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Cellular Biophysics
SS 20007
Manfred Radmacher
Ch. 13 Immune System
INSTITUT FÜRBIOPHYSIK
Universität Bremen
Cellular Biophysics Prof. Manfred RadmacherCh. 13 Immune System Universität BremenINSTITUT FÜRBIOPHYSIK
Immune system has several layers
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Cellular Biophysics Prof. Manfred RadmacherCh. 13 Immune System Universität BremenINSTITUT FÜRBIOPHYSIK
The immune system attacks pathogens
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From: http://pathmicro.med.sc.edu/ghaffar/innate.htm
macrophage attacking bacteria
Cellular Biophysics Prof. Manfred RadmacherCh. 13 Immune System Universität BremenINSTITUT FÜRBIOPHYSIK
The immune system is the largest organ
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Cellular Biophysics Prof. Manfred RadmacherCh. 13 Immune System Universität BremenINSTITUT FÜRBIOPHYSIK
The memory of the adaptive immune system is in the B cells
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Figure 24-4. A classic experiment showing that lymphocytes are required for adaptive immune responses to foreign antigens. An important requirement of all such cell-transfer experiments is that cells are transferred between animals of the same inbred strain. Members of an inbred strain are genetically identical. If lymphocytes are transferred to a genetically different animal that has been irradiated, they react against the “foreign” antigens of the host and can kill the animal. In the experiment shown, the injection of lymphocytes restores both antibody and cell-mediated adaptive immune responses, indicating that lymphocytes are required for both types of responses.
Cellular Biophysics Prof. Manfred RadmacherCh. 13 Immune System Universität BremenINSTITUT FÜRBIOPHYSIK
B and T lymphocytes can be resting or active
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Resting B lymphocyte Activated B lymphocyte producing antibodies
Cytotoxic T lymphocyte
Cellular Biophysics Prof. Manfred RadmacherCh. 13 Immune System Universität BremenINSTITUT FÜRBIOPHYSIK
The innate immune systems activates the adaptive immune system
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Figure 24-5. One way in which the innate immune system helps activate the adaptive immune system. Specialized phagocytic cells of the innate immune system, including macrophages (not shown) and dendritic cells ingest invading microbes or their products at the site of infection. The dendritic cells then mature and migrate in lymphatic vessels to a nearby lymph node, where they serve as antigen-presenting cells. The antigen-presenting cells activate T cells to respond to the microbial antigens that are displayed on the presenting cells' surface. The antigen-presenting cells also have special proteins on their surface (called costimulatory molecules) that help activate the T cells. Some of the activated T cells then migrate to the site of infection where they either help activate macrophages or kill infected cells, thereby helping to eliminate the microbes. As we discuss later, the costimulatory molecules appear on dendritic cells only after these cells mature in response to invading microbes.
Cellular Biophysics Prof. Manfred RadmacherCh. 13 Immune System Universität BremenINSTITUT FÜRBIOPHYSIK
The adaptive immune has a memory
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Figure 24-10. Primary and secondary antibody responses. The secondary response induced by a second exposure to antigen A is faster and greater than the primary response and is specific for A, indicating that the adaptive immune system has specifically remembered encountering antigen A before. The same type of immunological memory is observed in T-cell-mediated responses.
Cellular Biophysics Prof. Manfred RadmacherCh. 13 Immune System Universität BremenINSTITUT FÜRBIOPHYSIK
Clonal selection theory: each B cell produces only one type of
antibody
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Figure 24-8. The clonal selection theory. An antigen activates only those lymphocyte clones (represented here by single cells) that are already committed to respond to it. A cell committed to respond to a particular antigen displays cell-surface receptors that specifically recognize the antigen, and all cells within a clone display the same receptor. The immune system is thought to consist of millions of different lymphocyte clones. A particular antigen may activate hundreds of different clones. Although only B cells are shown here, T cells operate in a similar way.
Cellular Biophysics Prof. Manfred RadmacherCh. 13 Immune System Universität BremenINSTITUT FÜRBIOPHYSIK
If a clone is deleted no antibodies of this clone can be
generated anymore
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Cellular Biophysics Prof. Manfred RadmacherCh. 13 Immune System Universität BremenINSTITUT FÜRBIOPHYSIK
Antibodies recognize highly specific their antigen
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Specific binding of antibody and antigen
Cellular Biophysics Prof. Manfred RadmacherCh. 13 Immune System Universität BremenINSTITUT FÜRBIOPHYSIK
AFM images of antibodies
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From: Monika Fritz
Cellular Biophysics Prof. Manfred RadmacherCh. 13 Immune System Universität BremenINSTITUT FÜRBIOPHYSIK
How many different antibodies are needed?
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an antibody recognizes a part of the surface of an
antigen: the epitope
let's assume: epitopes are 2 by 3 amino acids in size
this gives: 206 different epitopes: ~60 million
they can not be encoded each by a single gene
Cellular Biophysics Prof. Manfred RadmacherCh. 13 Immune System Universität BremenINSTITUT FÜRBIOPHYSIK
The genes for antibodies are spliced together from several options
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Figure 24-37. The V-J joining process involved in making a human ! light chain. In the “germ-line” DNA (where the antibody genes are not being expressed and are therefore
not rearranged), the cluster of five J gene segments is separated from the C-region exon by a short intron and from the 40 V gene segments by thousands of nucleotide pairs.
During the development of a B cell, the randomly chosen V gene segment (V3 in this case) is moved to lie precisely next to one of the J gene segments (J3 in this case). The
“extra” J gene segments (J4 and J5) and the intron sequence are transcribed (along with the joined V3 and J3 gene segments and the C-region exon) and then removed by RNA
splicing to generate mRNA molecules in which the V3, J3, and C sequences are contiguous. These mRNAs are then translated into ! light chains. A J gene segment encodes the
C-terminal 15 or so amino acids of the V region, and the V-J segment junction coincides with the third hypervariable region of the light chain, which is the most variable part of
the V region.
Cellular Biophysics Prof. Manfred RadmacherCh. 13 Immune System Universität BremenINSTITUT FÜRBIOPHYSIK
heavy chains: 500 V segments * 4 J segments *
12 D segments:
24000 combintaions
How many combinations?
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light chains: 300 V segments * 4 J segments:
1200 combintaions
total number: 3 * 107
Cellular Biophysics Prof. Manfred RadmacherCh. 13 Immune System Universität BremenINSTITUT FÜRBIOPHYSIK
Where is biophysics in the immune system?
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specific molecular interactions in antigen
antibody recognition
chemotaxis of macrophages
system theory in development of immune system
Cellular Biophysics Prof. Manfred RadmacherCh. 13 Immune System Universität BremenINSTITUT FÜRBIOPHYSIK
Immune System Theory
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From: Sackmann Biophysik Skript
Ein Antigen Ag X (mit einer Determinanten) stimuliert die Synthese eines Antikörpers Ab1 (den sog. Idiotyp), der
seinerseits antigene Wirkung zeigt und einen zweiten Klon zur Produktion eines Antikörpers Ab2 (den sog. Anti-
Idiotyp) anregt, der zu Ab1 komplementär ist. Ab2 stimuliert dann Ab3 usw.
Cellular Biophysics Prof. Manfred RadmacherCh. 13 Immune System Universität BremenINSTITUT FÜRBIOPHYSIK
Immune System Theory
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From: Sackmann Biophysik Skript
Abb. 34.19: Schematische Darstellung des verzweigten Immunnetzwerkes. Das Antigen AgX mit mehreren Determinanten stimuliert mehrere Klone zur Produktion von Antikörpern Ab1 (idiotyp), die ihrerseits die
Synthese von anti-idiotypen Ab2 auslösen usw. Im Immunsystem sind sehr wahrscheinlich die B-Zellen an der
ersten Stufe (Ab1) beteiligt, während die Antwort ab Ab2 durch T-Zellen vermittelt wird.
Cellular Biophysics Prof. Manfred RadmacherCh. 13 Immune System Universität BremenINSTITUT FÜRBIOPHYSIK
Immune System Theory
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Derivation
Cellular Biophysics Prof. Manfred RadmacherCh. 13 Immune System Universität BremenINSTITUT FÜRBIOPHYSIK
Immune System Theory
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From: Sackmann Biophysik Skript
Abb. 34.20: Verhalten des Immunsystems bei ständiger Zugabe einer niedrigen Konzentration [X] des Antigens AgX. Situation der Niedrig-Dosen-Toleranz.
Cellular Biophysics Prof. Manfred RadmacherCh. 13 Immune System Universität BremenINSTITUT FÜRBIOPHYSIK
Immune System Theory
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From: Sackmann Biophysik Skript
Das Antigen AgX wird in höherer Konzentration injiziert. Die Unterdrückung der Ab1 durch Ab2 wird (durch
Bindung von AgX an Ab1) soweit gehemmt, daß die Unterdrücker Ab2 durch Ab3 selbst elminiert werden. Auch
spätere Zugaben von AgX werden durch Ab1 (B-Zellen) leicht eliminiert.
Cellular Biophysics Prof. Manfred RadmacherCh. 13 Immune System Universität BremenINSTITUT FÜRBIOPHYSIK
Immune System Theory
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From: Sackmann Biophysik Skript
Das Immunsystem toleriert eine hohe Konzentration des Antigens ([X] ist um einen Faktor 103 höher als bei der Niedrig-Zonen-Toleranz). Der Grund liegt in der Elimination der B-Zellen Ab1 durch die Population 2.
Die Konzentration [Ab2] steigt an, da die Helfer-Zellen 3 durch Ab4 eliminiert werden. Die 5. Stufe der
Hierarchie wird nicht mehr aktiviert.
Cellular Biophysics Prof. Manfred RadmacherCh. 13 Immune System Universität BremenINSTITUT FÜRBIOPHYSIK
Final remarks on the immune system
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tolerance against self antigens is trained in early childhood
tolerance against self antigens is trained in early childhood
there are auto-immune deseases
there are hints that allergies may be related to development
of immune system:
hygiene hypothesies
worm treatment
Cellular Biophysics Prof. Manfred RadmacherCh. 13 Immune System Universität BremenINSTITUT FÜRBIOPHYSIK
Applications of Antibodies: blood group test
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Cellular Biophysics Prof. Manfred RadmacherCh. 13 Immune System Universität BremenINSTITUT FÜRBIOPHYSIK
Applications of Antibodies: blood group test
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Experiment
http://upload.wikimedia.org/wikipedia/commons/thumb/c/ce/ABO_blood_group_diagram.svg/795px-ABO_blood_group_diagram.svg.png
Cellular Biophysics Prof. Manfred RadmacherCh. 13 Immune System Universität BremenINSTITUT FÜRBIOPHYSIK
Elisa
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http://www.biosystemdevelopment.com/technology.htm