Aston University, Birmingham (Aston)
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Mechanisms of pathology
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Defence against infections.
• Innate response- very early response involving cells such as neutrophils,
macrophages and dendritic cells.
• Which try to contain the invading pathogen very quickly and send off the right
signals to induce the adaptive immune response.
• This is a very rapid and quick response.
• Adaptive response is much more slow going.
• It is the second wave of the immune response because it happens once the innate
response has started.
• The ultimate aim of the adaptive response is to provide memory cells to give us long
lasting protection against that pathogen but also to produce those vital antibodies to
clear that pathogen as quickly as possible.
• It takes time for the entire immune response from start to finish to occur and to
generate those protective antibodies to efficiently clear the pathogen, it can take
anything up to 2-3 weeks.
• This is not a good strategy for us as we encounter new environmental pathogens.
• If we had to map out the same immune response every time we met the same
pathogen, this is extremely wasteful because it would take 3 weeks to generate
antibodies and then once we would have resolved that pathogen if we did not have
memory cells we would have to adopt a new innate and adaptive response to
generate new antibodies to clear that pathogen when we meet it for the second
time.
• Memory cells develop after the initial response to the pathogen. Meaning when we
encounter the same pathogen for a second time the memory cells are activated
much more quickly. They proliferate much more quickly allowing us to generate
those protective antibodies much more efficiently and quickly than we could have
done in the first exposure.
Immunological memory
• “The ability of the immune system to respond more rapidly and effectively to
pathogens that have been encountered previously”
• Basic definition of immunological memory on PowerPoint slide:
• We develop these cells which have the ability to proliferate and activate much more
quickly during reencounter with that pathogen for the second time.
• It is a specialized feature of the adaptive immune response; you get both T and B
memory cells.
• And you only get memory cells after you encounter the pathogens for the first time.
• So you need to develop that innate and adaptive immune response to the pathogen
the first time, to develop those memory cells in order for them to be reactivated in
the secondary encounter to the pathogen.
• There are differences between memory cells and naïve cells.
More rapid and effective.
• Memory cells are much more rapid and effective compared to our standard naïve
cells.
• The graph shows:
, • A primary response to an antigen, which will give you an antibody response after 2
to 3 weeks after the innate and adaptive immune responses have worked in
coordination to develop antibody response.
• Once you have cleared the pathogen, those antibodies will decrease in the serum,
but when you reencounter that pathogen or antigen, you develop much more
rapidly a much bigger titer of the antibodies against the antigen you have seen
before.
• This is termed the memory response.
• If you are being exposed to two different antigens, you will develop a memory
response to the antigen that you have seen before.
• But you will develop a primary response in much lower amounts, taking much longer
to that second antigen.
• Memory responses are about developing a much stronger, quicker response to the
antigen the second time that you see it.
Memory B cells arise in GC
• Memory B cells are critically important cells for this.
• The germinal center develops in the lymph node, during the activation of T cells via
the dendritic cells, bringing antigen in from the peripheral tissues.
• Once we get T cell activation, it drives the process of B cell activation and the
formation of that germinal center structure.
• The output of the germinal center are memory B cells, and also plasma cells.
• Plasma cells are those secreting those high quantities of antibodies.
• This is a very complex process involving multiple cell-cell interactions.
• The primary goal of this reaction is to develop memory B cells and also large
quantities of antibody via plasma cells to efficiently clear the pathogen.
Naïve vs memory B cells.
• Germinal center does several things to allow us to generate those memory B cells.
• Memory B cells, once they are produced after that primary response, produce
antibodies at a much higher affinity for the target antigen when they are reactivated.
• This comes from class switching from IgM to IgG.
• In the primary immune response, you make a lot of IgM antibody but subsequently
when you reencounter that pathogen you get class switching to the much higher
affinity antibody IgG.
• So during a primary immune response you make IgM and you’ll make some IgG but
during a memory response when you see that antigen for a second time, you
primarily make IgG.
• So you are making that high affinity class switched antibody.
• Memory B cell formation ensures that there are plenty of these cells around to
respond much more rapidly, when you see that infection or pathogen for a second
time.
• There is typically 10-100 fold more memory B cells for that particular pathogen than
there would be for naïve B cells for that pathogen.
• In the primary immune response, where you activate the innate immune response
and then generate the adaptive immune response, forming that germinal center
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