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T
cell summary
The T cell system involves several subpopulations of cells with
different functions. Although T cells were only discovered late
1950s-60s they are turning out to be the most important part of
our adaptive defense. The immune system does not know which microorganisms
it will encounter. It does not try to anticipate the future. So
just a few T cells specific for each antigen are produced. Both
Tc/s and Th cells are antigen specific. These are called the "virgin
lymphocyte pool". There may literally be just 10 or 20 cells
able to target a particular antigen on a microorganism, so the first
response to activation by antigen presenting cells is to multiply
in numbers. For as long as the T cells receive antigenic stimulation
they will continue to proliferate. Most of the daughter cells go
to attack the pathogen and are called "effector cells"
but a few are held back as "memory cells". These memory
cells don't get involved in the attack on pathogens rather, they
act as the filing system to record that the immune system has encountered
this particular antigen. The memory cells will act as the cell pool
for future proliferation if even more T cells are required.
T cells are what vaccines ultimately activate and produce. The
presentation of vaccine antigens to the immune system via antigen
presenting cells induces those Th cells that are specific for the
particular vaccine antigens to proliferate. Most of the T lymphocytes
will be effector cells which will quickly set to work to remove
the vaccine antigens. Some of the cells will be memory cells and
they now keep the code for the antigens in the vaccine. The next
time the immune system encounters the same antigens (on the microorganism
this time) the memory cells think; aha! We have seen this antigen
before! It wasn't part of us the first time around so it definitely
won't be part of us now!!' The memory cells respond far better to
antigenic stimulation than virgin lymphocytes. They proliferate
more quickly, produce more daughter cells and are more vehement
in their attack on the pathogen. In other words, the immune system
has adapted to its environment and learned that it is more likely
to encounter certain antigens than others. Based on experience,
it keeps a memory of those antigens it knows it will probably encounter
again and puts more effort into getting rid of antigens it has seen
before.
B
cells
B cells look a lot like T cells in their size and shape except
they never have granules present in their cytoplasm. The "B"
stands for Bursa of Fabricious, the organ only found in some birds
where B cells go to mature. B cells were first identified in birds
and found associated with this organ. Conveniently B can also stand
for bone marrow where B cells mature in non-bird species like ourselves.
In humans, B cells are released into the blood stream from the bone
marrow as fully functioning adult cells. They constitute between
5 and 15% of all mature lymphocytes.
B cells are of course antibody producing cells. Most B cells situate
themselves in immune organs such as the spleen and wait for their
activation. Like T cells each B cell is only able to respond to
one specific antigen and each B cell responds to a different antigen.
The B cells have antibody on their cell surface which acts as the
receptors for antigen. B cells can receive stimulation in two ways.
Typically most antigens are first processed by antigen presenting
cells and then presented to the B cells at the same time as presentation
to Th cells. The B cell Thus normally receives two stimulating events.
First its antibody receptors bind to the antigen and second it receives
cytokine stimulation from stimulated Th cells. This form of activation
is called "T dependent".
A few antigens can directly activate B cells. These antigens are
free floating in solution and have not been processed in any way.
They are usually very large molecules that can bind to numerous
antibody receptors on a B cell simultaneously. This multiple binding
seems to trigger the B cell into a response without any stimulation
from Th cells. An activated B cell responds in similar fashion to
Th or Tc cells. The few cells responding to an antigen proliferate
into large clone populations. Most cells become "plasma cells".
These are large cells with a lot of cytoplasm and are entirely given
over to producing antibodies. These antibodies are released into
the blood stream to be carried to the site of infection. The B cells
themselves do not migrate to an infection site, it would be a waste
of time and energy and they would get in the way. Antibodies are
the long distance smart bombs of the immune system. They diffuse
throughout the entire body and only bind to the particular antigen
they were made for. A few of the clone cells that result from antigen
activation become memory cells. Like the T memory cells they store
the information about previous encounters with pathogens and if
there is any subsequent challenge these cells will proliferate faster
and produce antibody more quickly compared to virgin B cells.
Antigen
presenting cells
What do Langerhan's cells, interdigitating cells, follicular dendritic
cells, B cells and macrophages all have in common? Yep, they are
all antigen presenting cells (APCs). APCs are a heterogeneous population
of cells sourced from cells of both the innate and adaptive immune
systems. Most APCs are probably derived from the phagocytic line
but we are not really sure. Clearly B cells are a very different
cell type, not phagocytic at all, and there may be other different
cell populations. We can't make up our mind which cells are just
different looking phagocytes and which are unique cell types. For
example, when skin Langerhan's cells migrate to lymph nodes they
become interdigitating cells. It's also possible to artificially
make tissue cells in to APCs if we give them certain cytokine stimuli.
We think that hair follicle cells in alopecia areata may start to
present their own antigens to T cells in prolonged episodes of hair
loss.
T cells and B cells are blind and need antigens to be presented
to them. This is done by APCs expressing antigens on their cell
surface in conjunction with a molecule called the Major Histocompatibility
Complex (MHC something else we will have to talk about in more detail
later) T cells then "see" the antigen using their TCRs
and B cells see antigens via their cell surface antibody. APCs are
found primarily in the skin lymph nodes spleen and thymus, the areas
of high T or B cell concentration.
It is intriguing to note that B cells can both present antigen
and be stimulated by it. Here we have cascade mechanism. Initially
B cells are stimulated by antigen presented by other APCs. Once
stimulated, the B cells themselves can join in antigen presentation
to recruit even more B and T cells to the inflammatory reaction.
Conclusions
Well I think that covers all the immune system cells and their
basic function. I hope you got all that! We have a wide range of
cells with different functions. Cell functions for different clones
overlap with other cell clone functions so that even if a part of
the immune system is knocked out the immune system will still try
to respond. For example if the entire adaptive immune system is
knocked out, neutrophils will attempt to fill the gap as best they
can. Their response is far from perfect but it does help. Knock
out Tc cells and Th cells will proliferate to fill the gap. Knock
out Th cells and both B and Tc cells will try to fill the gap and
so on. Most of the cells in the adaptive immune system collect themselves
into organs and that will be the subject of the next chapter.
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