ciliary processes with edema during the early stages ofinflammation, as the fluid is able to exude through thevessels but not through the ciliary epithelium5.

The walls of small blood vessels act as a microfilter,allowing the passage of water and solutes but blockingthat of large molecules and cells. Oxygen, carbondioxide, and some nutrients transfer across the wall bydiffusion but the main transfer of fluid and solutes is byultrafiltration6. The high colloid osmotic pressure insidethe vessel, due to plasma proteins, favors fluid return tothe vascular compartment.

Increased vascular permeability inacute inflammationThere are two mechanisms for increased permeability ofsmall vessels following tissue damage: toxins andphysical agents may cause necrosis of vascularendothelium, leading to abnormal leakage (injury-induced vascular leakage); and chemical mediators ofacute inflammation may cause retraction of endothelialcells, leaving intercellular gaps (chemical-mediatedvascular leakage).

As the vessels become leaky, they permit the passageof water, salts, and some small proteins from the plasmainto the damaged area (exudation). One of the mainproteins to leak out is the small soluble molecule,fibrinogen. Endothelial cells swell and partially retract sothat they no longer form a completely intact internallining. Expression of adhesion molecules on the capillaryendothelium allows white blood cells to adhere andeventually migrate.

CELLULAR EVENTSIn acute inflammation, the capillary hydrostatic pressureincreases and vascular permeability increases, allowingthe escape of larger molecules such as plasma proteinsinto the extravascular space. Consequently, much morefluid leaves the vessels than is returned to them, resultingin the net escape of protein-rich (<50 g/l) fluid (exudate).The proteins present include immunoglobulins, whichmay be important in the destruction of invading

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microorganisms, and coagulation factors (such asfibrinogen), which result in fibrin deposition on contactwith the extravascular tissues. Hence, acutely inflamedorgan surfaces are commonly covered by fibrinousexudate. There is considerable turnover of theinflammatory exudate.

Circulating neutrophils initially become closelyapposed to the endothelium (pavementing), then adhere tothe swollen endothelial cells (margination), then activelymigrate through the vessel basement membrane(emigration), passing into the area of tissue damage. Theseevents are mediated through expression of ligands on theblood cell surface that interact with adhesion molecules onthe endothelium1, 6. These leukocyte and endothelial celladhesion molecules are called selectins and integrins.Cytokines control the expression of the adhesionmolecules and thus orchestrate these cellular events. Later,small numbers of blood monocytes (macrophages) migratein a similar way, as do lymphocytes.

Theoretically, since the cornea is normally anavascular tissue, it cannot undergo inflammation.However, the nomenclature of ‘keratitis’ is widespread inthe clinical literature, even though many of theconditions included under that name are probably nottruly inflammatory. Neutrophils can gain access to thecornea from any break in the continuity of the surfaceepithelium, or by migrating from the limbal blood vesselsin response to any pathogens in the corneal stroma. Thepresence of inflammatory cells within the stroma canresult in the development of bystander stromal injuryfrom granulocytic enzymes, and the production ofleukocyte-associated growth factors that will stimulatecorneal neovascularization and increased inflammatoryinfiltrate. Deep stromal mycotic keratitis is almostexclusively a disease of horses. The histologic lesion isdistinctive: a deep stromal purulent keratitis in which theneutrophils are always karyorrhectic. They are mostnumerous adjacent to Descemet’s membrane, and thefungi are also found in greatest numbers adjacent to, orwithin, Descemet’s membrane. In many cases this is theonly location in which they can be found. Because the

BASIC OCULAR PATHOLOGY

Congestion and hyperemia are terms that refer toexcessive blood within the vascular system (3.1) due tothe dilation of blood vessels and increased blood flow totissues. Hyperemia of the sclera and conjunctiva are oneof the earliest signs of acute ocular inflammation. Thesechanges may be a sign of either local inflammation or,because of the interdependence of the structures in theeye, inflammation in the cornea or uveal tissues.

Edema is another manifestation of acute inflamm -ation. This is the result of increased vascular permeabilityand movement of low-protein fluid from within thevascular component to the extravascular tissues. Edemaof the cornea results in decreased corneal clarity;therefore, even minor degrees of disruption by edema,that in almost any other tissue would be insignificant andeven imperceptible, are significant in the eye3.

Serous exudate is not uncommon in early inflam -mation. This exudate consists of serum and plasmaproteins that have moved from within the blood vascularsystem to the extravascular space. This fluid tends to behigher in protein than the transudate seen with edema.(Transudate is fluid low in protein, which is producedprimarily by either an increase in hydrostatic pressure ordecreased blood osmotic pressure without a change inpermeability). Serous effusion from the choroid is anexample of a fluid exudate and it causes retinaldetachment, which can lead to blindness andphotoreceptor degeneration (3.2)1.

Any damage to blood vessels can result in fluideffusion into the globe. Hypertension is an example ofvascular damage that is due to a combination ofincreased blood flow and hypoxia4. This leads to damageto the blood vessel (3.3), itself resulting in fluid effusionand hemorrhage.

Changes in vessel caliberThe microcirculation consists of the network of smallcapillaries which lie between arterioles, which have thickmuscular walls, and venules, which have thin walls.Capillaries have no smooth muscle in their walls tocontrol their caliber, and are so narrow that red blood

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cells must pass through them in single file. The smoothmuscle of arteriolar walls forms precapillary sphinctersthat regulate blood flow through the capillary bed. Flowthrough the capillaries is intermittent; some precapillarysphincters form preferential channels for flow whileothers are usually shut down.

In blood vessels larger than capillaries, blood cellsflow mainly in the center of the lumen (axial flow), whilethe area near the vessel wall carries only plasma. Thisfeature of normal blood flow keeps blood cells awayfrom the vessel wall.

Following injury, the initial phase of the vascularcomponent is vascular constriction, which is transientand probably of little importance in acute inflammation.The subsequent phase of vasodilation resulting inhyperemia may last from 15 minutes to several hours,depending upon the severity of the injury. Experimentalevidence indicates that blood flow to the injured areamay increase up to tenfold.

Increased vascular permeabilityA single layer of endothelial cells line capillaries. In sometissues these form a blood–tissue barrier, composed of acomplete layer of tightly aligned endothelial cells (tightjunctions) around the vessel wall. In other tissues thereare areas of endothelial cell thinning, known asfenestrations. There are no tight junctions along theanterior border layer of the iris. The blood–eye barrier isat the level of the choroidal vascular endothelium3. Thus,any inflammatory cells or fluids that exude from the irisvessels almost immediately enter the aqueous humor.Therefore, any cytokines or growth factors present in theaqueous humor will have free access to the iris stroma.Heavy accumulation of edema or granulocytes is rarelyseen in the iris, even when there is massive accumulationwithin the aqueous humor, due to the absence of tightjunctions in the anterior border layer of the iris3.

The blood vessels within the ciliary processes arefreely permeable, and the blood–eye barrier exists at thelevel of tight junctions between adjacent ciliary epithelialcells. It is thus common to see marked distension of

OPHTHALMIC DISEASE IN VETERINARY MEDICINE

3.2 Histologic section of the subretinal space in the eye of a dog,containing eosinophilic fluid consistent with serous effusion (arrow).

3.2

3.1 Histologic section of cerebral blood vessels from a dog. Bloodvessels are distended with erythrocytes. The interstitial connectivetissue is edematous.

3.1 3.3 Choroidal blood vessel from a dog with hypertension. The vesselwall is thickened (arrow) and the surrounding choroid is hemorrhagic.

3.3

conjunctiva that has goblet (mucus producing) cells. As thedisease progresses, other inflammatory exudates may beseen, such as neutrophils (mucopurulent) or fibrin.

Fibrinous inflammation When the inflammatory exudate contains abundantfibrinogen, fibrin polymerizes into a thick fibrin coating.Exudation of fibrin as well as other proteins frequentlyoccurs in the anterior chamber of the eye.

Suppurative (purulent) inflammationThe terms ‘suppurative’ and ‘purulent’ denote theproduction of pus, which consists of dying and degenerateneutrophils, infecting organisms, and liquefied tissues. Thepus may become walled-off by granulation tissue orfibrous tissue to produce an abscess (a localized collectionof pus in a tissue). This is often seen in cases of caninedistemper in which the conjunctiva is covered with thick

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greenish exudate. Accumulation of pus in the anteriorchamber of the eye is termed hypopyon (3.8).

Necrotizing inflammation The products of inflammation (such as proteolyticenzymes) and vascular occlusion and thrombosis mayresult in widespread necrosis of the affected organ. Theterm necrotizing can be used to describe this kind ofinflammation (3.9). As with other types of inflammation,necrotizing inflammation can occur in conjunction withan influx of neutrophils (necropurulent) or hemorrhage(necrohemorrhagic). In the eye, necrotizing inflammationis seen most often in association with an infectious agent,such as bacteria, fungi, and some viruses8, 9, and withsome poorly defined idiopathic lesions10.

CAUSES OF INFLAMMATIONThe most common cause of inflammation is microbialinfection. These microbes include viruses, bacteria,protozoa, fungi, and parasites. Viruses lead to death ofindividual cells by intracellular multiplication. Bacteriasynthesize and release specific exotoxins, which initiateinflammation, or endotoxins, which are associated withtheir cell walls. Additionally, some organisms such asparasites and Mycobacterium spp. cause immunologically-mediated inflammation through hypersensitivity reactions.

It is important to note here that there is a differencebetween inflammation and infection. Infectious agents cancause inflammation but not all inflammatory reactions arecaused by infectious agents. Examples of noninfectiouscauses of inflammation are described below.

Hypersensitivity reactions A hypersensitivity reaction occurs when an altered stateof immunological responsiveness causes an inappropriateor excessive immune reaction that damages the tissues.

Physical agents Tissue damage leading to inflammation may occurthrough physical (perforating or blunt) trauma,ultraviolet or other ionizing radiation, burns, orexcessive cooling (‘frostbite’). Trauma to the eye canresult in a myriad of inflammatory responses; these mayinclude immune-mediated inflammation, such as in lens-induced uveitis, and inflammation as a result of infection,such as in sepsis due to secondary bacterial infection of aruptured globe.

Irritant and corrosive chemicals Corrosive chemicals (acids, alkalis, oxidizing agents)provoke inflammation through direct tissue damage. Theeye is susceptible and sensitive to damage by a variety ofcorrosive chemicals, damage which often first manifestsas corneal damage.

Tissue necrosisDeath of tissues from lack of oxygen or nutrientsresulting from inadequate blood flow (infarction) is apotent inflammatory stimulus. In the cornea, kerato -malacia is the specific term used to describe liquefactivenecrosis of corneal stroma. This is usually a sequela tobacterial or fungal contamination, and results from abystander effect of neutrophilic inflammation, as well asother causes.

BASIC OCULAR PATHOLOGY

lesion is chronic and deep, there is frequently healing ofthe overlying stroma and epithelium, creating a deep-seated stromal ‘abscess’ (3.4, 3.5).

Eosinophilic keratoconjunctivitis is another inflam -matory disease of horses7. Heavy infiltrations ofeosinophils into the conjunctiva and, sometimes, thecornea characterize this disease. The chemotactic agentfor the eosinophils is not well understood.

As previously noted, it is unusual to find largeamounts of granulocytes outside the blood vessels of theuveal tract in early inflammation, due to the imperviousnature of the vasculature. However, significant accumu -lations of granulocytes are not uncommon in the anteriorchamber (hypopyon) or adhered to the endothelium andthe posterior aspect of the cornea (keratic precipitates).Blood (hemorrhage) in the anterior chamber is calledhyphema (3.6, 3.7).

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APPEARANCE OF ACUTE INFLAMMATIONSpecific descriptive terms are used to describe thepathologic appearance of acute inflammation.

Serous inflammation In serous inflammation there is exudation of abundantprotein-rich fluid exudate with a relatively low cellularcontent, for instance in acute conjunctivitis. Vasculardilatation may be apparent to the naked eye, the seroussurfaces appearing injected, i.e. having dilated, blood-laden vessels on the surface, as in the conjunctiva in‘bloodshot’ eyes.

Catarrhal inflammation When mucus hypersecretion accompanies acute inflamm -ation of a mucous membrane, the appearance is describedas catarrhal. This type of inflammation is usually seen inthe acute stage of inflammation in tissue such as the

OPHTHALMIC DISEASE IN VETERINARY MEDICINE

3.6 Hyphema in the anterior chamber of the eye of a horse.

3.6

3.7 Photomicrograph of a dog with hyphema showing anaccumulation of free erythrocytes (arrow) in the anterior chamber. (D, Descemet’s membrane; C, corneal stroma.) H&E.

3.7

3.4 Histologic section of a cornea from a horse containing a denseaccumulation of neutrophils (arrow) consistent with a cornealstromal abscess. (D, Descemet’s membrane.) H&E.

3.4

3.5 Increased magnification of 3.4 shows the fungal hyphae (arrows)in Descemet’s membrane deep to the corneal stromal abscess.

3.5

3.9 Histologic section of equine choroid showing a large focal areaof necrosis surrounded by inflammatory cells.

3.9

3.8 Photograph illustrating hypopyon in the anterior chamber of anequine eye (arrow). This is an example of purulent exudate.

3.8

D

DC

Neutrophils are the most common cell in purulentexudate. In fact, pus is an accumulation of deadneutrophils (3.12).

Most bacteria have very strong chemotactic factorsthat attract neutrophils. Any accumulation of pusshould trigger the suspicion that bacteria are present.

The myeloperoxidase in neutrophils give pus its greencolor. As neutrophils die in large numbers withininflamed tissues, their contents are released into theextracellular fluids. These contents are also furtherchemotactic to other neutrophils.

EosinophilsEosinophilic granulocytes are so called because of thepresence of red-pink (the same color as erythrocytes)cytoplasmic granules when stained with Wright’s stain or withhematoxylin and eosin (H&E) (3.13). These granules vary insize and shape in the different species, being very large andglobular in the horse and quite small and rod-shaped in thecat. The granules contain major basic protein, which is toxicto parasites and causes lysis of mammalian epithelial cells.

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Eosinophils are similar to neutrophils in theirmaturation and release sequences. Like neutrophils,eosinophils are also end-cells that do not replicate afterrelease. They are more long-lived than neutrophils,persisting up to 8–12 days in tissue.

Eosinophils are most often associated with fungal andparasitic infection, hypersensitivity reactions, which maybe allergic or anaphylactic (3.14)12, and some neo -plasms13, including mast cell tumors14 and some typesof lymphoma15.

Once eosinophils reach the tissue, they can function inseveral ways. They can be bacteriocidal, although not aseffectively as neutrophils; although eosinophils have highlevels of peroxidase, they lack lysozyme. Eosinophils aremost effective at killing metazoan parasites, due to majorbasic protein released from the eosinophil granule, whichappears to be enhanced by mast cell products.

Basophils and mast cellsBasophils are the third type of granulocytic leukocyte(3.15). Produced in the bone marrow, they occur in thecirculation in very low numbers and emigrate intoextravascular tissues at sites of inflammation. They have

BASIC OCULAR PATHOLOGY

Another form of corneal necrosis is corneal sequestrum(3.10). This is devitalization of the corneal stroma,usually secondary to ulceration11. The condition is mostoften seen in cats, although a similar lesion has beendescribed in dogs and horses. In cats, the necrotic stromaacquires a characteristic brown/black discoloration. Thedead stroma becomes acellular and amorphous and isusually surrounded by a thin zone of lytic neutrophils.The lesion is slowly extruded through the corneal surface,with gradual turnover of the corneal stroma.

MANIFESTATIONS OF INFLAMMATIONThe manifestations of inflammation include cellular andbiochemical changes.

Cellular changes An increased leukocyte count due to an increase inneutrophil count in the peripheral blood often occursin acute inflammatory responses. The leukocytes res -pond to chemical attractants (chemotaxins) originatingfrom the site of injury. Leukocytes are released fromthe bone marrow into the blood in larger numbers thanare normally present under the influence of cytokines.

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Therefore, when a blood sample is taken, increased num -bers of neutrophils are counted. Some times, increasednumbers of monocytes can be present in severe or morechronic inflammation.

The major cells in inflammatory responses include:mast cells, neutrophils, eosinophils, macrophages,endothelial cells, and platelets. These cells react to avariety of signals, stimuli, and irritants in order toorchestrate the inflammatory response.

Granulocytes consist of neutrophils, eosinophils, andbasophils.

NeutrophilsNeutrophilic leukocytes are also known as polymorphs,segmented cells or segs, and polymorphonuclear cells(3.11). In some species, notably guinea pigs, birds, rep -tiles, and rabbits, the term heterophil is used to describethe functional counterpart. These cells are key cellsinvolved in the earliest events associated withinflammation. There are a large number of neutrophilswithin the body; for instance, a dog has approximately109/kg body weight. About half of these are movingrapidly along with the circulation. Others are sequesteredin vascular eddies or are temporarily lining the vascularwalls (the marginal pool). There are also vast numbers ofmature and nearly mature neutrophils held in reserve inthe bone marrow (the storage pool).

Neutrophils are formed in the bone marrow fromgranulocytic stem cells, the myeloblasts. The nucleus ofa very immature neutrophil is slightly indented; withmaturity, it assumes a ‘band’ shape. As the neutrophilcontinues to mature, the nucleus becomes hyper -indented to take on a multilobed configuration withmultiple constrictions.

Even with the vast numbers of neutrophils in thebody, there are severe infections in which tissue demandexceeds the vascular supply. The body responds byreleasing neutrophils from the storage pool in the bonemarrow to increase the number in the circulation. Thisincrease is called a neutrophilic leukocytosis. If the tissuedemand for neutrophils persists or even increases, manyof the immature forms or ‘bands’ will be released as well.This is referred to as a ‘left shift’.

There are two main types of cytoplasmic granules inneutrophils: azurophilic and neutrophil-specific. Azuro -philic (or primary) granules contain myelo peroxidase,lysozyme, defensins, and a variety of neutral proteases.These azurophilic granules are generally denser than theneutrophil-specific granules. Neutrophil-specific, orsecondary granules, contain lysozyme, collagenase,plasminogen activator, and histaminase. Both types ofgranules fuse with phagosomes to form phagolysosomes,where digestion of phagocytized material takes place. Ifactivated, the neutrophil-specific granules may also fusewith the plasma membrane, releasing their damagingenzymes out into the extracellular environment.

Neutrophils have a very short half-life; they probablyonly survive about 6 hours at a site of inflammation andlast less than a few days in blood. Therefore, the poolneeds to be continually replenished. Neutrophils leavethe blood in response to tissue damage. They migraterapidly to where they are needed, and emigrate throughthe wall in response to chemotactic signals. Such signalsinclude bacterial components, a factor of complementC5, fibrin, interleukin-8, and leukotriene B4.

OPHTHALMIC DISEASE IN VETERINARY MEDICINE

3.11 Blood smear from a dog showing three mature neutrophils.Note the lack of color in the cytoplasm and the multilobed nucleus.

3.11

3.10 Histologic section of feline cornea. The corneal stroma isamorphous (arrow) from coagulation necrosis and discolored brown,depicting a corneal sequestrum. H&E.

3.10

3.13 Blood smear from a horse showing an eosinophil. Note theeosinophilic granularity of the cytoplasm and the multilobed nucleus.

3.13

3.12 Histologic picture of the hypopyon seen in 3.8, showingaccumulations of neutrophils, cellular debris and necrosis (arrows). H&E.

3.12

3.14 Photomicrograph showing infiltrations of eosinophils in theconjunctiva of a horse with habronemiasis.

3.14

3.15 Blood smear showing a canine basophil. Note the bluegranularity of the cytoplasm that obliterates the nucleus.

3.15

Mononuclear phagocytesMacrophages are professional tissue phagocytes (3.18).The word macrophage is used to describe a monocytethat has emigrated from the blood to the tissue. The termhistiocyte is also used to describe these cells. There are anumber of factors that recruit monocytes to sites ofinflammation. Once there, however, they do not divide atthe site of inflammation. Compared to neutrophils, theyare more long-lived, surviving at an inflammatory site foras long as 1 month. In general, they are also slower toarrive at the site of inflammation, usually taking about48 hours. They appear as large cells with bean-shaped oroval nuclei with fine, diffusely scattered chromatin. Thecytoplasm stains a pale pink and may contain vacuoles orparticulate debris of phagocytozed foreign material.

The function of macrophages is primarily phago -cytosis and destruction of foreign material18. Inaddition to their phagocytic function, activatedmacrophages can become glassy, eosinophilic, ‘epi -thelioid’ macrophages. These cells produce and secretea wide variety of biologically active substances. Theseinclude: toxic oxygen metabolites, proteases, neutrophilchemotactic factors, nitric oxide, arachidonic acidmetabolites, growth factors that promote fibrosis, andangiogenesis factors.

When the inciting cause remains for a long time,macrophages will often fuse to form a multinucleatedgiant cell. These cells are metabolically active but theirphagocytic potential is significantly reduced. Macro -phages have been incriminated in proliferative neoplasm-like diseases such as systemic histiocytosis19.

Chemotaxis of leukocytesDuring the early phases of the inflammatory response,the normally inactive endothelium has to be activated toallow adhesion of neutrophils. Normally inactiveneutrophils have to be activated to enhance their capacityfor phagocytosis, bacterial killing, and generation ofinflammatory mediators. Neutrophils have to developthe ability to move actively, from vessels towards thespecific area of tissue damage. When leukocytes

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accumulate, their main function is phagocytosis andmicrobial killing.

The process whereby cells (such as neutrophils andmacrophages) ingest solid particles is termed phago -cytosis. The first step in phagocytosis is adhesion of theparticle to be phagocytozed to the cell surface. This isfacilitated by opsonization. The phagocyte then ingeststhe attached particle by sending out pseudopodiaaround it. These meet and fuse so that the particle lies ina phagocytic vacuole (also called a phagosome),bounded by cell membrane. Lysosomes, membrane-bound packets containing the toxic compounds des -cribed below, then fuse with phagosomes to formphagolysosomes. It is within these that intracellularkilling of microorganisms occurs.

BIOCHEMICAL CHANGESInflammation is mediated in large part by solublesubstances found in plasma called mediators. Manynoncellular mediators of inflammation can be measuredclinically. An increase in the concentration of acute-phase proteins in the blood is commonly seen. (Theseare normally present in small concentrations butincrease dramatically in response to acute inflamma -tion.) Produced by the liver, they are induced bycirculating cytokines. Specific acute-phase proteins, likefibrinogen, may be measured in blood to monitorinflammatory processes.

The movement of leukocytes from the vessel lumen tothe site of tissue damage is by chemotaxis, and ismediated by substances known as chemotactic factors(chemotaxins), which diffuse from the area of tissuedamage. All granulocytes and monocytes respond tochemotaxins, and respond to a concentration gradient,moving from an area of lesser concentration of the factorto an area of greater concentration of the factor.

Chemotaxins can be exogenous or endogenous. Mostexogenous chemotaxins are bacterial or other microbialproducts, e.g. endotoxin. Chemotaxins bind to receptorson the surface of leukocytes and activate secondarymessenger systems. These messenger systems work bystimulating increased intracytoplasmic calcium. Thecalcium then interacts with the cytoskeleton withresulting assembly of cytoskeletal specializationsinvolved in motility.

In large part the acute inflammatory response isorchestrated by plasma-derived and cell-derived chemi -cal mediators.

Plasma-derived factors The plasma contains four major protease cascadesystems that contribute to acute inflammation:complement, the kinins, the coagulation factors, and thefibrinolytic systems. These are interrelated and producevarious inflammatory mediators.

Complement system: the complement system consistsof approximately 20 known proteins and their cleavageproducts. It can be activated during the acuteinflammatory reaction in several ways. With tissuenecrosis, enzymes capable of activating complement arereleased from dying cells. During infection, the formationof antigen–antibody complexes can activate complementvia the classical pathway, while the endotoxins of Gram-negative bacteria activate complement via the alternative

BASIC OCULAR PATHOLOGY

a multilobed nucleus and large, globular basophilicgranules that can obliterate the nucleus.

Although mast cells are granulated, they are usuallynot considered granulocytes. These cells are related tobasophils but are present in connective and mucosaltissue and only very rarely in the circulation. They areparticularly abundant in skin, gastrointestinal mucosa,and respiratory tract, all host–environment interfaces.The nucleus is round to oval and contains a prominentnucleolus. Mast cells possess distinct spherical basophilicto metachromatic cytoplasmic granules.

Neither mast cells nor basophils are end-cells, andboth are capable of continued division at the site ofinflammation. These cells are not phagocytic and areonly sluggishly motile. Their main function is thedegranulation of their cytoplasmic contents whenstimulated, which releases a number of preformedproinflammatory products contained within the gran -ules. The end result is increased vascular permeability,vasodilation, anticoagulation, tissue destruction, andattraction of eosinophils.

LymphocytesLymphocytes are small round cells with a round,hyperchromatic nucleus and scant, light blue-stainingcytoplasm (3.16). Although lymphocytes all appear similarmorphologically, they come in two functional varieties, B-cells and T-cells. The B-lymphocytes are committed tomaking antibodies. They originate in the bone marrowand come to reside in extramedullary lymphoid issues. Theprecursors of T-lymphocytes migrate from the bonemarrow through the thymic cortex to differentiate intomature T-cells. Approximately 80–90% of the cells in thecirculation are T-cells, while B-cells are much moresedentary by comparison.

Lymphocytes are maintained in populations of clonesthat are each specific for a certain antigen. Eachlymphocyte clone is preprogrammed to recognize only asingle antigen. In an animal there may be lymphocytescapable of responding to 108 different antigens, most ofwhich have never been encountered. When challenged

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with a specific antigen, the population of cells thatrecognizes the antigen will proliferate in response16.

Functionally, lymphocytes can be divided into two broadclasses. The primary function of B-cells, as mentionedearlier, is to produce antibodies. B-cells have specificantibody on their surface that serves as a receptor to thehomologous specific antigen. When specific antigen isbound to the surface of B-cells they are induced to dividerepeatedly, forming a line of memory cells and a line ofantibody-producing cells called plasma cells17. These plasmacells only live for a few days but they work full-timeproducing large amounts of immunoglobulin (3.17). Plasmacells have a unique appearance. They are smoothly sphericalor elliptical with much more cytoplasm than a lymphocyte.The nucleus is usually eccentrically placed and thechromatin often is clumped at the periphery, creating a‘wagon-wheel’ appearance. The cytoplasm containsabundant protein-producing machinery such as roughendoplasmic reticulum, and therefore takes on a slightlybasophilic tone. In many cells an area of pallor just adjacentto the nucleus can be seen histologically. This represents thecell’s packaging machinery, the Golgi apparatus.

T-cells are roughly divided into T-helper cells and T-cytotoxic cells. The helper cells all have a CD4 moleculeon the surface, which allows the helper cell to recognizean antigen presented by an antigen-presenting cell (anycell with MHC II surface marker), usually a macrophage.The combination of T-helper cell and macrophage isessential in complexing with a B-cell to allow theproduction of antibodies. The second type of T-cells is theCD8 group. The CD8 molecule complexes withnonmacrophage-type cells, i.e. cells with MHC Imolecules on their surface. When the CD8 moleculealigns with an MHC I expressing cell that also has specificantigen on its surface, the T-cell destroys that cell.

Lymphocytes are drawn into sites of inflammation bya number of factors. Once at the site, they can eithercluster around blood vessels or form nodular aggregates.The presence of these nodular aggregates is usually anonspecific indication of chronic antigenic stimulation.In these cases, plasma cells are quite often also seen.

OPHTHALMIC DISEASE IN VETERINARY MEDICINE

3.16 Blood smear from a dog containing a lymphocyte. Note theround nucleus and the paucity of cytoplasm.

3.16 3.17 Twoplasma cellsfrom a dogin a bonemarrowaspirate. Thecells haveeccentricallyplacednuclei andabundantbasophiliccytoplasm.

3.17

3.18 Blood smear showing a canine monocyte. The nucleus ishorseshoe shaped and the cytoplasm is vacuolated.

3.18