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Lecture 4. Autoantibodies and chronic inflammation (AM_470656)

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Information on the basis of antibodies, function, role in vaccination and development of auto-antibodies. Antibodies as experimental tools, clinical drugs and engineering.

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  • January 2, 2023
  • 10
  • 2022/2023
  • Class notes
  • Prof. dr. r. mebius
  • All classes
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Molecular Cell Biology and Immunology
Lecture 4. Autoantibodies and chronic inflammation
INDEX
1. Antibody basics .......................................................................................................................................................................................... 1

1.1. Structure of the ab.............................................................................................................................................................................. 1

1.1.1. Isotypes ................................................................................................................................................................................................ 1

1.1.2. Flexibility .............................................................................................................................................................................................. 2

1.1.3. Behavior of the antibodies ................................................................................................................................................................... 2

1.2. IgA ...................................................................................................................................................................................................... 3

1.2.1. IgA and M cells ................................................................................................................................................................................ 3

2. Antibody functions ..................................................................................................................................................................................... 3

2.1. Fc receptors ........................................................................................................................................................................................ 4

3. Vaccination ................................................................................................................................................................................................ 4

4. Auto-antibodies .......................................................................................................................................................................................... 4

4.1. Example, systemic lupus eruthematosus (SLE) .................................................................................................................................... 5

4.2. Antibodies in Rheumatoid arthritis ..................................................................................................................................................... 5

Case ................................................................................................................................................................................................................ 6

4.3. Linear IgA bullous disease (LABD) ....................................................................................................................................................... 7

5. Antibodies as experimental tools ................................................................................................................................................................ 7

6. Antibody as clinical drugs ........................................................................................................................................................................... 7

7. ANtibody engineering ................................................................................................................................................................................. 8

7.1. Neutrophils as effector cells ............................................................................................................................................................. 10

8. Mechanisms and improvement ................................................................................................................................................................. 10

9. Take home messages ................................................................................................................................................................................ 10

, 1. ANTIBODY BASICS

There is an antigen presenting cell presenting to the CD4 helper
cell, that helps activate the B cell. These with the help of cytokines
turn into plasma cells and is able to secrete antibodies and they
loose the B cell receptor and they bind to the antigen. Later we
get a pool of the memory B cells. It is important to know that the
B cell receptor that binds the antigen is the same as the Ab
secreted (otherwise it would not recognize the ag anymore).

We have a primary and later response.

- When we get in contact with the 1st antigen exposure we produce IgM (1st response) and after we get somatic
hypermutation (higher affinity) and isotype switching (to get IgGs).
- After some time, the abs get eliminated and this time depends on the type of ab. In the case of SARS they are eliminated
a not long after the infection, this makes
the infection possible after the 1st one.
- If we get exposed a second time with the
same antigen, we have a quicker (faster
IgM and specially IgG) and higher affinity
response due to the memory cells.

In the case of measles, we get immunized naturally
or with vaccination and the protection is life-long.
This is not the case with all pathogens.

1.1. STRUCTURE OF THE AB

There are 2 heavy and 2 light chains that bind the same. Both have a variable domain
that is where the antigen binds (top part). There is a constant region that contains the
Fc region (important for the effector function).

For instance, immune cells express Fc receptors that bind the Fc tail. The complement
system can also bind the Fc tail, but the pathogen is bound by the variable domain.

Antibody engineering is used.




1.1.1. ISOTYPES
There are 5 major classes (M, D, G, A and E) and multiple subclasses (specially for
IgG: 1, 2, 3 and 4; IgA1 and IgA2). They all have different functions and some are
different:

- IgM is a large molecule, it is a pentamer coupled with the J chain.
o It is good as a platform for complement binding (good at
activating complement) but it is too large to diffuse into tissues.
→ It is a tread off in the things we can get from an antibody.

Serum levels:

- IgG are in high concentration, this molecule has a long ½ life. This two
things are related, because if there is a high half-life then the molecules
doesn’t get broken down that easily and there is more in the serum.


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