The Inflammatory Response

When the body is first invaded

When a bacterial infection is established in the body, the purpose of the immune system is to control or eradicate
it. The initial reaction of the immune system to an infection varies, depending on the site which has been invaded
and on the nature of the invader. There can be many "triggers", that can spur the immune system into action. Here
are some of the ways in which the immune system can be activated.

If the invasion is in an area of the body that is primarily defended by macrophages, such as the lungs or
intestines, then these macrophages will be the first immune cells on the scene. They begin to digest the
invading organism, and by presenting antigens (proteins from the destroyed bacteria), they stimulate other cells
of the immune system into action.

Some bacteria, for example Staphylococcus Aureus and Salmonella Typhi, produce chemotaxins when they
enter the body, which betray their presence to the immune system, by acting as "breadcrumbs" which reveal the
location of the invader. Chemotaxins are chemicals that activate phagocytes, the immune cells whose function
it is to consume and destroy the invading bacteria.

Some bacteria first encounter, and are recognised by, the complement system, which in turn produces chemical
messengers (cytokines) that warn other cells of the immune system that the body has been invaded.

The invader may be recognised by the acquired immune system, i.e. the lymphocytes. These cells either
directly fight the infection themselves, or control other cells to do so.

Immune Cascade

All of the above methods have the effect of inducing phagocytes to migrate to the site of invasion. Once they
reach that site, the phagocytes are activated and begin their task of digesting and destroying the invading
bacteria. Once activated, they also produce more cytokines, which further activate other cells of the immune
system. In a sense, the initial immune reaction leads to a cascade of further immune reactions. Below is a list of
the chemical signals that are produced, which cells produce them and the effects that they have on the
metabolism.

Cytokines involved in the Inflammatory Response

Producing
Cytokine Action
cell

Stimulation of various cells, e.g. T cells, acts to initiate inflammation, induces

Interleukin-1 Macrophages
hypothalamus to increase body temperature

Interleukin-2 T cells Causes proliferation of activated T and B cells, induces antibody synthesis
 Interleukin-3 T cells Induces growth and differentiation of immune cells in bone marrow

Interleukin-4 T cells Promotes B cell growth and differentiation

Interleukin-5 T cells Induces differentiation of B cells, and activates some Microphages

T cells,
Interleukin-6 Costimulator of T cells, induces growth in B cells
Macrophages

Interleukin-10 T cells Activates B cells and inhibits Macrophage function

Interleukin-12 Macrophages Activates T cells and NK cells

Interleukin-13 T cells Induces proliferation of B cells and differentiation of T cells

Gamma- T cells, NK
Activates Macrophages
Interferon cells

Tumor Causes activation of some Microphages. Induces inflammation and fever.

Necrosis Macrophages Induces catabolism of muscle and fat, thus leading to cachexia (bodily
Factor wasting)

Transforming T cells,
Inhibits T cell growth and Macrophage activation
Growth Factor Macrophages

Lymphotoxin T cells Similar to TNF, activates Microphages

Not actually a cytokine, but an important chemical mediator that induces

Histamine Mast cells
blood vessel dilation and increases cell wall permeability

As you can see from the list above, the cells of the immune system communicate and co-operate in a complex
fashion. The full operation of the immune system is far from understood. An important point to note is that
invading organisms, if they interfere with any of the chemicals above, or the cells that produce them, can cause a
profound change on the bodies immune response to that organism.

Effects of the inflammatory response.

The primary physical effect of the inflammatory response is for blood circulation to increase around the infected
area. In particular, the blood vessels around the site of inflammation dilate, permitting increased blood flow to the
area. Gaps appear in the cell walls surrounding the infected area, allowing the larger cells of the blood, i.e. the
immune cells, to pass. As a result of the increased blood flow, the immune presence is strengthened. All of the
different types of cells that constitute the immune system congregate at the site of inflammation, along with a
large supply of proteins, which fuel the immune response. There is an increase in body heat, which can itself have
an anti-biotic effect, swinging the balance of chemical reactions in favour of the host. The main symptoms of the
inflammatory response are as follows.

The tissues in the area are red and warm, as a result of the large amount of blood reaching the site.
 The tissues in the area are swollen, again due to the increased amount of blood and proteins that are present.
The area is painful, due the expansion of tissues, causing mechanical pressure on nerve cells, and also due to
the presence of pain mediators.

Once the inflammatory process has begun, it continues until the infection that caused it has been eradicated.
Phagocytes continue to consume and destroy bacteria, the acquired immune system binds and disposes of
harmful toxins. Pus is produced, pus being the debris that is left over from the battle between the invader and the
immune system. The colour of the pus depends on the organism causing the infection.

How does the inflammatory response end?

Ideally, the inflammatory response should only last for as long as the infection exists. Once the threat of infection
has passed, the area should return to normal existence.

The actual process by which the inflammatory response ends is now only beginning to be understood. The key
element is a phenomenon known as "Apoptosis".

When cells of the body die in a normal fashion, e.g. by being irreparably damaged or by being deprived of
nutrients, this is known as Necrotic death. Recently, research has shown that cells can also be killed in another
way, i.e. by "committing suicide". On receipt of a certain chemical signal, most cells of the body can destroy
themselves. This is known as Apoptotic death. There are two main ways in which cells can commit Apoptosis.

1. By receiving an Apoptosis signal. When an chemical signal is received that indicates that the cell should kill
itself, it does so.
2. By not receiving a "stay-alive" signal. Certain cells, once they reach an activated state, are primed to kill
themselves automatically within a certain period of time, i.e. to commit Apoptosis, unless instructed otherwise.
However, there may be other cells that supply them with a "stay-alive" signal, which delays the Apoptosis of the
cell. It is only when the primed cell stops receiving this "stay-alive" signal that it kills itself.

The immune system employs method two above. The immune cells involved in the inflammatory response, once
they become activated, are primed to commit Apoptosis. Helper T cells emit a stay-alive signal, and keep emitting
that signal for as long as they recognise foreign antigens in the body, prolonging the inflammatory response. It is
only when the infection has been eradicated, and there is no more foreign antigen that the helper T cells stop
emitting the stay-alive signal, thus allowing the cells involved in the inflammatory response to die off.

If foreign antigen is not eradicated from the body, or the helper T cells do not recognise that fact, or if the immune
cells receive the stay-alive signal from another source, then chronic inflammation may develop.

Copyright © The Crohnie 1996-2015: source http://primer.crohn.ie/the-inflammatory-response