3. Vorlesung Immunologie

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3. Vorlesung Immunologie
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3. Vorlesung Immunologie
Einführung - Angeborene und erworbene Immunität
Zellen und Organe des Immunsystems
Reifung der Lymphozyten - Apoptose
Antikörper (Ak) - Entstehung der Ak-Variabilität
Herstellung und Nutzung von Antikörpern
T-Zell-Rezeptoren (TcR) und T-Zellen
MHC (major histocompatibility complex) -Moleküle
Regulationsmechanismen (Vermeidung von Reaktionen gegen "Selbst")
Phylogenese der spezifischen Immunmechanismen
Zusammenfassung: Immunologie I; 2. Vorlesung (1/1)
1. Komponenten der angeborenen Immunität sind äußere Barrieren
(Haut), phagozytierende Zellen, lösliche Moleküle etc.
2. Die Rezeptoren der angeborenen Immunität (wie z.B. die TLR)
werden von Keimbahn-Genen kodiert.
3. Zu den löslichen Komponenten der angeborenen Immunität gehören
Akute-Phase-Proteine, das Komplement-System, Interferone etc.
4. Die wichtigsten Charakteristika der erworbenen Immunität sind:
a. Unterscheidung von Selbst und Fremd,
b. Vielfalt und Spezifität,
c. Adaptivität,
d. Gedächtnis.
5. Das immunologische Gedächtnis ermöglicht die Vakzinierung gegen
Infektionserreger.
Fig. 1.2 The eradication of smallpox by vaccination
Mr. John Wickett, of the World Health Organization, with
the last person to have contracted – and survived –
naturally occurring smallpox (hospital cook Ali Maow
Maalim in Merka, Somalia, on October 26, 1977).
courtesy Mr. John Wickett.
Somalia, 1977 Ali Maalim, last recorded case of
naturally-caused smallpox
http://www.cdc.gov/od/ogh/smallmaa.htm
● 2002 - Health experts blamed
rise of measles cases on poor
uptake of MMR vaccine
● 2005 - Mumps epidemic mainly
affected 13-24 year-olds who
were too old to have had MMR
vaccine as children
► Complications of mumps ◄
1 in 25: Deafness - usually with partial or
complete recovery
1 in 30: Pancreatitis Hospital admission
Mumps during pregnancy can cause
miscarriage
Quellen: http://news.bbc.co.uk/1/hi/health/7314144.stm
http://news.bbc.co.uk/2/hi/health/3643676.stm
Fig. 1.19 The principle of vaccination is illustrated by immunization with diphtheria toxoid.
Chemical modification of diptheria toxin produces a toxoid which has lost toxicity but retains
its epitopes. Thus, a primary antibody response to these epitopes is produced following
vaccination with toxoid. In a natural infection the toxin re-stimulates B memory cells, which
produce the faster and more intense secondary antibody response to the epitope, so
neutralizing the toxin.
Roitt, Brostoff & Male: Immunology. 5th ed. Mosby1998
Zellen des Immunsystems
● Phagozyten, weitere Leukozyten,
● Antigen-präsentierende Zellen
● T- & B-Lymphozyten (klonale Selektion)
 sie sind Träger und Produzenten
der „spezifischen“ Rezeptoren
Lymphozyten mit spezifischen Rezeptoren
T-Lymphozyten
B-Lymphozyten
B-Zellen
produzieren
Antikörper
TH1-Zellen
aktivieren
Makrophagen
TH2-Zellen
aktivieren
B-Zellen
TC-Zellen
TR/S-Zellen
töten Virusregulieren andere
infizierte Zellen
Immunzellen
erkennen fremde Antigene;
Rezeptoren sind durch somatisch rekombinierte Gene kodiert
Fig. 1.5 Lymphocytes are mostly small and inactive cells
The left panel shows a light micrograph of a small Iymphocyte in which the nucleus has been stained
purple by the hematoxylin and eosin dye, surrounded by red blood cells (which have no nuclei). Note the
darker purple patches of condensed chromatin of the Iymphocyte nucleus, indicating little transcriptional
activity, the relative absence of cytoplasm, and the small size. The right panel shows a transmission
electron micrograph of a small Iymphocyte. Again, note the evidence of functional inactivity: the
condensed chromatin, the scanty cytoplasm, and the absence of rough endoplasmic reticulum.
Photographs courtesy of N. Rooney.
„Spezifische“ Rezeptoren der
erworbenen Immunabwehr
B-Zell-Rezeptoren - Immunglobuline (Ig),
Antikörper
T-Zell-Rezeptoren - zellständige
Abwehrmoleküle
Variabilität entsteht in jedem Individuum auf
somatischer Ebene
naïve Zellen
ausdifferenzierte Zellen
B-Lymphozyt
Plasmazelle
lösl. Produkte
Antikörper
Rezeptoren
Oberflächen-Ig
T-Lymphozyt
keine Oberfl.-Ig, lösl. Ig = Ak
EffektorT-Lymphozyt
Zytokine,
Perforine,
Granzyme
etc.
Rezeptoren
TcR
TcR
Fig. 1.3 All the cellular
elements of the blood,
including the cells of the
immune system, arise
from pluripotent
hematopoietic stem cells
in the bone marrow.
Lymphatische Organe
Primäre lymphatische Organe:
Thymus, Bursa fabricii, Knochenmark
Sekundäre lymphatische Organe:
Milz, Lymphknoten, Peyersche Plaques,
Tonsillen, Appendix, Mucosa-assoziiertes
Gewebe, Lymphbahnen, zirkulierende
Lymphozyten (1 - 5 x 1011 Zellen/Tag),
Lymphbahnen, Blut
Roitt, Brostoff & Male: Immunology. 5th ed. Mosby1998
Fig. 1.2 The major lymphoid
organs of the mouse
Blut: 5-11 x 106 Lymphozyten
Hudson & Hay: Practical Immunology.
3rd ed. Blackwell 1991
aus: Practical Immunology. L. Hudson & F. C. Hay
Lymphozyten mit spezifischen Rezeptoren
T-Lymphozyten
B-Lymphozyten
B-Zellen
produzieren
Antikörper
TH1-Zellen
aktivieren
Makrophagen
TH2-Zellen
aktivieren
B-Zellen
TC-Zellen
TR/S-Zellen
töten Virusregulieren andere
infizierte Zellen
Immunzellen
erkennen fremde Antigene;
Rezeptoren sind durch somatisch rekombinierte Gene kodiert
Fig. 7.10 The thymus is critical for
the maturation of bone marrow
derived cells into T cells.
Mice with the scid mutation have a defect that
prevents lymphocyte maturation, whereas
mice with the nude mutation have a defect that
affects the development of the cortical
epithelium of the thymus. T cells do not
develop in either strain of mouse: this can be
demonstrated by staining spleen cells with
antibodies specific for mature T cells and
analyzing them in a flow cytometer, as
represented by the blue line in the graphs in
the bottom panels. Bone marrow cells from
nude mice can restore T cells to scid mice (red
line in graph on left), showing that, in the
correct environment, the nude bone marrow
cells are intrinsically normal and capable of
producing T cells. Thymic epithelial cells
from scid mice can induce the maturation of T
cells in nude mice (red line in graph on right),
demonstrating that the thymus provides the
essential microenvironment for T-cell
development.
Längsschnitt durch Knochen
von Säugetier und Vogel
C. Perrins, Pareys Naturführer
Plus Vögel, Parey, Hamburg ,
1987
Primary
lymphatic organs
Secondary
lymphatic organs
Thymus
T lymphocyte
with specific receptors
against foreign antigens
and self MHCs
Bone marrow
Bone marrow
Stem cells;
lymphatic precursor
cells
Lymphocytes
are provided with random receptors
one cell receives receptors of one specificity
Deletion of autoreactive cells
B lymphocyte
with specific receptors
against foreign antigens
Fig. 7.15 The cellular organization of the
human thymus.
Migrationsrichtung der
Thymozyten
Fig. 12.12 (1) Low-power scanning electron micrograph showing the architecture of bone and its
relationship to bone marrow. A cavity has been picked out and is drawn schematically on the right.
(2) Within the cavities of spongy bone, B-cell lymphopoiesis takes place, with maturation occurring in a
radial direction towards the centre (from the endosteum to the central venous sinus). Immature
progenitor cells adjacent to the endosteal cell layer mature into pre-B cells, many of which die and are
phagocytosed by bone-marrow macrophages containing tingible bodies. Cells which survive mature
further and reach the central venous sinus. Association with stromal cells, and the presence of
cytokines such as IL-7, are essential for all steps of B-cell maturation.
Roitt, Brostoff & Male: Immunology. 5th ed. Mosby1998
2. “Vermeidung" von Reaktionen gegen "selbst"
(eine Art „Selbsterkennen“)
2.1. Schutzmechanismen
a) Schutzmoleküle an Zelloberflächen (z.B. CD59 -Protectin),
um Komplementaktivierung zu verhindern
2.2. Erkennung von "selbst“, um Reaktionen
gegen "selbst" zu verhindern
a) Erkennung von MHC-Molekülen durch NK cells (KIR)
b) Erkennung von CD47 durch Makrophagen (SIRPα)
2.3. Toleranz und Regulationsmechnanismen
a) Elimininierung von selbst-reaktiven B- und TLymphozyten in den primären lymphatischen Organen
(“Lernprozess“)
b) Regulation der Aktivität der B- und T-Lymphozyten
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