Cellular Biophysics SS 20007 Manfr ed Radmacher€¦ · Cellular Biophysics Ch. 13 Immune System Prof. Manfred Radmacher Universit tBremen INSTITUTF R BIOPHYSIK The innate immune

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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The immune system attacks pathogens

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From: http://pathmicro.med.sc.edu/ghaffar/innate.htm

macrophage attacking bacteria


The immune system is the largest organ

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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.


B and T lymphocytes can be resting or active

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Resting B lymphocyte Activated B lymphocyte producing antibodies

Cytotoxic T lymphocyte


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.


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.


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.


If a clone is deleted no antibodies of this clone can be

generated anymore

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Antibodies recognize highly specific their antigen

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Specific binding of antibody and antigen


AFM images of antibodies

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From: Monika Fritz


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


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.


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


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


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.



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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.



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Derivation



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Abb. 34.20: Verhalten des Immunsystems bei ständiger Zugabe einer niedrigen Konzentration [X] des Antigens AgX. Situation der Niedrig-Dosen-Toleranz.



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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.



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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.


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


Applications of Antibodies: blood group test

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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


Elisa

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http://www.biosystemdevelopment.com/technology.htm

Documents

Cellular Biophysics SS 20007 Manfr ed Radmacher€¦ · Cellular Biophysics Ch. 13 Immune System Prof. Manfred Radmacher Universit tBremen INSTITUTF R BIOPHYSIK The innate immune