Back in the Roman Empire, immunists
were great landlords who had the power to form an army and do their own justice
without needing the agreement of local administrations. Immunity, from latin immunis, can be translated as
«exempt» which relates to the idea of privilege. From that point of
view, immunology could be the science of our “army” against diseases whereas
immunity would be the medical term applied for the privilege of not being sick.
Infantry and cavalry
Immunology can be defined by the
study of the immune system. The latter is a group of cells, tissues and
molecules that work together in order to act against a foreign threat that
could lead to infections or diseases. They are two types of immunity. On one
hand, innate immunity, the equivalent of the infantry, formed by cells that
identify danger and share the intel collected with the others (dendritic
cells), and cells who will destroy the intruder by releasing toxic molecules
and digesting him (granulocytes and macrophages). Innate immunity is called
unspecific for it answers as soon as there is an attack. It is the first line
of defense against our swear enemies, pathogens, as the definition for them is
anything that could start a disease. On the other hand, adaptive immunity, is
the cavalry which takes place a bit later. Its response is specific to an
intruder and the cells will memorize the enemy’s identity so as to be faster
the next attack. We distinguish two sub-groups within the adaptive immunity.
The humoral immunity which is led by B cells (LB) to produce antibodies. The
cellular immunity organized by several members of T cells (LT) community.
1: Innate and adaptive immune cells (Source: Adapted from Nature Reviews Cancer, 4, 11-22, 2004.)
Defense and attack establishment
Pathogen identification is different
for each immunity. For Innate immunity, it is founded on recognition of
particular patterns, pathogen associated molecular patterns. Those are the
banner of the enemy, the pathogen’s features, and are fragments of sugar or DNA
connected to a particular bacteria or virus. Innate immunity cells can also
detect damage associated with molecular patterns. When a cell is in a rough
state, some proteins which are normally within the cell are exposed around in
the environment and are associated as alarm signals. Those small molecules are
then recognized by receptors, much like locks and keys. This joining, just as a
soldier ringing an alarm bell, will trigger a signal inside the cell. Specific
structures will start forming (inflammasome, proteasome and phagosome) and can
be related to intelligence centres and prisons. All these events will finally
lead to an inflammatory response, a stimulation of innate immunity as well as
the enlisting and production of soldiers. The cavalry (adaptive immunity) will
be mobilized by means of messengers, the cytokines. The latter are small
functional signalization proteins who will coordinate the immune cells
interactions in the cellular environment.
2: Pathogen recognition by innate immunity (Source: Adapted from
Back-up and strategic strike
Concerning adaptive immunity,
pathogens recognition takes place in secondary lymphoid organs through antigen
receptors (locks) localized on our cavalrymen, T and B cells. Secondary lymphoid
organs are the equivalent of the army’s headquarters. They are particular zones
where immune cells gather together to share information. B cells will connect
directly to an antigen and will be transformed in plasmocytes in the purpose of
synthesizing specific antibodies against the antigen. Antibodies are the same
as yellow stickers stuck on our enemy and screaming to the world it must be
killed. The pathogen, covered with antibodies, will be addressed to our
infantry’s Spartacus, macrophages. They will literally destroy it in one bite,
since they will phagocytize (more or less gulp), digest and annihilate the
intruder. However, T cells, who are more of a strategic mindset, will need to
have the antigen presented to them through an intermediate called antigen
presenting cells (APC: mainly dendritic cells but sometimes macrophages and
LB). Those APC have a determinant role as they share information for
identifying the enemy to adaptive immune cells. There are several events that
should occurred for lymphocytes to be activated. First of all, the
immunological synapse. It can be represented as a handshake between the cavalry
and an infantry colonel just before an intel meeting. This physical connection
is done between MHC protein (Major Histocompatibility Complex) and the T cell
receptor (TCR). Secondly, costimulation proteins will gather near the synapse
to reinforce the interaction. Finally, the last signal allowing the cell
activation will be our little messengers, cytokines, which will be released around
the cells. Only then the cavalry will be able to act and to take arms in the
purpose of destroying our opponent and establishing an immune memory so as to
act faster face to another attack.
3: The immunological synapse between APC and LT (Source: Adapted from
Establishing and maintaining peace
Once the immune response is
launched, the immune cells will work together to destroy the pathogen. Immune
cells will phagocytose and release molecules (perforin, granzyme) to bombard
the enemy and to puncture its membrane and annihilate him. However, those
defense systems could be dangerous if let unattended for a long period of time.
It is a necessity to stop the immune response to avoid tissular damages such as
necrosis or weakening of cells foundation. Several mechanisms are going to take
place to reign in our soldiers. Let us begin with regulator T cells (Treg)
whose purpose is to regulate the immune response. They provide a tolerance for
our own antigens with the aim of avoiding autoimmune diseases. They are both
mediator and actor, just so would be a sergeant. Furthermore, receptor
internalization mechanisms will occur within the cells, so as our G.I. will not
be able to answer to the messengers. Apoptotic or stagnant cells will be
digested by macrophages or simple stay inactive within the cell environment.
Those mechanisms act like safeguard to avoid the immune system uproar.
mechanisms are complex, and many immune cells are still discovered nowadays.
Establishment and resolution of the immune response are well known and have
been studied in from and through. Innate and adaptive immunity bring an
immunitary defense and protection against pathogens. However, this system is
not without flaw since autoimmune disease exists and conducts our own soldiers
to attack ourselves. Finally, some cancer cells and viruses can escape our
vigilance thanks to mutations which give rise to a lack of acknowledgement of
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