Editor-in-Chief Peter J. Delves, Department of Immunology, University College London Medical School, Windeyer Building,...
913 downloads
1600 Views
214MB Size
Report
This content was uploaded by our users and we assume good faith they have the permission to share this book. If you own the copyright to this book and it is wrongfully on our website, we offer a simple DMCA procedure to remove your content from our site. Start by pressing the button below!
Report copyright / DMCA form
Editor-in-Chief Peter J. Delves, Department of Immunology, University College London Medical School, Windeyer Building, 46 Cleveland Street, London W1P 6DB, UK
Consultant Editor Ivan M. Roitt, Department of Immunology, University College London Medical School, Windeyer Building, 46 Cleveland Street, London W1P 6DB, UK
Editorial Advisory Board A. Basten, Centenary Institute of Cancer Medicine and Cell Biology, Locked Bag No. 6, Newtown NSW 2042, Australia C. A. Bona, Department of Microbiology, Mount Sinai Medical School, 1 Gustave Levy Place, New York, NY 10029-6574, USA J. Brostoff, Centre for Allergy Research, Department of Immunology, University College London Medical School, Windeyer Building, 46 Cleveland Street, London W1P 6DB, UK B. Cinader, Department of Immunology, Medical Sciences Building, University of Toronto, 1 King’s College Circle, Toronto, Ontario M5S 1A8, Canada F. E. G. Cox, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Steet, London WC1E 7AT, UK M. Feldmann, Kennedy Institute of Rheumatology, 1 Asponlea Road, Hammersmith, London W6 8LH C. E. Grossi, National Institute for Cancer Research, University of Genoa, Via De Toni 14, 16132 Genoa, Italy J. P. Hearn, Reproductive Health Research Programme (HRP), World Health Organisation, 1211 Geneva 27, Switzerland L. E. Hood, Department of Molecular Biotechnology, University of Washington, GJ - N, 4909 25 Ave NE, Seattle, WA 98195, USA T. J. Kindt, Division of Intramural Research, National Institute for Allergy and Infectious Diseases, National Institutes of Health, Building 10, 9000 Rockville Pike, Bethesda, MD 20892, USA G. Klein, Microbiology & Tumor Biology Center (MTC), Karolinska Institutet, PO Box 280, S-171 77 Stockholm, Sweden P. J. Lachmann, Department of Clinical and Veterinary Medicine, University of Cambridge, SmithKline Beecham Microbial Immunology Laboratory, Madingley Road, Cambridge CB3 OES, UK I. McConnell, Department of Clinical and Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 OES, UK F. Melchers, Basel Institute for Immunology, Grenzacherstrasse 487, Basel, CH-4005, Switzerland P. J. Morris, Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DU, UK J. R. Pattison, University College London Medical School, Administration, Gower Street, London WC1E 6BT
G. A. W. Rook, Department of Bacteriology, University College London Medical School, Windeyer Building, 46 Cleveland Street, London, W1P 6DB, UK N. R. Rose, Department of Molecular Microbiology & Immunology & of Pathology, The Johns Hopkins Medical Institutions, 615 North Wolfe Street, Baltimore, MD 21205, USA F. S. Rosen, The Center for Blood Research, Harvard Medical School, 800 Huntington Avenue, Boston, MA 02115-6303, USA M. Steward, Immunology Unit, Department of Clinical Sciences, London School of Hygiene & Tropical Medicine, Keppel Street, London WC1E 7HT T. Tada, JIFF - International Immunology, Takasakiya Building 5F, 1-1-17 Mukogaoka, Bunkyo-ku, Tokyo 1130033, Japan E. R. Unanue, Department of Pathology, Washington University School of Medicine, Box 8188, 660 South Euclid Avenue, St Louis, MO 63110, USA R. Van Furth, Formerly of Leiden University, Medical Centre, Laan van Oud Poelgeest 44, 2341 NL Oegstgeest, The Netherlands H. Von Boehmer, Institut Necker, INSERM 373, Rue de Vaugirard 156, 75730 Paris Cedex 15, France
Plate 1
Plate 1 Lymph node. (A) Section of mouse lymph node showing recirculating IgD+ B cells around their portal of entry. The high endothelial venules (H) located in the T zone (T) are stained blue. IgD+ cells are also seen in the walls of the intranodal lymphatics on the edge of the T zone and in the follicles (F). En route to the follicles recirculating B cells travel along the walls of the intranodal lymphatics (arrows) where encounter with antigen from the lymph may occur. (B) Section of a formalin-fixed rat lymph node demonstrating large numbers of plasma cells in the medullary cords (M). These are stained brown with anti-Ig. Formalin-fixation has destroyed the surface Ig on the B cells. T - T zone; F - follicle; E - efferent lymphatic. (Kindly provided by Ian MacLennan, University of Birmingham Medical School, UK. Reproduced from MacLennan et al., 1997, Immunological Reviews 156, 53-66 with permission.)
Plate 2
Plate 2 Bone marrow. Trephine biopsy from a 45 year old man (Haematoxylin and eosin stain) Trephine biopsy examination of bone marrow is used commonly to diagnose both hematological and nonhematological conditions. (Kindly provided by Michael Watts, University college Hospitals, London, UK with permission.)
Plate 3
Plate 3 Lymphocyte, neutrophil and monocyte. Bottom left is a small lymphocyte, center is a polymorphonuclear neutrophil and top right is a monocyte showing the characteristic ‘horseshoe-shaped’ nucleus and moderately abundant pale cytoplasm. Two additional neutrophils are partly in the field of view at the top right. Romanowsky stain. (Kindly provided by the Michael Watts, University College Hospitals, London, UK with permission.)
Plate 4
Plate 4 Tonsil. Section of a normal human palatine tonsil. At upper right (pink) is the stratified squamous epithelium of the surface of the tonsil. This epithelium is highly folded. Beneath it is a collagen fiber layer (blue). At lower center is the lymphoid tissue (red). Apart from the pair of palatine tonsils, there is a pair of lingual tonsils and a pair of pharyngeal tonsils (adenoids) which contribute to the Waldeyer’s ring of lymphoid tissue. (With permission from Photo Science Library.)
Plate 5
Plate 5 Antibody binding to a hapten. Stereo view of the 40-50 antibody combining site with VL on the left and VH on the right and colored to display concave (dark gray) and convex (green) molecular surfaces. The 40-50 binding site is a groove mostly on the surface of the light chain. The bound hapten, ouabain, is shown in yellow. (Kindly provided by Steven Sheriff, Bristol-Myers Squibb Pharmaceuticals Research Institute, Princeton, USA. Reproduced from Jeffrey et al., 1995, Journal of Molecular Biology 248, 344-360 with permission.)
Plate 6
Plate 6 Antibody paratope. (A) Stereo diagram of a ribbon structure of the VH: VL domain showing the side-chains of the contact residues that comprise the paratope of the N10 anti-Staphylococcal nuclease antibody. The heavy chain is colored green, the light chain yellow, CDR regions silver and contact residues (with side-chains shown) are magenta. Figure produced with RIBBONS (Carson 1991). (B) Contact molecular surface (cyan dots) of the N10 antibody (blue with contact residues in yellow) calculated by the method of Connolly (1983) and displayed using GRASP (Nicholls et al 1991.) Note the U-shape of the contact surface with the single heavy chain CDR3 contact residue Asn H-96 located just inside the open end of the U. (C) The N10 antibody paratope with the light chain on the left. Surface representation of the calculated DG residue contribution to binding by the N10 antibody and ihe Staphylococcal nuclease antigen residues. A color scale was constructed of the DG residue values, from blue ( 2.0 kcal/mol) to red (+2.0 kcal/mol). Thus, blue colors represent negative (‘‘attractive’’) residue contributions, red colors represent positive (‘‘repulsive’’) contributions. Figure produced with GRASP (Nicholls et al 1991). (Kindly provided by Steven Sheriff, Bristol-Myers Squibb Pharmaceuticals Research institute, Princeton, USA. Reproduced from Bossart-Whitaker et al., 1995, Journal of Molecular Biology 253, 559-575 with permission.)
Plate 7
Plate 7 (A) Addison’s Disease. Adrenal gland from patient with Addisons disease, showing atrophy of the cortex and infiltration with mononuclear cells. (B) Another area from same adrenal gland, photographed at higher magnification. (Kindly provided by P E Bigazzi, University of Conneticut Health Center, USA with permission.)
Plate 8
Plate 8 Allergens. Molecular modeling of the cockroach calycin allergen, Bla g 4. The Ca backbone structures for two models of Bla g 4 (designated bg12A-1 and bg12A-2) were modeled on the X-ray crystal coordinates for butterfly bilin-binding protein (BBP) and are compared with rat urinary protein allergen (RUP), for which the X-ray crystal structure has also been determined. The yellow spheres are conserved amino acid residues that form motifs which define the ligand-binding proteins, or calycins. (Kindly provided by M D Chapman, University of Virginia, USA with permission.)
Plate 9
Plate 9 Antibody-antigen interaction. (A) Conformational differences in antibody D1.3 VL CDR3 induced by differing antigen side-chains. Hen egg lysozyme (HEL) residue Gln121 makes two main-chain hydrogen bonds; to the carbonyl oxygen of D1.3 VL Phe91 and the amide nitrogen of D1.3 VL Ser93. Replacement of the glutamine by histidine in Turkey egg lysozyme (TEL) induces a conformational change in the backbone of VL CDR3 which allows the formation of a hydrogen bond between the histidine and the carbonyl oxygen of VL Trp92. (B) The effect of a Trp-Asp mutation on the interaction surface area of the D1.3-HEL complex (dots) and the mutant D1.3-HEL surface (solid line) demonstrates the loss of interaction surface area in the mutant complex. A 150 ( 2 loss in surface area accounts for the reduction in affinity of the mutant D1.3-HEL reaction. (C) Hydrogen bonding network of the D1.3-HEL interface A mediated by bound solvent molecules; 25 water molecules form hydrogen bonds linking the antibody and antigen, directly or through other water molecules. (D) Water molecules in contact with the D1.3-HEL buried surface. Including the 25 bridging water molecules, nearly 50 solvent sites are in contact with the buried surface defined by the D1.3-HEL interface. Many of these water molecules fill internal cavities, further stabilizing the complex. (Kindly provided by B C Braden and R J Poljak, Center for Advanced Research in Technology, USA with permission.)
Plate 10
Plate 10 HLA-A2. The residues forming the domain interfaces are highlighted in color on the Ca backbone stereogram. Filled and colored Ca atoms make contacts r4 A˚. Red, a1, a2 residues in interface with b2M; green, b2M residues in interface with a1a2; blue a3 residues in interface with b2M; yellow, b2M residues in interface a3; pink, a1a2 residues in interface with a3; orange, a3 residues in interface with a1a2. (A) A view perpendicular to a1a2 pseudodyad with the binding cleft viewed end-on (a1a2-a3 interface not shown). (B) A side view with the molecule rotated 90 about the pseudodyad (a3–b2M interface not shown). (Reprinted with permission from Saper MA, Bjorkman PJ and Wiley DC (1991) Refined structure of the human histocompatibility antigen HLA-A2 at 2.6 A˚ resolution. Journal of Molecular Biology 219: 277-319.)
Plate 11
Plate 11 CD8. Three-dimensional molecular model of the N-terminal region of a CD8 homodimer consisting of two a chains; (A) ribbon presentation, (B) stick presentation. The structural data for the N-terminal 113 amino acids are based on crystallography (protein data base: 1CD8). The three-dimensional model for each monomer was generated with RasMol version 2.5 (Roger Sayle, Greenford, Middlesex, UK), and the two monomers were combined as described (Leahy et al. (1992) Cell 68: 1145). The color coding represents groups; blue corresponds to the CDR1-like loop, light blue to the CDR2-like loop, and lime to the CDR3like loop. The monomers are distinguished in brightness of color. (Kindly provided by GF Weber and H Cantor, Dana-Faber Cancer Institute, USA with permission.)
Plate 12
Plate 12 Dendritic cell. Colored scanning electron micrograph. (With permission from Photo Science Library.)
Plate 13
Plate 13 Monoclonal antibodies to lysozymes. Hen egg white lysozyme in complex with the Fab fragments of monoclonal antibodies raised against it. An exploded-view collage indicating how three different anti-lysozyme Fab’s interact with lysozyme (center) in the x-ray structures of their respective complexes. The proteins are represented by their Ca chains and their interacting surfaces are outlined by juxtaposed dot surfaces. Note that the three crystal structures on which this diagram is based each contain only one Fab species; the Fabs do not crystallize together. (Photograph courtesy of Steven Sheriff and David Davies, NIH, USA.)
Plate 14
Plate 14 High endothelial venules in lymph node. (A) Rat mesenteric lymph node. Composite of about 200 scanning electron micrograph images. The capsule and the marginal sinus (MS) are seen at the top. The high endothelial venules (HEVs) are distributed mainly in the inner cortex and further in the interfollicular areas. The lymphatic labyrinths filled with lymphocytes are demonstrated in the inner cortex. S. medullary sinus. The lymphatic labyrinths and medullary sinuses are tinged in pale and dark blue, respectively. (B) Fractured portion of the inner cortex. An HEV is longitudinally opened at the lower left. The lymphatic labyrinth (L.L.) is shown near the HEV. (Kindly provided by Yechen He, Harbin Medical University, China, with permission.)
Plate 15
Plate 15 Germinal center. (a, b) Follicular T cell numbers rapidly increase during germinal center development. In a non-responding spleen (a) T cells in the white pulp are largely confined to the T zone (T) with only occasional T cells in the follicles (F); red pulp (R). (b) 7 days after primary immunization with antigen large numbers of T cells are found within the developing germinal center and surrounding follicular mantle – up to 10% of these have incorporated the thymidine analogue BrdU during a 2-hour pulse indicating that they are in cell cycle. (c, d) A pulse chase experiment where centrobtasts in the dark zone (D) of a rat splenic germinal center are labeled during a 5-hour pulse with BrdU. In panel c the spleen is taken at the end of the pulse when almost all centroblasts are labeled but the majority of centrocytes in the light zone (L) are not labeled. The spleen in d was taken 7 hours later when centrocytes derived from the proliferating centroblasts are labeled. F - follicular mantle; M - marginal zone; T - T zone. (Kindly provided by Ian MacLennan, University of Birmingham Medical School, UK. Reproduced from MacLennan et al., 1997, Immunological Reviews 156, 53-66 with permission.)
Plate 16
Plate 16 Delayed-type hypersensitivity. Brucellosis. Delayed-type hypersensitivity (DTH) reaction in the finger following needlestick injury. When vaccinating cattle, veterinarians are prone to needle stick injury. In those who have been sensitized by previous infection, albeit subclinical, this can be followed within 2448h by a DTH reaction which ranges from the local reaction shown here, to a severe, generalized response which resembles many aspects of the infection itself. (Photograph courtesy K Hughes and the late J Forbes.)
Plate 17
Plate 17 Lymphotoxin knockout mice. Absence of germinal centers in mice lacking lymphotoxin a (LTa / mice). Wild-type (left panel) and LT / (right panel) mice were immunized intra-peritoneally with 108 sheep red blood cells and 10 days later spleen sections were analyzed by staining with the germinal center marker peanut agglutinin (blue) and with anti-IgD (brown). (Kindly provided by David Chaplin, Washington University School of Medicine, USA. Reproduced from Matsumoto, M et al. 1997, Immunological Reviews 156, 137-144 with permission.)
Plate 18
Plate 18 Cutaneous anaphylaxis. (A) (above left) Acute urticaria with marked erythema and whealing. (B) (above) Urticaria showing central clearing and an annular pattern. (C) (left) Symptomatic dermographism, marked linear whealing has occurred at sites of scratching. (Kindly provided by MHA Rustin and CH Ortey, The Royal Free Hospital, UK.)
Plate 19
Plate 19 H-2K polymorphism. Ribbon diagrams of the H2-Kb molecule with the vesicular stomatitis virus 8mer (RGYVYQGL) bound. Polymorphic residues in the a1 domain (exon 2) are highlighted in blue, a2 (exon 3) in red, and a3 (exon 4) in purple. (A) T cell receptor view of the complex. (B) (right) side view of the molecule. (Kindly provided by JA Frelinger and EJ Collins, University of North Carolina, USA with permission.)
Plate 20
Plate 20 Antibody complementarity determining regions (CDRS). Computer graphic model of the structure of the VH component of NEWM human antibody. The CDRs loop out from the scaffold structure of the framework regions (blue) to provide the antigen binding surface at one end of the molecule. The framework residues marked are those most commonly involved in maintaining the correct conformation of the CDR loops. (Reproduced with permission from Harris WJ and Cunningham CC (1995) Antibody Therapeutics; Austin TX: RG Landes.)
Copyright © 1998 Elsevier Ltd. All Rights Reserved. Encyclopedia of Immunology
ISBN: 0-12-226765-6
Plate 21
Plate 21 T celts in lymph node. (A) T ceils proliferating during the priming process in association with interdigitating dendritic cells (IDC) in the T zone of a lymph node 3 days after immunization with hapten-protein antigen. The proliferating cells are stained red indicating that DNA in their nuclei contain the thymidine analogue BrdU, which was given as a 2 hr pulse before the node was taken. The IDC are identified by their expression of MHC class II molecules stained blue: staining on serial sections for the B-cell associated molecule B220 and CD4 indicates that the proliferating cells are T cells and the class II+ cells in contact with them are IDC. (B, C, D) Antigen-specific T cells are maintained long-term during a chronic follicular response in the popliteal lymph node draining the site of infection with murine mammary tumor virus MMTV (SW). Serial sections from the node taken 4 months after infection show a germinal center G stained in panel (B) with PNA (peanut agglutinin). T cells are shown in panel (C) and Vb6 T cells in panel (D); these are present in the follicular mantle F, germinal center and T zone T. The superantigen-reactive T cells are selectively conserved in the responding node but are depleted from other lymphoid tissues. (Kindly provided by Ian MacLennan, University of Birmingham Medical School, UK. Reproduced from MacLennan I et al., 1997, Immunological Reviews 156, 53-66 with permission.)
Plate 22
Plate 22 Cancer immunotherapy. False-color scanning electron micrograph of two lymphokine-activated killer (LAK) cells. In LAK immunotherapy, a patient’s peripheral blood mononuclear cells are removed and cultured with interleukin-2 (IL-2) to allow LAK cells to develop. (With permission from Photo Science Library.)
Plate 23
Plate 23 Lymphatic vessel. Light micrograph of a vessel in the human lymphatic system, showing a one-way valve. The vessel is red; the W-shaped valve (center) allows fluid to pass from right to left, but prevents bacflow of lymph. (With permission from Photo Science Library.)
Plate 24
Plate 24 Interleukin-1 receptor (IL-1R). Soluble IL-1R (s-IL1R) complexed to IL-1b. Left, Ribbon diagram showing domains 1, 2 and 3 of s-IL1R colored light, medium and dark blue, respectively. IL-1b is yellow, with site A residues in green and site B residues in red. Right, Ribbon diagram with the b-strands shown as arrowed ribbons in green, a-helices in red, and the connecting loops in purple. The structure is oriented so that the carboxy terminus of s-IL1R and the cell membrane, if present, are at the bottom of the picture. (Kindly provided by Guy Vigers, Amgen Inc, Boulder, Colorado, USA. Reproduced from Vigers, G.P.A. et al. Nature 1997, 386, 190-194 with permission.)
Plate 25
Plate 25 Peptide-MHC interaction. Pockets in the HLA-DR1 peptide binding site. Side view of the molecular surface of the HLA-DR1 peptide-binding site with She influenza hemagglutinin peptide 306-318. Peptide side-chains are labeled in one letter code. (Reproduced by copyright permission from Stern, LJ et al Nature 1994; 368; 215-221.)
Plate 26
Plate 26 Immunocytochemistry. (A) DAB peroxidase-labeled anti-B lymphocyte antibody in human tonsil tissue. (B) DAB peroxidase-labeled anti-T lymphocyte antibody in human tonsil tissue. (C) Peroxidase-labeled anti-S100 antigen antibody in a skin sample. (D) AEC peroxidase-labeled anticytomegalovirus antibody in reproductive tract. (E) Antibody against factor VIII-vWB antigen labeled with AEC peroxidase. (F) DAB peroxidase labeled antidesmin in human muscle tissue. (G) Anti-EMA antigen in a case of cervical cancer. (H) Antibodies against vimentin in a human sarcoma tissue. (I) AntiAE1/AE3 (cytokeratin) antibody labeled with AEC peroxidase in human tissue. (Kindly provided by CD MacKenzie, Environmental Pathobiology Laboratory, USA, with permission.)
Plate 27
Plate 27 An ‘antigen’s eye view’ of sequence diversity in human antibodies. Sequence diversity is plotted on a scale of blue (more conserved) to red (more diverse). The VH domain is to the right and the Vk domain is to the left of each representation. (A) Germline diversity is focused at the center of the antigen binding site. (B) Somatic hypermutation spreads diversity to regions at the periphery of the binding site that are highly conserved in the germline V gene repertoire. Somatic hyper-mutation is therefore complementary to germiine diversity. The CDRH3 region was not included in this analysis and is therefore shown in gray. The end of CDRL3 (also excluded) lies at the center of the binding site and is not visible in this representation. (Reproduced with permission from Tomlinson M et al (1996) Journal of Molecular Biology 256: 813-817.)
Plate 28
Plate 28 Stat 1 knockout mice. STAT1-deficient mice are extremely susceptible to viral infections. Transcriptional responses to interferons (IFNs) are mediated by tyrosine phosphorylation and nuclear translocation of transcription factors of the signal transducer and activator of transcription (STAT) family. Disruption of the gene for STAT1 in embryonic stem cells and in mice revealed that the STAT1 protein is required for all transcriptional responses to IFN (both type I and type II). STAT1-deficient mice grow and develop similar to wild-type animals, but show comprised innate immunity to viral disease. These animals fail to survive in the presence of otherwise innocuous pathogens, including mouse hepatitis virus. Histological examination of liver tissue from STAT1-deficient animals dying of disease showed multifocial hepatic necrosis with syncytial cell formation (A) and scant inflammatory response, consistent with viral hepatitis (caused by infection with mouse hepatitis virus). Analysis of hepatic tissue taken from wild-type siblings demonstrated no pathology (B) (Photograph courtesy of JE Durbin and DE Levy.)
Plate 29
Plate 29 Staphylococcus aureus septicemia. The bacteria may spread as emboli to peripheral vessels. (Kindly provided by Asa Ljungh, Lund University, Sweden.)
Plate 30
Plate 30 Human thymus. The thymus is divided into lobules separated by septa of connective tissue (white spaces) which may contain blood vessels (examples at center and far right). The body of the thymus is divided into an outer cortex (ink blue stain) and inner medulla; the medulla is less densely packed with lymphocytes. The pink, circular features within the medulla are called Hassal’s corpuscles, cyst-like structures that may represent degenerated epithelial cells. (With permission from Photo Science Library.)
Plate 31
Plate 31 Heat shock protein. Immunofluorescence with monoclonal antibody W27 against heat shock protein (HSP) 70 (A, C) and the DNA-binding fluorescent moiecuie 40 ,6-diamidino-2-phenylindole (DAPI) (B, D). Staining of control (A, B) and heat shock activated (C, D) HeLa cells showing HSP 70 nuclear translocation in response to heat shock activation. (Kindly provided by Santa Cruz Biotechnology, Inc. USA, with permission.)
Plate 32
Plate 32 Rheumatoid arthritis. Three-dimensional representation of HLA class II molecule containing the antigenic processed peptide in the antigen-binding groove (light blue stretch, top of the figure). The five amino acid sequence QR/RRAA (‘shared epitope’) is common among all HLA alleles correlated to rheumatoid arthritis. (Kindly provided by A La Cava and S Albani, University of Carolina, USA, with permission.)
Plate 33
Plate 33 (A) Secretory component (the polymeric Ig receptor). Paired immunofluorescence staining for IgA and SC in tissue section from human nasal mucosa; the same field is shown after incubation with ‘red’ anti-IgA + ‘green’ anti-SC, (i) (red filtration) and (ii) (double exposure). IgA alone is present in immunocytes and throughout the stroma; SC alone is present in the Golgi zones (arrows) adjacent to nuclei of glandular acinar cells; both IgA and SC (mixed color) are present basolaterally on acinar cells and apically in their cytoplasm.
Plate 34
Plate 34 (B) Paired immunofluorescence staining for IgA and total SC, or for unoccupied and bound SC, in tissue sections of human colonic mucosa. (i) left part (red filtration) and right part (double exposure), comparable fields in adjacent sections of gland incubated with ‘red’ anti-SC and with ‘red’ anti-IgA + ‘green’ anti-SC, respectively. Prominent SC-containing granules are present in the Golgi zones, whereas the rest of the cytoplasm and the basolateral aspects of columnar epithelial cells are positive for both SC and IgA (mixed color). Goblet cells are devoid of both markers. (ii) (red filtration), (iii) (left part, double exposure), and (iv) (green filtration), same field in a section of gland incubated with ‘red’ anti-I determinant (specific for unoccupied SC) + ‘green’ anti-A determinant (accessible on free as well as bound SC). The two antigenic determinants show distinct differential distribution with a relative dominance of I in the Golgi zones, and of A in the remaining cytoplasm and weakly also basolaterally. Right part of (iii) (double exposure) shows a comparable field after prolonged exposure time for red (anti-I) emission. Note that neither of the two anti-SC reagents produced fluorescence of elements in the lamina propria.
Plate 35
Plate 35 (C) (i) Paired immunofluorescence staining to demonstrate in vitro SC affinity to IgA immunocytes in section of human colonic mucosa preincubated with free SC followed by ‘red’ anti-SC + ‘green’ anti-IgA. Note in double exposure (center) that most IgA cells show varying degree of mixed color as evidence for binding of SC to cytoplasmic polymeric IgA (pIgA), whereas a few cells (probably pure monomer producers) lack SC-binding and are therefore only green. The purely red cells in the double exposure are SC-binding IgM immunocytes. The columnar epithelial cells of the glands at top and bottom contain innate SC and transport pIgA; they therefore show mixed cytoplasmic color with the exception of the Golgi zones which contain SC but no IgA. (ii) Similar SC-affinity test on section of human salivary gland. Double exposure (center) shows various tints of yellow in IgA immunocytes located between acini A and duct D on the figure; in several immunocytes the yellow color is restricted to areas close to the nucleus (arrow), suggesting accumulation of pIgA. One immunocyte (at the bottom) is purely green, suggesting production of only monomeric IgA. Acini and duct are faintly double-stained for unoccupied SC and translocated pIgA. (Kindly provided by P Brandtzaeg, F-E Johansen, P Kraj#ci and IB Natvig, University of Oslo, Norway, with permission.)
Plate 36
Plate 36 (A) Anti-lysozyme binding site Surface complementarity between the antigen, hen egg-white lysozyme and the antibody HyHEL-5 binding site. In this ( thick, centers of atoms are connected by sticks and atomic volumes are shown as Conolly dot cross-reaction through the antigen-antibody complex, 5 A surfaces. Atom color-coding; oxygen, red; nitrogen, blue; sulfur, yellow; carbon in lysozyme, white; carbon in VL domain, magenta; carbon in VH domain, brown. The intermolecular interface, approximately traced by a line dividing the antigen atoms (lower part) from those of the antibody (upper part), consists of tightly packed regions, and occasional loosely packed regions, ‘cavities’. The intermolecular cavities, for example the one delimited by lysozyme residue Arg 68 and the antibody residues L 91, H 33 and H 35 (blue arrow, on the top), are not any larger, however, than the occasional intramolecular cavities (white arrow, on the bottom). Crystallographic coordinates by Sheriff S et al. (1987), Proceedings of the National Academy of Science of the USA 84: 8075-8079, with permission.
Plate 37
Plate 37 (B) Electrostatic fields at the surface of the HyHEL-5 antibody binding site. This monoclonal antibody is specific to lysozyme, a protein with an exceptionally high positive charge. Using the crystallographic coordinates of the HyHEL-5 VH and VL domains (Sheriff et al, (1987) Proceedings of the National Academy of Science of the USA 84: 8075-8079, with permission.) molecular surface envelope was generated by the program GRASP (A Nicholls, Columbia University 1991) and was color-coded by the electrostatic field produced by all the formally charged residues in the molecule: red, negative potential; blue, positive potential; color intensity proportional to the strength of the field). At the center of the binding site there is a deep, electronegative cavity ‘below’ which is a protruding side-chain of the Arg residue L93, with a weaker, positive, electrostatic field. In the HyHEL-5-lysozyme complex, the central negatively charged cavity becomes occupied by the two positively charged lysozyme side-chains, Arg 45 and Arg 68. The positive field generated by the antibody residue Arg L93 gives rise to a dipole, close to the antibody surface, perhaps helping to preorient the antigen at its approach to the binding site.
Plate 38
Plate 38 (C) Comparison of anti-digoxin and anti-lysozyme binding sites. In these ‘elevation plots’, points of the molecular surfaces, generated by the program GRASP, have been color-coded according to its distance normal to a three-dimensional envelope of the molecule. The envelope was defined, and constructed, as a smooth, curved plane connecting the ‘highest’ peaks of the molecular surface. The deepest protrusions on the surface of the molecule are shown in blue, the most elevated points of the surface are shown in red. The binding site of the 26-10 antibody directed against the hapten digoxin is a deep, narrow well (high ‘global’ curvature); the binding sites of the anti-lysozyme antibodies D1.3 (crystallographic coordinates by Bhat TN et al, (1990) Nature 347: 483-486, HyHEL-5 and HyHEL-10 (coordinates by Padlan EA et al, (1989) Proceedings of the National Academy of Science of the USA 86: 5938-5942) are all larger and more shallow (low ‘global’ curvature). The D1.3 binding site contains a smaller, deep ‘local’ hole in its surface (complementary to the lysozyme residue Gin 121), the HyHEL-5 binding site contains a similar but shallower hole (complementary to Arg ’68,). The HyHEL-10 elevation plot shows virtually no local depressions. (Kindly provided by J Novotny and M Davis, Bristol-Myers Squibb Research Institute, USA with permission.)
Plate 39
Plate 39 Antibody cross-reaction. DB3 antibody binding site in complex with four different cross-reacting steroid haptens. The elevation plots shown here were prepared as described in the legend to Plate 6 (C). Surface color-coding is from red (most elevated) to blue (the deepest). Crystallographic coordinates by Arevalo JH et al (1994). Journal of Molecular Biology 241: 663-680. Upper left, DB3 with progesterone; upper right DB3 with 3-aetiocholanolone (5-bandrostane-3, 17-dione); lower left, DB3 with 5-a-pregnane-3-b-hemisuccinate; lower right, DB3 with 3-progesterone-11-a-olsucinate. Haptens are shown in stick representations; carbons are color-coded white, oxygens red. It can be seen that the overall shape of the binding site does not change on engaging the crossreacting ligands; rather, the steroids orient themselves differently with respect to the binding site cavity. At the periphery of the binding site, however, changes to the shape of the surface can be seen, due to surface side-chain rearrangements. (Kindly provided by J Novotny and M Davis, Bristol-Myers Squibb Research Institute, USA with permission.)
Plate 40
Plate 40 Epitopes on neuraminidase. The two energetic epitopes (NC41 and NC10) on the surface of the influenza N9 neuraminidase. The calculated ‘energetic’ epitopes (Tulip WR et al, (1994) Biochemistry 343: 7986-7994) were color-coded, antibody-antigen from green (residues with free energy contributions stabilizing the complex), through white (‘neutral’ residues), to red (residues whose contributions to the free energy of binding destabilize the complex). Although the two epitopes overlap by about 80%, their binding free energy attribution is strikingly different. (Kindly provided by J Novotny and M Davis, Bristol-Myers Squibb Research Institute, USA with permission.)
Plate 41
Plate 41 Superantigen. Molscript model of Staphylococcus enterotoxin A (SEA) interacting with two MHC class II molecules. SEA is colored red, MHC class II and bound peptide blue and purple, respectively. On the left-hand side MHC class II b-chain contacts the SEA coordinated zinc ion (yellow) through a histidine residue on the MHC class II b chain (His81, illustrated as ball-and-chain). The right-hand side shows the interaction between MHC class II a chain and SEA. This point of interaction is centered around a phenylalanine residue in SEA (Phe47, illustrated as ball-and-chain) and a lysine residue in MHC class II a chain (Lys39, illustrated as ball-and-chain). (Kindly provided by T Kalland, M Dohlsten, P Antonsson and Morten Sogaard with permission.)
Plate 42
Plate 42 Systematic Lupus erythematosus. The ‘butterfly rash’ seen in up to 40% of SLE patients. (Kindly provided by DA Isenberg, Bloomsbury Rheumatology Unit, UK with permission.)
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved. Published by Elsevier Ltd.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved. Published by Elsevier Ltd.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved. Published by Elsevier Ltd.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved. Published by Elsevier Ltd.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved. Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved. Published by Elsevier Ltd.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved. Published by Elsevier Ltd.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
Copyright © 1998 Elsevier Ltd. All Rights Reserved.
Encyclopedia of Immunology
ISBN: 0-12-226765-6
