roebe 0.5.123
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- data/lib/roebe/yaml/kernel_config/kernel_config.yml +79 -0
- data/lib/roebe/yaml/linux_kernel_settings.yml +11 -0
- data/lib/roebe/yaml/ls_colors.yml +17 -0
- data/lib/roebe/yaml/main_avi.yml +1 -0
- data/lib/roebe/yaml/main_editor.yml +1 -0
- data/lib/roebe/yaml/main_jpg.yml +1 -0
- data/lib/roebe/yaml/main_pdf.yml +1 -0
- data/lib/roebe/yaml/main_png.yml +1 -0
- data/lib/roebe/yaml/mark_this_directory.yml +1 -0
- data/lib/roebe/yaml/mime/mime.yml +615 -0
- data/lib/roebe/yaml/mime_types.yml +37 -0
- data/lib/roebe/yaml/monitors/monitors.yml +127 -0
- data/lib/roebe/yaml/n_people_in_these_countries.yml +31 -0
- data/lib/roebe/yaml/name_for_the_wireless_interface.yml +1 -0
- data/lib/roebe/yaml/pdf/pdf1.yml +1 -0
- data/lib/roebe/yaml/pdf/pdf2.yml +1 -0
- data/lib/roebe/yaml/pdf/pdf3.yml +1 -0
- data/lib/roebe/yaml/pdf/pdf4.yml +1 -0
- data/lib/roebe/yaml/pdf/pdf5.yml +1 -0
- data/lib/roebe/yaml/pdf/pdf6.yml +1 -0
- data/lib/roebe/yaml/pdf/pdf7.yml +1 -0
- data/lib/roebe/yaml/pdf/pdf8.yml +1 -0
- data/lib/roebe/yaml/pdf/pdf9.yml +1 -0
- data/lib/roebe/yaml/peoples_age.yml +6 -0
- data/lib/roebe/yaml/ports/ports.yml +50 -0
- data/lib/roebe/yaml/posix_character_classes.yml +13 -0
- data/lib/roebe/yaml/project_base_directory.yml +0 -0
- data/lib/roebe/yaml/rufnummern_in_/303/266sterreich/rufnummern_in_/303/266sterreich.yml +5 -0
- data/lib/roebe/yaml/size_of_countries.yml +197 -0
- data/lib/roebe/yaml/statistics/statistics.yml +17 -0
- data/lib/roebe/yaml/sternzeichen/sternzeichen.yml +16 -0
- data/lib/roebe/yaml/system/system.yml +80 -0
- data/lib/roebe/yaml/temperature_of_the_planets_in_our_solar_system/temperature_of_the_planets_in_our_solar_system.yml +22 -0
- data/lib/roebe/yaml/test/README.md +4 -0
- data/lib/roebe/yaml/test/umlaute.yml +2 -0
- data/lib/roebe/yaml/the_beginning_of_linux/the_beginning_of_linux.yml +29 -0
- data/lib/roebe/yaml/use_colours.yml +1 -0
- data/lib/roebe/yaml/world_capitals/world_capitals.yml +204 -0
- data/lib/roebe/yaml/world_geography_and_people/world_geography_and_people.yml +13 -0
- data/lib/roebe.rb +7 -0
- data/roebe.gemspec +104 -0
- data/test/hello_world/hello_world.rb +1 -0
- data/test/misc/README.md +2 -0
- data/test/misc/arity_example.rb +44 -0
- data/test/misc/display_the_shell_colours.rb +48 -0
- data/test/misc/fetch_a_specific_key_from_a_hash.rb +26 -0
- data/test/misc/fork_example.rb +15 -0
- data/test/misc/hello_world.rb +1 -0
- data/test/misc/heredoc_example.rb +9 -0
- data/test/misc/minimal_irc_bot/minimal_irc_bot.rb +33 -0
- data/test/misc/name_of_this_script.rb +12 -0
- data/test/misc/read_keypresses.rb +79 -0
- data/test/misc/readline/README.md +1 -0
- data/test/misc/readline/completion_for_a_static_list.rb +33 -0
- data/test/misc/simple_sigint_example.rb +51 -0
- data/test/misc/simple_user_input_via_stdin_or_Readline_example.rb +14 -0
- data/test/misc/tcp_socket_example.rb +28 -0
- data/test/misc/tracer.rb +39 -0
- data/test/misc/with_border.rb +22 -0
- data/test/testing_cat.rb +3 -0
- data/test/testing_class_configuration/testing_class_configuration.rb +81 -0
- data/test/testing_core_functionality_of_ruby/README.md +6 -0
- data/test/testing_core_functionality_of_ruby/file_test.rb +1 -0
- data/test/testing_core_functionality_of_ruby/verbose_file_copy.rb +5 -0
- data/test/testing_google_url_cleaner.rb +25 -0
- data/test/testing_http_status_codes.rb +13 -0
- data/test/testing_identical.rb +17 -0
- data/test/testing_move_file.rb +14 -0
- data/test/testing_permission_ascii_format.rb +23 -0
- data/test/testing_sql_paradise.rb +17 -0
- data/test/testing_the_roebe_shell.rb +31 -0
- data/test/testing_twentyfour_hours_notation.rb +37 -0
- data/test/testing_zenity.rb +26 -0
- metadata +2877 -0
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english('Immunology') {
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}
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'+TEMPLATE1
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body_css_class 's2px padt2px marpad2px BG_IMG_RUBY NO_REPEAT VERDANAs BG_Black White'
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font_size '1.0em'
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doc('mar0px pad0px s0_4em') {
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# ========================================================================= #
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# === History of Immunology
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# ========================================================================= #
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h1 dot108?+
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'History of Immunology',
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'lightblue'
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p_default {
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e 'Nearly 2,500 years ago, in his History of the Peloponnesian War,
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<b class="gold">Thucydides</b> wrote about a plague epidemic:'
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br
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e '<b class="italic">„No one caught the disease twice,“</b> he
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said, <b class="italic">„or if he did, the second attack was
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never fatal.“</b>',
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'marl1em'
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}
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# ========================================================================= #
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# === MACROPHAGES TAG
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# ========================================================================= #
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div(id: 'macrophages'){
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h4 'Macrophages'
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p_default {
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e '- Macrophages can form <b>multinucleate giant cells</b> (MGCs)'
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}
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}
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# ========================================================================= #
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# === CD8 versus CD4
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# ========================================================================= #
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h2 'MHC-I versus MHC-II','gold'
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p_default {
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e '<b>MHC-I</b>: bindet an den <b>CD8 Rezeptor</b>.'
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e '<b>MHC-II</b>: bindet an den <b>CD4 Rezeptor</b>.'
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}
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# ========================================================================= #
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# === Protein A-Chromatographie zur Antikörperreinigung
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# ========================================================================= #
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h2 'Protein A-Chromatographie zur Antikörperreinigung',
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'FI gold'
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p('s1em ind1em marr2em'){
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e 'Die Affinitätschromatographie an Protein A-Sepharose ist
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eine der verbreitetsten Methoden zur Antikörperreinigung.'
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br
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e 'Protein A ist ein bakterielles Zellwandprotein von
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<b class="gold">Staphylococcus aureus</b> mit einer
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spezifischen Affinität zur Fc-Region von Immunglobulinen
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der G-Klasse (IgG).'
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br
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e 'Protein A hat ein Molekulargewicht von 42 kDa und weist
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eine hohe pH-Stabilität von pH 2-10 auf.'
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br
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e 'Die Bindungsaffinität zum Fc-Teil von Antikörpern ist
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pH-abhängig und nach Bindung von Antikörpern in Gegenwart
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neutraler oder leicht alkalischer Puffer lassen sich die
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Immunglobuline mit einem abfallenden pH-Gradienten eluieren.'
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br
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e 'Abhängig von Herkunft (Spezies) und Subklasse des Antikörpers
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kann die Bindungsstärke von Protein A erheblich variieren.'
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br
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e 'Für Antikörper mit geringer Bindungsaffinität zu Protein A,
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wie zB IgG aus der Maus, kann eine weitere Affinitätsmatrix,
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Protein G-Sepharose, verwendet werden.'
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br
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e 'Protein G ist ein Zelloberflächenprotein aus Streptokokken
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der G-Gruppe und unterscheidet sich in seinem Affinitäts-Spektrum
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von Protein A'
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}
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# ========================================================================= #
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# === T-Lymphocyten
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# ========================================================================= #
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h3 'T-Lymphocyten'
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p_default {
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e 'Die T-Lymphocyten haben den CCR 7 Rezeptor. Damit werden sie
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in den Paracortex gelockt (homing)'
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}
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# ========================================================================= #
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# === The lymphoid lineage
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# ========================================================================= #
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h3 'The lymphoid lineage'
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p_default {
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e 'The <b>lymphoid lineage</b> consists of <b>T‐lymphocytes</b>,
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<b>B‐lymphocytes</b>, and <b>natural killer (NK) cells</b>.'
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}
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# ========================================================================= #
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# === CYCLOSPORIN
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# ========================================================================= #
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h4 'Cyclosporin'
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div_default {
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e '<b>Cyclosporin A</b> kommt in Pilzen vor.'
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br
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e 'Wenn der Wirkstoff vom Körper aufgenommen wird, lagert es sich
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in den T-Lymphozyten an Rezeptoren an.'
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br
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e 'Der Wirkstoff führt in mehreren Reaktionsschritten dazu, dass
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Interleukin 2 nicht mehr von den T-Zellen hergestellt wird.'
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br
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e 'Interleukin 2 ist ein Botenstoff und wird benötigt, um das
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Immunsystem zu aktivieren. Er ist an der Entstehung einer
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Entzündungsreaktion beteiligt. Cyclosporin kann somit also
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auch AutoImmunkrankheiten verursachen, da es die Aptoptose
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in den Thymocyten unterbindet.'
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}
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# ========================================================================= #
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# === Natürliche Killerzellen steuern die Wundheilung (08.09.2021)
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#
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# See: https://www.media.uzh.ch/de/medienmitteilungen/2021/Wundheilung.html
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# ========================================================================= #
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h3 'Natürliche Killerzellen steuern die Wundheilung (08.09.2021)'
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p_default {
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e 'Natürliche Killerzellen töten nicht nur Krebszellen oder
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virusinfizierte Zellen ab. Sie steuern bei Hautverletzungen auch
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die Balance zwischen Wundheilung und Bakterienabwehr.'
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br
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e 'Wird der Heilungsprozess beschleunigt, schwächt dies die Immunabwehr,
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wie Forschende der Universität Zürich zeigen. Relevant ist dies sowohl
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für die Behandlung von Hautverletzungen wie auch die Bekämpfung
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antibiotikaresistenter Keime.'
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br
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e 'Natürliche Killerzellen sind ein bestimmter Typ von Immunzellen.
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Sie erkennen abnormale Körperzellen wie Tumor- und virusinfizierte
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Zellen und töten diese ab. Ein internationales Forschungsteam unter
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der Leitung von Christian Stockmann, Professor am Institut für
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Anatomie der Universität Zürich (UZH), hat nun herausgefunden,
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dass Killerzellen eine weitere, überraschende Funktion haben:
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Sie kontrollieren die Wundheilung in der Haut.'
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br
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e '«Wir konnten diese Zellen in Mäusen genetisch so verändern,
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dass das Wachstum von Blutgefässen beschleunigt wird und sich
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Hautwunden schneller schliessen. Allerdings wird dadurch die
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Immunabwehr abgeschwächt, was die Anfälligkeit für bakterielle
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Infektionen erhöht», sagt Stockmann.'
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br
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e 'Beschleunigte Wundheilung birgt höheres Infektionsrisiko'
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br
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e 'In der Biomedizin wird intensiv nach Möglichkeiten gesucht,
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um Wundheilungsprozesse zu beeinflussen. Versucht wird vor
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allem, die Gefässneubildung anzuregen und zu beschleunigen –
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entweder direkt oder indirekt über die Beeinflussung der
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Immunantwort. «Unsere Ergebnisse zeigen, dass man bei
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solchen Ansätzen möglicherweise ein erhöhtes Infektionsrisiko
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in Kauf nimmt. Daher ist hier Vorsicht geboten», so
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Stockmann.'
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br
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e 'Eine weitere offene Frage ist, inwiefern Natürliche Killerzellen
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nicht nur das Tempo, sondern auch die Qualität der Wundheilung –
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etwa die Zusammensetzung des Bindegewebes oder die Regeneration
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von Haarfollikel, Drüsen und anderen Hautkomponenten –
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beeinflussen.'
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br
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e '«Die spannendste Frage ist, wie wir es schaffen können,
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die Wundheilung zu beschleunigen und gleichzeitig die
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Immunabwehr gegen Wundinfektionen zu stärken», sagt
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der Anatom und Immunologe Stockmann.'
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br
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e 'Killerzellen gegen antibiotikaresistente Bakterien einsetzen'
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br
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e 'Der Wissenschaftler sieht aber noch weiteres Potenzial:
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Bei Krebstherapien werden heute auch Therapeutika
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eingesetzt, die Killerzellen aktivieren und stimulieren,
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so dass diese vermehrt die Krebszellen abtöten.'
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br
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e '«Unsere Daten weisen darauf hin, dass diese Medikamente
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auch bei bakteriellen Infektionen nützlich sein könnten –
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was angesichts der zunehmend antibiotikaresistenten
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Keime unbedingt weiter erforscht werden sollte», sagt
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Stockmann.'
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br
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e 'Natürliche Killerzellen kommunizieren laufend mit anderen
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Abwehrzellen und beeinflussen deren Aktivität. Dazu sondern
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sie Botenstoffe ab, sogenannte Zytokine. In ihrer Studie
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stellten die Forschenden fest, dass Killerzellen auch
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Hautverletzungen infiltrieren, in denen sehr niedrige
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Sauerstoffkonzentrationen herrschen. In solchen Geweben
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stellen Killerzellen ihre Genaktivität um und passen
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sich so dem Sauerstoffmangel an. Verantwortlich für
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diese Umstellung sind sogenannte HIF-Signalfaktoren.'
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br
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e 'Fehlt in Mäusen einer dieser Signalfaktoren namens
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HIF-1α, ist die Ausschüttung bestimmter Zytokine beeinträchtigt.
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Als Reaktion darauf wird das Wachstum von Blutgefässen in der
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Haut und damit die Wundheilung beschleunigt, während die
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Bekämpfung bakterieller Infektionen gedrosselt wird.
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Die Balance verschiebt sich so in Richtung Wundheilung.'
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}
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# ========================================================================= #
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# === Famous quotes in Immunology
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# ========================================================================= #
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h2 'Famous quotes in Immunology',
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'gold'
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div_default {
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boldbr pretty_link('Jules Bordet','BOLD steelblue')
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p_default {
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equote 'Life is the maintenance of an equilibrium
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that is perpetually threatened.'
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}
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}
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# ========================================================================= #
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# === Inflammation
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# ========================================================================= #
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h2 'Inflammation',
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'gold'
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div_default {
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e '<b class="lightblue">Inflammation</b> is a series of events that surround
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an immune response and display a number of characteristic features,
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including local swelling (edema), redness (due to capillary dilation),
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pain, and <b>heat</b>.'
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}
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# ========================================================================= #
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# === interferon tag
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# ========================================================================= #
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h2 'Interferon',
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'gold'
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div_default {
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p_default {
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e 'Interferon Alpha hat (mind.) 15 Gene, Beta und Gamma nur je
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1. Die Alpha-Varianten zeigen <b>unterschiedliche Spezifität</b>.'
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}
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}
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# ========================================================================= #
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# === PRR
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# ========================================================================= #
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h2 'PRR: <i>pattern recognition receptors</i>'
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div(id: 'PRR') {
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e 'PRRs sind auf der Oberfläche von Phagocyten zu finden - sie werden
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dort auch exprimiert. Dies hilft den Immunzellen Pathogene zu erkennen
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und die Phagocytose zu ermöglichen.'
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}
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# ========================================================================= #
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# === IKAROS TAG
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# ========================================================================= #
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div(id: 'ikaros'){
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h4 'Ikaros','','ikaros'
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p_default {
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e 'Ikaros ist ein "<i>differentiation factor</i>" der <b>leukocyte lineage</b>.'
|
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br
|
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e 'Ikaros interagiert mit Aiolos (einem <i>lymphoid restricted
|
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transcription factor</i>, der gemeinsam mit Ikaros die
|
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<b>Lymphocyte Differentiation</b> steuert)'
|
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br
|
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e '<b>Ikaros</b> besitzt einen Zinkfinger:'
|
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br
|
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dimg 'science/biology/IKAROS.jpg',
|
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'marl2em bblack1'
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}
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}
|
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# ========================================================================= #
|
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# === Exam questions
|
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# ========================================================================= #
|
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h2 'Exam questions'
|
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div_default {
|
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e 'Describe the receptors, their ligands and soluble molecules that provide
|
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three distinct signals for full T cell activation, including their
|
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functional relevance.'
|
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br
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e 'Polarizing cytokines can be secreted, which in turn causes
|
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T cells to specialize.'
|
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br
|
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e 'IL-1α and IL-1β are pro-inflammatory cytokines, produced following
|
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damage to the host (release of DAMPs) or upon innate recognition of
|
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PAMPs.'
|
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br
|
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e 'The activities of IL-1 form a <b>direct bridge between innate
|
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and adaptive immunity</b>.'
|
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br
|
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e 'Sources used:'
|
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br
|
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abr_self 'https://www.frontiersin.org/articles/10.3389/fimmu.2020.621931/full'
|
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}
|
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# ========================================================================= #
|
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# === Describe the differences between a naïve T cell and an effector T cell.
|
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# ========================================================================= #
|
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div_default {
|
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e 'Describe the differences between a naïve T cell and an effector T
|
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cell.'
|
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br
|
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e 'If a naive T cell encounters an appropriate antigen then said
|
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naïve cell is activated into different types of T cells.'
|
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br
|
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e 'Each naïve T cell has a unique T cell receptor (TCR) that
|
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recognizes a specific antigen.'
|
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+
br
|
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e 'Sources used:'
|
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br
|
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abr_self 'https://www.akadeum.com/blog/what-are-naive-cells/'
|
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}
|
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+
# ========================================================================= #
|
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|
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# === Q3: Name two co-stimulatory molecules expressed on naïve T cells,
|
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# including their ligands and their function
|
316
|
+
# ========================================================================= #
|
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|
+
div_default {
|
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e 'Q3: Name two co-stimulatory molecules expressed on naïve T cells,
|
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|
+
including their ligands and their function'
|
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+
br
|
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|
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e 'The most prominent co-stimulatory molecule is <b>CD28</b>, which
|
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controls the activation of naïve and memory T cells by antigen
|
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presented on professional antigen-presenting cells.'
|
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|
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br
|
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|
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e 'This has a practical implication as well, as blocking of the
|
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CD28-CD80/86 pathway can be used to induce tolerance in autoimmune
|
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+
diseases where the disease-inducing autoantigens are not known.'
|
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|
+
br
|
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|
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e 'APCs need activation signals to provide co-stimulatory ligands,
|
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|
+
for example through the activation of Toll-like receptors.'
|
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|
+
br
|
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|
+
e 'Sources used:'
|
333
|
+
br
|
334
|
+
abr_self 'https://arthritis-research.biomedcentral.com/articles/10.1186/ar2414'
|
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|
+
abr_self 'https://www.youtube.com/watch?v=1FVAFy6qruY'
|
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|
+
}
|
337
|
+
# ========================================================================= #
|
338
|
+
# === Q4: Name cytotoxic effector proteins and their action on target cells?
|
339
|
+
# ========================================================================= #
|
340
|
+
div_default {
|
341
|
+
e 'Q4: Name cytotoxic effector proteins and their action on target cells.'
|
342
|
+
br
|
343
|
+
e 'Sources used:'
|
344
|
+
br
|
345
|
+
abr_self ''
|
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|
+
}
|
347
|
+
# ========================================================================= #
|
348
|
+
# === Q5: Name the major functional CD4+ T-cell subsets in the current
|
349
|
+
# immunological paradigm on CD4+ T-cell differentiation, including
|
350
|
+
# master-regulator transcription factors involved in their development
|
351
|
+
# and cytokines relevant for their polarization.
|
352
|
+
# ========================================================================= #
|
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|
+
div_default {
|
354
|
+
e 'Q5: Name the major functional CD4+ T-cell subsets in the current
|
355
|
+
immunological paradigm on CD4+ T-cell differentiation, including
|
356
|
+
master-regulator transcription factors involved in their development
|
357
|
+
and cytokines relevant for their polarization.'
|
358
|
+
br
|
359
|
+
e 'Sources used:'
|
360
|
+
br
|
361
|
+
abr_self ''
|
362
|
+
}
|
363
|
+
# ========================================================================= #
|
364
|
+
# === Q6: Imagine you are member in a research team that is supposed to
|
365
|
+
# develop vaccines against extracellular bacteria: which functional
|
366
|
+
# subtype of CD4+ T cells should be induced by such vaccines and
|
367
|
+
# what effector functions would this CD4+ T cell subtype perform?
|
368
|
+
# ========================================================================= #
|
369
|
+
div_default {
|
370
|
+
e 'Q6: Imagine you are member in a research team that is supposed to
|
371
|
+
develop vaccines against extracellular bacteria: which functional
|
372
|
+
subtype of CD4+ T cells should be induced by such vaccines and
|
373
|
+
what effector functions would this CD4+ T cell subtype perform?'
|
374
|
+
br
|
375
|
+
e 'Sources used:'
|
376
|
+
br
|
377
|
+
abr_self ''
|
378
|
+
}
|
379
|
+
# ========================================================================= #
|
380
|
+
# === Q7: What are the main functions exerted by Interleukin-2? Which
|
381
|
+
# molecules form the IL-2 receptor?
|
382
|
+
# ========================================================================= #
|
383
|
+
div_default {
|
384
|
+
e 'Q7: What are the main functions exerted by Interleukin-2? Which
|
385
|
+
molecules form the IL-2 receptor?'
|
386
|
+
br
|
387
|
+
e 'Sources used:'
|
388
|
+
br
|
389
|
+
abr_self ''
|
390
|
+
}
|
391
|
+
# ========================================================================= #
|
392
|
+
# === Q8: What are the main functions exerted by Interleukin-4?
|
393
|
+
# ========================================================================= #
|
394
|
+
div_default {
|
395
|
+
e 'Q8: What are the main functions exerted by Interleukin-4?'
|
396
|
+
br
|
397
|
+
e 'Sources used:'
|
398
|
+
br
|
399
|
+
abr_self ''
|
400
|
+
}
|
401
|
+
# ========================================================================= #
|
402
|
+
# === Q9: Describe the major suppressive mechanisms that Tregs can perform.
|
403
|
+
# ========================================================================= #
|
404
|
+
div_default {
|
405
|
+
e 'Q9: Describe the major suppressive mechanisms that Tregs can perform.'
|
406
|
+
br
|
407
|
+
e 'Sources used:'
|
408
|
+
br
|
409
|
+
abr_self ''
|
410
|
+
}
|
411
|
+
# ========================================================================= #
|
412
|
+
# === Q10: Describe briefly the major pathways how cytotoxic T cells kill
|
413
|
+
# their target cells (extrinsic and intrinsic): which molecules
|
414
|
+
# are involved, how do they act?
|
415
|
+
# ========================================================================= #
|
416
|
+
div_default {
|
417
|
+
e 'Q10: Describe briefly the major pathways how cytotoxic T cells kill
|
418
|
+
their target cells (extrinsic and intrinsic): which molecules are
|
419
|
+
involved, how do they act?'
|
420
|
+
br
|
421
|
+
e 'Sources used:'
|
422
|
+
br
|
423
|
+
abr_self ''
|
424
|
+
}
|
425
|
+
# ========================================================================= #
|
426
|
+
# === Q11: How can CD4+ T cells co-stimulate CD8+ T cells (name
|
427
|
+
# involved molecules and required cell-cell interactions)?
|
428
|
+
# ========================================================================= #
|
429
|
+
div_default {
|
430
|
+
e 'Q11: How can CD4+ T cells co-stimulate CD8+ T cells (name involved
|
431
|
+
molecules and required cell-cell interactions)?'
|
432
|
+
br
|
433
|
+
e 'Sources used:'
|
434
|
+
br
|
435
|
+
abr_self ''
|
436
|
+
}
|
437
|
+
e 'Q12: What are TH1 effector functions in infections by intracellular bacteria?
|
438
|
+
|
439
|
+
Q13: Name TH2 cell effector functions in helminth infections?
|
440
|
+
Q14: What is immunological synapse and how it is formed?
|
441
|
+
|
442
|
+
Immunological memory (Clara Pernold)
|
443
|
+
Q1) Explain the benefits of immune memory in comparison to primary response.
|
444
|
+
Contrast the features of an antibody response during a primary infection with
|
445
|
+
that during a memory response.
|
446
|
+
Q1) Describe the roles of B cells in immunological memory: What is the difference
|
447
|
+
between “constitutive” and “reactive” humoral memory and the cell types
|
448
|
+
responsible?
|
449
|
+
Q1) What are the different stages of B cell related memory?
|
450
|
+
Q1) What is the role of CD40/CD40L and BLIMP-1?
|
451
|
+
Q1) What is the role of IL-7 receptor during the memory response?
|
452
|
+
Q1) CD45 is a molecule, which is often used to discern between T cell phenotypic
|
453
|
+
subsets.
|
454
|
+
a) What is the differential expression pattern of this molecule?
|
455
|
+
b) How do such molecular variants arise?
|
456
|
+
c) What are the relevant cellular phenotypes elucidated using CD45 as a
|
457
|
+
marker and how do these phenotypes relate to function?
|
458
|
+
Q1) Outline the major differences between a primary and secondary T cell
|
459
|
+
response.
|
460
|
+
Q1) Memory T cells can be divided into two main subsets, describe their
|
461
|
+
phenotype. How does the expression of molecules relate to cellular function?
|
462
|
+
Describe the biological relevance of Tcm and Tem when controlling
|
463
|
+
previously encountered antigen over the time course of a secondary
|
464
|
+
infection.
|
465
|
+
Describe the phenotypes of Tcm, Tem and Trm
|
466
|
+
What is the function of the following cell surface molecules: CD62L, CCR7,
|
467
|
+
CD103, CD69?
|
468
|
+
What leads to T-cell exhaustion and how do the functional and phenotypic
|
469
|
+
characteristics of exhausted cells change over time?
|
470
|
+
'
|
471
|
+
|
472
|
+
p_default {
|
473
|
+
e 'What is immune senescence? How would the phenotype of an immune
|
474
|
+
cell change?'
|
475
|
+
br
|
476
|
+
e 'Older adults are predisposed to a higher risk of latent virus
|
477
|
+
reactivation.'
|
478
|
+
}
|
479
|
+
# ========================================================================= #
|
480
|
+
# === Q2: What is the meaning of “autofluorescence” in flow cytometry? What is causing
|
481
|
+
# “autofluorescence”? How is autofluorescence determined in a
|
482
|
+
# flow cytometry experiment – e.g. draw an example as histogram?
|
483
|
+
# ========================================================================= #
|
484
|
+
div_default {
|
485
|
+
e 'Immunological Methods (Kerstin Mair)'
|
486
|
+
br
|
487
|
+
e 'Q1: Interpret this pseudocolor plot showing flow cytometry data: what phenotypes
|
488
|
+
of lymphocytes can you identify? What can be concluded about the abundance of
|
489
|
+
individual phenotypes?'
|
490
|
+
br
|
491
|
+
embed_remote_image 'https://i.imgur.com/5xZgcfZ.png'
|
492
|
+
}
|
493
|
+
# ========================================================================= #
|
494
|
+
# === Q2: What is the meaning of “autofluorescence” in flow cytometry? What is causing
|
495
|
+
# “autofluorescence”? How is autofluorescence determined in a
|
496
|
+
# flow cytometry experiment – e.g. draw an example as histogram?
|
497
|
+
# ========================================================================= #
|
498
|
+
div_default {
|
499
|
+
e 'Q2: What is the meaning of '+squote('autofluorescence')+' in flow
|
500
|
+
cytometry? What is causing '+squote('autofluorescence')+'? How is
|
501
|
+
autofluorescence determined in a flow cytometry experiment – e.g.
|
502
|
+
draw an example as histogram?'
|
503
|
+
br
|
504
|
+
}
|
505
|
+
# ========================================================================= #
|
506
|
+
# === Q3: Name a) similarities and b) differences between flow cytometry
|
507
|
+
# and mass cytometry.
|
508
|
+
# ========================================================================= #
|
509
|
+
div_default {
|
510
|
+
e 'Q3: Name a) similarities and b) differences between flow cytometry
|
511
|
+
and mass cytometry.'
|
512
|
+
br
|
513
|
+
e 'Let us first define these two methods.'
|
514
|
+
br
|
515
|
+
e 'Flow Cytometry (FC) is a technique used to examine the
|
516
|
+
chemical and physical properties of a population of cells.
|
517
|
+
This is done with the help of a laser beam. The cells will
|
518
|
+
flow through that laser beam.'
|
519
|
+
br
|
520
|
+
e 'Mass cytometry (MC) is a variation of flow cytometry in which
|
521
|
+
antibodies are labeled with heavy metal ion tags rather
|
522
|
+
than fluorochromes. The advantage here is that we can combine
|
523
|
+
many more antibody specificities in a single sample.
|
524
|
+
The cells used in MC are incubated with a cocktail of antibodies
|
525
|
+
that have been previously conjugated with heavy metal isotopes
|
526
|
+
via a polymer chain of chelating groups.'
|
527
|
+
br
|
528
|
+
abr_self 'https://imperialbiosciencereview.com/2020/09/25/flow-cytometry-vs-mass-cytometry-cytof/'
|
529
|
+
}
|
530
|
+
# ========================================================================= #
|
531
|
+
# === Q4: For what reasons might it be relevant to sort lymphocyte
|
532
|
+
# subsets?
|
533
|
+
# ========================================================================= #
|
534
|
+
div_default {
|
535
|
+
e 'Q4: For what reasons might it be relevant to sort lymphocyte
|
536
|
+
subsets?','lightblue'
|
537
|
+
br
|
538
|
+
e 'This may be useful to determine
|
539
|
+
Which T cell populations mediate highly effective
|
540
|
+
adoptive immunotherapy.'
|
541
|
+
br
|
542
|
+
e 'Adoptive cell transfer (ACT) is an ex-vivo expansion and
|
543
|
+
re-infusion of antigen (Ag)-specific T cells to patients.'
|
544
|
+
br
|
545
|
+
e 'A straightforward and functionally significant means of
|
546
|
+
classifying T cell subsets can be accomplished by assessing
|
547
|
+
for the co-expression of the lymphoid homing molecules
|
548
|
+
L-selectin (CD62L) and CC-chemokine receptor 7 (CCR7).
|
549
|
+
T cells which display these 2 molecules have a
|
550
|
+
propensity to home to secondary lymphoid structures
|
551
|
+
where they can actively survey professional
|
552
|
+
antigen presenting cells for the presence of cognate
|
553
|
+
Antigenes.'
|
554
|
+
br
|
555
|
+
e 'Human lymphocytes can be divided into:'
|
556
|
+
br
|
557
|
+
cmd ' T lymphocytes (CD3+, CD4+, CD8+),'
|
558
|
+
cmd ' B lymphocytes (CD19+), and'
|
559
|
+
cmd ' Natural Killer (NK) lymphocytes (CD16+, CD56+).'
|
560
|
+
br
|
561
|
+
e 'Sources:'
|
562
|
+
br
|
563
|
+
abr_self 'https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3501135/'
|
564
|
+
}
|
565
|
+
# ========================================================================= #
|
566
|
+
# === Q5: Name two methodologies that are used to sort lymphocyte
|
567
|
+
# subsets and explain briefly their functional principle.
|
568
|
+
# ========================================================================= #
|
569
|
+
div_default {
|
570
|
+
e 'Q5: Name two methodologies that are used to sort lymphocyte
|
571
|
+
subsets and explain briefly their functional principle.',
|
572
|
+
'lightblue'
|
573
|
+
br
|
574
|
+
}
|
575
|
+
# ========================================================================= #
|
576
|
+
# === Q6: How does the proliferation dye CFSE (also named CFDA-SE) allow the
|
577
|
+
# differentiation of individual daughter cell generations in
|
578
|
+
# proliferation assays analysed by flow cytometry? Briefly describe
|
579
|
+
# the principle.
|
580
|
+
# ========================================================================= #
|
581
|
+
div_default {
|
582
|
+
e 'Q6: How does the proliferation dye CFSE (also named CFDA-SE) allow the
|
583
|
+
differentiation of individual daughter cell generations in proliferation
|
584
|
+
assays analysed by flow cytometry? Briefly describe the principle.',
|
585
|
+
'lightblue'
|
586
|
+
br
|
587
|
+
e 'This dye allows us to monitor the <b>proliferation of
|
588
|
+
lymphocytes</b>.'
|
589
|
+
br
|
590
|
+
e 'CFSE stands short for carboxyfluorescein diacetate succinimidyl
|
591
|
+
ester.'
|
592
|
+
br
|
593
|
+
e 'The idea is for CFSE to covalently label long-lived intracellular
|
594
|
+
molecules with the highly fluorescent dye, carboxyfluorescein.'
|
595
|
+
br
|
596
|
+
e 'CFSE can go through membranes.'
|
597
|
+
br
|
598
|
+
e 'Its succinimidyl group covalently binds to intracellular
|
599
|
+
lysine residues and other free primary amines, producing
|
600
|
+
green fluorescence.'
|
601
|
+
br
|
602
|
+
e 'This stable linkage ensures retention of the dye within
|
603
|
+
the cell once incorporated, without leaching onto
|
604
|
+
surrounding cells. This feat of CFSE has led to widespread
|
605
|
+
use in fluorescence microscopy or flow cytometry to
|
606
|
+
study cell division, proliferation and migration. The
|
607
|
+
dye has an excitation wavelength around 492 nm and
|
608
|
+
an emission wavelength around 517 nm.'
|
609
|
+
br
|
610
|
+
e 'Note that <b>CFDA-SE</b> is NOT fluorescent.'
|
611
|
+
br
|
612
|
+
e 'Each cell division can be assessed by measuring the
|
613
|
+
corresponding decrease in cell fluorescence via Flow
|
614
|
+
cytometry.'
|
615
|
+
br
|
616
|
+
e 'Sources:'
|
617
|
+
br
|
618
|
+
abr_self 'https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3185625/'
|
619
|
+
}
|
620
|
+
# ========================================================================= #
|
621
|
+
# === Q7: Name two methods to analyze cell lysis and briefly describe one of the
|
622
|
+
# methods.
|
623
|
+
# ========================================================================= #
|
624
|
+
div_default {
|
625
|
+
e 'Q7: Name two methods to analyze cell lysis and briefly describe one of
|
626
|
+
the methods.','lightblue'
|
627
|
+
br
|
628
|
+
}
|
629
|
+
# ========================================================================= #
|
630
|
+
# === Q8: What are the requirements for intracellular cytokine staining
|
631
|
+
# by flow cytometry.
|
632
|
+
# ========================================================================= #
|
633
|
+
div_default {
|
634
|
+
e 'Q8: What are the requirements for intracellular cytokine staining
|
635
|
+
by flow cytometry?','lightblue'
|
636
|
+
br
|
637
|
+
e '<b class="lightgreen">Intracellular cytokine staining</b>
|
638
|
+
(ICS) is a method of cytokine analysis that provides information
|
639
|
+
on the type of cytokines that are produced upon (antigen-specific)
|
640
|
+
stimulation of T cells and B cells. We can detect immunological
|
641
|
+
biomarkers in the form of expressed cytokines.'
|
642
|
+
br
|
643
|
+
e 'ICS can reveal which subtype of CD4+ T helper cell is induced
|
644
|
+
under certain culture conditions, and indicates whether a
|
645
|
+
biological or compound alters T cell polarization in vitro.
|
646
|
+
Rather than looking at the total amount of secreted cytokines
|
647
|
+
produced by all the cells in culture, which is generally
|
648
|
+
analyzed by ELISA or CBA, ICS will provide information on
|
649
|
+
cytokine production by each individual cell. This allows
|
650
|
+
us to analyze the proportion of cells that produce a
|
651
|
+
cytokine of interest, or allows for quantification of
|
652
|
+
the amount of cells producing multiple cytokines (i.e.
|
653
|
+
the rate of polyfunctionality).'
|
654
|
+
br
|
655
|
+
e 'This can help, for example, to unravel the polarization,
|
656
|
+
strength and specificity of immune responses upon
|
657
|
+
immune-modulating therapies.'
|
658
|
+
}
|
659
|
+
# ========================================================================= #
|
660
|
+
# === Q9: Describe the steps that have to be done for an ELISpot assay.
|
661
|
+
# ========================================================================= #
|
662
|
+
div_default {
|
663
|
+
e 'Q9: Describe the steps that have to be done for an ELISpot assay. '+
|
664
|
+
DONE_IMAGE,'lightblue'
|
665
|
+
br
|
666
|
+
e 'The ELISPOT assay can be used to assess cytokine secretion,
|
667
|
+
that is, to enumerate cytokine-secreting cells.'
|
668
|
+
br
|
669
|
+
e 'ELISPOT is an abbreviation towards <b>Enzyme-Linked Immunospot
|
670
|
+
assay</b>.'
|
671
|
+
br
|
672
|
+
e 'The ELISpot assay represents the convergence of
|
673
|
+
plate-based Enzyme Linked Immunosorbent Assays (ELISAs)
|
674
|
+
with membrane-based Western blotting technologies. It is
|
675
|
+
is a common method for the measurement of cellular immunity.
|
676
|
+
ELISPOT was developed for the detection of secreted proteins,
|
677
|
+
such as cytokines and growth factors.'
|
678
|
+
br
|
679
|
+
e 'ELISPOT evaluates the strength of T cell-mediated immune
|
680
|
+
activity. The limit of detection in an ELISPOT assay is
|
681
|
+
typically 1 cell in 100000 cells.'
|
682
|
+
br
|
683
|
+
e 'The ELISPOT method was first reported by Czerkinsky et al.,
|
684
|
+
in 1983. The method was originally developed to quantify
|
685
|
+
immunoglobulin-secreting cells.'
|
686
|
+
br
|
687
|
+
e 'Parameters that can be evaluated include:'
|
688
|
+
br
|
689
|
+
le 'spot number','gold'
|
690
|
+
le 'spot size','gold'
|
691
|
+
le 'spot intensity','gold'
|
692
|
+
br
|
693
|
+
e 'ELISPOT enables the comprehensive screening of patient
|
694
|
+
derived peripheral blood mononuclear cells to reveal
|
695
|
+
the antigenic restriction of T-cell responses.'
|
696
|
+
br
|
697
|
+
e 'The majority of Elispots are performed on polyvinylidene
|
698
|
+
fluoride (PVDF) membrane plates. Alternatively a
|
699
|
+
nitrocellulose membrane can be used.'
|
700
|
+
br
|
701
|
+
e 'The <b class="lightgreen">steps</b> for an
|
702
|
+
ELISPOT (standard assay variant) include:'
|
703
|
+
br
|
704
|
+
le '- Coat the membrane with the capture antibody. These
|
705
|
+
antibodies are often cytokine-specific and they are now
|
706
|
+
immobilized on membrane-bottomed 96-well plates. The
|
707
|
+
antibody thus is the first layer in the individual
|
708
|
+
wells, so they can be found on the bottom of the
|
709
|
+
wells. The capture antibody must be specific to the
|
710
|
+
secreted (target) protein.'
|
711
|
+
le '- Add the cells, usually peripheral blood mononuclear
|
712
|
+
cells, also called PBMCs). These are seeded in the presence
|
713
|
+
or absence of stimulating antigens.'
|
714
|
+
le '- Over time, activated cells (also called "responding
|
715
|
+
cells") begin to secrete cytokines, which bind to the
|
716
|
+
capture Antibody in the immediate vicinity of
|
717
|
+
the expressing cell.'
|
718
|
+
le '- Wash to remove away the cells.'
|
719
|
+
le '- Add a second cytokine-specific biotinylated
|
720
|
+
Ab which binds to the cytokine-Ab complex.
|
721
|
+
This is called the <b>detection antibody</b> and
|
722
|
+
it will bind specifically to the bound protein.'
|
723
|
+
le '- Add streptavidin-enzyme conjugate. Spot detection
|
724
|
+
is accomplished through substrate deposition following
|
725
|
+
either a one-step (enzyme-conjugated, cytokine-specific
|
726
|
+
Ab) or two-step (biotinylated Ab/streptavidin-enzyme)
|
727
|
+
antibody binding process. Once the signals are
|
728
|
+
developed, spot numbers can be tallied manually
|
729
|
+
or through use of image-based spot readers with
|
730
|
+
accompanying analysis software. The frequency
|
731
|
+
and total number of responder cells is determined
|
732
|
+
by comparing the number of spots between
|
733
|
+
stimulated and untreated/control wells.'
|
734
|
+
br
|
735
|
+
e 'Sources used:'
|
736
|
+
br
|
737
|
+
abr_self 'https://www.future-science.com/doi/10.4155/bio-2022-0010'
|
738
|
+
abr_self 'https://www.sciencedirect.com/topics/immunology-and-microbiology/enzyme-linked-immunospot-assay'
|
739
|
+
}
|
740
|
+
# ========================================================================= #
|
741
|
+
# === Peyersche Plaques
|
742
|
+
# ========================================================================= #
|
743
|
+
h2 'Peyersche Plaques',
|
744
|
+
'gold'
|
745
|
+
div_default {
|
746
|
+
e '<b>Plasmazellen</b>, die mit Peyersche Plaques assoziiert vorliegen,
|
747
|
+
sezernieren in der Regel Antikörper der Klasse
|
748
|
+
<b class="lightblue">IgA</b>.'
|
749
|
+
}
|
750
|
+
# ========================================================================= #
|
751
|
+
# === Erkältung
|
752
|
+
# ========================================================================= #
|
753
|
+
h2 'Erkältung',
|
754
|
+
'gold'
|
755
|
+
div_default {
|
756
|
+
e 'Man kann eine Erkältung unter Umständen durch folgende
|
757
|
+
Maßnahmen verkürzen:'
|
758
|
+
br
|
759
|
+
e '- Ausruhen und viel Schlaf'
|
760
|
+
e '- Tee und ausreichend Wasser'
|
761
|
+
br
|
762
|
+
e 'In der Regel dauert es zwischen drei bis zehn Tage, bis
|
763
|
+
eine Erkältung überwunden ist.'
|
764
|
+
}
|
765
|
+
# ========================================================================= #
|
766
|
+
# === Slogans tag. Slogan tag.
|
767
|
+
# ========================================================================= #
|
768
|
+
h2 'Immuno-Slogans',
|
769
|
+
'gold'
|
770
|
+
p_default {
|
771
|
+
e '- Innate and adaptive immune signaling are heavily Ub-mediated.'
|
772
|
+
e '- <b>Cytokines</b> can act in an autocrine manner.'
|
773
|
+
e '- IgM is particular useful because it shows a high potential for
|
774
|
+
cross-linking antigens.'
|
775
|
+
e '- The Microbiome educates the immune system.'
|
776
|
+
e '- The human body, curiously enough, acts as an incubator of
|
777
|
+
a unique microbiome.'
|
778
|
+
e '- Jedes Toxin ist potenziell in der Forschung nützlich, da
|
779
|
+
Toxine an Proteine binden können und man so, im Prinzip, auch
|
780
|
+
das zugehörige Bindungsprotein finden kann. Daduch erhält man
|
781
|
+
eventuell einen Hinweis auf dessen Rolle im Kommunikationssystem
|
782
|
+
des Körpers.'
|
783
|
+
e '- Antikörper in der späten Immunantwort haben eine höhere Affinität
|
784
|
+
zum Antigen.'
|
785
|
+
e '- Inflammataion is a general, nospecific reaction to noxious
|
786
|
+
stimuli such as toxins and pathogens.'
|
787
|
+
e '- <b>Bacterial pathogens</b> sense their environment, and in
|
788
|
+
response, virulence genes are induced or repressed through
|
789
|
+
spatial and temporal regulation.'
|
790
|
+
e '- Chemokine and cytokine mediators are released by
|
791
|
+
injured cells.'
|
792
|
+
e '- A basic tenet of multicellularity is that one does not go
|
793
|
+
around randomly killing good cellular citizen.'
|
794
|
+
e '- Converting Actin Nucleation to a motile force is
|
795
|
+
done by <i class="lightgreen">Listeria monocytogenes</i>.'
|
796
|
+
e '- The miasma theory was the leading theory of disease
|
797
|
+
origin, until it was eventually displaced in the 19th
|
798
|
+
century by the germ theory of disease.'
|
799
|
+
e '- Neutrophils expel extracellular traps (NETs) to entrap
|
800
|
+
and exterminate micro-organisms.'
|
801
|
+
e '- An allergic reaction results from the immune system
|
802
|
+
being oversensitive, treating essentially harmless
|
803
|
+
invaders as dangerous enemies that must be fought down.'
|
804
|
+
e "- In some types of <b>hepatitis</b> people die not from
|
805
|
+
the hepatitis virus itself, but from the immune system's
|
806
|
+
<b>destruction of the liver</b>."
|
807
|
+
e "- Macrophages are the body's natural scavengers: they are
|
808
|
+
the <b>all-purpose trash disposal units</b> of the body."
|
809
|
+
e '- Parasites have forced organisms to evolve immune
|
810
|
+
systems. Examples are the restriction enzymes bacteria use
|
811
|
+
to cut up invading viruses, as well as the CRISPR/Cas
|
812
|
+
defence system and the white blood cells in the human
|
813
|
+
body to destry bacteria.'
|
814
|
+
e '- Antigene können die Bildung von Antikörpern
|
815
|
+
hervorrufen.'
|
816
|
+
e '- The immune system has been shaped by genetic evolution. It
|
817
|
+
meets threats shaped by genetic evolution.'
|
818
|
+
e '- The total number of combinatorial arrangements of
|
819
|
+
immunoglobulins (Ig) in an individual is greater than
|
820
|
+
10⁹ (Jerne 1993).'
|
821
|
+
e '- Infectious agents may see humans as a rich sanctuary
|
822
|
+
for propagating their genome.'
|
823
|
+
e '- Initiation and escalation of an immune response carries
|
824
|
+
a significant metabolic cost to the cell.'
|
825
|
+
e '- The relatively invariant nature of PRRs is a strength,
|
826
|
+
as well as a weakness, of the innate immune system.'
|
827
|
+
e '- The PRRs are <b>hard‐wired receptors</b>.'
|
828
|
+
e '- Pathogens vary greatly in size and lifestyle.'
|
829
|
+
e '- Anatomic and chemical barriers are the initial
|
830
|
+
defenses against infection.'
|
831
|
+
e '- The average human requires the production of almost
|
832
|
+
4 × 10¹¹ leukocytes (400 billion) per day.'
|
833
|
+
}
|
834
|
+
# ========================================================================= #
|
835
|
+
# === Links
|
836
|
+
# ========================================================================= #
|
837
|
+
h2 'Links',
|
838
|
+
'gold'
|
839
|
+
p_default {
|
840
|
+
abr_self :local_bioinformatics,
|
841
|
+
css_class: 'steelblue BOLD'
|
842
|
+
abr_self :local_cellbiology,
|
843
|
+
css_class: 'steelblue BOLD'
|
844
|
+
abr_self :local_genetics,
|
845
|
+
css_class: 'steelblue BOLD'
|
846
|
+
abr_self :local_biotechnology,
|
847
|
+
css_class: 'steelblue BOLD'
|
848
|
+
abr_self :local_molecular_therapies,
|
849
|
+
css_class: 'steelblue BOLD'
|
850
|
+
}
|
851
|
+
}}
|