The role of antibodies Flashcards
What’s special about IgG3?
It has a large hinge region comparing to other IgGs and because of it, it can get to sites where other antibodies can’t but it is more prone to degradation so it’s shorter lived.
What is special about IgA?
It forms a dimer, which allows to make immune complexes to bind the target and take it out of circulation.
Disseminated salmonella infection
- Salmonella goes from the gut to the mesenteric lymph node,
-mesenteric lymph node works as a gatekeeper but if it will fail with constraining the spread of the bacteria it can get to the blood, - It can get to the spleen, bone marrow and liver,
- Then it returns back to the gut
Salmonella is at low risk when its in the gut, it becomes a risk when it becomes disseminated. The molecule which protects from dissemination is an antibody.
How can you model salmonella infection in the mouse model?
You can infect the mouse with salmonella and then it will spread to sites like spleen and liver. This gives you the way of monitoring both the development of the immune response and how immune system works to control the infection.
What does the existence of antibodies do for you?
It gives a pre-existing protective barrier that works very quickly. Antibodies buy the host’s time to make a functional immune response to clear the pathogen.
What do vaccines against bacteria contain?
For example:
- Capsule
- LPS
- cell wall-associated antigens
- secreted antigens
What is the problem between different salmonella types?
Because antibodies are very specific, if LPS O-antigen has a single sugar change in LPS, which limits the cross-protection between different salmonella types despite otherwise high homology.
O-antigen is a shield against antibodies targeting surface proteins, if the target protein is ‘big’, it leaves a gap in LPS for the antibody to be able to access it and bind, but if it is ‘small’ then there is no gap in LPS layer and the antibody cannot bind. There are specific antibodies which are not able to bind to their target and cannot be protective.
Serum bactericidal assay (SBA)
Mix together the pathogen, the antibody and the complement. If you have antibodies which are specific to the pathogen, it will make a hole in the pathogen and kill it. This assay is important for vaccinations and shows the effectiveness of the immune response. If you have only the complement, it is not sufficient enough to kill the bacteria, you also need specific antibodies. Antibodies themselves also are not as successful as antibody plus complement.
What is a connection between C3 from complement with antibodies?
C3 is important for making antibody responses. But, it is less essential for the antibody responses that already function. We know that because for example if we take C3 KO mice and take immune serum from WT mice and transfer it into our C3 KO mouse and then infect with the pathogen. If there are antibodies already present C3 is not essential but it is essential for making first antibody responses.
What can intra-vital microscopy be used for?
It can be used to follow the infection, and it also shows that vaccinations enhance the efficacy of bacterial capture.
How are macrophages restricting the bacterial spread within organs?
They are not essential for killing the pathogen but help by restricting bacterial spread within organs. We know that because if we compare the number of bacteria and observe under the microscope in the organ with the vaccine and macrophages and with vaccine but without macrophages we can see that the number of the bacteria didnt increase much when macrophage KO but the bacteria spread more around the organ.
how to check role of antibodies and complement on macrophages in vitro on the human model?
Use infection of human macrophage cell line (THP1) give pathogen and give or don’t antibodies and complement. When are both antibodies and complement, macrophages take up pathogen the most. If the complement or C3 are missing then macrophages take up pathogen less.
Summary
- Having a specific antibody for the pathogen is not everything, as LPS can hide antigens so that antibodies cannot bind to them.
- Both specificity and effector function of antibodies are important
- Different elements of pathogens are used in vaccines
- Antibodies are really important in boosting the immune response, however, a lot of other elements of the immune system are required for the effective immune response
What can antibodies do?
- Neutralise toxins
- Flag the pathogen (opsonisation)
- Activate complement (IgG and IgM)
- Agglutination
- IgG can cross the placenta by IgG receptor on the placenta
Which antibodies contribute to classical pathway of complement activation?
- IgM
- IgG3
- IgG1
- IgG2
