Interest in the immune
system started with Edward Jenner noticing that those milkmaids who contracted
cowpox were immune to smallpox. He inoculated a young boy with cowpox and then
with smallpox. The boy did not become sick. This sparked interest in the idea of
becoming immune to diseases. Louis Pasteur continued this work with the effect
of cholera on chickens. He found that aged pathogens had a lesser effect on the
body and thus the subject would not develop the disease. As well, if later
exposed to the unaltered pathogen, the subject would not react to it. This led
to today’s vaccine, which is an introduction of a weak pathogen to the body
for later immunization to it.
Today it is known that
immunization to foreign pathogens in the body is regulated by the body’s
defense system called the immune system. The system generates cells and other
proteins used to protect the body from the harm caused by microorganisms and
their products, which can be toxic. An example is bacterial endotoxin. The human
body has elements that keep antigens either out of the body or, once they are in
the body, fights them. Skin and mucous membranes keep foreign microorganisms out
of the body. The secretion of fatty acids and enzymes, fever, and activation of
white blood cells are the mechanisms that fight the foreign microorganisms once
they enter the body. The immune system has the ability to recognize the
difference between cells of the body and foreign cells. As well, the system has
memory of previous pathogens allowing for quick recognition and action if the
pathogen ever enters the body again.
There
are two “arms” to the immune system, the innate immune system and the
aquired immune system. Lymphocytes recognize and respond to specific foreign
material whereas macrophages and neutrophils nonspeicifcally destroy pathogens.
When
a pathogen enters the body there are many cells involved in destroying it. For
these cells to interact together a form of communication exists. The secretion
of a protein called a cytokine, by the different cells of the immune system is
what allows this communication. For example Interleukin 6 (IL-6) is a cytokine
produced by bone marrow, T-cells and activated macrophages. This cytokine
targets B cells, plasma cells, myeloid stem cells and hepatocytes. IL-6 promotes
differentiation of B cells into plasma cells, which then produce antibodies and
is involved in recruiting cells to sites in the inflammatory response. IL-6 is
the fist cytokine at the site of an infection and is important in stimulation of
other cells in the immune response.
During
an immune response macrophages become activated by stimuli such as cytokines
interferon gamma (IFN-y) such as produced by T cells. When active, macrophages
also produce cytokines that in turn activate T cells and other cells of the
immune system. These cytokines include Interleukin 1 (IL-1), Interleukin
6(IL-6), Interleukin 10 (IL-10) and Tumor Necrosis Factor
alpha
(TNFα). Other than cytokine production macrophages also engulf pathogens,
pulling them inside and destroying them in a process called phagocytosis. As
well, they secrete inflammatory mediators and cytotoxic proteins, which
eliminate virus-infected cells, tumor
cells and intracellular bacteria.
For a cell to be
stimulated by a cytokine a signal must be sent from the cell membrane to the
nucleus so that gene transcription can be initiated and the specific protein
produced. This is called cell signaling because a signal is sent via a cascade
of proteins and enzymes in the cell from the membrane where the original signal
is received to the nucleus where a response is generated.
One such pathway is driven by
Mitogen-Activated Protein Kinases (MAPk). The MAPk pathway is stimulated by
extra cellular signals which initiate a cascade of phosphorylation events
ultimately causing responses such as growth, differentiation, inflammation and
apoptosis. At each step an enzyme catalyzes the conversion of a proenzyme to an
active enzyme for use in the next step, these enzymes are known as kinases.
When the ligand bonds with the receptor the first step is activated by
small G proteins like Ras, Rap-1 or Rac. The cascade may then follow one or more
of three major paths, which are the MAPK/ERK pathway, SAPK/JNK pathway or the
p38 MAPK pathway. Each pathway induces a different response from the cell. ERK
(Extra-cellular Regulated Kinase) generally stimulates cell growth or
differentiation while the others affect inflammation and apoptosis.
There is evidence that
the elements in crude aqueous extracts of the Echinacea root may activate
macrophages. Echinacea is an herb originally used by the Native Americans to
cure respiratory infections. Today it is used to treat upper respiratory tract
infections and cancer. Research confirms that Echinacea is stimulates the immune
system through the activation of macrophages. It stimulates macrophages to
produce of IL-1, IL-6 TNFα and nitric oxide as well as increasing
phagocytosis. This research shows that Echinacea polysaccharide could
potentially be the basis of a novel immunotherpeutic tool. However, not much is
known about how Echinacea interacts with the cell to produce immunomodulatory
effects.