Flashcards in IMI7: Immune memory and vaccination Deck (99)
What did the German scientist Emil von Behring and the Japanese physician Shibasaburo Kitasato discover in 1890?
that the transfer of serum from a mouse immunised against tetanus to a non-immunised mouse could completely protect the latter from a normally fatal challenge with virulent tetanus bacteria.
What did Emil von Behring and the Shibasaburo Kitasato's observation support?
Paul Ehrich's model of humoral factors being the critical mediators of immunity, and is relatively short-lived. .
What did subsequent adoptive transfer experiments show? (where various sets of cells from immunised mice are transferred to immunologically naive mice)
That certain subsets of B and T lymphocytes are the key elements in the potentially life-long immunity that we develop after infection or vaccination.
What is the primary role of B cells in immunity?
the development and production of high affinity specific antibodies.
Why do B cells need to have the ability to develop and produce high affinity specific antibodies?
To be pre-armed against re-infection, the body needs both an abundance of antibodies in the body fluids (be it blood, lymphatics or mucosal surfaces), and cells that can accelerate the production of more antibody when a re-infection occurs. For any given antibody, these two jobs are done by different B cell subsets.
Where are high affinity antibodies produced?
Germinal centre of the secondary lymphoid organs
What are the two cell types that emerge from the germinal centre reaction?
Effector B cells that make antibodies
The resting cell that is ready to respond next time
What is the effector B cells that make antibodies called?
What is the resting cell that is ready to respond next time called?
Memory B cell
What is the quickest response that the adaptive immune system can provide? Why?
Having sufficient levels of antibody when a pathogen invades - If the antibody can intercept the pathogen before it gets a chance to properly invade or proliferate, then the infection will be stopped before it even begins.
What is opsonisation?
Marking a pathogen for phagocytosis
What is complement fixation?
Promoting the rupture of membranes
What is neutralisation?
Preventing the successful invasion of cells by the pathogen
The antibodies in our body fluids are produced mainly by what? Where do they take up residence?
long-lived plasma cells
in our bone marrow and mucosal tissues (gut, lung)
Despite being a _____ _______ cell type, long lived plasma cells appear to be able to survive extremely long periods of time.
Why do long-lived plasma cells survive a very long time?
In part, because they express very low levels of the B cell receptor (BCR), which means they are not easily activated when encountering antigen. thus the long-lived cells do not boost body-wide antibody production, but rather are responsible for maintaining a baseline of antibody production in the long term.
What are long-lived plasma cells responsible for?
maintaining a baseline of antibody production in the long term.
Early in the response, many of these memory cells will retain what type of immunoglobulin production, having not class-switched?
Later in the response, the majority of memory cells leaving the germinal centre will have class switched to what? depending on what? What has happened to the affinity?
IgG, IgA or IgE, depending on the nature of the signals provoked by the pathogen. These will also have Ig with a higher affinity for the target.
What kind of metabolic rates do memory B cells have?
Do naive or memory B cells have a faster rate of response to a pathogen?
memory B cells
Why do memory B cells respond more quickly to pathogens than naïve B cells?
In part because they have more of the activating receptors such as CD40, CD80 and CD86 on their surface. They are also more sensitive to stimulation by PAMPs.
What restrictions to proliferation and activation do naïve and memory B cells have in common?
They require T cell help, BCR binding and an innate signal (through cytokine signals and/or sensing of PAMPs) to trigger their activation and proliferation.
When B cells are activated what happens to them?
Some of these cells then differentiate into plasma cells to produce antibodies, while others – particularly the lower affinity IgM subset – will migrate to the germinal centre to undergo further affinity maturation.
Why would a memory B cell, which has already undergone affinity maturation, return to the germinal centre for more?
To adapt to pathogens mutating – particularly to antigenic drift:
- It keeps diverse Igs with low affinity as memory B cells, making it more likely that some of those will still be able to recognise a modestly mutated antigen.
-This will then act as a basis for producing new high affinity immunoglobulins against this modified strain of pathogen, protecting against a wider variety of virus strains.
Once a pathogen has been defeated, what happens to the amount of antigen present?
What does the reduction of antigen in the blood do to B cell production?
It first triggers more of the cells to leave the germinal centre as plasma cells, some of which will migrate to the local mucosal niche or the bone marrow, to become long lived plasma cells.
Once the pathogen has been defeated what happens to the remaining cells in the germinal centre?
Most of the remaining cells in the germinal centre will stop proliferating and die, so there is space in the lymph node for a new germinal centre to form around the next batch of antigen to arrive.
What controls which memory B cells and plasma cells remain as the long-lived memory?
This is not yet known