell types in blood, and most plasma constituents as well, can circulate        rather freely from blood to connective tissue and back again.  Thus,        most of the mobile cellular components of ordinary connective tissue are        interchangeable with those in blood.
Cell names may differ between blood and ordinary connective        tissue.  The cells which are called macrophages in ordinary connective tissue are called monocytes in blood.  Blood cells similar to tissue mast        cells are called basophils .  From this point of view, the term " white        blood cell " is not only very nonspecific but is also a misnomer.  "Circulating        connective tissue cell" (still nonspecific) better fits the functional location        of these mobile cell types.
Bone and cartilage are special forms of connective tissue, made by specialized osteoblasts and      chondroblasts, with uniquely solidified ground substance.  These forms      are described on a separate page, as skeletal      tissue .
 
haemopoiesis (blood cell formation).  
Transport  
The circulatory system is the familiar mechanism for moving materials around      the body.  However, blood vessels do not go quite far enough.  Most      cells are not situated directly against capillaries, but rather some tens      or even hundreds of micrometers (several cell diameters) away from the nearest      blood vessel.  
Connective tissue (more specifically the stabilized water        in the ground substance) provides the final pathway for diffusion of nutrients,        oxygen, waste and metabolites to and from the cells of the body.
Subcutaneous and intramuscular injection of drugs also        makes use of connective tissue as the initial transport medium.
All blood vessels are embedded in connective tissue.  The only cells      which receive their sustenance directly from the blood are the endothelial      cells lining the vessels themselves.  All other cells are supplied via      diffusion through intermediary connective tissue.
The transport functions of blood and connective tissue        cannot be separated.  In essence, blood is        really just a mobile fraction of connective tissue.  The heart and        circulatory system simply facilitate the movement of this traveling tissue.
Whenever you find an elaborate capillary bed closely associated        with a group of cells (such as the capillary network enveloping skeletal        muscle fibers or encircling secretory acini), you can predict that these        cells must have some exceptionally high demand for transport in or out,        since a resting cell can live quite happily at some distance from the nearest        blood supply.  Rich capillary supply is characteristic of muscle and        brain (supplying oxygen), lung (acquiring oxygen), intestinal villi (collecting        nutrients), exocrine glands (delivering raw materials for secretion), and        endocrine glands (collecting hormones).
Immunological surveillance and defense
(For more about the immune system, see outside      links and CRR      Lymphatic System .)
Connective tissue serves as a transportation route not only for the body's      normal economy but also for invading microorganisms.  To provide defense      against this eventuality, an army of various cell types are deployed throughout      the connective tissue.
Connective tissue forms the principal battleground for        invasions:  Bacteria do not easily proliferate within epithelia --cell        membranes block entry into cells, and there is little extracellular food        for bacteria within epithelia.  On the other hand, connective tissue        offers a potential paradise.  The abundant extracellular material provides        all the necessary nutrients as well as an ideal warm, humid, oxygenated        environment.  Without vigorous immunological defenses within the connective        tissue, any small break in the epithelium would convert the body into an        excellent bacterial culture.
Inflammation is a specific function        of connective tissue.
Ordinary connective tissue includes two resident cell types with immunological      function, mast cells and macrophages .  (Resident cells, which essentially remain fixed in place waiting      for action, are distinguished from wandering or immigrant cells which migrate in and out of the tissue.)
Mast cells are secretory alarm cells.  They are very fragile, rupturing at any        disturbance.  The release of their granules (stored secretory product)        triggers a number of physiological defense mechanisms, including inflammation .
Macrophages remove and digest        the by-products of both bacterial warfare and normal growth and degeneration.  Monocytes, which are circulating cells in the blood, differentiate        into macrophages when they enter connective tissue.  Macrophages are        mobile (amoeboid movement) over short distances within a local region of        connective tissue.  But when an invasion requires reinforcements, monocytes can increase the macrophage population many-fold.
Other fixed cells (i.e., fibroblasts and fat cells ) are primarily structural, although        fibroblast activity (cell proliferation and secretion of collagen )        is an important aspect of the healing process.
Wandering connective tissue cells, also called white      blood cells , travel in and out of connective tissue.  Five basic      types may be considered:
Lymphocytes circulate through both blood and connective tissue.  They possess in        their secretory product and on their cell membranes the ability to recognize        and bind to foreign substances.  
Neutrophils (properly, neutrophilic granulocytes; the name derives from the staining        properties, neither acidophilic nor basophilic, of these cells' specific        granules).  These phagocytic cells travel in blood until called out        into peripheral tissues.  An inflammatory response (triggered in part by mast cells ) summons neutrophils        to the affected area.  Neutrophils have the ability to approach, engulf,        and kill most bacteria.  To view an electron micrograph, see WebPath .
Eosinophils , like        neutrophils, are named according to their characteristic staining; their        cytoplasmic granules are eosinophilic.  Eosinophils        are involved in responses to allergy and parasites.
Basophils , like neutrophils        and eosinophils, are named according to their characteristic staining. Their        cytoplasmic granules are basophilic.  Basophils        are the circulating equivalent of tissue mast cells .  
Monocytes are circulating        precursors of macrophages .  
[Additional images of WBC types, at WebPath .]
The distribution of the wandering immune cells reflects ongoing physiological      and pathological processes.
Neutrophils are normally confined to circulating blood, where they remain ready for        defensive reactions.  A gathering of neutrophils (polymorphonuclear        neutrophilic leukocytes, or PMNs) outside of blood signifies an acute inflammation ,        with tissue damage and/or presence of infectious microorganisms.  
Lymphocytes accumulate later        and may indicate chronic inflammation .  In        some regions (as in tonsils and        in lamina propria along the        gut), accumulations of lymphocytes are part        of a normal (nonpathological) interaction with antigens (foreign materials)        which cross the epithelium.  
For more about the immune system, see outside      links and CRR      Lymphatic System .
Mechanical Support  
The mechanical quality of most ordinary connective tissue is affected only      indirectly by the cells which occur within it (unlike epithelial      tissue , which consists entirely of cells).
An exception is adipose tissue ,        where the sheer bulk of many adipocytes can offer        mechanical protection by cushioning impact.
The major determinant of the mechanical properties of most connective tissue      is the extracellular matrix which is secreted by the      cells within it ( fibroblasts in ordinary connective      tissue, osteoblasts and chondroblasts in bone and cartilage respectively).
In ordinary connective tissue, the ground substance is too fluid to provide much strength.  The jelly-like ground substance      of ordinary connective tissue serves mainly to prevent extracellular water      from pooling in the lowest part of your body.  But ground      substance can be a major structural feature in special forms such as cartilage and bone .
In most connective tissue, extracellular fibers form      the main structural elements.  
Collagen offers flexibility with high tensile strength.  Densely packed collagen fibers provide strength with resistance to        tearing and stretching.  Loosely packed collagen fibers allow free        movement within definite limits.
Reticular fibers (really, a special form of collagen )        provide a delicate supporting framework for individual cells, especially        when such cells accumulate en masse to form a large solid organ such as        the spleen or the liver.
Elastin , as the name suggests, is stretchy like        rubber bands, helping restore normal shape after distortion.  In elastic        ligaments and arteries dense elastic fiber concentrations convey strong        elastic properties while a lesser concentration of collagen serves simply        as a mechanical stop to prevent over-stretching under severe stress.  
Growth and Repair.  The most common fixed cell of ordinary connective      tissue proper is the fibroblast .  Fibroblasts      are normally quiescent in the adult.  During growth and also during repair      after injury fibroblasts are active secretory cells which manufactures the fibers and ground substance of      connective tissue.  They also retain the ability to multiply when necessary,      as during wound healing, and possibly to differentiate into other mesenchymally      derived cell types (such as vascular endothelium and smooth muscle).  Myofibroblasts resemble fibroblasts but have an      additional contractile ability, useful for example for closing wounds.  
A scar is collagen deposited by fibroblasts during repair. ( WebPath illustrates scar formation.)
According to recent research ( PLoS      Genetics 2006 ), genetically differentiated      fibroblasts may also be responsible for guiding localized patterns of tissue      organization during growth and repair.
Energy Economics.  Connective tissue is involved in several interrelated      ways with energy storage and thermoregulation.  
The burden of reserve energy storage falls almost entirely on adipocytes .
Many other cells, especially muscle cells, have short-term        energy stores in the form of intracellular glycogen.  A larger, but        still comparatively small, energy reserve is also provided by glycogen in hepatocytes (the epithelial cells        of liver ).  But adipocytes exceed all other cell types for calories stored per cell.
Accumulations of subcutaneous fat cells also provide thermal insulation.  And specialized brown      fat (also called multilocular fat) is responsible for generating heat to maintain body temperature under circumstances when insulation is not sufficient.  This heat-producing function is especially significant for infants (and      other small mammals) and may be related to metabolic rate in adult humans.
Haemopoiesis.  The process of blood cell formation also falls      to connective tissue.  The connective tissue of bone marrow is      specialized for this role.  (Pass over this lightly now.      You should learn more in Year Two.)