roebe 0.5.187

data/lib/roebe/www/immunology/immunology.rb

@@ -0,0 +1,1527 @@
+english('Immunology') {
+autoextend
+ruby_favicon
+default_template '
+
+p.default {
+  margin: 0.5em;
+  margin-left: 2em;
+}
+
+a,
+a:links,
+a:visited,
+a:link {
+  color:          lightblue;
+  text-decoration: none;
+}
+
+a:hover {
+  color:          tomato;
+  text-decoration: underline;
+}
+
+div.default {
+  padding: 8px;
+  margin: 4px;
+}
+
+/*
+ * The <b> tag in a paragraph will be colourized lightblue.
+ */
+
+p b {
+  color: lightblue;
+}
+
+'
+body_css_class 's2px padt2px marpad2px BG_IMG_RUBY NO_REPEAT VERDANAs BG_Black White'
+default_font_size_and_hyperlinks
+
+# =========================================================================== #
+# === gold_cheader_h2
+# =========================================================================== #
+def gold_cheader_h2(i)
+  cheader_h2(i,'gold')
+end
+
+# =========================================================================== #
+# === COMMON_CSS_CLASS_FOR_HYPERLINKS
+# =========================================================================== #
+COMMON_CSS_CLASS_FOR_HYPERLINKS = 'steelblue BOLD'
+
+doc('mar0px pad0px s0_4em widescreen_width') {
+  # ========================================================================= #
+  # === The immune system - an Introduction
+  # ========================================================================= #
+  cheader_h1 'The immune system - an Introduction','gold'
+  div(id: 'the_immune_system'){
+    p_default_le {
+      e 'The normal function of the immune system is
+      <b>host defense</b>.'
+      br
+      e 'Immunity is <b>systemic</b>. This means that <b>protective
+      mechanisms can act anywhere in the body</b>.'
+    }
+  }
+  # ========================================================================= #
+  # === History of Immunology
+  # ========================================================================= #
+  gold_cheader_h2 'History of Immunology'
+  p_default_le {
+    e 'Nearly 2,500 years ago, in his History of the Peloponnesian War,
+    <b class="gold">'+
+    string_link(:thucydides, content: 'Thucydides')+
+    '</b> wrote about a plague epidemic:'
+    br
+    l2em '<b class="italic lightblue">„No one caught the disease twice,“</b>
+    he said, <b class="italic lightblue">„or if he did, the second attack
+    was never fatal.“</b>'
+    brbr
+    e 'Historically, the term <i>immunity</i> meant <b>protection from 
+    infectious disease</b>.'
+  }
+  # ========================================================================= #
+  # === Zytotoxische T-Zelle
+  # ========================================================================= #
+  gold_cheader_h2 'Zytotoxische T-Zelle'
+  div(id: 'zytotoxische_T_Zelle'){
+    p_default_le {
+      e 'Zytotoxische T-Zellen bekämpfen virus-infizierte Zellen.'
+      br
+      e 'Wichtig für die zytotoxischen T-Zellen auf molekularer Ebene
+      ist die Erkennung infizierter Zellen mithilfe des
+      T-Zell-Rezeptors (auf der zytotoxischen T-Zelle)
+      sowie des MHC-I-Proteins auf Seiten der infizierten
+      Zielzelle.'
+      br
+      e 'MHC-I-Proteine befinden sich auf der Oberfläche aller
+      kernhaltigen, körpereigenen Zellen. An sie gebunden sind
+      Antigenpeptide, die aus dem Inneren der jeweiligen Zelle
+      stammen.'
+      br
+      e 'Gesunde, nicht infizierte Körperzellen präsentieren
+      somit eine variable Mischung verschiedenster,
+      zellspezifischer Selbst-Peptide. Dadurch weisen sie
+      sich so vor den Zellen des Immunsystems als „gesund“
+      aus.'
+      br
+      e 'Sind sie dagegen von einem Virus infiziert, gelangen
+      auch virusspezifische Antigenpeptide auf die MHC-Moleküle
+      und signalisieren so den Immunzellen den Erregerbefall
+      der Zielzelle.'
+      br
+      e 'Binden die aktivierten Zytotoxischen T-Zellen im
+      Gewebe an ihren spezifischen MHC-I-Peptid-Komplex,
+      schütten sie Perforine und Granzyme aus, welche
+      die gebundene Zielzelle abtöten. Zudem produzieren
+      und sezernieren aktivierte Zytotoxische T-Zellen
+      auch Proteine wie das Interferon-γ, welches in
+      benachbarten Zellen die Expression von MHC-I-Proteinen
+      fördert. Dies führt zu einer verstärkten Präsentation
+      von intrazellulär abgebauten Peptiden. Im Falle
+      einer beispielsweise mit einem Virus infizierten
+      Zelle werden dadurch auch vermehrt virale
+      Peptide präsentiert, welche wiederum von
+      spezifisch geprägten Zytotoxischen T-Zellen
+      erkannt werden. Die Immunantwort wird so
+      insbesondere im infizierten Bereich verstärkt.'
+      br
+      e 'Zytotoxische T-Zellen sind somit wichtige Mittler der zellulären
+      Immunantwort und zielen darauf ab, intrazelluläre Infektionen (vor
+      allem durch Viren) aufzuhalten, indem die infizierten Zellen durch
+      induzierte Apoptose vernichtet werden.'
+    }
+  end
+  # ========================================================================= #
+  # === MACROPHAGES TAG
+  # ========================================================================= #
+  gold_cheader_h2 'Macrophages'
+  div(id: 'macrophages'){
+    p_default_le {
+      e '<b>Macrophages</b> can form <b class="lightblue">multinucleate
+      giant cells</b> (MGCs)'
+      br
+      e "- Macrophages are the body's natural scavengers: they are the
+      <b>all-purpose trash disposal units</b> of the body."
+      br
+      e 'The <b>precursors of tissue macrophages</b> are <b>Monocytes</b>.
+      When blood monocytes are recruited into tissues, they become
+      macrophages.'
+      br
+      e 'Interestingly <b>activated macrophages</b> can fuse to <b>form
+      multinucleate giant cells</b>. Macrophages can become activated
+      upon binding osponins on the surface of microbes.'
+      br
+      e 'The macrophages in Drosophila are called <b>Hemocytes</b>.'
+    }
+  }
+  # ========================================================================= #
+  # === NK cells
+  # ========================================================================= #
+  gold_cheader_h2 'NK cells'
+  p_default_le {
+    e 'NK cells participate in the early control against <b>virus
+    infection</b>.'
+  }
+  # ========================================================================= #
+  # === MHC-II
+  # ========================================================================= #
+  # http://localhost/programming/ruby/src/roebe/lib/roebe/www/immunology/immunology.cgi#mhc_ii
+  # ========================================================================= #
+  gold_cheader_h2 'MHC-II'
+  p_default_le {
+    e 'Der <b>MHC-II</b> wird von <b>antigenpräsentierenden Zellen</b>
+    (APC) exprimiert.'
+    br
+    e 'Der MHC-Klasse-II-Komplex besteht aus zwei membranverankerten
+    Proteinuntereinheiten - α- und β-Untereinheit. Diese Untereinheiten
+    wiederum bestehen aus zwei Domänen: α1 und α2, sowie β1 und β2.'
+    br
+    e 'Beide Untereinheiten sind in der Zellmembran verankert.'
+    br
+    e 'Die folgenden Bilder stellen diese Struktur dar:'
+    br
+    dimg 'science/immunology/MHC_II_Structure_larger_picture.jpg',
+         'mar0_5em mars3em round_black3'
+    dimg 'science/immunology/MHC_II_Structure.png',
+         'mar0_5em mars3em round_black3'
+  }
+  # ========================================================================= #
+  # === CD8 versus CD4
+  # ========================================================================= #
+  gold_cheader_h2 'MHC-I versus MHC-II'
+  p_default_le {
+    e '<b>MHC-I</b>:  bindet an den <b>CD8 Rezeptor</b>.'
+    e '<b>MHC-II</b>: bindet an den <b>CD4 Rezeptor</b>.'
+  }
+  # ========================================================================= #
+  # === The complement system
+  # ========================================================================= #
+  gold_cheader_h2 'The complement system'
+  p_default_le {
+    e 'The classical pathway of the complement system can be activated
+    by <b>antibodies</b>.'
+  }
+  # ========================================================================= #
+  # === Class Switching 
+  # ========================================================================= #
+  # http://localhost/programming/ruby/src/roebe/lib/roebe/www/immunology/immunology.cgi#class_switching
+  # ========================================================================= #
+  gold_cheader_h2 'Class Switching'
+  p_default_le {
+    e '<b>Class switching</b> requires the action of <b>helper T
+    cells</b>.'
+  }
+  # ========================================================================= #
+  # === Protein A-Chromatographie zur Antikörperreinigung
+  # ========================================================================= #
+  gold_cheader_h2 'Protein A-Chromatographie zur Antikörperreinigung'
+  p_default_le {
+    e 'Die Affinitätschromatographie an Protein A-Sepharose ist
+    eine der verbreitetsten Methoden zur Antikörperreinigung.'
+    br
+    e 'Protein A ist ein bakterielles Zellwandprotein von 
+    <b class="gold">Staphylococcus aureus</b> mit einer 
+    spezifischen Affinität zur Fc-Region von Immunglobulinen 
+    der G-Klasse (IgG).'
+    br
+    e 'Protein A hat ein Molekulargewicht von 42 kDa und weist 
+    eine hohe pH-Stabilität von pH 2-10 auf.'
+    br
+    e 'Die Bindungsaffinität zum Fc-Teil von Antikörpern ist 
+    pH-abhängig und nach Bindung von Antikörpern in Gegenwart
+    neutraler oder leicht alkalischer Puffer lassen sich die
+    Immunglobuline mit einem abfallenden pH-Gradienten eluieren.'
+    br
+    e 'Abhängig von Herkunft (Spezies) und Subklasse des Antikörpers 
+    kann die Bindungsstärke von Protein A erheblich variieren.'
+    br
+    e 'Für Antikörper mit geringer Bindungsaffinität zu Protein A, 
+    wie zum Beispiel dem IgG Molekül aus der Maus, kann eine weitere
+    Affinitätsmatrix, <b>Protein G-Sepharose</b>, verwendet
+    werden.'
+    br
+    e 'Protein G ist ein Zelloberflächenprotein aus Streptokokken
+    der G-Gruppe und unterscheidet sich in seinem Affinitäts-Spektrum
+    von Protein A'
+  }
+  # ========================================================================= #
+  # === The innate immune system                                 (innate tag)
+  # ========================================================================= #
+  # http://localhost/programming/ruby/src/roebe/lib/roebe/www/immunology/immunology.cgi#the_innate_immune_system
+  # ========================================================================= #
+  gold_cheader_h2 'The innate immune system'
+  p_default_le {
+    e 'The mechanism of innate immunity provide effective initial defence
+    against infections. Both anatomic and chemical barriers are the
+    <b>initial defenses against infection</b>.'
+    br
+    e 'An additional role of innate immunity is to <b>initiate</b> the
+    <b>adaptive immune response</b>.'
+    br
+    e 'Innate immunity is also called natural immunity or <b>native
+    immunity</b>.'
+    br
+    e 'The relatively invariant nature of PRRs is a strength, as well as
+    a weakness, of the innate immune system.'
+    br
+    e 'The four principal components of innate immunity are:'
+    br
+    counter 'barriers (such as physical or chemical barriers)','mars3em lightgreen'
+    counter 'phagocytic cells, dendritic cells and natural killer cells','mars3em lightgreen'
+    counter 'blood proteins, such as the complement system
+    or mediators of inflammation','mars3em lightgreen'
+    counter 'cytokines','mars3em lightgreen'
+    br
+    e 'The cellular innate immune response to microbes consists of
+    which two main types of reactions:'
+    br
+    reset_the_counter
+    counter 'inflammation','mars3em lightgreen'
+    counter 'anti-viral defense','mars3em lightgreen'
+    br
+    e 'Cells of the innate immune system can  be trained by epigenetic
+    changes. The latter prepares macrophages for a stronger response to
+    a possible re-exposure with PAMPs.'
+  }
+  # ========================================================================= #
+  # === Adaptive immunity
+  # ========================================================================= #
+  gold_cheader_h2 'Adaptive immunity'
+  p_default_le {
+    e 'Adaptive immune system reaches its full activity about a week
+    after first contact with an antigen. Molecules recognized by
+    lymphocytes are referred to as <b>antigens</b>.'
+    br
+    e 'The adaptive immune system has <b>far higher specificity and
+    diveresity in antigen recognition than the innate immune 
+    system</b>.'
+    br
+    e '<b>Adaptive immunity</b> can be <b>grouped into</b>:'
+    br
+    reset_the_counter
+    counter 'humoral immunity','mars2em lightgreen'
+    counter 'cell-mediated immunity','mars2em lightgreen'
+    br
+    e '<b>Antibodies</b> are <b>the mediators of humoral immunity</b> of
+    the adaptive immune system.'
+  }
+  # ========================================================================= #
+  # === Lymphocytes in general
+  # ========================================================================= #
+  gold_cheader_h2 'Lymphocytes in general'
+  p_default_le {
+    e '<b>Lymphocytes</b> are an enormously heterogeneous group of cells.'
+    br
+    e 'There are two broad classes of lymphocytes:'
+    br
+    l2embre 'the B-lymphocytes','mars1em lightgreen'
+    l2embre 'the T-lymphocytes','mars1em lightgreen'
+    br
+    e 'The anatomy of lymphoid organs promotes cell-cell interactions that
+    are required for antigen recognition by lymphocytes.'
+    br
+    e 'Secondary lymphoid organs <b>concentrate</b> the immunological
+    repertoire. Afferent lymphatic vessels bring antigens to a lymph node.'
+  }
+  # ========================================================================= #
+  # === B-Lymphocytes
+  # ========================================================================= #
+  gold_cheader_h2 'B-Lymphocytes / B-cells'
+  p_default_le {
+    e 'B-Lymphocytes are the only cells capable of producing antibodies.
+    (A plasma cell is ultimately a B-lymphocyte.)'
+    br
+    e '<b>B-lymphocytes</b> derive from <b>lymphoid progenitor cells</b>.'
+    br
+    e 'The Ig-molecule that is initially expressed on the surface of a
+    differentiated B cell is <b>IgM</b>.'
+    br
+    e 'A <b>B cell</b> responds to protein antigens only after it has
+    been activated by a CD4+ T helper cell.'
+    br
+    e 'Lymphocyte recirculation is determined by adhesion molecules:
+    homing receptors in particular.'
+  }
+  # ========================================================================= #
+  # === T-Lymphocyten                                           (T cells tag)
+  # ========================================================================= #
+  # http://localhost/programming/ruby/src/roebe/lib/roebe/www/immunology/immunology.cgi#t_lymphocyten_t_cells
+  # ========================================================================= #
+  gold_cheader_h2 'T-Lymphocyten / T-cells'
+  p_default_le {
+    e 'Die <b>T-Lymphocyten</b> besitzen den <b>CCR 7 Rezeptor</b>. Damit
+    werden sie in den Paracortex gelockt (<i>homing</i>).'
+    br
+    e '<b>Cell-mediated immunity</b> is mediated by T lymphocytes.'
+    br
+    e 'The two most important subtypes of T lymphocytes are:'
+    br
+    reset_the_counter
+    counter 'helper T cells','mars2em lightgreen'
+    counter 'cytotoxic T lymphocytes (CTLs)','mars2em lightgreen'
+    br
+    e 'The primary job of CTLs is to kill cells that produce foreign antigens,
+    such as cells infected by viruses or intracellular bacteria. CTLs thus
+    destroy infected cell. In doing so they also <b>eliminate the reservoirs
+    of infection</b>.'
+    br
+    e 'Helper T cells on the other hand are renowned for their ability
+    to secrete cytokines. They secrete <b>Interleukin-2</b> specifically,
+    which in turn <b>will stimulate clonal expansion of these helper
+    T lymphocytes</b>.'
+    br
+    e 'The T cell response is restricted to proteins. This is due to
+    the constraint that their TCR can only recognize small peptides
+    presented on  major histocompatibility complex (MHC) proteins on
+    the surface of antigen-presenting cells.'
+  }
+  # ========================================================================= #
+  # === The lymphoid lineage
+  # ========================================================================= #
+  gold_cheader_h2 'The lymphoid lineage'
+  p_default_le {
+    e 'The <b>lymphoid lineage</b> consists of <b>T‐lymphocytes</b>,
+    <b>B‐lymphocytes</b>, and <b>natural killer (NK) cells</b>.'
+  }
+  # ========================================================================= #
+  # === The lymph node
+  # ========================================================================= #
+  # http://localhost/programming/ruby/src/roebe/lib/roebe/www/immunology/immunology.cgi#the_lymph_node
+  # ========================================================================= #
+  gold_cheader_h2 'The lymph node'
+  p_default_le {
+    dimg 'science/immunology/structure_of_a_lymph_node.jpg',
+         'mar0_5em mars5em round_black3'
+  }
+  # ========================================================================= #
+  # === The immune synapse
+  # ========================================================================= #
+  gold_cheader_h2 'The immune synapse'
+  p_default_le {
+    e 'The <b>immune synapse</b> closely pairs together 
+    a T cell with an APC.'
+  }
+  # ========================================================================= #
+  # === Cytokines                                             (cytokines tag) 
+  # ========================================================================= #
+  gold_cheader_h2 'Cytokines'
+  p_default_le {
+    e 'Cytokines are the <b>messenger molecules</b> of the immune system.'
+    br
+    e '<b>Cytokines</b> can act in an autocrine manner.'
+    br
+    e 'Most cytokines are <b>close to where they are produced</b>. They
+    can, however had, also enter circulation and may then <b>act at a distance</b>
+    that is away from the site of their initial production - which is called
+    <b>endocrine action</b>.'
+    br
+    e 'An example for a cytokine is the <b>Tumor necrosis factor</b>.'
+    br
+    e 'Chemokine and cytokine mediators are <b>released by injured
+    cells</b>.'
+  }
+  # ========================================================================= #
+  # === Neutrophils                         (neutrophil tag, neutrophils tag) 
+  # ========================================================================= #
+  # http://localhost/programming/ruby/src/roebe/lib/roebe/www/immunology/immunology.cgi#neutrophils
+  # ========================================================================= #
+  gold_cheader_h2 'Neutrophils'
+  p_default_le {
+    e 'The largest fraction of blood leukocytes is yielded by
+    <b>neutrophils</b>. Neutrophilas are the most abundant population of
+    circulating white blood cells and mediate the earliest phases of
+    inflammatory reactions.'
+    br
+    e 'Neutrophils are rather short-lived and are an important component of
+    the early inflammatory response. Their half life is only about 9 hours.'
+    br
+    e 'Neutrophils expel extracellular traps (NETs) to entrap and
+    exterminate micro-organisms. This is also called <b>NETosis</b>.'
+    br
+    e 'When a neutrophil phagocytoses a bacterium it will also produce ROS
+    (reactive oxygen species), which is one important component of <b>NETosis</b>.
+    ROS will, in turn, cause granules in a neutrophil to pop up, which then
+    activates an enzyme called <b>Neutrophil elastase</b>. This enzyme destroys
+    chromatin - the protein parts. Thus, the chromatin will expand.'
+    br
+    e 'Production of neutrophils is stimulated by Granulocyte colony-stimulating
+    factor: <b>G-CSF</b>.'
+    br
+    e 'Neutrophils may migrate to sites of infection within a few hours after
+    the entry of microbes.'
+  }
+  # ========================================================================= #
+  # === Evolution and the immune system                       (evolution tag)
+  # ========================================================================= #
+  # http://localhost/programming/ruby/src/roebe/lib/roebe/www/immunology/immunology.cgi#evolution_and_the_immune_system
+  # ========================================================================= #
+  gold_cheader_h2 'Evolution and the immune system'
+  p_default_le {
+    e 'The immune system has been shaped by <b>genetic evolution</b>.
+    It meets threats shaped by genetic evolution.'
+    br
+    e 'The <b>innate immune system</b> evolved before the emergence
+    of vertebrates. One can find innate immunity even in plants
+    already.'
+    br
+    e 'The adaptive immune system has been found in cartilaginous
+    fish.'
+    br
+    e 'A hallmark of many pathogenic microbes is that they have evolved
+    to resist innate immunity.'
+    br
+    e 'Toll-like receptors are highly evolutionary conserved membrane
+    receptors that start a signal transduction cascade ending up
+    with the activation of the transcription factor NFκB (nuclear
+    factor κB)'
+    br
+    e 'Approximately 500 million years ago, jawless fish, such as lampreys
+    and hagfish, developed an immune system containing lymphocyte-like
+    cells that may function like lymphocytes in more advanced species.
+    The more specialized defense mechanisms that constitute adaptive
+    immunity are found in vertebrates only.'
+  }
+  # ========================================================================= #
+  # === Effector mechanisms - effector cells and effector molecules
+  # ========================================================================= #
+  # http://localhost/programming/ruby/src/roebe/lib/roebe/www/immunology/immunology.cgi#effector_cells
+  # ========================================================================= #
+  gold_cheader_h2 'Effector mechanisms - effector cells and effector molecules'
+  p_default_le {
+    e '<b>Antigen elimination</b> often requires the participation of
+    <b>effector cells</b>.'
+    br
+    e 'The effector mechanisms of the adaptive immune system include
+    antibodies and effector T cells.'
+  }
+  # ========================================================================= #
+  # === CYCLOSPORIN
+  # ========================================================================= #
+  gold_cheader_h2 'Cyclosporin'
+  p_default_le {
+    e '<b>Cyclosporin A</b> kommt in Pilzen vor.'
+    br
+    e 'Wenn der Wirkstoff vom Körper aufgenommen wird, lagert es sich in
+    den T-Lymphozyten an Rezeptoren an.'
+    br
+    e 'Der Wirkstoff führt in mehreren Reaktionsschritten dazu, dass
+    Interleukin 2 nicht mehr von den T-Zellen hergestellt wird.'
+    br
+    e '<b>Interleukin 2</b> ist ein Botenstoff und wird benötigt, um das
+    Immunsystem zu aktivieren. Er ist an der Entstehung einer
+    Entzündungsreaktion beteiligt. Cyclosporin kann somit also
+    auch AutoImmunkrankheiten verursachen, da es die Aptoptose
+    in den Thymocyten unterbindet.'
+  }
+  # ========================================================================= #
+  # === Das Immunsystem und der Darm
+  # ========================================================================= #
+  gold_cheader_h2 'Das Immunsystem und der Darm'
+  p_default_le {
+    e 'Etwa 80% aller Abwehrzellen sind im Darmbereich tätig.'
+  }
+  # ========================================================================= #
+  # === Transplantationen
+  # ========================================================================= #
+  gold_cheader_h2 'Transplantationen'
+  p_default_le {
+    e 'Die genetische Beziehung zwischen Spender und Empfänger entscheidet
+    darüber ob eine Abstoßung erfolgt oder nicht.'
+    br
+    e 'Das Ziel der nach Transplantation lebenslang erfolgenden
+    Unterdrückung des Immunsystems ist die Verhinderung von
+    Abstoßungsreaktionen. Diese Immunsuppression erfolgt medikamentös.'
+  }
+  # ========================================================================= #
+  # === Natürliche Killerzellen steuern die Wundheilung (08.09.2021)
+  #
+  # See: https://www.media.uzh.ch/de/medienmitteilungen/2021/Wundheilung.html
+  # ========================================================================= #
+  gold_cheader_h2 'Natürliche Killerzellen steuern die Wundheilung (08.09.2021)'
+  p_default_le {
+    e 'Natürliche Killerzellen töten nicht nur Krebszellen oder
+    virusinfizierte Zellen ab. Sie steuern bei Hautverletzungen auch
+    die Balance zwischen Wundheilung und Bakterienabwehr.'
+    br
+    e 'Wird der Heilungsprozess beschleunigt, schwächt dies die Immunabwehr,
+    wie Forschende der Universität Zürich zeigen. Relevant ist dies sowohl
+    für die Behandlung von Hautverletzungen wie auch die Bekämpfung
+    antibiotikaresistenter Keime.'
+    br
+    e 'Natürliche Killerzellen sind ein bestimmter Typ von Immunzellen.
+    Sie erkennen abnormale Körperzellen wie Tumor- und virusinfizierte
+    Zellen und töten diese ab. Ein internationales Forschungsteam unter
+    der Leitung von Christian Stockmann, Professor am Institut für
+    Anatomie der Universität Zürich (UZH), hat nun herausgefunden,
+    dass Killerzellen eine weitere, überraschende Funktion haben:
+    Sie kontrollieren die Wundheilung in der Haut.'
+    br
+    e squote('Wir konnten diese Zellen in Mäusen genetisch so verändern,
+    dass das Wachstum von Blutgefässen beschleunigt wird und sich
+    Hautwunden schneller schliessen. Allerdings wird dadurch die
+    Immunabwehr abgeschwächt, was die Anfälligkeit für bakterielle
+    Infektionen erhöht')+', sagt Stockmann.'
+    br
+    e 'Beschleunigte Wundheilung birgt höheres Infektionsrisiko'
+    br
+    e 'In der Biomedizin wird intensiv nach Möglichkeiten gesucht,
+    um Wundheilungsprozesse zu beeinflussen. Versucht wird vor
+    allem, die Gefässneubildung anzuregen und zu beschleunigen –
+    entweder direkt oder indirekt über die Beeinflussung der
+    Immunantwort. '+squote('Unsere Ergebnisse zeigen, dass man bei 
+    solchen Ansätzen möglicherweise ein erhöhtes Infektionsrisiko
+    in Kauf nimmt. Daher ist hier Vorsicht geboten')+', so
+    Stockmann.'
+    br
+    e 'Eine weitere offene Frage ist, inwiefern Natürliche Killerzellen
+    nicht nur das Tempo, sondern auch die Qualität der Wundheilung –
+    etwa die Zusammensetzung des Bindegewebes oder die Regeneration
+    von Haarfollikel, Drüsen und anderen Hautkomponenten –
+    beeinflussen.'
+    br
+    e squote('Die spannendste Frage ist, wie wir es schaffen können,
+    die Wundheilung zu beschleunigen und gleichzeitig die
+    Immunabwehr gegen Wundinfektionen zu stärken')+', sagt
+    der Anatom und Immunologe Stockmann.'
+    br
+    e 'Killerzellen gegen antibiotikaresistente Bakterien einsetzen'
+    br
+    e 'Der Wissenschaftler sieht aber noch weiteres Potenzial:
+    Bei Krebstherapien werden heute auch Therapeutika
+    eingesetzt, die Killerzellen aktivieren und stimulieren,
+    so dass diese vermehrt die Krebszellen abtöten.'
+    br
+    e squote('Unsere Daten weisen darauf hin, dass diese Medikamente
+    auch bei bakteriellen Infektionen nützlich sein könnten –
+    was angesichts der zunehmend antibiotikaresistenten
+    Keime unbedingt weiter erforscht werden sollte')+
+    ', sagt Stockmann.'
+    br
+    e 'Natürliche Killerzellen kommunizieren laufend mit anderen
+    Abwehrzellen und beeinflussen deren Aktivität. Dazu sondern sie
+    Botenstoffe ab, sogenannte Zytokine. In ihrer Studie stellten die
+    Forschenden fest, dass Killerzellen auch Hautverletzungen
+    infiltrieren, in denen sehr niedrige Sauerstoffkonzentrationen
+    herrschen. In solchen Geweben stellen Killerzellen ihre Genaktivität
+    um und passen sich so dem Sauerstoffmangel an. Verantwortlich für
+    diese Umstellung sind sogenannte HIF-Signalfaktoren.'
+    br
+    e 'Fehlt in Mäusen einer dieser Signalfaktoren namens
+    HIF-1α, ist die Ausschüttung bestimmter Zytokine beeinträchtigt.
+    Als Reaktion darauf wird das Wachstum von Blutgefässen in der
+    Haut und damit die Wundheilung beschleunigt, während die
+    Bekämpfung bakterieller Infektionen gedrosselt wird.
+    Die Balance verschiebt sich so in Richtung Wundheilung.'
+  }
+  # ========================================================================= #
+  # === Famous quotes in Immunology
+  # ========================================================================= #
+  gold_cheader_h2 'Famous quotes in Immunology'
+  div_default_le {
+    boldbr pretty_link('Jules Bordet','BOLD steelblue')
+    br
+    p_default_le {
+      equote 'Life is the maintenance of an equilibrium
+      that is <b>perpetually threatened</b>.','mars2em'
+    }
+  }
+  # ========================================================================= #
+  # === Inflammation                                       (inflammation tag)
+  # ========================================================================= #
+  gold_cheader_h2 'Inflammation'
+  p_default_le {
+    e '<b class="lightblue">Inflammation</b> is a series of events that surround
+    an immune response and display a number of characteristic features,
+    including local swelling (edema), redness (due to capillary dilation),
+    pain, and <b>heat</b>.'
+    br
+    e 'Inflammataion is a general, nospecific reaction to noxious stimuli
+    such as <b>toxins</b> and <b>pathogens</b>.'
+    br
+    e '<b>Leukocytes</b> will be recruited and accumulate in the tissue.
+    Their activation will lead to the destruction of the microbes.'
+  }
+  # ========================================================================= #
+  # === The immune response
+  # ========================================================================= #
+  gold_cheader_h2 'The immune response'
+  p_default_le {
+    e 'The collective and coordinated response to the introduction of
+    foreign substances is called <b>the immune response</b>.'
+    br 
+    e 'Initiation and escalation of an immune response does not come for
+    free: it carries <b>a significant metabolic cost for the cell</b>.'
+  }
+  # ========================================================================= #
+  # === Passive Immunity 
+  # ========================================================================= #
+  gold_cheader_h2 'Passive Immunity'
+  p_default_le {
+    e 'One main benefit of <b>passive immunity</b> is that it <b>can confer
+    resistance rapidly</b>.'
+    br
+    e 'An example where <b>passive immunity</b> is physiologically important
+    can be seen by the <b>transfer of maternal antibodies to the fetus</b>.'
+  }
+  # ========================================================================= #
+  # === Antigens and Antigen-presenting cells
+  # ========================================================================= #
+  gold_cheader_h2 'Antigens and Antigen-presenting cells'
+  p_default_le {
+    e 'Antigens can be distinguished into the following two types:'
+    br
+    cmd '(1) foreign antigens'
+    cmd '(2) self-antigens'
+    br
+    e 'The most specialized antigen-prsenting cell is the dendritic cell.
+    It will capture microbial antigens that enter from the external
+    environment.'
+  }
+  # ========================================================================= #
+  # === Somatische Rekombination
+  # ========================================================================= #
+  gold_cheader_h2 'Somatische Rekombination'
+  p_default_le {
+    e ''
+    br
+  }
+  # ========================================================================= #
+  # === Immunologic memory                                       (memory tag)
+  # ========================================================================= #
+  gold_cheader_h2 'Immunologic memory'
+  p_default_le {
+    e 'Only active immune responses will generate immunologic memory.'
+    br
+    e 'Memory T cells react more rapidly to antigen challenges than do
+    naive T cells.'
+    br
+    e 'Some memory lymphocytes are <i>on patrol</i> in the tissues, scanning
+    for reintroduction of their specific antigens.'
+  }
+  # ========================================================================= #
+  # === Immunogens
+  # ========================================================================= #
+  gold_cheader_h2 'Immunogens'
+  p_default_le {
+    e 'Substances that stimulate immune responses are called immunogens.'
+  }
+  # ========================================================================= #
+  # === Clonal selection hypothesis
+  # ========================================================================= #
+  gold_cheader_h2 'Clonal selection hypothesis'
+  p_default_le {
+    e 'The <b>clonal selection hypothesis</b> states that lymphocytes
+    that are specific for a large number of antigens already exist before
+    exposure to the antigen. When an antigen is encountered, it selects
+    the specific cells and thus activates them.'
+  }
+  # ========================================================================= #
+  # === The autoimmune response - reactions against self
+  # ========================================================================= #
+  gold_cheader_h2 'The autoimmune response - reactions against self'
+  p_default_le {
+    e 'Self-molecules can elicit an immune response, which is generally
+    called the <b>autoimmune response</b>.'
+    br
+    e 'Examples for autoimmune diseases are <b>type I diabetes</b>
+    and <b>multiple sclerosis</b>.'
+    br
+    e 'The fact that autoimmune diseases exist shows that immune
+    responses can cause tissue injuries that may harm the body
+    more than the effects of pathogenic microbes may.'
+  }
+  # ========================================================================= #
+  # === Immune homeostasis
+  # ========================================================================= #
+  gold_cheader_h2 'Immune homeostasis'
+  p_default_le {
+    e 'In immunology the term <b>homeostasis</b> means that all normal
+    immune responses wane with time after antigen simulation, thus
+    returning the immune system to its resting (basal) state again.'
+    br
+    e '<b>Contraction</b> in immunology - which is a somewhat equivalent
+    term to homeostasis - happens primarily by apoptosis. Here the expanded
+    lymphocyte clones will die and homestasis is eventually restored
+    again.'
+  }
+  # ========================================================================= #
+  # === Immuntoleranz tag                                     (tolerance tag)
+  # ========================================================================= #
+  # http://localhost/programming/ruby/src/roebe/lib/roebe/www/immunology/immunology.cgi#immuntoleranz
+  # ========================================================================= #
+  gold_cheader_h2 'Immuntoleranz'
+  p_default_le {
+    e '<b>Immuntoleranz</b> (= <b>Immunologische Nichtreaktivität</b>;
+    = <b>Immunologic unresponsiveness</b>) bezeichnet eine ausbleibende
+    Reaktion des Immunsystems gegenüber einem Antigen.'
+    br
+    e 'Dieses Phänomen wurde postuliert, um zu erklären, warum ein
+    Individuum normalerweise keine Immunreaktion gegen das körpereigene
+    Material zeigt, obwohl dieses für ein anderes Individuum <b>immunogen</b>
+    sein kann.'
+    br
+    e 'Die <b>Immuntoleranz</b> spielt eine wichtige Rolle bei der Auslösung
+    von Autoimmunkrankheiten. Intolerante Z-Tellen dürfen nicht überleben.'
+    br
+    e 'Eine zentral wichtige Rolle bei der Immuntoleranz haben die
+    <b>regulatorischen T-Lym­pho­zyten</b>, die in einem anderen Abschnitt
+    auf dieser Webseite genauer beschrieben werden. Regulatorische
+    T-Lymphocyten entfernen selbst-reaktive T-Lymphocyten und
+    B-Lymphozyten.'
+    br
+    e 'Avoiding <b>self-tolerance</b> against self antigens also means
+    avoiding <b>autoimmune disease</b>.'
+    br
+    e "Self-tolerance is vital for preventing harmful reactions
+    against one's own cells."
+  }
+  # ========================================================================= #
+  # === Regulatory T cells
+  # ========================================================================= #
+  # http://localhost/programming/ruby/src/roebe/lib/roebe/www/immunology/immunology.cgi#regulatory_t_cells
+  # ========================================================================= #
+  gold_cheader_h2 'Regulatory T cells'
+  p_default_le {
+    e 'The primary function of regulatory T cells is to <b>inhibit immune
+    responses</b>. That is, regulatory T-lymphocytes have the capacity to
+    <b>suppress an immune response</b>.'
+    br
+  }
+  # ========================================================================= #
+  # === Interferon tag
+  # ========================================================================= #
+  gold_cheader_h2 'Interferon'
+  p_default_le {
+    e 'Interferone wurden im Jahre 1957 entdeckt, von
+    Jean Lindenmann und Alick Isaacs.'
+    br
+    e '<b>Interferon Alpha</b> (im Menschen) umfasst (mindestens) 15 Gene,
+    Beta und Gamma hingegen nur je ein Gen. Die Alpha-Varianten zeigen
+    <b>unterschiedliche Spezifität</b>.'
+    e
+    e 'Wie wirken die Interferone?'
+    br
+    e 'Interferone verhindern effektiv die Vervielfältigung von Viren
+    in den menschlichen Zellen.'
+  }
+  # ========================================================================= #
+  # === IKAROS TAG
+  # ========================================================================= #
+  gold_cheader_h2 'Ikaros'
+  p_default_le(id: 'ikaros') {
+    e 'Ikaros ist ein "<i>differentiation factor</i>" der <b>leukocyte
+    lineage</b>.'
+    br
+    e 'Ikaros interagiert mit Aiolos (einem <i>lymphoid restricted
+    transcription factor</i>, der gemeinsam mit Ikaros die 
+    <b>Lymphocyte Differentiation</b> steuert)'
+    br
+    e '<b>Ikaros</b> besitzt einen Zinkfinger:'
+    br
+    dimg 'science/biology/IKAROS.jpg',
+         'marl2em bblack1'
+  }
+  # ========================================================================= #
+  # === Exam questions
+  # ========================================================================= #
+  fancy2 'Exam questions','gold'
+  p_default_le {
+    e 'Describe the receptors, their ligands and soluble molecules that provide
+    three distinct signals for full T cell activation, including their
+    functional relevance.'
+    br
+    e 'Polarizing cytokines can be secreted, which in turn causes T cells
+    to specialize.'
+    br
+    e 'IL-1α and IL-1β are pro-inflammatory cytokines, produced following
+    damage to the host (release of DAMPs) or upon innate recognition of
+    PAMPs.'
+    br
+    e 'The activities of IL-1 form a <b>direct bridge between innate
+    and adaptive immunity</b>.'
+    br
+    e 'Sources used:'
+    br
+    selfy 'https://www.frontiersin.org/articles/10.3389/fimmu.2020.621931/full'
+  }
+  # ========================================================================= #
+  # === Describe the differences between a naïve T cell and an effector T cell.
+  # ========================================================================= #
+  gold_cheader_h2 'Describe the differences between a naïve T cell 
+  and an effector T cell'
+  p_default_le {
+    e '<b>Lymphocytes</b> that have not encountered a particular antigen are
+    said to be naive.'
+    br
+    e 'If a naive T cell encounters an appropriate antigen then said naïve
+    cell is activated into different types of T cells.'
+    br
+    e 'Each naïve T cell has a unique T cell receptor (TCR) that
+    recognizes a specific antigen.'
+    br
+    e 'Sources used:'
+    br
+    selfy 'https://www.akadeum.com/blog/what-are-naive-cells/'
+  }
+  # ========================================================================= #
+  # === Q3: Name two co-stimulatory molecules expressed on naïve T cells,
+  #     including their ligands and their function
+  # ========================================================================= #
+  p_default_le {
+    e 'Q3: Name two co-stimulatory molecules expressed on naïve T cells,
+    including their ligands and their function'
+    br
+    e 'The most prominent co-stimulatory molecule is <b>CD28</b>, which
+    controls the activation of naïve and memory T cells by antigen
+    presented on professional antigen-presenting cells.'
+    br
+    e 'This has a practical implication as well, as blocking of the
+    CD28-CD80/86 pathway can be used to induce tolerance in autoimmune
+    diseases where the disease-inducing autoantigens are not known.'
+    br
+    e 'APCs need activation signals to provide co-stimulatory ligands,
+    for example through the activation of Toll-like receptors.'
+    br
+    e 'Sources used:'
+    br
+    selfy 'https://arthritis-research.biomedcentral.com/articles/10.1186/ar2414'
+    selfy 'https://www.youtube.com/watch?v=1FVAFy6qruY'
+  }
+  # ========================================================================= #
+  # === Q4: Name cytotoxic effector proteins and their action on target cells?
+  # ========================================================================= #
+  p_default_le {
+    e 'Q4: Name cytotoxic effector proteins and their action on target cells.'
+    br
+    e 'Sources used:'
+    br
+    selfy ''
+  }
+  # ========================================================================= #
+  # === Q5: Name the major functional CD4+ T-cell subsets in the current
+  #     immunological paradigm on CD4+ T-cell differentiation, including
+  #     master-regulator transcription factors involved in their development
+  #     and cytokines relevant for their polarization.
+  # ========================================================================= #
+  p_default_le {
+    e 'Q5: Name the major functional CD4+ T-cell subsets in the current 
+    immunological paradigm on CD4+ T-cell differentiation, including
+    master-regulator transcription factors involved in their development
+    and cytokines relevant for their polarization.'
+    br
+    e 'Sources used:'
+    br
+    selfy ''
+  }
+  # ========================================================================= #
+  # === Q6: Imagine you are member in a research team that is supposed to
+  #     develop vaccines against extracellular bacteria: which functional
+  #     subtype of CD4+ T cells should be induced by such vaccines and
+  #     what effector functions would this CD4+ T cell subtype perform?
+  # ========================================================================= #
+  p_default_le {
+    e 'Q6: Imagine you are member in a research team that is supposed to
+    develop vaccines against extracellular bacteria: which functional
+    subtype of CD4+ T cells should be induced by such vaccines and
+    what effector functions would this CD4+ T cell subtype perform?'
+    br
+    e 'Sources used:'
+    br
+    selfy ''
+  }
+  # ========================================================================= #
+  # === Q7: What are the main functions exerted by Interleukin-2? Which
+  #         molecules form the IL-2 receptor?
+  # ========================================================================= #
+  p_default_le {
+    e 'Q7: What are the main functions exerted by Interleukin-2? Which
+    molecules form the IL-2 receptor?'
+    br
+    e 'Sources used:'
+    br
+    selfy ''
+  }
+  # ========================================================================= #
+  # === Q8: What are the main functions exerted by Interleukin-4?
+  # ========================================================================= #
+  p_default_le {
+    e 'Q8: What are the main functions exerted by Interleukin-4?'
+    br
+    e 'Sources used:'
+    br
+    selfy ''
+  }
+  # ========================================================================= #
+  # === Q9: Describe the major suppressive mechanisms that Tregs can perform.
+  # ========================================================================= #
+  p_default_le {
+    e 'Q9: Describe the major suppressive mechanisms that Tregs can perform.'
+    br
+    e 'Sources used:'
+    br
+    selfy ''
+  }
+  # ========================================================================= #
+  # === Q10: Describe briefly the major pathways how cytotoxic T cells kill
+  #          their target cells (extrinsic and intrinsic): which molecules
+  #          are involved, how do they act?
+  # ========================================================================= #
+  p_default_le {
+    e 'Q10: Describe briefly the major pathways how cytotoxic T cells kill 
+    their target cells (extrinsic and intrinsic): which molecules are
+    involved, how do they act?'
+    br
+    e 'Sources used:'
+    br
+    selfy ''
+  }
+  # ========================================================================= #
+  # === Q11: How can CD4+ T cells co-stimulate CD8+ T cells (name
+  #          involved molecules and required cell-cell interactions)?
+  # ========================================================================= #
+  p_default_le {
+    e 'Q11: How can CD4+ T cells co-stimulate CD8+ T cells (name involved
+    molecules and required cell-cell interactions)?'
+    br
+    e 'Sources used:'
+    br
+    selfy ''
+  }
+  # ========================================================================= #
+  # === Q12: 
+  # ========================================================================= #
+  p_default_le {
+    e 'Q12: What are TH1 effector functions in infections by
+    intracellular bacteria?'
+  }
+  # ========================================================================= #
+  # === Q13: Name TH2 cell effector functions in helminth infections? 
+  # ========================================================================= #
+  p_default_le {
+    e 'Q13: Name TH2 cell effector functions in helminth infections?'
+  }
+  # ========================================================================= #
+  # === Q14: What is immunological synapse and how it is formed?
+  # ========================================================================= #
+  p_default_le {
+    e 'Q13: Name TH2 cell effector functions in helminth infections?'
+  }
+  # ========================================================================= #
+  # Immunological memory (Clara Pernold)
+  # ========================================================================= #
+  # ========================================================================= #
+  # === Q15) Explain the benefits of immune memory in comparison to
+  #          primary response. Contrast the features of an antibody
+  #          response during a primary infection with that during a
+  #          memory response.
+  # ========================================================================= #
+  p_default_le {
+    e 'Q15) Explain the benefits of immune memory in comparison to
+    primary response. Contrast the features of an antibody response
+    during a primary infection with that during a memory response.'
+  }
+  # ========================================================================= #
+  # === Q16) Describe the roles of B cells in immunological memory:
+  #     What is the difference between “constitutive” and “reactive”
+  #     humoral memory and the cell types responsible?
+  # ========================================================================= #
+  p_default_le {
+    e 'Q16) Describe the roles of B cells in immunological memory: What is
+    the difference between “constitutive” and “reactive” humoral memory
+    and the cell types responsible?'
+  }
+
+e '
+Q1) What are the different stages of B cell related memory?
+Q1) What is the role of CD40/CD40L and BLIMP-1?
+Q1) What is the role of IL-7 receptor during the memory response?
+Q1) CD45 is a molecule, which is often used to discern between T cell phenotypic
+subsets.
+a) What is the differential expression pattern of this molecule?
+b) How do such molecular variants arise?
+c) What are the relevant cellular phenotypes elucidated using CD45 as a
+marker and how do these phenotypes relate to function?
+Q1) Outline the major differences between a primary and secondary T cell
+response.
+
+Q1) Memory T cells can be divided into two main subsets, describe their
+    phenotype. How does the expression of molecules relate to cellular function?
+    Describe the biological relevance of Tcm and Tem when controlling
+    previously encountered antigen over the time course of a secondary
+    infection.
+    Describe the phenotypes of Tcm, Tem and Trm
+    What is the function of the following cell surface molecules: CD62L, CCR7,
+    CD103, CD69?
+    What leads to T-cell exhaustion and how do the functional and phenotypic
+    characteristics of exhausted cells change over time?
+    '
+  p_default_le {
+    e 'What is immune senescence? How would the phenotype of an immune
+    cell change?'
+    br
+    e 'Older adults are predisposed to a higher risk of latent virus
+    reactivation.'
+  }
+  # ========================================================================= #
+  # === Q2: What is the meaning of “autofluorescence” in flow cytometry? What is causing
+  #     “autofluorescence”? How is autofluorescence determined in a
+  #     flow cytometry experiment – e.g. draw an example as histogram? 
+  # ========================================================================= #
+  p_default_le {
+    e 'Immunological Methods (Kerstin Mair)'
+    br
+    e 'Q1: Interpret this pseudocolor plot showing flow cytometry data: what phenotypes
+    of lymphocytes can you identify? What can be concluded about the abundance of
+    individual phenotypes?'
+    br
+    embed_remote_image 'https://i.imgur.com/5xZgcfZ.png'
+  }
+  # ========================================================================= #
+  # === Q2: What is the meaning of “autofluorescence” in flow cytometry? What is causing
+  #     “autofluorescence”? How is autofluorescence determined in a
+  #     flow cytometry experiment – e.g. draw an example as histogram? 
+  # ========================================================================= #
+  p_default_le {
+    e 'Q2: What is the meaning of '+squote('autofluorescence')+' in flow
+    cytometry? What is causing '+squote('autofluorescence')+'? How is
+    autofluorescence determined in a flow cytometry experiment – e.g.
+    draw an example as histogram?'
+  }
+  # ========================================================================= #
+  # === Q3: Name a) similarities and b) differences between flow cytometry
+  #         and mass cytometry. 
+  # ========================================================================= #
+  p_default_le {
+    e 'Q3: Name a) similarities and b) differences between flow cytometry
+    and mass cytometry.'
+    br
+    e 'Let us first define these two methods.'
+    br
+    e 'Flow Cytometry (FC) is a technique used to examine the
+    chemical and physical properties of a population of cells.
+    This is done with the help of a laser beam. The cells will
+    flow through that laser beam.'
+    br
+    e 'Mass cytometry (MC) is a variation of flow cytometry in which
+    antibodies are labeled with heavy metal ion tags rather
+    than fluorochromes. The advantage here is that we can combine
+    many more antibody specificities in a single sample.
+    The cells used in MC are incubated with a cocktail of antibodies
+    that have been previously conjugated with heavy metal isotopes
+    via a polymer chain of chelating groups.'
+    br
+    selfy 'https://imperialbiosciencereview.com/2020/09/25/flow-cytometry-vs-mass-cytometry-cytof/'
+  }
+  # ========================================================================= #
+  # === Q4: For what reasons might it be relevant to sort lymphocyte
+  #         subsets? 
+  # ========================================================================= #
+  p_default_le {
+    e 'Q4: For what reasons might it be relevant to sort lymphocyte
+    subsets?','lightblue'
+    br
+    e 'This may be useful to determine
+    Which T cell populations mediate highly effective
+    adoptive immunotherapy.'
+    br
+    e 'Adoptive cell transfer (ACT) is an ex-vivo expansion and
+    re-infusion of antigen (Ag)-specific T cells to patients.'
+    br
+    e 'A straightforward and functionally significant means of
+    classifying T cell subsets can be accomplished by assessing
+    for the co-expression of the lymphoid homing molecules
+    L-selectin (CD62L) and CC-chemokine receptor 7 (CCR7).
+    T cells which display these 2 molecules have a
+    propensity to home to secondary lymphoid structures
+    where they can actively survey professional
+    antigen presenting cells for the presence of cognate
+    Antigenes.'
+    br
+    e 'Human lymphocytes can be divided into:'
+    br
+    cmd '  T lymphocytes (CD3+, CD4+, CD8+),'
+    cmd '  B lymphocytes (CD19+), and'
+    cmd '  Natural Killer (NK) lymphocytes (CD16+, CD56+).'
+    br
+    e 'Sources:'
+    br
+    selfy 'https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3501135/'
+  }
+  # ========================================================================= #
+  # === Q5: Name two methodologies that are used to sort lymphocyte
+  #         subsets and explain briefly their functional principle. 
+  # ========================================================================= #
+  p_default_le {
+    e 'Q5: Name two methodologies that are used to sort lymphocyte
+    subsets and explain briefly their functional principle.',
+    'lightblue'
+  }
+  # ========================================================================= #
+  # === Q6: How does the proliferation dye CFSE (also named CFDA-SE) allow the
+  #     differentiation of individual daughter cell generations in
+  #     proliferation assays analysed by flow cytometry? Briefly describe
+  #     the principle.
+  # ========================================================================= #
+  p_default_le {
+    e 'Q6: How does the proliferation dye CFSE (also named CFDA-SE) allow the
+    differentiation of individual daughter cell generations in proliferation
+    assays analysed by flow cytometry? Briefly describe the principle.',
+    'lightblue'
+    br
+    e 'This dye allows us to monitor the <b>proliferation of
+    lymphocytes</b>.'
+    br
+    e 'CFSE stands short for carboxyfluorescein diacetate succinimidyl
+    ester.'
+    br
+    e 'The idea is for CFSE to covalently label long-lived intracellular
+    molecules with the highly fluorescent dye, carboxyfluorescein.'
+    br
+    e 'CFSE can go through membranes.'
+    br
+    e 'Its succinimidyl group covalently binds to intracellular
+    lysine residues and other free primary amines, producing
+    green fluorescence.'
+    br
+    e 'This stable linkage ensures retention of the dye within
+    the cell once incorporated, without leaching onto
+    surrounding cells. This feat of CFSE has led to widespread
+    use in fluorescence microscopy or flow cytometry to
+    study cell division, proliferation and migration. The
+    dye has an excitation wavelength around 492 nm and
+    an emission wavelength around 517 nm.'
+    br
+    e 'Note that <b>CFDA-SE</b> is NOT fluorescent.'
+    br
+    e 'Each cell division can be assessed by measuring the
+    corresponding decrease in cell fluorescence via Flow
+    cytometry.'
+    br
+    e 'Sources:'
+    br
+    selfy 'https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3185625/'
+  }
+  # ========================================================================= #
+  # === Q7: Name two methods to analyze cell lysis and briefly describe one of the
+  #         methods.
+  # ========================================================================= #
+  p_default_le {
+    e 'Q7: Name two methods to analyze cell lysis and briefly describe one of
+    the methods.','lightblue'
+    br
+  }
+  # ========================================================================= #
+  # === Q8: What are the requirements for intracellular cytokine staining
+  #         by flow cytometry.
+  # ========================================================================= #
+  p_default_le {
+    e 'Q8: What are the requirements for intracellular cytokine staining
+    by flow cytometry?','lightblue'
+    br
+    e '<b class="lightgreen">Intracellular cytokine staining</b>
+    (ICS) is a method of cytokine analysis that provides information
+    on the type of cytokines that are produced upon (antigen-specific)
+    stimulation of T cells and B cells. We can detect immunological
+    biomarkers in the form of expressed cytokines.'
+    br
+    e 'ICS can reveal which subtype of CD4+ T helper cell is induced
+    under certain culture conditions, and indicates whether a
+    biological or compound alters T cell polarization in vitro.
+    Rather than looking at the total amount of secreted cytokines
+    produced by all the cells in culture, which is generally
+    analyzed by ELISA or CBA, ICS will provide information on
+    cytokine production by each individual cell. This allows
+    us to analyze the proportion of cells that produce a
+    cytokine of interest, or allows for quantification of
+    the amount of cells producing multiple cytokines (i.e.
+    the rate of polyfunctionality).'
+    br
+    e 'This can help, for example, to unravel the polarization,
+    strength and specificity of immune responses upon
+    immune-modulating therapies.'
+  }
+  # ========================================================================= #
+  # === Q9: Describe the steps that have to be done for an ELISpot assay.
+  # ========================================================================= #
+  p_default_le {
+    e 'Q9: Describe the steps that have to be done for an ELISpot assay. '+
+      DONE_IMAGE,'lightblue'
+    br
+    e 'The ELISPOT assay can be used to assess cytokine secretion,
+    that is, to enumerate cytokine-secreting cells.'
+    br
+    e 'ELISPOT is an abbreviation towards <b>Enzyme-Linked Immunospot
+    assay</b>.'
+    br
+    e 'The ELISpot assay represents the convergence of
+    plate-based Enzyme Linked Immunosorbent Assays (ELISAs)
+    with membrane-based Western blotting technologies. It is
+    is a common method for the measurement of cellular immunity.
+    ELISPOT was developed for the detection of secreted proteins,
+    such as cytokines and growth factors.'
+    br
+    e 'ELISPOT evaluates the strength of T cell-mediated immune
+    activity. The limit of detection in an ELISPOT assay is
+    typically 1 cell in 100000 cells.'
+    br
+    e 'The ELISPOT method was first reported by Czerkinsky et al.,
+    in 1983. The method was originally developed to quantify
+    immunoglobulin-secreting cells.'
+    br
+    e 'Parameters that can be evaluated include:'
+    br
+    reset_the_counter
+    counter 'spot number','gold mars3em'
+    counter 'spot size','gold mars3em'
+    counter 'spot intensity','gold mars3em'
+    br
+    e 'ELISPOT enables the comprehensive screening of patient
+    derived peripheral blood mononuclear cells to reveal
+    the antigenic restriction of T-cell responses.'
+    br
+    e 'The majority of Elispots are performed on polyvinylidene
+    fluoride (PVDF) membrane plates. Alternatively a 
+    nitrocellulose membrane can be used.'
+    br
+    e 'The <b class="lightgreen">steps</b> for an
+    ELISPOT (standard assay variant) include:'
+    br
+    le '- Coat the membrane with the capture antibody. These
+    antibodies are often cytokine-specific and they are now
+    immobilized on membrane-bottomed 96-well plates. The 
+    antibody thus is the first layer in the individual 
+    wells, so they can be found on the bottom of the
+    wells. The capture antibody must be specific to the
+    secreted (target) protein.'
+    le '- Add the cells, usually peripheral blood mononuclear
+    cells, also called PBMCs). These are seeded in the presence
+    or absence of stimulating antigens.'
+    le '- Over time, activated cells (also called "responding
+    cells") begin to secrete cytokines, which bind to the
+    capture Antibody in the immediate vicinity of
+    the expressing cell.'
+    le '- Wash to remove away the cells.'
+    le '- Add a second cytokine-specific biotinylated
+    Ab which binds to the cytokine-Ab complex.
+    This is called the <b>detection antibody</b> and
+    it will bind specifically to the bound protein.'
+    le '- Add streptavidin-enzyme conjugate. Spot detection
+    is accomplished through substrate deposition following
+    either a one-step (enzyme-conjugated, cytokine-specific
+    Ab) or two-step (biotinylated Ab/streptavidin-enzyme)
+    antibody binding process. Once the signals are
+    developed, spot numbers can be tallied manually
+    or through use of image-based spot readers with
+    accompanying analysis software. The frequency and total number
+    of responder cells is determined by comparing the number of
+    spots between stimulated and untreated/control wells.'
+    br 
+    e 'Sources used:'
+    br
+    selfy 'https://www.future-science.com/doi/10.4155/bio-2022-0010',
+              css_class: 'steelblue'
+    selfy 'https://www.sciencedirect.com/topics/immunology-and-microbiology/enzyme-linked-immunospot-assay',
+              css_class: 'steelblue'
+  }
+  # ========================================================================= #
+  # === Peyersche Plaques
+  # ========================================================================= #
+  gold_cheader_h2 'Peyersche Plaques'
+  p_default_le {
+    e '<b>Plasmazellen</b>, die mit Peyersche Plaques assoziiert vorliegen,
+    sezernieren in der Regel Antikörper der Klasse 
+    <b class="lightblue">IgA</b>.'
+  }
+  # ========================================================================= #
+  # === Phagocytes
+  # ========================================================================= #
+  gold_cheader_h2 'Phagocytes'
+  p_default_le(id: 'Phagocytes') {
+    e 'The ability to discriminate friend from foe is of p­aramount
+    importance for any self‐respecting phagocyte.'
+    br
+    e "Phagocytes' primary function is to identify, ingest and destroy
+    microbes."
+  }
+  # ========================================================================= #
+  # === The Phagosome 
+  # ========================================================================= #
+  gold_cheader_h2 'The Phagosome'
+  p_default_le {
+    e 'The Phagosome has the <b>licence to kill</b>.'
+    br
+    e 'It can be created by professional phagocytes, such as
+    macrophages, neutrophils, and dendritic cells (DCs).'
+  }
+  # ========================================================================= #
+  # === Vaccination and Immunology
+  # ========================================================================= #
+  gold_cheader_h2 'Vaccination and Immunology'
+  p_default_le {
+    e '<b>Vaccination</b> remains the most effective method for preventing 
+    infections.'
+    br
+    e '<b>Generating memory responses</b> is a very important goal of
+    vaccination.'
+  }
+  # ========================================================================= #
+  # === PRR                                                        (PRR TAG)
+  # ========================================================================= #
+  gold_cheader_h2 'PRR: <i>pattern recognition receptors</i>'
+  p_default_le(id: 'PRR') {
+    e 'PRRs sind auf der Oberfläche von Phagocyten zu finden - sie werden
+    dort auch exprimiert. Dies hilft den Immunzellen Pathogene zu erkennen
+    und die Phagocytose zu ermöglichen.'
+    br
+    e 'PRRs on phagocytic cells recognize and are activated by PAMPs.'
+    br
+    e 'Each PRR is specific for a distinct PAMP. The PRRs are
+    <b>hard‐wired receptors</b>.'
+    br
+    e 'Phagocytosis of a single bacterium by a Dendritic Cell is quite
+    likely able to stimulate multiple categories of PRR simultaneously.
+    The assumption to be made here is that several signal transduction
+    pathways may act together, signifying that a robust response
+    is warranted.'
+    br
+    e '<b>TLRs</b> act as sensors for <b>PAMPs</b>.'
+  }
+  # ========================================================================= #
+  # === Erkältung
+  # ========================================================================= #
+  h2 'Erkältung',
+     'gold'
+  p_default_le {
+    e 'Man kann eine Erkältung unter Umständen durch folgende Maßnahmen
+    verkürzen:'
+    br
+    e '- Ausruhen und viel Schlaf'
+    e '- Tee und ausreichend Wasser'
+    br
+    e 'In der Regel dauert es zwischen drei bis zehn Tage, bis eine
+    Erkältung überwunden ist.'
+  }
+  # ========================================================================= #
+  # === Slogans tag. Slogan tag.
+  # ========================================================================= #
+  h2 'Immuno-Slogans',
+     'gold'
+  p_default_le {
+    e '- Innate and adaptive immune signaling are heavily Ub-mediated.'
+    br
+    e '- IgM is particular useful because it shows a high potential for
+    cross-linking antigens.'
+    br
+    e '- The Microbiome educates the immune system.'
+    br
+    e '- The human body, curiously enough, acts as an incubator of
+    a unique microbiome.'
+    br
+    e '- Jedes Toxin ist potenziell in der Forschung nützlich, da
+    Toxine an Proteine binden können und man so, im Prinzip, auch
+    das zugehörige Bindungsprotein finden kann. Daduch erhält man
+    eventuell einen Hinweis auf dessen Rolle im Kommunikationssystem
+    des Körpers.'
+    br
+    e '- <b>Bacterial pathogens</b> sense their environment, and in
+    response, virulence genes are induced or repressed through
+    spatial and temporal regulation.'
+    br
+    e '- A basic tenet of multicellularity is that one does not go
+    around randomly killing good cellular citizen.'
+    br
+    e '- Converting Actin Nucleation to a motile force is
+    done by <i class="lightgreen">Listeria monocytogenes</i>.'
+    br
+    e '- The miasma theory was the leading theory of disease origin,
+    until it was eventually displaced in the 19th century by the
+    germ theory of disease.'
+    br
+    e '- An allergic reaction results from the immune system being 
+    oversensitive, treating essentially harmless invaders as dangerous
+    enemies that must be fought down.'
+    br
+    e '- Most cells of the immune system are replaced every few days
+    to weeks.'
+    br
+    e "- In some types of <b>hepatitis</b> people die not from the
+    hepatitis virus itself, but from the immune system's <b>destruction 
+    of the liver</b>."
+    br
+    e '- Parasites have forced organisms to evolve immune systems. Examples 
+    are the restriction enzymes bacteria use to cut up invading viruses,
+    as well as the CRISPR/Cas defence system and the white blood cells
+    in the human body to destroy bacteria.'
+    br
+    e '- The total number of combinatorial arrangements of immunoglobulins
+    (Ig) in an individual is greater than 10⁹ (Jerne 1993).'
+    br
+    e '- Infectious agents may see humans as a rich sanctuary for
+    propagating their genome.'
+    br
+    e '- Pathogens vary greatly in size and lifestyle.'
+    br
+    e '- The battle of humanity versus microorganisms will continue in the
+    years to come.'
+    br
+    e '- The average human requires the production of almost 4 × 10¹¹
+    leukocytes (400 billion) per day.'
+    br
+    e '- <b>Rapid gene exchange</b> enables pathogens to avoid the host
+    immune system by expressing novel proteins not recognized by host
+    antibodies.'
+    br
+    e '- Immunology, in its modern form, is an experimental science.'
+    br
+    e '- <b>Smallpox</b> was the first disease that had been eradicated
+    worldwide by a program of vaccination.'
+    br
+    e '- A reaction to a microbial antigen is detectable only in individuals
+    who have previously encountered the antigen.'
+    br
+    e '- Many control mechanisms become active in immune responses to prevent
+    excessive activation of lymphocytes, which may cause collateral damage
+    to normal tissues.'
+    br
+    e '- The immune system has to combat many and diverse microbes.'
+    br
+    e '- An effective immune response eliminates the microbes that initiated
+    the response.'
+    br
+    e '- Hematopoiesis is the process of the lifelong regeneration of
+    our blood cells.'
+    br
+    e '- The ability to discriminate between self and non-self is 
+    the essence of immunity.'
+  }
+  # ========================================================================= #
+  # === Glossar
+  # ========================================================================= #
+  # http://localhost/programming/ruby/src/roebe/lib/roebe/www/immunology/immunology.cgi#glossar
+  # ========================================================================= #
+  gold_cheader_h2 'Glossar'
+  glossar_table(
+    'Infektion:','Eindringen von Krankheitserregern in den Körper.'
+  )
+  # ========================================================================= #
+  # === Links
+  # ========================================================================= #
+  h2 'Links',
+     'gold'
+  p_default_le {
+    selfy :local_bioinformatics,
+              css_class: COMMON_CSS_CLASS_FOR_HYPERLINKS
+    selfy :local_cellbiology,
+              css_class: COMMON_CSS_CLASS_FOR_HYPERLINKS
+    selfy :local_genetics,
+              css_class: COMMON_CSS_CLASS_FOR_HYPERLINKS
+    selfy :local_antibodies,
+              css_class: COMMON_CSS_CLASS_FOR_HYPERLINKS
+    selfy :local_biotechnology,
+              css_class: COMMON_CSS_CLASS_FOR_HYPERLINKS
+    selfy :local_molecular_therapies,
+              css_class: COMMON_CSS_CLASS_FOR_HYPERLINKS
+  }
+}}