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Rochester Institute of Technology RIT Scholar Works Theses Thesis/Dissertation Collections 7-23-1992 Rheumatoid arthritis and myasthenia gravis as examples of autoimmune diseases Michael Collins Follow this and additional works at: http://scholarworks.rit.edu/theses Recommended Citation Collins, Michael, "Rheumatoid arthritis and myasthenia gravis as examples of autoimmune diseases" (1992). Thesis. Rochester Institute of Technology. Accessed from This Thesis is brought to you for free and open access by the Thesis/Dissertation Collections at RIT Scholar Works. It has been accepted for inclusion in Theses by an authorized administrator of RIT Scholar Works. For more information, please contact [email protected]. ROCHESTER INSTITUTE OF TECHNOLOGY A Thesis Submitted to the Fine and Applied Arts in Faculty of The College of Candidacy for the Degree of MASTER OF FINE ARTS Rheumatoid Arthritis Examples of and Myasthenia Gravis Autoimmune Diseases By Michael Collins 7/23/92 as Approvals Advisor: G. Hintz Associate Advisor: B. Cole Date: Associate Advisor: Dr. D. Merrill Date: 7- 3/- 92.. Associate Advisor: R. Wabnitz Date: g-)7· <J;Z ~n ~ R. Roger Remington Special Assistant to the Dean for Graduate Affairs: Po BerReRA Date: 1"//' I" "'2.,- Dean, College of Imaging Arts and Sciences: M. Lucas Date: 7-8'--(6 I, Michael Collins , hereby grant permission to the Wallace Memorial Library of RIT, to reproduce my thesis in whole or in part. Any reproduction will not be for commercial use or profit. Date: 7/ z '6/ 'f z. Introduction is Autoimmunity individual's own an inappropriate immune healthy body diseases have been identified, Some ways. are broad ranging in One disease and very specific to they blocked weakening muscle is inhibited. disorder is of and degraded the patient's by limbs, feature of this Accompanying articular cartilage and the bone beneath it. focus examples of autoimmune undergraduate the In order to properly result is a The rheumatoid arthritis. the of synovial joints the inflammation is the destruction diseases. It consists of use would be textbook on immunology. cellular and chemical skeletal of upon rheumatoid arthritis and myasthenia gravis as Their intended illustrations. the as nervous stimulation of the throughout the body. will of The antibodies. is inflammation condition This myasthenia gravis. disease is example of an autoimmune This thesis different tissues in different scope. gradual predominant affect of autoimmune variety the neuromuscular junction. The receptors muscle cells are Another wide particular organs, while others are more example of an autoimmune affects A tissues. response against an interactions understand of twelve full as reproductions I have chosen color in an to concentrate upon these pathologies. the pathophysiology of an autoimmune condition, a full discussion of the normal immune response is necessary to provide background. provokes an immune This discussion begins response. The immune task of monitoring all internal regions of the When a foreign substance is detected, it is 1 with a definition system body is charged with for foreign attacked by of what an the substances. immune response. The normal immune supposed to system be in the from body substance; in other words, it molecule which order for can a molecule a a foreign an Dictionary of healthy and distinguish inducing capable of (The New Penguin antigen In is distinguishes structure that is potentially threatening "self" from immune "non-self." response Any is termed Biology, 1990). to provoke an immune response, a "read" by The either determinant (Barrett 1988, 38; Tizard 1988, interact which will The antigenic directly determinants an such as a is with the immune determinants instructions. The group When of genes which is of self antigens immune response bacterium, it is single called is bacterium, each and pollen grains are insulting substance originate from is the part of in antigen accordance with genetic defines the distinctive the the system. major antigenic histocompatibility invading mounted against an determinants complex. organism, Rather, it the molecules on the immune which response body cells of in an the (Tizard 1988, 30). two other common sources of antigens. foreign antigen it is not necessary for the Cancer cells and, if significantly different from normal cells, as foreign and attacked germinal event body by as a an to originate from outside the body. within be interpreted foreign and or antigenic not mounted against the entire organism. provoking However, to be identified The the epitope the bacterium. There may be a variety of different antigens upon a Viruses will 18) are structured mounted against various antigenic compose code the immune system and interpreted as foreign. This precise the antigenic molecule is called portion of it portion of must consist of a series of chemical elements which act as a code. is an immune (Fig. 1). response is phagocytosis of mononuclear phagocytic system the (MPS). The mononuclear phagocytic system and is composed Macrophages entirely may be known lining of mature macrophages by of spleen sinusoids and another name when example, a macrophage 4). a component part of found throughout the body, but are in the lung, liver, is Macrophages within A they migrate macrophage blood vessel, attracted against the Once antigen to into tissues may and wait an antigen chemicals for keep it in the are antibodies, linkage lymph node. particular prevalent Macrophages For tissues. as macrophages itself to an antigen. a the bone monocytes. , marrow and When they are (Barrett 1988, 86). free surface, such as the lining of a Alternatively, it may be chemically from some distance away, in is detected, the which case macrophage will endeavor it will move to bind the from getting away (Barrett 1988, 100). Opsonins body which coat antigens fibronectin, antigens and then Some examples of opsonins and the complement protein lock into makes attachment of C3b. Opsonins receptors upon macrophages. the macrophage to the are by to make attachment macrophages or other phagocytic cells easier. bind to particularly antigen. an antigen to adhere are promonocytes within then drift through the circulatory system as mature (Roitt 1991, 4). the liver is termed a Kuppfer Cell (Roitt 1991 from originate found in the immune system, This antigen much more efficient. There is a tendency for on a negative charge cell in have negative attachment 1988,45). by particles or cells suspended (Tizard 1988, 43). charges, they neutralizing any If both the in body fluids to take antigen and phagocytic will repel each other slightly. negative charge on the Opsonins antigen (Tizard aid After the is accomplished, the attachment it antigenic substance and seals the macrophage surrounds The within a vacuole. towards the macrophage's center while lysosomes antigen is moved to kill it provide enzymes (Barrett 1988, 101). Another Humoral part of immunity the immune system is involves antibodies what is circulating in Medical Desk Dictionary, 1986). An antibody is molecule, produced in response to an globulin There and five distinct are best studied weight of classes of is the IgG 150,000 daltons, One pair, the antigen antigen or a (Barrett 1988, 25). most well-known a molecular and consists of two pairs of polypeptide chains. one end, the parallel and heavy bound together chains ends of (Keeton 1986, 775). Antibodies play a the by "Y" diverge, forming upper segments of It is the top two side. immunoglobulin, (Barrett 1988, 48). IgG has Adjacent to both divergent chain, one on each an fluids (Webster's body immunoglobulins. The pair, is arranged in heavy disulfide bonds. Towards shape. class humoral immunity. called "Y" the shape a is "Y" shape which central role a light bind in the immune response, so it may not be surprising that antibodies play a central role in many autoimmune Plasma diseases. the cells are from B-lymphocytes, are a type of white producers of antibodies. as part of blood with one specific antigen. cell except antigen that one No other antigen will bringing (Tizard 1988, 202). scattered across response cells are derived (Fig. 2). B-lymphocytes Each B-cell is specifically designed to particular antigen is the first step in plasma cell cell. the immune Plasma for about which the have any it is effect upon a B- specific. maturation of react Contact with an the B-cell into a B-cells have immunoglobulin molecules their surface to act as antigen receptors (Barrett 4 1988, 116). B-cells are to differentiate. A the helper T-cell, is it presented to in order by cell which mediates the sometimes necessary. a they immune response, known Helper T-cells cell, such as a macrophage, with must MHC have class II and lymphokines. These lymphokines include B-cell B-cell differentiation factor promoting the maturation of Helper T-cells also secrete a B-cells to molecules effectiveness of macrophages There lymphokines classified as without the help of which assist factor in which increase the (Tizard 1988, 244). are some antigens which will provoke differentiation growth T- (Tizard 1988, 204). plasma cells of variety (BCDF), both as antigen for it to activate (Sheehan 1990, 31). Once activated, the helper cell produces (BCGF) than just contact with antigen if will sometimes require more activation and helper T-cell. These antigens of a T-cell independent B-cell antigens are (Sheehan 1990, 34). Myasthenia Gravis Myasthenia characterized include gravis by is an autoimmune increased fatigability slurred speech, nasal voice, proximal extremities. The condition (Bullock 1992, 1092). The receptors of the specific neuromuscular Each individual does nerve not physically lies within an contact most focus the comes the is chiefly of skeletal muscle. drooping is which of Typical symptoms eyelids and weakness of the commonly seen in young adults the disease is the acetylcholine junction. muscle cell of innervation. This innervation disease body requires from a branch muscle cell. indentation in the direct nervous of a nerve fiber Rather, the terminal muscle which end of the cell, called the neuromuscular synaptic cleft surrounded (Fig. 3). The terminal by end of the neuron the muscle cell. The terminal end small portion of the muscle cell which encircles plate. gap may The neuron (Ross, Reith stimulate the muscle to contract The across the synapse to bind is subneural clefts. The to regions of this between the The .5 Angstrom units, with These allowing muscle cell. be This ions propagated to open into the along the 1991, 71). When the is broken cell. muscle form high (Ross, acetylcholine receptors are of units of the muscle Their total it appearing on 1987, 296). in the binds to them, electrical charge of of and stimulate it to the the muscle cell If strong enough, a shift in polarity fiber by these junctional folds are the only 4 Angstrom neuron releases more acetylcholine than acetylcholine surface the between the synaptic cleft and the interior causes a change stream which the junctional folds receptors change shape when acetylcholine a channel as sodium neuron across units at their widest points. the exterior of the muscle cell (Salpeter nerve muscle. surface which (Seybold 1991, 77). The 7.8 Angstrom receptors are height is 11 the that are embedded in the bilipid membrane protein molecules a small crevices are termed subneural clefts are called acetylcholine receptors cell. These upon by acetylcholine, Rather, the undulating Reith and Romrell 1989, 210). Located muscle Romrell 1 989, 208). The faces the each other. completely called the motor end with receptors on not a smooth concave surface. creases arranged parallel plateaus and by releasing surface of the muscle cell which synapse it is almost the neuron and the is separated from actually touching called the synaptic cleft diffuses of is contract will (Seybold acetylcholine, it usually releases is necessary to depolarize a muscle. However, is normally broken down very quickly into its two component 6 This breakdown is implemented parts: acetic acid and choline. enzyme cholinesterase, (Seybold 1 991 back to the In the immune a substance 71 ). After this transpires, the , neuron known causes this unfortunate event antigenic is at determinants which are (Vincent 1990, 182). Thus, the for remains undetermined. making for may gamma and a total of located sites not on other is locations binding The 5 subunits the two alpha site. on similar enter to binds what the body possessing acetylcholine receptors in the ensuing immune (Fig. 5). Of positive all for circulating (Seybold 1991, 72). of acetylcholine to the receptors , These have been designated 71). alpha component is repeated twice, (Salpeter 1987, 296). Acetylcholine binds to components. binding to bind. Blockage of this to the identical spot In the majority binding site where of cases antibodies bind to the receptor, but overlap and block the acetylcholine This is called steric acetylcholine. could prevent the It has been hindrance (Drachman et al. Alternatively, the antibody may bind directly to the location which Exactly acetylcholine receptors binding delta. The supposed by receptors are composed of subunits arranged be due to the antibody acetylcholine the barrel (Seybold 1991 staves of a may acetylcholine receptors How the antibody blocks the beta, very unclear. Myasthenia gravis, 90% test patients with generalized alpha, this time antibodies generated response would cross react with like acetic acid and choline move acetylcholine receptors. some unknown antigen antibodies specific synapse as myasthenia gravis, antibodies produced block and degrade hypothesized that the to be reabsorbed and reconstituted (Fig. 4). condition system in the present normally by the opening Or, it may bind of to the receptor 1987, 93). on in a the receptor way the central ionic channel (Seybold which 1991, 72). Acetylcholine 10 to 14 days receptors are they (Tizard 1 988, 523). The formation may disrupt the disease receptors ability of antibody tiny clusters on the cross membrane bind to linked enzymatically degraded (Drachman et al. 1987, 92; Dixon can now comprehend impeded from stimulating the Acetylcholine is released by contract. they the time. drawn together into are endocytosed fibers during of nervous impulses is myasthenia gravis. synapse. However, the total antibodies as well as complement-mediated damage result is receptors. Therefore, not enough ions the muscle to occur, and the muscle abnormal muscle weakness and and fatigability are will not (Bullock 1992, 1092). There is available. no cure for myasthenia This usually begins with gravis, but effective treatments are dosages medications, such as pyridostigmine 8 6) Fisher 1983, 277). receptor of in from lysosomes (Fig. how the transmission muscle the to the number of This is due to for depolarization The with process relies on with enzymes and degrade the also antibodies and normally into the accelerated endocytosis of released interfere more than one antigen at a numbers of receptors available are reduced. blockage from membrane attack process contributes This surface, where groups and One may their endocytosis. molecules to Receptors may become into (Seybold 1991, 72). receptor antibodies by accelerating this which Every cell. complement proteins muscle cell's membrane and remains controversial Anti-acetylcholine blood of complement The degree to receptor replacement. fixing the muscle Antibodies bound to are endocytosed and replaced. acetylcholine receptors are capable of complexes by recycled constantly of anticholinesterase bromide, ambenonium chloride or neostigmine bromide (Seybold 1991, 84). These from enzyme cholinesterase and choline. With extra breaking intact dosage be will of into bind to the may cause acetic acid more increased likely Hence, neurotransmitter. However, sufficient to cause muscle contraction. of anticholinesterase desensitization will acetylcholine in the synapse, it is acetylcholine that the few receptors remaining depolarization down inhibit the medications will fatigability the postsynaptic membrane (Seybold 1991 , over due to Other 96). therapies include corticosteroids, plasmapheresis and azathioprine (Seybold 1991 , 86). In 12% of all cases, hyperplasia of the thymus is evident, sometimes requiring thymectomy. The prognosis for patients myasthenia gravis with utilizing the the caveat that activities current therapies available they may be required with is generally good, to avoid extremely fatiguing (Seybold 1991, 84). Rheumatoid Arthritis The most common clinical manifestations of rheumatoid arthritis are pain and swelling feet are of joints in the the most likely extremities. The of flare-ups common between aging and the Studies of twins and Some of of the hands and the knees, ankles, patients experience and remissions, while others endure a constant attack fluctuating intensity (Samter three times more joints to be affected, but involvement elbows, wrists and hips are not infrequent. occasional small in et al. women frequency familial predisposing individuals to of 1988, 1365). Rheumatoid than men. developing 9 a direct the disease (Samter et al. groups show 1988, 1367). There is arthritis is correlation 1988, 1366). that genetic factors play a role in rheumatoid arthritis (Samter et al. The joints synovial healthy bones a the region of to are covered with matrix hyaline Hyaline cartilage. surrounding small surfaces of cartilage dispersed in body define the anatomy briefly joint (Fig. 7). First, the articulating synovial homogeneous typically involved Therefore, it is necessary rheumatoid arthritis. of a are a is the composed of Within these lacunae live chondrocytes, which are specialized cells responsible for the production of matrix. The matrix 1989, 124). The point of the collagen are formed like composed of and Romrell the highest archways with free articulating two the two surface and the archway down adjacent to the bone (Weiss 1983, 251). fiber arrangement can also dimensional felt-like composed of fibrils adjacent to the archway anchor points of The collagen is (Ross, Reith materials, collagen fibrils and ground substance lacunae. spaces called The pattern. be to a three compared ground substance of hyaline cartilage proteoglycans, glycosaminoglycans and glycoproteins is (Ross, Reith and Romrell 1989 123). Surrounding the joint is a capsule of connective tissue called the joint capsule. The filled fluid. The joint with dense the and area enclosed loose synovial by the capsule is called the joint space and it is capsule is connective tissue. vascularized The interior tissue, lining These phagocytic type B. space the joint capsule is synoviocytes are categorized types. The first type is simply a precursor for the other The cell. of two, and into three is called a second sort of synoviocyte exhibits macrophage-like behavior and is known as the type A cell. The last It is both membrane, composed of a one to three layer thick surface of cells termed synoviocytes. type C composed of responsible (Firestein, Tsai for the and secretion of the fluid Zvaifler 1987, 449). 10 which cell is called fills the joint There into the joint First, the space. fenestrated. Also, the layers between them membrane Zvaifler The antigen which rheumatoid arthritis long chain of events (Utsinger, This body and provokes an damage may be due to alteration of as immune reaction. reaction are somehow an enzyme in the inflammatory the antibody molecule reveals a new antigenic Some genetically response against known been identified. It is believed that this not yet the antibodies produced in the immune determinant. immune highly true basement and the adjacent connective tissue initiates the has Possibly this process. capillaries within the joint capsule are of synoviocytes possess no unidentified antigen enters the altered. substances to pass Ehrich 1985, 153). and However, it easy for are two characteristics which make predisposed individuals will mount an this newly created antigen, generating antibodies against antibodies, or rheumatoid factor (Fig. 8) (Utsinger, Zvaifler and Ehrich 1985, 152). Hence, these antigenic antibodies rheumatoid factor tend to settle Zvaifler and activate the and form immune within soft connective will become chemically bound to complexes. These immune tissues and hyaline cartilage complexes (Utsinger, Ehrich 1985, 151). As immune complexes aggregate, complement cascade in what is called a type III they hypersensitivity (Tizard 1988,490). Current dogma breaks rheumatoid arthritis exudative phase and chronic phase. polymorphonuclear cells The the joint capsule. immune cells within in the joint The down into two exudative phase space and changes chronic phase centers upon the joint capsule (Ziff 11 phases: the is focused on in the cells lining interactions between 1990, 127). Blood proteins and cellular histological vascular a synovial joint is cells around the small before releasing digestive location ideal. The of with into the synovial joints to (Fig. 9). neutrophils first engulf the immune complex (Tizard 1988, 44). Unfortunately, the enzymes immune of aggregated infiltration complement will act as a chemotactic agent for neutrophils, which then move Under ideal conditions, observable the capsule, along vessels of dilation (Samter 1988, 1369). Blood phagocytose the antigen complexes The first region. perivascular blood serum permeability allowing blood elements into the in change inflammatory vessel increase complement will in complexes rheumatoid arthritis hyaline complexes often settle within cartilage. is far from This is understandable, considering that between 60 to 78 percent of hyaline cartilage's net weight most of this water such as is is bound, (Ross, Reith some immune complexes, to neutrophils are unable but may water still be able to and is bound so Romrell 1989, 123). Though loosely as to allow materials, the cartilage matrix. settle within Therefore, to internalize the sequestered immune complexes, make contact and bind with them. Under these circumstances, neutrophils release the contents of their lysosomes onto the cartilage. These contents include collagenase which may damage the and proteoglycans (Fig. Another complication involving contents which occurs upon cell neutral proteinases and cartilage 10) (Roitt 1991, by degrading causing more edema collagen fibrils 333). neutrophils is the release of cellular death. These contents include kininogens and vasoactive amines which promote vascular enzymes promote mast cell directly degranulation (Utsinger, Zvaifler 12 of and dilation histamine and edema. when Other released, thus Ehrich 1985, 154). Also, type A cells of the synovial inflammatory lining phagocytose in the process. mediators immune complexes, releasing They release enzymes such as acidic and neutral proteinase which attack proteoglycan and (Utsinger, Zvaifler Ehrich 1985, 100). Another observed the cartilage. is the It has been theorized that enzymes which degrade the during proliferate phenomenon chondrocytes cartilage matrix. rheumatoid arthritis lacunae enlargement of the may produce Chondrocytes (Utsinger, Zvaifler within and to also tend Ehrich 1985, 155). One hallmark Pannus is the ingrowth is the stimulus most likely candidate. cartilage There immature from the are three synovial cells recesses of the insert themselves between the cartilage these is attacked from both characteristics cellular form is occur It is unclear multiplying and marginal edge of fibers outside and cartilage. and proliferate. from within. classified as active pannus. nutrition. sequentially or cells and blood It is unclear whether or not the They also Thus, the Pannus showing There is vessels. acellular, and it is capable of seem across advancing the precisely The first type of pannus. of pannus which appears as mature granulation avascular and blocking its known types collagen including fibroblasts, inflammatory dense, tissue into the joint. of synovial formation. pannus for this, but lymphokines from helper T-cells what appears as is of chronic rheumatoid arthritis killing highly also a tissue, A third type is cartilage by these three types of pannus independently (Fig. 11) (Utsinger, Zvaifler and Ehrich 1985, 155). During the chronic phase, blood factor for macrophages, which complement may act as a chemotactic then move into the synovial joints to 13 Macrophages then phagocytose antigen complexes. pathogenic material to lymphocytes, which will in turn interact to more antibodies which add to the aggregation of (Utsinger, Zvaifler Besides lnterleukin-1 . interleukin-2 and lnterleukin-1 also promotes the release of B-cell growth the synovium (Fig. Not only do factor, in an lymphokines, such as macrophage aggregation patients immune response mounted against response is believed the primary factor in macrophages stimulate the chronic feedback It is of possible connective that the tissue by dendritic Ehrich 1985, 156). on factor helper T-cells, but release of and macrophage have been found to have damaged (Samter lymphocytes cellular which and during differentiation, perpetuation of for this the cartilage et al. may play a role in is that then stimulate macrophages and an endless positive mutual Ehrich 1985, 157). during with the perpetuation the routine turnover growth and repair. natural process pathology. 14 an 1988, 1389). However, it interactions involved may be involved some vital control mechanism causing the and enzymes perpetuation of rheumatoid arthritis (Utsinger, Zvaifler rheumatoid arthritis B-cells. Ehrich 1985, 156). and inflammation continues in system growth of circulating in their blood. This may indicate that perpetuating the immune so the activity through the with rheumatoid arthritis antibodies to collagen release excitatory way promote macrophage stimulating factor (Utsinger, Zvaifler T-cells to destructive 12) (Utsinger, Zvaifler macrophages act causes which stimulate helper T-cells Some complexes presentation, macrophages influence lymphocytes through the release of interleukin-1 cells of immune produce Ehrich 1985, 153). and antigen present the of But possibly may be defective, (Utsinger, Zvaifler and Ehrich 1985, 157) Rheumatoid arthritis can not implemented to be cured, but treatment reduce pain and swelling recommended to reduce stress on afflicted maintaining joint mobility may be reduced by inflammatory drugs modifiable with azathioprine and muscle while maintaining tone (Porth 1990, 1107). the administration of useful Rest is for Inflammation aspirin and other nonsteroidal anti (Porth 1990, 1108). Rheumatoid approved. may be mobility. joints. Exercise is immunosuppressant drugs, though is FDA plans If inflamed arthritis seems as of yet synovial tissue is to be only unresponsive to drug therapies, then surgical removal of the synovium, or synovectomy, may be Other performed. In extreme, mobility surgical cases total joint and reduce pain treatments include repair of damaged tendons. replacements with prosthetics will increase (Porth 1990, 1109). Conclusion Myasthenia autoimmune healthy gravis and rheumatoid arthritis are diseases, tissues by a category the immune of ailments system. both involving Myasthenia examples of a mistaken attack on gravis causes harm through cross reactivity between an antigen and acetylcholine receptors. Rheumatoid immune complex leukocytes these arthritis and is in diseases, blood conditions a category of autoimmune which cause complement. has been identified 15 diseases known lesions through the activity Neither of the and no cures antigens which as of trigger have been found. Technique At all times I tried to illustrate the various cells as alive and inside the body, Scanning electron micrographs proved a valuable cells appear may My rather than as distorted due to left artifacts based choices of color were they his textbooks. For example, I because that is cartilage illustrations. I stained with My would few sit down application the be judgment, as while slide preparations. source, though the some specimens. tempered by to seeing the tissue in used the color for hyaline in Frank Netter"s appears to represent the loose and because that is how it medical dense appears when eosin. consistent with a pad of throughout the 12 illustrations. drawing lab computer in Adobe Illustrator begin and chose not I paper and a pencil and make a Once I had something that I to trace my sketches because to was drawing utilize they happy the outlines of the the Adobe Streamline drawn were allowed me reasonably roughly. Drawing to further refine my and experiment with composition. Once the outline was completed alias. The easier to select reason delineated it by for this with adjacent pixels of changed it capsule Adobe Illustrator. I pen tool drawings fairly into the would go objects with with was rough sketches. with, I joint hematoxylin and technique first what color in look might by processing light blue chose chose shades of pink connective tissue of the appear on aesthetic consideration of what color a student might they the was that the outlines color. with was much easier to tool since The blends select 16 Photoshop without anti- outlines without anti-alias where much magic wand identical I brought it into next or step fills. if the they were composed of was filling If a blend in the and a outlines were areas fill had to be left black until all were complete. In the illustration entitled What is outlining in Adobe Illustrator seemed an antigen?, the forms unnecessary (Fig. 1). For the created a tan circle, and then added the shadows and airbrush tool. crevices in the drawn added with The drawn frame with a the finger tool. The with lines, work of straight with I the viruses then the highlights were the airbrush. B-lymphocytes cancer cells were of highlights pollen pollen granules were added with the tool then smoothed and blended pencil were The were simple so the immune response. I copied out of changed the color of the illustration I had the cell from magenta to green using the color control menu, then added more texture. The bacteria were also extracted The background surface of response was created texture clone initially from the immune the illustration in two steps (Fig. 2). as a separate document. the texture into the background. appear as a wall of cloning process, cloning identically reselect a depicting I first drew I then I did utilized not want portion of the immune a small portion of the the rubber stamp to the background to textured tiles, so I would different illustration. frequently stop the the original texture and start again. A large portion of drawing tools, the yellow macrophage's texture was drawn with the then cloned using the same start and stop method used for the background. I added The lymphocytes circular response the core shadow with were constructed by area, then adding reflected light white with the highlight. The texture paintbrush tool was adjusted drawn with 17 the making with the airbrush to 50% opacity to the pencil blur in a selected a radial airbrush tool. tool. tool and a dab of intensify The the plasma cell had to be drawn with the paint brush and airbrush tool since the radial blend only works in a perfect circle. document separate The nucleus and pasted endoplasmic reticulum was The bacteria and rotated. highlights drawn and details were forward (Fig. 7). fill the of of Everything the bone by filled 50% with are the same rough All antibody duplicated, drawing resized color, then shadows, tools. drawn drawn as a flat as a small color or blend, except for the portion, then duplicated to space. The neutrophils appearing in the illustrations were not imported outlines (Figs. 9 form the tool and converted it to a selection. with pen tool, I selectively portion of and the background behind the the In the illustration representing with lines (Fig. 10). Some fibers were were The drawn panoramic flat bed by aesthetic reasons. a neutrophil view of refined pencil moving and drawing with and the while airbrush leaving nuclei and a the painting tools. eating through collagen, the blue, each one pixel wide the cartilage undergoing destruction drawing, which was distorting right. then scanned on a in photoshop (Fig. 11). First the image various areas. Then a blend from blue to red background from left to The or then rotated to appear broken. scanner and opened recomposed various Then fills with edges of the highlights cell still visible. of various shades of landscape began as a relatively drawn Instead, I delineated the 10). added purple shadows and white arterioles were rendered with fibers on a The opacity. the pencil tool. with solid red the blend drawn the synovial joint was relatively straight was which was cell at hand were added with The anatomy illustration texture into the throughout the thesis antibodies was a radial Then the 18 This was was added surface plane was was purely for to the filled with a blend, allowing it to lighten pencil texture for the in the paintbrush "colorize" The utilized in the Out from the bursting drawing. To of all junction was too make the material appear transparent the muscle and the Color-Aid shapes of the receptors pen tool and I the pannus of rendered. the same The paper and receptor which was The ions streaming and 6). yellow portraying the The majority neuron, then scanned into in the foreground receptors pair of were painted Photoshop 2.0. were then masked off with in the middle background ground and repeatedly duplicated, the resized and out of the receptors were stippled in with the tool. The acetylcholine molecules started out as green and yellow spheres a separate document. lightly altering the in the foreground my favorites (Figs. 4 are The of neutrophil the illustrations of my thesis work, the illustrations, including were all largest diameter explosion area. with airbrush onto pencil selected the maintain the tool but set it to color only, and then proceeded to pencil neuromuscular rotated. So, I the rubber stamp set to 30% opacity to clone areas into the these canyon and pannus. I wanted to those areas. explosion opaque it neared the horizon line. as The component parts were their juxtaposition. then pasted in, each Straight lines connecting the two in time portions molecules completed them. The orientation cylindrical drawing forms for the to show the basic form. You must for these two illustrations began muscle cells The make a straight (Fig. 3). I first difficulty lay line attempted When the cylinder is at an oblique angle the to the length of the perpendicular the basic making in how the linear blend perpendicular 19 with a blend worked. cylinder. is difficult to discern. It had drawn the But this did The have been would cylinder as a easier to discern the perpendicular horizontal, then rotated the whole image later. fiber was outlined with the pen shadow was added with the airbrush tool. of neuromuscular the muscle portion of it if I not occur to me at the time. nerve in from the angle cell was began tool, then filled The inset with yellow. was a selection pasted junction illustrations. The dark rings, as one circle A A bands, or drawn in brown. Then, the upper right selected, duplicated and placed in a pattern, working from front to back, gradually adjusting the opacity setting to reduce contrast as distance increased. The illustration blends in the all of demonstrating the objects, then airbrush tool adjacent using to the image tend to selected reactivity shadow and (Fig. 5). Since the antibody opted not to utilize the a new one cross Straight stand out as gray line neutral gray initiated highlights were with earlier. in with large, I Instead, I drew one pixel wide, each objects linear intensified molecules were so antibody file I had been using various shades of next. was an otherwise drawn full color artificial, so I set the airbrush tool to color only, the pink hue of the muscle, and added it to the antibody as reflected light. 20 Figure 1 An antigen immune is any substance which response. is capable of evoking an Figure 2 Depicted above are macrophage the (yellow) cellular interactions engulfs some of an bacteria, immune response. A then activates a B-cell (pur T-cell releases chemical mediators ple) and a T-cell (red). The helper larger plasma cell, which cause the B-cell to differentiate into the much which produces antibodies specific for that bacteria. Figure 3 This is an orientation neuromuscular of muscle cells. junction. illustration designed to show the location of junction. A nerve fiber branches out to innervate The inset is the a number a magnified view of a single neuromuscular Figure 4 The terminal called the muscle end of the nerve lies within an neuromuscular synaptic cleft. to contract by indentation in the The releasing acetylcholine, nerve may muscle stimulate which moves across the muscle's the surface. synapse to bind receptor then changes shape, allowing ions to stream in and out. with specialized receptors on cell, the The Figure 5 Myasthenia reactivity. gravis is believed to be Antibodies incidence, is very similar ceptors of muscle cells. incapacitating them. caused by a process called cross are produced against an antigen in chemical structure These antibodies that, by co to the acetylcholine re bind to the receptors, thereby Figure 6 Antibodies bind to during myasthenia gravis. Not binding to acetylcholine, but also it acetylcholine receptors only does this block the receptors promotes their endocytosis by the from muscle cell. Figure 7 The synovial joints are rheumatoid arthritis. synovial joint. figures 9 and The 12. the most This cut typically involved away region within view shows the small region of the the body in major structures of black rectangle is the magnified in Figure 8 Antibodies are protein molecules which bind with an antigen as part of the the antibody attach to immune response. Normally, the binding antigen as a step towards the antigen's destruction. In rheumatoid ar sites of thritis, an forming which antibody binds to the structure of the immune system then bind to the the system an unknown antigen antibody. interprets synthesizes rheumatoid altered antibodies. together, they are called When immune A that is capable of trans region of as a foreign factors, the antibody is revealed antigen. The immune which are antibodies antibodies and antigens are complexes. an that bound Figure 9 The immune ticular complexes of rheumatoid arthritis cartilage. towards the complexes. Phagocytic cells from the articular cartilage after tend to settle blood, called within ar neutrophils, move chemically sensing these aggregated Figure 10 Neutrophils normally attempt to engulf immune complexes before they release their digestive enzymes. However, if the immune complexes are the cartilage matrix, neutrophils release enzymes di rectly onto the cartilage. These enzymes damage the collagen fibrils com sequestered within posing the cartilage. Figure 11 This is a microscopic panoramic view of the articular cartilage undergoing destruction from rheumatoid arthritis. Neutrophils move across the cor roded surface in search of sequestered immune complexes. The neu trophils continue to ingest material at left shows a formation which can damage of until pannus, cartilage and an they burst ingrowth fuse joints. open. of The background the synovial membrane Figure 12 This illustration shows some of the chemical interactions between cells within the joint capsule. Macrophages activate helper T-cells through anti gen presentation. The helper T-cells attract more macrophages by re lymphokines. Lymphokines induce macrophages to release IL-1 leasing which , in turn causes the dendritic cells to release enzymes that are de The T-cells and macrophages work in concert to pro cells. The plasma cells pro mote the B-cells to differentiate into plasma duce antibodies which add to the formation of new immune complexes, structive to cartilage. perpetuating the inflammatory response. Selected Bibliography Barrett, James T. Textbook of Immunology an introduction in immunochemistry anH Immunofrioloqy- St. Louis: C. V. Mosby Company, 1988. 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The Body Victorious: The Illustrated Immune System and Other Defences of Story the Human Body. New York: of 0\ir Delacorte Press, 1987. Porth, Carol Mattson. Pathophysiology: Concepts Philadelphia: J. B. Lippincott Roitt, Ivan of Altered Health States 4 eri Company, 1990 Fssential Immunology 7 ed. Cambridge: Blackwell Scientific Publications, 1991 Ross, Michael H., Edward J. Reith and Lynn J. Romrell. Histology: A Tevt Baltimore: Williams and Wilkins, 1989. AtJas. 2 qh Salpeter, Miriam M., ed. The Vertebrate Neuromuscular Junction New York: Alan R. Liss Inc., 1987. Samter, Max, David W. Talmage, Michael M. Claman, eds. Frank, K. Frank Austen, Immunological Diseases 4 eH and Boston: Little Brown Henry N. and Company, 1988. Seybold, Marjorie E. "Update on Myasthenia Gravis." Hospital Medicine. 27:4 (April 1991): 71-88. Tizard, Ian R.. Immunology: an Introduction 2 ed. Philadelphia: Saunders College Publishing, 1988. Utsinger, Peter D., Nathan J. Zvaifler, George E. Ehrlich, eds. Rheumatoid Arthritis. Philidelphia: J. B. Lippincott, 1985. Vincent, Angela. "Autoimmunity Biochemical Society to Acetylcholine Receptors in Myasthenia Transactions 19 (September 1990): 180-183. Webster's Medical Desk Dictionary. 1986 ed. Weiss, Leon, ed. Histology: Cell and "Humoral" Tissue Biology 5 ed. New York: Elsevier Biomedical, 1974. Ziff, Morris. "Rheumatoid Arthritis Rheumatology. 17:2 Gravis." - (1990) Its Present 127-133. Future." and The Journal of